Does Mouth Taping Help You Sleep?Yifei Fang - Getty Images
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Sipping on chamomile tea, popping a melatonin, diffusing lavender essential oil—we will try any natural sleep aid to get a better night’s rest. The latest bedtime routine trend on social media? Mouth taping for sleep. But what is mouth taping? Does it actually work? Experts are skeptical.
Meet the Experts: Angela Holliday-Bell, M.D., board-certified physician, certified sleep specialist, and host of ; Bijoy E. John, M.D., sleep specialist and founder and medical director of Sleep Wellness Clinics of America and Sleep Fix Academy; James Rowley, M.D., AASM Board of Directors president and spokesperson; Abhay Sharma, M.D., sleep physician leading the University of South Florida’s ENT Sleep and Snoring Center.
If you find yourself curious about the effectiveness of this controversial trend, you’re not alone. Ahead, our experts explain what mouth taping is, whether it might help you sleep, why it can be dangerous, and what to know before you consider trying it.
What is mouth taping?
Mouth taping involves placing a type of tape over the mouth to prevent mouth breathing, forcing the individual to breathe through their nose while sleeping, says Angela Holliday-Bell, M.D., board-certified physician, certified sleep specialist, and host of .
While many social media users have demonstrated the technique using special shaped stickers that mold to your mouth, any tape that is safe to use on human skin (like this one) can theoretically be used for mouth taping.
Does mouth taping help with snoring?
While there isn’t an extensive amount of scientific literature on the subject, the limited research that has been done shows that yes, it can decrease snoring, says Abhay Sharma, M.D., sleep physician leading the University of South Florida’s ENT Sleep and Snoring Center. “Snoring occurs when tissue in the throat vibrates during breathing. Mouth opening while sleeping worsens snoring because it allows the tongue to fall back, which narrows the airway—this can increase snoring,” he explains. The theory behind mouth taping is that by forcing nasal breathing, you maximize your airway by preventing that collapse, says Dr. Sharma.
Still, mouth taping is no guarantee that you won’t keep your partner up with your snores, says Bijoy E. John, M.D., sleep specialist and founder and medical director of Sleep Wellness Clinics of America and Sleep Fix Academy. He agrees that the main cause of snoring while sleeping is from the tongue collapsing backwards resulting in narrowing of the airway, but “mouth taping has no direct impact in this process,” he notes.
Potential benefits of mouth taping
Humans have evolved, like other mammals, to breathe through the nose, says Dr. Sharma. “Any type of mouth breathing is working against normal human physiology,” he explains. By closing the mouth, air now can be directed through the nose into the upper airway and into the lungs, says Dr. John. “This can reduce rapid breathing and the workload on the body,” he explains.
Breathing through your nose allows you to filter air that you breathe in while sleeping and also warms and humidifies the air which can reduce irritation as it travels through your airways and into your lungs, explains Dr. Holliday-Bell. “Breathing through your nose also aids in the elasticity of the lungs and leads to more oxygen absorption in your blood.” All of these things help to improve your sleep quality, she notes. The thought is that mouth taping can lead to nose breathing in hopes of obtaining the above benefits.
Again, the research is limited on this trend, but people who have tried mouth taping report numerous benefits, says Dr. Sharma. Here are a few he highlights:
Potential risks of mouth taping
While mouth taping may seem like an easy fix to better sleep, there are important risks to be aware of before you try locking your lips at night.
If someone truly needs to breathe through their mouths while sleeping due to nasal obstruction or other reasons, mouth taping can lead to difficulty breathing at night, says Dr. Holliday-Bell. “It can also lead to aspiration (where contents of your stomach get into your lungs due to reflux or vomiting).” Some people may experience irritation from the tape being used as well, she adds.
For those with sleep apnea, people’s throats close off at night while they sleep, points out Dr. Sharma. “Mouth opening is an emergency response to restriction in nasal breathing. As a result, anyone with sleep apnea, especially more severe cases, could significantly worsen the obstruction.” This could even put their life at risk, he notes. Along with sleep apnea, medical conditions like asthma, congestive heart failure, emphysema, and COPD could also pose a risk when it comes to mouth opening, says Dr. John.
Another risk to keep in mind is that mouth taping can reduce oxygen levels while you are sleeping, which could lead to serious sleep disorders, like obstructive sleep apnea, sleep disruptions, asphyxiation and even death, says James Rowley, M.D., AASM Board of Directors president and spokesperson.
Should you try mouth taping?
Though there are no guidelines for using this remedy, it is especially important to rule out significant obstructive sleep apnea prior to even considering mouth taping, says Dr. Sharma. “In addition, you need to ensure you have an open nasal airway—anyone who has nasal obstruction issues could be putting their life in danger by mouth taping.” If both issues have been ruled out, mouth taping can be a technique to use to decrease snoring, Dr. Sharma notes.
If you are someone who tends to wake up with dry mouth or have been told you mouth breathe at night, taping could have some benefit, says Dr. Sharma. “Again, the major point to make here is to confirm any health condition, especially sleep apnea, has been ruled out,” he advises. Dr. John agrees that “those who are otherwise healthy and training for competitions could potentially try” mouth taping.
When to see a doctor about mouth taping
If you snore or are considering options for improving your sleep, talk to your doctor about trying mouth taping, advises Dr. Sharma. “The first step would be ruling out sleep apnea and any nasal disorders,” he notes.
Most importantly, you should talk to your doctor to pinpoint a root cause of mouth breathing, says Dr. Sharma. “Problems like allergies, a deviated septum or tonsil hypertrophy all could be contributing to a restricted airway at night.”
As with many social media trends, mouth taping can be dangerous and should not be used as a method to address specific sleep concerns, says Dr. Rowley. “If you are snoring excessively, it could be a sign of a larger issue, such as obstructive sleep apnea, which requires personalized treatment from a sleep specialist.” If you are wondering if a sleep trend is safe or “right” for you, consult with your primary healthcare provider, he advises. You can also use theAASM Sleep Center Locator tool to find an accredited sleep center in your area.
Sipping on chamomile tea, popping a melatonin, diffusing lavender essential oil—we will try any natural sleep aid to get a better night’s rest. The latest bedtime routine trend on social media? Mouth taping for sleep. But what is mouth taping? Does it actually work? Experts are skeptical.
Meet the Experts: Angela Holliday-Bell, M.D., board-certified physician, certified sleep specialist, and host of The Art of Sleep; Bijoy E. John, M.D., sleep specialist and founder and medical director of Sleep Wellness Clinics of America and Sleep Fix Academy; James Rowley, M.D., AASM Board of Directors president and spokesperson; Abhay Sharma, M.D., sleep physician leading the University of South Florida’s ENT Sleep and Snoring Center.
If you find yourself curious about the effectiveness of this controversial trend, you’re not alone. Ahead, our experts explain what mouth taping is, whether it might help you sleep, why it can be dangerous, and what to know before you consider trying it.
What is mouth taping?
Mouth taping involves placing a type of tape over the mouth to prevent mouth breathing, forcing the individual to breathe through their nose while sleeping, says Angela Holliday-Bell, M.D., board-certified physician, certified sleep specialist, and host of The Art of Sleep.
While many social media users have demonstrated the technique using special shaped stickers that mold to your mouth, any tape that is safe to use on human skin (like this one) can theoretically be used for mouth taping.
Does mouth taping help with snoring?
While there isn’t an extensive amount of scientific literature on the subject, the limited research that has been done shows that yes, it can decrease snoring, says Abhay Sharma, M.D., sleep physician leading the University of South Florida’s ENT Sleep and Snoring Center. “Snoring occurs when tissue in the throat vibrates during breathing. Mouth opening while sleeping worsens snoring because it allows the tongue to fall back, which narrows the airway—this can increase snoring,” he explains. The theory behind mouth taping is that by forcing nasal breathing, you maximize your airway by preventing that collapse, says Dr. Sharma.
Still, mouth taping is no guarantee that you won’t keep your partner up with your snores, says Bijoy E. John, M.D., sleep specialist and founder and medical director of Sleep Wellness Clinics of America and Sleep Fix Academy. He agrees that the main cause of snoring while sleeping is from the tongue collapsing backwards resulting in narrowing of the airway, but “mouth taping has no direct impact in this process,” he notes.
Potential benefits of mouth taping
Humans have evolved, like other mammals, to breathe through the nose, says Dr. Sharma. “Any type of mouth breathing is working against normal human physiology,” he explains. By closing the mouth, air now can be directed through the nose into the upper airway and into the lungs, says Dr. John. “This can reduce rapid breathing and the workload on the body,” he explains.
Breathing through your nose allows you to filter air that you breathe in while sleeping and also warms and humidifies the air which can reduce irritation as it travels through your airways and into your lungs, explains Dr. Holliday-Bell. “Breathing through your nose also aids in the elasticity of the lungs and leads to more oxygen absorption in your blood.” All of these things help to improve your sleep quality, she notes. The thought is that mouth taping can lead to nose breathing in hopes of obtaining the above benefits.
Again, the research is limited on this trend, but people who have tried mouth taping report numerous benefits, says Dr. Sharma. Here are a few he highlights:
Improvement in dry mouth in the morning
Less snoring
Feeling more rested
Better sleep
Potential risks of mouth taping
While mouth taping may seem like an easy fix to better sleep, there are important risks to be aware of before you try locking your lips at night.
If someone truly needs to breathe through their mouths while sleeping due to nasal obstruction or other reasons, mouth taping can lead to difficulty breathing at night, says Dr. Holliday-Bell. “It can also lead to aspiration (where contents of your stomach get into your lungs due to reflux or vomiting).” Some people may experience irritation from the tape being used as well, she adds.
For those with sleep apnea, people’s throats close off at night while they sleep, points out Dr. Sharma. “Mouth opening is an emergency response to restriction in nasal breathing. As a result, anyone with sleep apnea, especially more severe cases, could significantly worsen the obstruction.” This could even put their life at risk, he notes. Along with sleep apnea, medical conditions like asthma, congestive heart failure, emphysema, and COPD could also pose a risk when it comes to mouth opening, says Dr. John.
Another risk to keep in mind is that mouth taping can reduce oxygen levels while you are sleeping, which could lead to serious sleep disorders, like obstructive sleep apnea, sleep disruptions, asphyxiation and even death, says James Rowley, M.D., AASM Board of Directors president and spokesperson.
Should you try mouth taping?
Though there are no guidelines for using this remedy, it is especially important to rule out significant obstructive sleep apnea prior to even considering mouth taping, says Dr. Sharma. “In addition, you need to ensure you have an open nasal airway—anyone who has nasal obstruction issues could be putting their life in danger by mouth taping.” If both issues have been ruled out, mouth taping can be a technique to use to decrease snoring, Dr. Sharma notes.
If you are someone who tends to wake up with dry mouth or have been told you mouth breathe at night, taping could have some benefit, says Dr. Sharma. “Again, the major point to make here is to confirm any health condition, especially sleep apnea, has been ruled out,” he advises. Dr. John agrees that “those who are otherwise healthy and training for competitions could potentially try” mouth taping.
When to see a doctor about mouth taping
If you snore or are considering options for improving your sleep, talk to your doctor about trying mouth taping, advises Dr. Sharma. “The first step would be ruling out sleep apnea and any nasal disorders,” he notes.
Most importantly, you should talk to your doctor to pinpoint a root cause of mouth breathing, says Dr. Sharma. “Problems like allergies, a deviated septum or tonsil hypertrophy all could be contributing to a restricted airway at night.”
As with many social media trends, mouth taping can be dangerous and should not be used as a method to address specific sleep concerns, says Dr. Rowley. “If you are snoring excessively, it could be a sign of a larger issue, such as obstructive sleep apnea, which requires personalized treatment from a sleep specialist.” If you are wondering if a sleep trend is safe or “right” for you, consult with your primary healthcare provider, he advises. You can also use theAASM Sleep Center Locator tool to find an accredited sleep center in your area.
Madeleine, Prevention’s assistant editor, has a history with health writing from her experience as an editorial assistant at WebMD, and from her personal research at university. She graduated from the University of Michigan with a degree in biopsychology, cognition, and neuroscience—and she helps strategize for success across Prevention’s social media platforms.
Engineered stone, a popular choice for countertops, has proven
popular due to its aesthetic appeal, cost, durability, and
versatility. However, in recent years there has been focus on the
serious health concerns linked to engineered stone including
long-term respiratory illness and premature death. In this article,
we will delve into what engineered stone is, the serious
respiratory health problems it poses for workers, and the call for
the ban of its use in Australia.
What is engineered stone?
Engineered stone, often known by but not limited to brand names
like Caesarstone, Silestone, or Quantum Quartz, is a popular
material used for kitchen and bathroom countertops, as well as
other interior surfaces. It is made by combining crushed natural
stone, such as quartz, with polymer resins and pigments to create a
durable and attractive surface. The result is a versatile material
with a wide range of colours and patterns that mimics the look of
natural stone at a much cheaper cost, hence the popularity.
What exactly are the health risks linked to engineered
stone?
While engineered stone offers many advantages, there is a
notable downside associated with its production and fabrication.
Engineered stone contains a high concentration of crystalline
silica, a naturally occurring mineral found in quartz, which poses
a significant respiratory health risk when airborne. The fine dust
produced during the cutting, grinding, and polishing of engineered
stone surfaces can be inhaled by workers and lead to severe health
problems, including:
i. Silicosis–
prolonged exposure to respirable crystalline silica dust can lead
to silicosis, an irreversible and often debilitating lung disease.
Silicosis causes scarring of lung tissue, leading to symptoms such
as coughing, breathlessness, and increased susceptibility to
respiratory infections. There is no cure for silicosis and if
developed, life expectancy is diminished.
ii. Lung cancer – inhaling
crystalline silica over an extended period is associated with an
increased risk of lung cancer. Most cases are not curable and
significantly reduce a worker's life expectancy.
iii. Chronic Obstructive Pulmonary Disease
(COPD)– silica exposure can
contribute to the development of COPD, a progressive lung condition
which includes emphysema and chronic bronchitis and is
characterised by breathing difficulties and shortness of
breath.
Silica dust exposure also increases the risk of developing
chronic kidney disease, autoimmune disorders (such as scleroderma
and systemic lupus erythematosus) and other adverse health effects,
including an increased risk of activating latent tuberculosis, eye
irritation and eye damage. The risk posed by engineered stone is
being touted as the new asbestos in terms of the
health ramifications for workers in Australia.
In response to growing concern over the health risks associated
with engineered stone, the NSW government has previously introduced
amendments to the Work Health and Safety Act 2011 (NSW)
which were designed to safeguard the health and well-being of
workers in the engineered stone industry.
These measures included reduced exposure limits, mandatory
health assessments, improved monitoring, and compliance as well as
education and training, and dust control measures which required
employers to implement effective dust control measures, including
proper ventilation, wet cutting methods, and the use of suitable
personal protective equipment.
To date however, persons conducting a business in this industry,
workers and regulators have failed to ensure the health and safety
of all workers working with engineered stone. In particular, the
lack of effective monitoring and compliance, despite some smaller
and sporadic wins, remains a big issue within the industry.
SafeWork Australia (SWA) has called for a
complete ban of the use of engineered stone in Australia. It has
undertaken significant work since 2018 to improve WHS arrangements
to prevent dust diseases including silicosis. This has included
amendments to NSW WHS legislation, however in February 2023 WHS
ministers agreed to SWA's recommendations to address workplace
exposure to respirable crystalline silica through national
awareness and change in behaviour initiatives, and further
regulation for all materials across all industries (which includes
engineered stone).
SWA undertook extensive analysis and consultation on the impacts
of a prohibition on the use of engineered stone and provided its
decision in a report to WHS Ministers on 16 August 2023 for
their consideration. The expert analysis undertaken shows that dust
from engineered stone poses unique hazards, and there is no
evidence that lower silica engineered stone is safer to work with,
meaning there is no safe level of exposure for workers. SWA has
recommended a prohibition on the use of all engineered stone,
irrespective of the crystalline silica content. There is also a
recommendation of the introduction of a licensing scheme to ensure
appropriate controls are in place to protect worker health when
engineered stone already in place needs to be removed, repaired, or
modified.
Silicosis and dust diseases pose an unacceptable health risk to
workers in Australia, and it is important to note that there are
significant financial and non-financial costs associated with being
diagnosed with silicosis or a dust disease, including significant
physical and emotional harm, the reduced ability to work, reduced
quality of life and ultimately premature death of workers. There
are also significant costs to the public health system and in turn
our economy.
SWA recommends urgent government intervention, due to the
disproportionate number of silicosis cases in engineered stone
workers, the younger age of diagnosis of silicosis and dust related
diseases in engineered stone workers, and the impacts on workers,
their families, and the wider community. The decision to prohibit
the use of some or all engineered stone is a matter for WHS
ministers who will meet later this year. It is clear that while
engineered stone revolutionised interior design, the long-term
health risks for workers involved in its fabrication and
installation outweighs the gain.
The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.
Anyone who has experienced a red air day knows the metallic taste of air pollution that leaves a sting in your nose and lungs. On red air days when pollution hits unhealthy levels people are advised to stay inside and avoid outdoor activities especially the elderly, children, pregnant women, and those who suffer from respiratory illnesses.
Now, guess what is the leading cause of toxic air in most places?
MIAMI - JULY 11: Exhaust flows out of the tailpipe of a vehicle at , "Mufflers 4 Less", July 11, ... [+] 2007 in Miami, Florida. Florida Governor Charlie Crist plans on adopting California's tough car-pollution standards for reducing greenhouse gases under executive orders he plans to sign Friday in Miami. (Photo by Joe Raedle/Getty Images)
Getty Images
Internal combustion engines fueled by gas or diesel are spewing dirty pollution into our lungs and atmosphere. More than two thirds of Americans rely on personal automobiles for day-to-day travel. And transportation is now the United States’ largest source of the greenhouse gas emissions accelerating climate change, with light-duty vehicles alone responsible for nearly 60% of that sector’s climate pollution.
Tackling our pervasive air pollution problem requires cutting tailpipe pollution from the cars we drive. Fortunately, we have a proven tool to make vehicles cleaner so we can all breathe easier: tailpipe emissions standards.
Last week the U.S. Environmental Protection Agency pulled this tool out of the clean air toolbox. The EPA made history by adopting new multi-pollutant rules for light-duty and smaller medium-duty vehicles limiting tailpipe pollution that poisons the air we breathe and accelerates climate change. These updated standards compel automakers to adopt the latest clean technologies to ensure new vehicles will be cleaner than ever before.
Everyone, everywhere should have the choice to make their next car a clean car. Americans who care about reducing pollution deserve the choice to drive electric.
Polluters Want You to Loathe the EPA’s Limits on Pollution
Air pollution harms 36 percent of the U.S. population—or nearly 120 million people. According to the American Lung Association, more than 1 in 3 Americans live in places with unhealthy levels of air pollution, which affects lung development in children and can cause emphysema, asthma, chronic bronchitis, and other respiratory diseases. People of color and lower-income individuals are disproportionately impacted by air pollution.
Anyone who likes breathing cleaner air should celebrate this moment. But corporations that profit from selling the vehicles that pollutes our air and the petroleum that burns a hole in our wallets view these standards as a threat. They say these standards threaten American freedoms and consumer choice.
But the truth is that these updated pollution limits are long overdue and will benefit all Americans by cleaning the air we breathe and giving consumers the choice to get off the expensive fossil fuel rollercoaster.
Consider the American Fuel & Petrochemical Manufacturers’ launch of a “major seven-figure issue campaign across seven critical states—Pennsylvania, Wisconsin, Michigan, Nevada, Arizona, Ohio and Montana—and the Beltway, all aimed at informing Americans about the Biden administration’s efforts to ban new gas, diesel and flex fuel vehicles from the U.S. market.”
In other words, profit-driven corporate polluters responded to the EPA’s updated tailpipe emissions standards by actively manipulating the American public into thinking the standards are unwarranted. Their public disinformation campaign wants people to think the rules are a ban on gas cars.
That is simply false. By law, the EPA does not and cannot ban technologies or modes of transportation. The EPA’s standards are technology-neutral, performance-based, and informed by science and peer-reviewed research.
The Clean Air Act, signed into law in 1970, authorizes and directs the EPA to establish National Ambient Air Quality Standards to protect public health and welfare, to regulate hazardous air pollutant emissions. The Clean Air Act also directs the EPA to regulate emissions from vehicles and engines, and to adapt the standard over time.
The earliest standards for light-duty vehicles required a 90 percent reduction in emissions from hydrocarbons, nitrogen oxides, and carbon monoxide—which drove the development of new engine and emission control technologies, such as the catalytic converter, and a switch to unleaded fuel.
Before the Clean Air Act was signed, our cities choked on air pollution so thick that breathing New York City’s air was as bad as smoking two packs of cigarettes per day, and Los Angeles suffered through unhealthy levels of air pollution more than 200 days a year.
(Original Caption) 6/13/1979-Los Angeles, CA- A lone spectator views a smog-covered downtown Los ... [+] Angeles 6/13. Sun-scorched southern California, still broiling in sweltering 100-degree mercury level now faces a grimy layer of eye-stinging smog. The hot, desert winds responsible for both the current heat wave and clear skies had diminished by late 6/13 and pollution officials issued gloomy predictions of filthy air quality.
Bettmann Archive
50 years later, our air is far cleaner. But despite decades of progress in reducing harmful emissions, air pollution from motor vehicles continues to harm public health, welfare, and the environment. Gas-powered vehicles will always belch ozone, climate pollution, particulate matter, and other toxic chemicals into our air.
These same corporate polluters who are fighting the EPA’s clean air action today have fought against clean air for decades, all for the same reason – profit.
The EPA’s updated standards help level the playing field for more advanced technologies, like battery electric vehicles, to compete in the market. They signal to the auto industry that now is the time to capitalize on fast-falling EV battery costs to deliver more affordable clean vehicle options for all consumers.
Most importantly, the EPA’s rules fix market failures that have allowed corporate fossil fuel profiteers to dump pollution and rising fuel costs on the American public, contaminating the air we breathe while compromising our health and the stability of the climate.
Better Tailpipe Pollution Standards Mean Better Quality of Life
By setting responsible limits on tailpipe pollution the EPA’s updated standards put the U.S. on a new trajectory for cleaner air, better health, and a stable climate. These rules also mean more affordable clean vehicle models on the road for decades to come, saving consumers money every year over the vehicles’ lifetimes. Today, EV models are cheaper to fill than gas vehicles in every state, putting money back in people’s wallets with every trip they take
Data shows electric vehicles are cheaper to fill up than gas vehicles in every state.
Energy Innovation
The EPA’s final rule adopts more stringent emissions standards for criteria pollutants and greenhouse gases for model years 2027-2032 for light-duty vehicles (passenger vehicles), as well as Class 2b and 3 medium-duty vehicles (classes are based on the gross vehicle weight rating; a Ford F-250 is a class 2b vehicle, whereas a Ford F-350 is a class 3 vehicles).
Reduce harmful air pollutants to the tune of 8,700 tons of particulate matter, 36,000 tons of nitrogen oxides, and 150,000 tons of volatile organic compounds in 2055. These pollutants contribute to smog, soot, and bad air days.
Provide $13 billion in annual health benefits.
Reduce approximately 7.2 billion metric tons in net transportation sector CO2 emissions between 2027 and 2055 (the largest source of greenhouse gas emissions at 29 percent of our overall total).
Provide regulatory incentives for vehicle manufacturers to produce engines that emit fewer harmful pollutants, helping more people choose cleaner cars.
Increase zero-emission battery electric vehicle sales over time, ranging from 26% of all new vehicle sales in 2027 to 56% in 2032
Provide $99 billion in annualized net benefits to society through the year 2055; this includes $46 billion in reduced annual fuel costs and nearly $16 billion in reduced maintenance and repair costs for drivers.
Save consumers an average of $6,000 over the lifetime of a new clean vehicle.
Expand consumer choice for American drivers.
Strong Standards Plus New Incentives Will Clean the Air for Generations to Come
The EPA’s updated standards combined with new clean vehicle incentives in the Inflation Reduction Act and new funding in the Bipartisan Infrastructure Law are poised to transform the way we get around. Tax incentives and new funding for vehicles, infrastructure, manufacturing, and the entire clean vehicle supply chain can propel the U.S. toward a transportation transformation.
As it has done for the past 50 years, the EPA is improving air quality. These updated standards reflect significant investments in clean vehicle technologies that the auto industry is already making, and they support growing consumer demand for clean air and a climate safe future.
In time, the updated standards could leave toxic red air days in the rearview mirror - something that will help us all breathe easier.
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Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with irreversible airflow limitation and a leading cause of death worldwide. COPD is characterized by chronic bronchitis and emphysema, and is associated with malnutrition, muscle weakness, and an increased risk of infection. Although pulmonary tests are considered as the gold standard for COPD diagnosis, they cannot detect early stages of COPD, leading to underdiagnosis. This emphasizes the need for specific biomarkers for early diagnosis, classification, and clinical interventions.
Recent studies suggested that changes in lipids, amino acids, glucose, nucleotides, and microbial metabolites in lungs and intestine, can effectively diagnose early COPD. Metabolomics, a discipline that analyzes different metabolites from body fluids, has emerged as a prominent technique for COPD assessment. However, there are no studies that identify and summarize the metabolites that significantly change during COPD.
A recent review by Dr. Wenqian Wu, Dr. Zhiwei Li, Dr. Tiantian Zhang, and Dr. Hongmei Zhao from the Peking Union Medical College, along with Dr. Yongqiang Wang from 302 Hospital of China Guizhou Aviation Industry Group, and Dr. Chuan Huang at the Chinese Academy of Medical Sciences, provided an in-depth account of the advances in metabolomics of COPD over the last five years, highlighting some potential diagnostic markers and therapeutic targets. Their study was made available online on December 8, 2023, and published in Volume 1, Issue 4 of the journal Chinese Medical Journal Pulmonary and Critical Care Medicine.
Sharing the motivation behind their study, Dr. Tiantian Zhang and Dr. Hongmei Zhao explain, “In addition to altered metabolites from body fluids, increasing evidence has shown that metabolites from pulmonary and intestinal microbes could help us understand the pathogenesis of COPD and the complex regulation underlying this disease.”
Many studies have reported that the three major nutrients, namely protein, lipids, and glucose, along with nucleotide metabolites are closely associated with COPD development and progression.
They found that levels of lipids like sphingolipids and their metabolites, cholesterol, and high-density lipoprotein (HDL), are significantly changed in individuals with COPD. This leads to oxidative stress, inflammation, lipotoxicity, and thus impaired lung function. Various studies suggested that reversing abnormal lipid metabolism and administration of beneficial lipids, might alleviate COPD effects and cardiopulmonary comorbidities.
Dysregulation of amino acid metabolism led to accumulation of harmful metabolites, such as desmosine, isodesmosine, and elastin peptide, which aggravate the damage to the lungs. Furthermore, COPD patients have abnormal levels of amino acids and reduced synthesis capacity of antioxidant carnosine. Some studies suggested that supplementation with amino acids and N-acetylcysteine might be able to regulate amino acid metabolism in COPD.
Glucose metabolism is crucial for energy generation and triggering the immune system. However, this metabolism is dysfunctional in COPD patients resulting in chronic fatigue, muscle weakness and an impaired immune response to pathogens. Further investigation revealed that COPD patients have impaired nucleotide metabolism leading to abnormal levels of adenosine triphosphate (ATP), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). Nucleotide metabolism impacts on metabolic processes and further studies are warranted to investigate the correlation between nucleotide metabolism and metabolism of lipids, amino acids, and glucose.
Besides metabolic disorders, microorganisms and their metabolites also play a key role in COPD pathogenesis. Individuals with COPD are prone to microbial colonization in their lower respiratory tract. The authors found that both pulmonary and intestinal microbes and their metabolites invade and impact the lungs. Different studies have identified certain common bacteria associated with lung disorders - Streptococcus, Haemophilus influenzae (H. influenzae), Pseudomonas aeruginosa, Campylobacter, to name a few. H. influenzae forms biofilm in the lower airways that acts as a bacterial depot leading to recurrent infections, microbial resistance, evasion of host immune system. Although current studies mainly focus on the bacterial microbiome, fungi and viruses are equally important and demand further studies.
Interestingly chronic lung disorders like COPD impair the gut membrane, increasing gut permeability, microbial movement, and endotoxin release resulting in gut dysbiosis (disease induced imbalance in microbial populations), and a weakened immune response. The intestinal microbiome of COPD patients consists predominantly of microorganisms that reduce lung function, further establishing the correlation between gut microbiome and COPD. On the other hand, gut microorganisms and their metabolites like short chain fatty acids might play a crucial role in alleviating COPD. Thus, gut microflora might be a potential marker for early diagnosis and treatment of COPD.
Overall, this study suggested that efficient regulation of lipid, amino acid, glucose, and nucleotide metabolism along with pulmonary and gut microbial metabolism is essential for COPD management. Dietary modifications to a low-carbohydrate diet and increasing fiber, antioxidant, and vitamin uptake help in COPD prevention.
Dr. Zhang and Dr. Zhao conclude by saying, “Dietary regulation prevents or suppresses respiratory infections by regulating the intestinal microenvironment, which is surprisingly effective in alleviating the symptoms of COPD. We emphasize that intensified dietary management may be among the most feasible methods to improve metabolism in the body.”
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Reference
Titles of original papers: Advances in metabolomics of chronic obstructive pulmonary disease
Journal: Chinese Medical Journal Pulmonary and Critical Care Medicine
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
Patients with severe emphysema experienced significant and durable clinical improvements over 24 months with bronchoscopic lung volume reduction (BLVR) using the Spiration Valve System (SVS), which maintained an acceptable safety profile, according to study findings published in the Annals of the American Thoracic Society.
In the EMPROVE trial of patients with severe heterogeneous emphysema (ClinicalTrials.gov Identifier: NCT01812447), BLVR/SVS demonstrated improvements in lung function, dyspnea, and quality-of-life (QOL) over 24 months of use. For the current report, researchers evaluated follow-up data from patients enrolled in EMPROVE to assess BLVR/SVS efficacy and safety for patients’ second year of device use.
EMPROVE, a prospective, open-label, randomized controlled trial, enrolled 172 patients at 31 sites across Canada and the United States from October 2013 to mid-December 2019. Patients, who were at least 40 years of age, initially were assigned in a 2:1 ratio to the treatment group (n=113) and to a control group (n=59). After the initial 12 months of EMPROVE, 96 patients remained evaluable in the treatment group and 43 patients in the control group. After the 24-month follow-up period, 80 patients in the treatment group and 34 patients in the control group remained evaluable.
At baseline, no between-group differences were discernible in participants’ high-resolution computed tomography, plethysmography, pulmonary function, or QOL.
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The results of the EMPROVE study indicate a marked improvement in lung function, QOL, and dyspnea in patients in the SVS treatment group, which remained durable for at least 24 months.The results of the EMPROVE study indicate a marked improvement in lung function, QOL, and dyspnea in patients in the SVS treatment group, which remained durable for at least 24 months.
The researchers found forced mean (SD) expiratory volume in 1 second (FEV1) improved significantly and continued across 24 months in the treatment group (n=71) compared with the control group (n=30) (-0.082L [0.156] vs 0.005L [0.163], respectively). In the treatment group, 19.7% (14/71) of patients showed FEV1 response at 24 months, although this was not statistically significant compared with the control group (P =.57).
The St. George’s Respiratory Questionnaire and the COPD (chronic obstructive pulmonary disease) Assessment Test showed that significant improvement was maintained.
The researchers noted the modified Medical Research Council dyspnea scale score indicated the treatment group experienced significantly less dyspnea vs the control group. No between-group differences were noted in adverse events at 24 months. Acute COPD exacerbation rates were similar (treatment group, 13.7% [14/102]; control group, 15.6% [7/45]). Pneumothorax rates were low (treatment group, 1.0% [1/102]; control group, 0.0% [0/45]).
The researchers stated there were no occurrences of unexpected serious device-related adverse events (SAEs) between 12 and 24 months; however, 2 device-related deaths occurred from baseline to 12 months. Overall mortality rates at 24 months were 18% in the treatment group and 15% in the control group (P =.81). Patients who died at 24 months vs those who survived were older at baseline and had a significantly lower 6-minute-walk distance and poorer lung function at baseline.
Study limitations include the unblinded design, which lead to potential bias that was reflected in the subjective parameters of the control group.
“The results of the EMPROVE study indicate a marked improvement in lung function, QOL, and dyspnea in patients in the SVS treatment group, which remained durable for at least 24 months,” the researchers concluded. The study authors wrote, “The safety profile remains satisfactory, with minimal device-related issues in this longer follow-up period.”
Disclosure: This research was supported byOlympus Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
It is learnt that a group of residents from Panaji have reportedly filed two petitions in the Bombay High Court at Goa, urging urgent directions to the government and the Imagine Panaji Smart City Development Corporation (IPSCDL) to alleviate the inconvenience and dust pollution caused by unplanned Smart City projects. The ongoing works has left most of the roads and lanes being dug up. This has caused a lot of dust pollution affecting the health of the residents especially children and the elderly population. Imagine a newborn or an infant breathing in dust-filled air. Dust particles are known for their potential to cause respiratory and cardiovascular health problems. They can also irritate eyes, throat and skin.
Regular dust inhalation can greatly increase one's risk of lung disease and cancer because it weakens the lungs and contributes to disorders like chronic bronchitis. For people with respiratory conditions like asthma, chronic obstructive pulmonary disease (COPD) or emphysema even small increases in dust concentration can make their symptoms worse. According to health experts, air pollution also plays a major part in exacerbating other ailments such as diabetes and sleep apnea. It would hence be in the fitness of things to screen residents of Panaji city for any lung disease due to dust pollution. A white-paper on the respiratory health of residents of Panaji would be welcome.
Adelmo Fernandes, Vasco
Respect sanctity of Basilica
Recently the Central Govt announced a package of Rs 17 crore for the preparation of the works to be undertaken as there will be the Exposition of the Relics of St Francis Xavier fondly known as Goemch Saib.
This happens once in ten years, where the pilgrims and people of other faiths from all over the world and India visit Old Goa to have a lifetime closer look at the Holy Relics of the saint.
The Basilica is under the Archaeological Survey of India and hence the area that has been earmarked as heritage site and has to be maintained by the Govt of India. Catholics should pray that the money sanctioned is used for the purpose that will make the area used as a pilgrimage site and not to promote tourism that will destroy the sanctity of the Spiritual Heritage site. For the Catholics and people of India, it is a blessing and we hope that with the visit of the Pope, Goa and India will be blessed with his prayers giving us hope to live for Jesus and to spread the message of Love and Not hatred. Praise God.
Gregory E D'souza, Siolim
SAG ground finally finds good use
The large open space beside the railway bridge and Taniya Hotel in Vasco, belonging to Sports Authority of Goa (SAG) which was idle for so many years and filled with sewage and tall grass, has finally found some good use for itself. Right after dumping tonnes of mud for the land reclamation process, the ground has generously contributed itself towards various events such as parking space for Vasco Saptah, cricket tournaments, political gatherings, shopping exhibitions etc. For the recent political gathering of the BJP, which took place on that ground itself, it was mentioned by MLA Daji Salkar and the CM that the open space would be converted into a multi-facility sports complex. If this promise finds its manifestation, then this will stand testament to a great leap in the development of the port town, which citizens are eagerly looking forward to.
Milind Jakati, Vasco
Train toll plaza workers to respond to accidents
Despite the availability of modern technology and notwithstanding innumerable first-aid and safety signages, passengers struggle to come to terms with ghastly accidents on highways. The National Highways Authority of India (NHAI) in conjunction with a public sector unit of the ministry of health, is planning to strengthen the Incident Management System (IMS).
The IMS strives to respond to unplanned events and service interruption by restoring the services and events to the originally planned state through a plethora of arms. A few crucial amenities like availability of ambulances will be spruced up so that the " golden hour"— one hour following the accident— is not gone abegging.
Real-time tracking system, too, demands fresh innovation to make it foolproof. As regards to immediate medical aid, the number of trauma centres on highways, if any, require more additions.
It is beyond doubt that all passengers have heard about ‘toll-free phone number’ in exigencies but whether or not the exact number is known to them is anyone's guess. A very vital step undertaken by the NHAI towards ensuring passenger safety is to train the toll plaza workers for instantaneous response to accidents. Education and awareness are two sensitive, and invariable, cogs in the passenger security wheel.
Ganapathi Bhat, Akola
PM’s words just an empty rhetoric
Narendra Modi while on a visit to the North East recently had spoken about protecting our borders which the Congress and earlier governments did not do. Many do not realise that Modi has no problem about protecting borders. The moment our neighbouring country adopts a threatening posture, Modi cedes the territory to them like to China on our northern and north-eastern borders where we gave given lakhs of square kilometers of our land to them. There is no need for protecting borders as far as Modi is concerned!
Multiple treatable traits (TTs) were found to be highly prevalent in patients with COPD/advanced emphysema who were eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV), according to study findings published in Respiratory Medicine.
Investigators in The Netherlands conducted a prospective multicenter randomized controlled trial (the SoLVE study; ClinicalTrials.gov Identifier: NCT03474471) to explore the impact of pulmonary rehabilitation on 16 treatable traits in patients with COPD/advanced emphysema receiving EBV treatment. As a secondary outcome, the researchers also characterized TTs associated with severely impaired health-related quality of life (HRQL) using the St. George’s Respiratory Questionnaire (SGRQ).
Eligible patients had a physician diagnosis of COPD/severe emphysema, forced expiratory volume in 1 second (FEV1) of no more than 45% predicted, FEV1/forced vital capacity (FVC) ratio less than 70%, total lung capacity (TLC) greater than 100% predicted, and residual volume greater than 175% predicted. Included patients had a COPD Assessment Test total score of at least 10. Patients with low exercise capacity (6-minute walk test <160 m) and/or severe respiratory failure (partial pressure of carbon dioxide [PaCO2]>8.0kPA and/or partial pressure of oxygen<6.0kPa) were excluded as were those with significant immunodeficiency, bronchiectasis, chronic bronchitis, or previous lobectomy.
The trial included 97 participants (mean [SD] age, 62.4 [6.8] years; 72.9% women). Among the participants, the mean smoking pack years was 39; 58.8% had frequent exacerbations; and 34.0% had at least 1 hospitalization in the previous year.
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COPD patients with advanced emphysema eligible for BLVR with EBV display a spectrum of treatable traits which were highly prevalent. Having more TTs and more specifically anxiety, depression or fatigue, is associated with a worse HRQL.
TTs assessed were: (1) severe dyspnea; (2) very severe airflow limitation; (3) frequent exacerbations; (4) poor exercise capacity; (5) low physical activity; (6) hypoxemia; (7) hypercapnia; (8) underweight; (9) obesity; (10) low muscle mass; (11) decreased bone mineral density; (12) impaired handgrip force; (13) impaired quadriceps force; (14) severe fatigue; (15) anxiety; and (16) depression.
The mean (SD) TTs per participant was 8.1 (2.5; range 2-15); the most prevalent TTs included low physical activity (95%), poor exercise capacity (94%), and severe fatigue (75%).
Overall, participants were characterized by severe lung hyperinflation, severe airflow limitation, and poor HRQL (median total SGRQ score was 60).
When participants were stratified by low vs high SGRQ total score (less than 60 points vs 60 or greater points), the researchers found that the most significant predictors of having a higher SGRQ total score were severe fatigue, depression, and anxiety. A significant although moderate positive correlation was found between the sum of TTs present in a participant and that participant’s SGRQ total score (r=0.53; P <.001).
Study limitations include the strict inclusion/exclusion criteria, which may have affected the prevalence of specific TTs; lack of examination of some significant TTs (eg, persistent systemic inflammation, adherence to pharmacotherapy, family/social support); and lack of a comparator severe COPD group not eligible for BLVR-EBV.
The study authors concluded that “COPD patients with advanced emphysema eligible for BLVR with EBV display a spectrum of treatable traits which were highly prevalent. Having more TTs and more specifically anxiety, depression or fatigue, is associated with a worse HRQL. Findings of this study advocate a multidimensional assessment and management of this specific COPD phenotype.”
Expanded savings programs build on company’s longstanding commitment to addressing barriers to access and affordability for patients
AstraZeneca announced it will expand the savings programs for its entire US inhaled respiratory portfolio, helping eligible patients pay no more than $35 per month for their medicine.* Expanding the savings programs will help make its inhalers more affordable to the most vulnerable patients living with asthma and chronic obstructive pulmonary disease (COPD), including those who are uninsured and underinsured.
Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “AstraZeneca’s expanded savings programs build on our longstanding commitment to addressing barriers to access and affordability for patients living with respiratory diseases to ultimately help patients lead healthier lives. We remain dedicated to addressing the need for affordability of our medicines, but the system is complex and we cannot do it alone. It is critical that Congress bring together key stakeholders to help reform the healthcare system so patients can afford the medicines they need, not just today, but for the future.”
Starting June 1, 2024, eligible patients will pay no more than $35 per month for all AstraZeneca US inhaled respiratory medicines, including:
AIRSUPRA® (albuterol and budesonide)
BEVESPI AEROSPHERE® (glycopyrrolate and formoterol fumarate) Inhalation Aerosol
BREZTRI AEROSPHERE® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol
SYMBICORT® (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol
In addition, AstraZeneca substantially reduced the list price of SYMBICORTon January 1, 2024. The Company will continue to provide discounts and rebates off the list price to help patients afford its inhaled respiratory medicines.
For more than 50 years, AstraZeneca has served respiratory patients by investing in the research and development of new drug-device combinations, as well as next-generation biologics and novel mechanisms to address the vast unmet needs of these chronic, often debilitating diseases. AstraZeneca remains dedicated to transforming patient outcomes, while ensuring access and affordability of our innovative medicines.
*Terms and conditions apply. Government restrictions exclude people enrolled in federal government insurance programs from co-pay support.
IMPORTANT SAFETY INFORMATION
AIRSUPRA® (albuterol and budesonide)
Contraindications: Hypersensitivity to albuterol, budesonide, or to any of the excipients
Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient continues to experience symptoms after using AIRSUPRA or requires more doses of AIRSUPRA than usual, it may be a marker of destabilization of asthma and requires evaluation of the patient and their treatment regimen
Paradoxical Bronchospasm: AIRSUPRA can produce paradoxical bronchospasm, which may be life threatening. Discontinue AIRSUPRA immediately and institute alternative therapy if paradoxical bronchospasm occurs. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister
Cardiovascular Effects: AIRSUPRA, like other drugs containing beta2-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, and/or other symptoms. If such effects occur, AIRSUPRA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. Therefore, AIRSUPRA, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
Do Not Exceed Recommended Dose: Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
Hypersensitivity Reactions, Including Anaphylaxis: Can occur after administration of albuterol sulfate and budesonide, components of AIRSUPRA, as demonstrated by cases of anaphylaxis, angioedema, bronchospasm, oropharyngeal edema, rash, and urticaria. Discontinue AIRSUPRA if such reactions occur
Risk of Sympathomimetic Amines with Certain Coexisting Conditions: AIRSUPRA, like all therapies containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines
Hypokalemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients. The decrease in serum potassium is usually transient, not requiring supplementation
Immunosuppression and Risk of Infections: Due to possible immunosuppression from the use of inhaled corticosteroids (ICS), potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
Oropharyngeal Candidiasis: Has occurred in patients treated with ICS agents. Monitor patients periodically. Advise patients to rinse his/her mouth with water, if available, without swallowing after inhalation
Hypercorticism and Adrenal Suppression: May occur with very high doses in susceptible individuals. If such changes occur, consider appropriate therapy
Reduction in Bone Mineral Density: Decreases in bone mineral density have been observed with long-term administration of ICS. For patients at high risk for decreased bone mineral density, assess initially and periodically thereafter
Glaucoma and Cataracts: Have been reported following the long-term administration of ICS, including budesonide, a component of AIRSUPRA
Effects on Growth: Orally inhaled corticosteroids, including budesonide, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of AIRSUPRA have not been established in pediatric patients, and AIRSUPRA is not indicated for use in this population
Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, and dysphonia
Drug Interactions: AIRSUPRA should be administered with caution to patients being treated with:
Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
Short-acting bronchodilators (concomitant use of additional beta-agonists with AIRSUPRA should be used judiciously to prevent beta-agonist overdose)
Beta-blockers (may block pulmonary effects of beta-agonists and produce severe bronchospasm)
Diuretics or non-potassium-sparing diuretics (may potentiate hypokalemia or ECG changes). Consider monitoring potassium levels
Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants (Use AIRSUPRA with extreme caution; may potentiate effect of albuterol on the cardiovascular system)
Use AIRSUPRA with caution in patients with hepatic impairment, as budesonide systemic exposure may increase. Monitor patients with hepatic disease
BEVESPI AEROSPHERE® (glycopyrrolate and formoterol fumarate) Inhalation Aerosol
CONTRAINDICATIONS
All long-acting beta2-adrenergic agonists (LABAs), including formoterol fumarate, are contraindicated in patients with asthma without use of an inhaled corticosteroid. BEVESPI is not indicated for the treatment of asthma. BEVESPI is contraindicated in patients with hypersensitivity to glycopyrrolate, formoterol fumarate, or to any component of the product.
WARNINGS AND PRECAUTIONS
The safety and efficacy of BEVESPI AEROSPHERE in patients with asthma have not been established. BEVESPI AEROSPHERE is not indicated for the treatment of asthma
Use of LABAs as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When LABAs are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone. Available data do not suggest an increased risk of death with use of LABAs in patients with chronic obstructive pulmonary disease (COPD)
BEVESPI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition
BEVESPI should not be used for the relief of acute symptoms (ie, as rescue therapy for the treatment of acute episodes of bronchospasm). Acute symptoms should be treated with an inhaled short-acting beta2-agonist (SABA)
BEVESPI should not be used more often or at higher doses than recommended, or with other LABAs, as an overdose may result
If paradoxical bronchospasm occurs, discontinue BEVESPI immediately and institute alternative therapy
If immediate hypersensitivity reactions occur, in particular, angioedema, urticaria, or skin rash, discontinue BEVESPI at once and consider alternative treatment
BEVESPI can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, blood pressure, or symptoms. If such effects occur, BEVESPI may need to be discontinued
Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
Be alert to hypokalemia and hyperglycemia
Worsening of narrow-angle glaucoma or urinary retention may occur. Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction, and instruct patients to contact a physician immediately if symptoms occur
ADVERSE REACTIONS
The most common adverse reactions with BEVESPI (≥2% and more common than placebo) were cough, 4.0% (2.7%) and urinary tract infection, 2.6% (2.3%).
DRUG INTERACTIONS
Use caution if administering additional adrenergic drugs because the sympathetic effects of formoterol may be potentiated
Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of formoterol
Use with caution in patients taking non-potassium-sparing diuretics, as the ECG changes and/or hypokalemia may worsen with concomitant beta2-agonists
The action of adrenergic agonists on the cardiovascular system may be potentiated by monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval. Therefore, BEVESPI should be used with extreme caution in patients being treated with these agents
Use beta-blockers with caution as they not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in patients with COPD
Avoid co-administration of BEVESPI with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects
INDICATION
BEVESPI AEROSPHERE is a combination of glycopyrrolate, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA), indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
LIMITATION OF USE
Not indicated for the relief of acute bronchospasm or for the treatment of asthma.
BREZTRI AEROSPHERE® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol
BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients
BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with use of LABA in patients with COPD
BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition
BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist
BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs
Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation
Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap
Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients
Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI
Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy
Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur
If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy
Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy
Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles
Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content
Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur
Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur
Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines
Be alert to hypokalemia or hyperglycemia
Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%)
BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system
BREZTRI should be administered with caution to patients being treated with:
Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects)
Adrenergic drugs (may potentiate effects of formoterol fumarate)
Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm)
Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI
Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored
INDICATION
BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
LIMITATIONS OF USE
Not indicated for the relief of acute bronchospasm or for the treatment of asthma.
SYMBICORT® (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol
Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are used in fixed dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone
SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms
SYMBICORT should not be initiated in patients during rapidly deteriorating episodes of asthma or COPD
Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason
Localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. Patients should rinse the mouth after inhalation of SYMBICORT
Lower respiratory tract infections, including pneumonia, have been reported following the administration of ICS
Due to possible immunosuppression, potential worsening of infections could occur. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur, particularly at higher doses. Particular care is needed for patients who are transferred from systemically active corticosteroids to ICS. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available ICS
Caution should be exercised when considering administration of SYMBICORT in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors
As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT
Immediate hypersensitivity reactions may occur, as demonstrated by cases of urticaria, angioedema, rash, and bronchospasm
Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
Long-term use of ICS may result in a decrease in bone mineral density (BMD). Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating SYMBICORT and periodically thereafter
ICS may result in a reduction in growth velocity when administered to pediatric patients
Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of ICS, including budesonide, a component of SYMBICORT. Close monitoring is warranted in patients with a change in vision or history of increased intraocular pressure, glaucoma, or cataracts
In rare cases, patients on ICS may present with systemic eosinophilic conditions
SYMBICORT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients
The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, pharyngitis, rhinitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis
The most common adverse reactions ≥3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection
SYMBICORT should be administered with caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents
Beta-blockers may not only block the pulmonary effect of beta-agonists, such as formoterol, but may produce severe bronchospasm in patients with asthma
ECG changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with concomitant beta-agonists. Use caution with the coadministration of SYMBICORT
INDICATIONS
SYMBICORT is indicated for the treatment of asthma in patients 6 years and older not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA (also see DOSAGE AND ADMINISTRATION).
SYMBICORT 160/4.5 is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and to reduce COPD exacerbations.
SYMBICORT is NOT indicated for the relief of acute bronchospasm.
Asthma is a chronic, inflammatory respiratory disease with variable symptoms that affects as many as 262 million people worldwide,1 including approximately 25 million in the US.2
Patients with asthma experience recurrent breathlessness and wheezing, which varies over time, and in severity and frequency.3 These patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.4-5
There are an estimated 136 million asthma exacerbations globally per year,6 including approximately 10 million in the US2; these are physically threatening and emotionally significant for many patients7 and can be fatal.3,8
Inflammation is central to both asthma symptoms4 and exacerbations.9 Many patients experiencing asthma symptoms use a SABA (e.g., albuterol) as a rescue medicine10-12; however, taking a SABA alone does not address inflammation, leaving patients at risk of severe exacerbations,13 which can result in impaired quality of life,14 hospitalization15 and frequent oral corticosteroid (OCS) use.15 Treatment of exacerbations with as few as 1-3 short courses of OCS are associated with an increased risk of adverse health conditions including type 2 diabetes, depression/anxiety, renal impairment, cataracts, cardiovascular disease, pneumonia and fracture.16 International recommendations from the GINA no longer recommend SABA alone as the preferred rescue therapy.3
About COPD
COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.17 Affecting an estimated 16 million Americans, COPD is the third leading cause of death due to chronic disease and the sixth overall leading cause of death in the US.18-19
About AIRSUPRA®
AIRSUPRA (albuterol and budesonide), formerly known as PT027, is a first-in-class SABA/ICS rescue treatment for asthma in the US, to be taken as needed. It is an inhaled, fixed-dose combination rescue medication containing albuterol (also known as salbutamol), a SABA, and budesonide, a corticosteroid, and has been developed in a pMDI using AstraZeneca’s Aerospheredelivery technology.
The FDA approval of AIRSUPRA was based on MANDALA and DENALI Phase III trials (Approval press release). In MANDALA, AIRSUPRA significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate-to-severe asthma when used as an as-needed rescue medication in response to symptoms. For patients treated with AIRSUPRA 180 mcg/160 mcg the annualized total systemic corticosteroids dose when compared with albuterol 180 mcg was statistically significantly different, with a reduction in mean annualized dose of 40 mg per patient. In DENALI, AIRSUPRA significantly improved lung function compared to the individual components albuterol and budesonide in patients with mild to moderate asthma.
About BEVESPI AEROSPHERE®
BEVESPI AEROSPHERE (glycopyrronium and formoterol fumarate) is a fixed-dose dual bronchodilator in a pMDI, combining glycopyrronium, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-agonist (LABA). PMDIs are an important choice for COPD patients where limited lung function, advanced age and reduced dexterity or cognition are significant considerations for patients to achieve therapeutic benefits from their medicines. BEVESPI AEROSPHERE is the only LABA/LAMA with Aerosphere delivery technology. Results from an imaging trial have shown that BEVESPI AEROSPHERE effectively delivers medicine to both the large and small airways.
About BREZTRI AEROSPHERE®
BREZTRI AEROSPHERE (budesonide, glycopyrrolate, and formoterol fumarate) is a single-inhaler, fixed-dose triple-combination of formoterol fumarate, a LABA, glycopyrronium bromide, a LAMA, with budesonide, an ICS, and delivered in a pressurized metered-dose inhaler. BREZTRI AEROSPHEREis approved to treat COPD in more than 50 countries worldwide including the US, EU, China and Japan, and is currently being studied in Phase III trials for asthma.
About SYMBICORT®
Symbicort (budesonide and formoterol fumarate dihydrate) is the number one ICS/LABA combination therapy in asthma and chronic obstructive pulmonary disease (COPD) in China. It is a combination formulation containing budesonide, an ICS that treats underlying inflammation, and formoterol, a LABA with a fast onset of action, in a single inhaler. Symbicort was launched in 2000 and is approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbuhaler or Symbicort pMDI (pressurised metered-dose inhaler).
About AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company.
AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.
With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.
About AZ&Me™
AstraZeneca’s patient assistance program, AZ&Me Prescription Savings Program (AZ&Me), is part of the Company’s commitment to addressing barriers to access and affordability to improve medication adherence, enhance patient care, and help patients lead healthier lives. AZ&Me is just one of the ways that AstraZeneca makes its life-changing medicines widely available, accessible, and affordable.
For over 40 years, AstraZeneca has offered a patient assistance program through AZ&Me and prior legacy free drug programs, making it one of the longest standing patient assistance programs in the country. Since 2007, over five million people have benefited from this program. In addition to its patient assistance programs, AstraZeneca offers other affordability programs and resources to help increase patients’ access to medicines and reduce their out-of-pocket costs including a co-pay savings program for commercially-insured patients and additional affordability resources. Each of these programs offer financial support to particular patient populations, consistent with applicable legal requirements.
The goal of AZ&Me is to help patients who have been prescribed an AstraZeneca medication and are having difficulty affording it. Patients enrolled in AZ&Me receive their AstraZeneca medicine for free. To learn more, visit AZ&Me.com.
Global Initiative for Asthma. Updated May 2023. Accessed: March 2024. www.ginasthma.org
Price D, et al. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009.
Papi A, et al. Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2018;6(6): 1989-1998.e3.
Data on File. REF-173201. AstraZeneca Pharmaceuticals LP.
Sastre J, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016;9:13.
Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014;40(4):364-372.
Wark PA, et al. Asthma exacerbations. 3: Pathogenesis. Thorax. 2006;61(10):909-915.
Johnson DB, et al. Albuterol. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan 10.
Montemayor T, et al. Albuterol: Often Used and Heavily Abused. Respiratory Care. November 2021, 66 (Suppl 10) 3603775.
Nwaru BI, et al. Overuse of short-acting β2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020;55(4):1901872.
Lloyd A, et al. The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Prim Care Respir J. 2007;16(1):22-27.
Bourdin A, et al. ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions. Eur Respir J. 2019;54(3):1900900.
Price DB, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193-204.
GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. [Online]. Accessed: March 2024. goldcopd.org/2024-gold-report/
Chronic obstructive pulmonary disease (COPD) is kind of lung disease which happen due to chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible.
The global market for Emphysema Treatment was estimated to be worth US$ million in 2023 and is forecast to a readjusted size of US$ million by 2030 with a CAGR of % during the forecast period 2024-2030.
The global pharmaceutical market is 1475 billion USD in 2022, growing at a CAGR of 5% during the next six years. The pharmaceutical market includes chemical drugs and biological drugs. For biologics is expected to 381 billion USD in 2022. In comparison, the chemical drug market is estimated to increase from 1005 billion in 2018 to 1094 billion U.S. dollars in 2022. The pharmaceutical market factors such as increasing demand for healthcare, technological advancements, and the rising prevalence of chronic diseases, increase in funding from private & government organizations for development of pharmaceutical manufacturing segments and rise in R&D activities for drugs. However, the industry also faces challenges such as stringent regulations, high costs of research and development, and patent expirations. Companies need to continuously innovate and adapt to these challenges to stay competitive in the market and ensure their products reach patients in need. Additionally, the COVID-19 pandemic has highlighted the importance of vaccine development and supply chain management, further emphasizing the need for pharmaceutical companies to be agile and responsive to emerging public health needs.
Global Market Research Publisher QYResearch announces the release of its lastest report “Emphysema Treatment - Global Market Share and Ranking, Overall Sales and Demand Forecast 2024-2030”. Based on historical analysis (2019-2023) and forecast calculations (2024-2030), this report provides a comprehensive analysis of the global Emphysema Treatment market, including market size, share, demand, industry development status, and forecasts for the next few years. Provides advanced statistics and information on global market conditions and studies the strategic patterns adopted by renowned players across the globe.
【Get a free sample PDF of this report (Including Full TOC, List of Tables & Figures, Chart)】
Some of the Key Questions Answered in this Report:
What is the Emphysema Treatment market size at the regional and country-level
What are the key drivers, restraints, opportunities, and challenges of the Emphysema Treatment market, and how they are expected to impact the market
What is the global (North America, Europe, Asia-Pacific, Latin America, Middle East and Africa) sales value, production value, consumption value, import and export of Emphysema Treatment
Who are the global key manufacturers of the Emphysema Treatment Industry, How is their operating situation (capacity, production, sales, price, cost, gross, and revenue)
What are the Emphysema Treatment market opportunities and threats faced by the vendors in the global Emphysema Treatment Industry
Which application/end-user or product type may seek incremental growth prospects,What is the market share of each type and application
What focused approach and constraints are holding the Emphysema Treatment market
What are the different sales, marketing, and distribution channels in the global industry
What are the upstream raw materials andof Emphysema Treatment along with the manufacturing process of Emphysema Treatment
What are the key market trends impacting the growth of the Emphysema Treatment market
Economic impact on the Emphysema Treatment industry and development trend of the Emphysema Treatment industry
What are the Emphysema Treatment market opportunities, market risk, and market overview of the Emphysema Treatment market
Overall, this report strives to provide you with the insights and information you need to make informed business decisions and stay ahead of the competition.
All findings, data and information provided in the report have been verified and re-verified with the help of reliable sources. The analysts who wrote the report conducted in-depth research using unique and industry-best research and analysis methods.
The report provides a detailed analysis of the market size, growth potential, and key trends for each segment. Through detailed analysis, industry players can identify profit opportunities, develop strategies for specific customer segments, and allocate resources effectively.
The Emphysema Treatment market is segmented as below:
By Company
Pulmonx
Bioxyne
Intrexon
Icure Pharmaceuticals
Kamada
Emphasys Medical
Pfizer
Olympus
BTG
PneumRx and Uptake Medical
Halozyme Therapeutics
Mariposa Health
Uptake Medical
Segment by Type
Centrilobular emphysema
Panlobular emphysema
Segment by Application
Hospital
Clinics
Surgical center
This information will help stakeholders make informed decisions and develop effective strategies for growth. The report's analysis of the restraints in the market is crucial for strategic planning as it helps stakeholders understand the challenges that could hinder growth. This information will enable stakeholders to devise effective strategies to overcome these challenges and capitalize on the opportunities presented by the growing market. Furthermore, the report incorporates the opinions of market experts to provide valuable insights into the market's dynamics. This information will help stakeholders gain a better understanding of the market and make informed decisions.
Each chapter of the report provides detailed information for readers to further understand the Emphysema Treatment market:
Chapter One: Introduces the study scope of this report, executive summary of market segments by Type, market size segments for North America, Europe, Asia Pacific, Latin America, Middle East & Africa.
Chapter Two: Detailed analysis of Emphysema Treatment manufacturers competitive landscape, price, sales, revenue, market share and ranking, latest development plan, merger, and acquisition information, etc.
Chapter Three: Sales, revenue of Emphysema Treatment in regional level. It provides a quantitative analysis of the market size and development potential of each region and introduces the future development prospects, and market space in the world.
Chapter Four: Introduces market segments by Application, market size segment for North America, Europe, Asia Pacific, Latin America, Middle East & Africa.
Chapter Five, Six, Seven, Eight and Nine: North America, Europe, Asia Pacific, Latin America, Middle East & Africa, sales and revenue by country.
Chapter Ten: Provides profiles of key players, introducing the basic situation of the main companies in the market in detail, including product sales, revenue, price, gross margin, product introduction, recent development, etc.
Chapter Eleven: Analysis of industrial chain, key raw materials, manufacturing cost, and market dynamics. Introduces the market dynamics, latest developments of the market, the driving factors and restrictive factors of the market, the challenges and risks faced by manufacturers in the industry, and the analysis of relevant policies in the industry.
Chapter Twelve: Analysis of sales channel, distributors and customers.
Chapter Thirteen: Research Findings and Conclusion.
Table of Contents
1 Emphysema Treatment Market Overview
1.2 Emphysema Treatment Market by Type
1.3 Global Emphysema Treatment Market Size by Type
1.4 Key Regions Market Size by Type
1.4.1 North America Emphysema Treatment Sales Breakdown by Type (2019-2024)
1.4.2 Europe Emphysema Treatment Sales Breakdown by Type (2019-2024)
1.4.3 Asia-Pacific Emphysema Treatment Sales Breakdown by Type (2019-2024)
1.4.4 Latin America Emphysema Treatment Sales Breakdown by Type (2019-2024)
1.4.5 Middle East and Africa Emphysema Treatment Sales Breakdown by Type (2019-2024)
2 Emphysema Treatment Market Competition by Company
2.1 Global Top Players by Emphysema Treatment Sales (2019-2024)
2.2 Global Top Players by Emphysema Treatment Revenue (2019-2024)
2.3 Global Top Players by Emphysema Treatment Price (2019-2024)
2.4 Global Top Manufacturers Emphysema Treatment Manufacturing Base Distribution, Sales Area, Product Type
2.5 Emphysema Treatment Market Competitive Situation and Trends
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NHS hospitals have been hit by a UK-wide shortage of a life-saving drug used to keep alive patients who are at risk of dying because they cannot breathe without medical intervention.
Doctors have been told to ration their use of the liquid form of salbutamol, which plays a vital role in treating people suffering from severe asthma attacks or chronic obstructive pulmonary disease (COPD), which usually involves emphysema or chronic bronchitis.
A “safety critical” national patient safety alert issued by the Department of Health and Social Care (DHSC) and NHS England warns that 2.5mg and 5mg dose vials of salbutamol liquid are in short supply. The latter is “out of stock until mid-April 2024”.
The scarcity is so acute that hospitals were advised to “place urgent orders for unlicensed imports of salbutamol nebuliser liquid – do not wait for supplies to be exhausted before placing orders for imports”.
The drug is administered via a nebuliser, which pushes air through the liquid to create a mist that relaxes the patient’s muscles and reopens their airways.
The Guardian revealed in January that drug shortages in the UK were running at record levels, prompting fears among doctors that patients’ lives could be put at risk.
One specialist lung doctor who routinely uses nebules of the drug when patients can no longer breathe unaided said: “This is a worry. This is a life-saving drug that is the bread-and-butter medicine we use when patients with serious breathing problems are acutely unwell.
“We are being asked to ration it, and not to use it where possible and to use alternatives. We’ve been advised to use it sparingly – only if it’s absolutely essential. This isn’t a crisis at the moment. But it’s a worry that a life-saving drug is having to be rationed.”
The patient safety alert also told hospital bosses that in order to conserve supplies for use in the most serious cases, doctors should:
Wean all patients off nebulisers as soon as their condition has stabilised.
Consider no longer using nebuliser liquid for patients experiencing a mild to moderate asthma attack or flare-up of COPD and instead use a salbutamol pressurised metered-dose inhaler (pMDI).
When a patient does need nebuliser liquids, use them “when required rather than regularly”.
Supplies need to be used as far as possible only with “acute, severe exacerbations of COPD and asthma”, people who cannot breathe due to an attack of anaphylaxis – a life-threatening allergic reaction to eating something – and those who cannot use a pMDI.
The shortage does not affect the availability of salbutamol inhalers, the blue-coloured “reliever” inhalers that patients with lung conditions such as asthma use if they develop shortness of breath.
The scarcity only involves nebules, or vials, of liquid salbutamol, which is sold under various brand names including Ventolin. Patients are put on a salbutamol nebuliser when repeated inhalation of the drug through a tube has not helped them regain their capacity to breathe independently.
Doctors voiced concern about the situation. Dr Tim Cooksley, the immediate past president of the Society for Acute Medicine, said: “Salbutamol is commonly used to treat acutely unwell medical patients with breathing problems and there is not a ready alternative to it. It is an important part of daily practice and there is a risk of significant harm to these patients if supply issues are not resolved quickly.”
The charity Asthma and Lung UK posted a message on its website telling patients that “the supply of salbutamol nebuliser liquid is currently limited in the UK”.
It said: “Alternatives are available that healthcare professionals will be able to prescribe.” In addition, “nebuliser liquid from other countries that have similar high standards of licensing to the UK will also be made available.”
The DHSC said the shortage had come to an end after it arranged alternative supplies.
A spokesperson said: “Recent short-term disruption to the supply of salbutamol nebuliser liquid has now been resolved. This was caused by one supplier experiencing a manufacturing issue. The department quickly engaged with suppliers and others in the supply chain to ensure supplies were available for UK patients.”
People living with chronic obstructive pulmonary disease (COPD) may find that cold weather worsens their symptoms. This can lead to shortness of breath and coughing more than usual.
“COPD” is an umbrella term for a group of progressive lung diseases that can cause a person to experience airflow blockages and breathing difficulties.
Symptoms of COPD may include fatigue, wheezing, coughing, and shortness of breath. Cold weather may cause these symptoms to flare up or worsen.
In this article, we explore the impact of cold weather on COPD and offer tips for managing the condition in colder temperatures.
COPD is an umbrella term for bronchitis and emphysema. These conditions typically develop as a result of long-term exposure to irritants, such as chemicals and tobacco smoke, which damage the lungs and airways.
Although cold weather does not cause COPD, it can affect COPD symptoms. This may be because this type of weather can cause a person’s mouth and airways to become narrow, irritated, and dry. Ultimately, this can worsen or trigger symptoms in people living with COPD.
A 2022 study suggests that cold temperatures can trigger phlegm and cough symptoms in people living with COPD.
Cold weather can worsen existing respiratory conditions, including COPD.
Cold air, in particular, can affect a person’s lungs and health. Often, this type of air is dry, which can irritate the airways of people living with preexisting lung diseases. This can lead to coughing, wheezing, and shortness of breath.
Among those living with respiratory conditions, exposure to cold temperatures can exacerbate symptoms within a few hours or days.
Moreover, during periods of cold weather, common respiratory viruses such as the flu can replicate more effectively. This means it is easier for them to spread and cause infections. If a person living with COPD acquires a respiratory infection, this can also worsen their chronic symptoms.
Cold weather can pose challenges for individuals with COPD. However, it does not mean that individuals with COPD or other lung conditions should avoid going outside altogether.
Outdoor activities are crucial for maintaining overall health and well-being. However, it is essential to take precautions to minimize the impact of cold weather on respiratory symptoms.
A person living with COPD may consider the following tips to stay warm when outside during cold temperatures:
Layering: Dressing in layers helps trap warm air close to the body. This includes wearing a thermal base layer, insulating layers, and a windproof outer layer.
Wearing accessories: Wearing a warm hat, gloves, and scarf can help keep the head, hands, and neck warm.
Putting a scarf or mask over the mouth and nose: Covering the face and mouth with a scarf or mask can help humidify and warm the air before it reaches the lungs.
Practicing breathing techniques: Breathing through the nose instead of the mouth can help warm the air a person is breathing.
Keeping moving: When outside, keep moving, as this will generate heat and help a person feel warmer.
As well as staying warm while outside, a person living with COPD can also take steps to stay warm while indoors. Some examples of staying warm while inside include:
Maintaining indoor warmth: Keep the indoor environment at a comfortable temperature to prevent the onset of symptoms. Proper insulation and heating are crucial, especially during colder months.
Using a humidifier: Adding moisture to the air can prevent it from becoming too dry, reducing the risk of irritation to the respiratory tract.
Wearing warm clothing indoors: Dressing warmly, even when inside, can help individuals with COPD stay comfortable and reduce the strain on their respiratory system.
Using warm bedding: Consider using extra bedcovers or a heated blanket to help stay warm during the night.
Closing windows and drawing curtains: This can help insulate a room, keeping heat in and cold out.
Other tips for managing COPD and maintaining lung health can include:
Getting regular exercise:Regular physical activity can improve lung function and overall health. Consult with a healthcare professional to determine suitable exercise routines.
Managing medications: Adhering to prescribed medication regimens is crucial for managing COPD symptoms. Discuss any concerns or adjustments needed during colder months with a healthcare professional.
Getting flu vaccines: Healthcare professionals recommend annual flu vaccinations for individuals with COPD to reduce the risk of respiratory infections, which can exacerbate symptoms, especially in colder seasons.
Avoiding triggers: Common triggers that can exacerbate COPD symptoms include smoke, strong odors, pollen, chemicals, and fumes.
While cold weather can potentially exacerbate COPD symptoms, it should not deter individuals from maintaining an active lifestyle in the outdoors.
With proper precautions, such as dressing warmly, protecting the airways, and following medical advice, individuals with COPD can navigate the challenges posed by cold weather.
MEMBERS of the Heathcote Men’s Shed will breathe easier thanks to a donation from the Lions Club.
Club members visited the Men’s Shed last week to present them with a cheque for $18,000 towards a new dust extraction system.
Men’s Shed president Terry Hoctor said the system will be invaluable.
“When everyone is working in here, it gets pretty dusty,” he said.
“It’s not good for any of us and particularly those with emphysema, asthma and other breathing problems.
“The dust extraction system is amazing. It takes it all away from each of the machines and collects it all for disposal at the back of the shed.”
Initially, the system was quoted at $26,000.
“That was way beyond our means,” said Mr Hoctor. “We sell a lot of our work, from nest boxes to novelty animals, at the local market but we couldn’t possibly make that much.
“We are very grateful to the Lions Club for helping us out. Their donation enabled us to have the system installed and we’re all breathing much easier.”
Lions Club treasurer Frank Dailey said the group was happy to help.
“We are really pleased that this will benefit so many people and happy that we were in a position to help out,” he said.
Boehringer makes significant investment to improve the affordability of and access to its full range of inhaler products for COPD and asthma
Expansive program builds on the company's century-long commitment to patients with respiratory illnesses
RIDGEFIELD, Conn., March 7, 2024 /PRNewswire/ -- Boehringer Ingelheim today announced it will cap out-of-pocket costs at $35 per month for eligible patientsi for all the company's inhaler products. Boehringer's new program will dramatically decrease costs at the pharmacy counter for the most vulnerable patients, including those who are uninsured or underinsured. This reinforces the company's long-standing commitment to ensure access to important medicines for patients.
Boehringer Ingelheim 2024
"Patients have counted on Boehringer Ingelheim for nearly 140 years to tackle challenges across diseases, including respiratory illnesses," said Jean-Michel Boers, President and CEO, Boehringer Ingelheim USA Corporation. "The U.S. healthcare system is complex and often doesn't work for patients, especially the most vulnerable. While we can't fix the entire system alone, we are bringing forward a solution to make it fairer. We want to do our part to help patients living with COPD or asthma who struggle to pay for their medications. This new program supports patients with predictable, affordable costs at the pharmacy counter. We will also continue to advocate for substantive policy reforms to improve the healthcare system."
Starting June 1, 2024, eligible patients will pay no more than $35 a month at retail pharmacies for all Boehringer Ingelheim inhalers, including:
Boehringer's program builds on the company's long-standing commitment to supporting patients. The company will continue to provide access to free products for eligible patients and comprehensive patient support programs as well. In addition, Boehringer will decrease the list price on some of its inhaler products and will continue providing significant discounts and rebates off the list price of its medicines to insurers, pharmacy benefits managers and other parties, although unfortunately, these reductions are not always passed on to patients.
About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units, Human Pharma and Animal Health. Learn more at www.boehringer-ingelheim.com/us/
i Terms and conditions apply. Government restrictions exclude people enrolled in federal government insurance programs from co-pay support.
ATROVENT HFA (ipratropium bromide HFA) Inhalation Aerosol is a prescription maintenance treatment for bronchospasm (airway narrowing) in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Important Safety Information
Do not use ATROVENT HFA if you are allergic to ipratropium or any of the ingredients in ATROVENT HFA or to atropine or similar drugs.
ATROVENT HFA is not a rescue medicine and should not be used for treating sudden breathing problems. Your doctor may give you other medicine to use for sudden breathing problems.
Allergic reactions may occur, including itching, swelling of the face, lips, tongue, or throat (involving difficulty in breathing or swallowing), rash, hives, bronchospasm (airway narrowing), or anaphylaxis. Some of these may be serious. If you experience any of these symptoms, stop taking ATROVENT HFA at once and call your doctor or get emergency help.
ATROVENT HFA can cause the narrowing of the airways to get worse (paradoxical bronchospasm) which may be life threatening. If this happens, stop taking ATROVENT HFA at once and call your doctor or get emergency help.
ATROVENT HFA may increase eye pressure which may cause or worsen some types of glaucoma. Do not get the spray into your eyes. The spray may cause eye pain or discomfort, blurred vision, enlarged pupils, seeing halos or colored images along with red eyes. If you have any of these symptoms, stop taking ATROVENT HFA and call your doctor right away.
Dizziness and blurred vision may occur with ATROVENT HFA. Should you experience these symptoms, use caution when engaging in activities such as driving a car or operating appliances or machinery.
ATROVENT HFA may cause difficulty with urination. Symptoms may include difficulty passing urine and/or painful urination. If you have any of these symptoms, stop taking ATROVENT HFA and call your doctor right away.
The most common side effects reported with use of ATROVENT HFA were bronchitis, COPD flare-up (exacerbation), shortness of breath and headache.
Tell your doctor about all medicines you are taking, including eye drops. Ask your doctor if you are taking any anticholinergic medicines because taking them together with ATROVENT HFA can increase side effects.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088.
(9/16) CL-AT-0017
Combivent Respimat (ipratropium bromide and albuterol) Inhalation Spray
Indication for Use
COMBIVENT RESPIMAT (ipratropium bromide and albuterol) is indicated for use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm (airway narrowing) and who require a second bronchodilator.
Important Safety Information
Do not use COMBIVENT RESPIMAT if you are allergic to any of the ingredients in COMBIVENT RESPIMAT or to atropine or other similar drugs.
COMBIVENT RESPIMAT can cause the narrowing of the airways to get worse (paradoxical bronchospasm) which may be life threatening. If this happens, stop taking COMBIVENT RESPIMAT at once and call your doctor or get emergency help.
COMBIVENT RESPIMAT can cause serious heart-related side effects, such as palpitations, chest pain, rapid heart rate, high blood pressure, tremor, or nervousness. Call your doctor if you experience any of these symptoms.
Avoid spraying COMBIVENT RESPIMAT into your eyes. COMBIVENT RESPIMAT may increase eye pressure which may cause or worsen some types of glaucoma. If you have sudden vision changes, eye pain or visual halos, stop taking COMBIVENT RESPIMAT and call your doctor right away.
COMBIVENT RESPIMAT may cause difficulty with urination.
Dizziness and blurred vision may occur with COMBIVENT RESPIMAT. Should you experience these symptoms, use caution when engaging in activities such as driving a car or operating appliances or other machines.
Do not use COMBIVENT RESPIMAT more often than your doctor has directed. Deaths have been reported with similar inhaled medicines in asthma patients who use the medicine too much. Seek medical attention if your treatment with COMBIVENT RESPIMAT becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual.
Allergic reactions may occur, including itching, swelling of the face, lips, tongue, or throat (involving difficulty in breathing or swallowing), rash, hives, bronchospasm (airway narrowing), or anaphylaxis. Some of these may be serious. If you experience any of these symptoms, stop taking COMBIVENT RESPIMAT at once and call your doctor or get emergency help.
Tell your doctor about all your medical conditions, especially if you have narrow-angle glaucoma, prostate or urinary problems, a history of heart conditions (such as irregular heartbeat, high blood pressure), thyroid disorder, or diabetes. Also tell your doctor if you are pregnant or nursing. Tell your doctor about all medicines you are taking, especially heart medications or drugs to treat depression.
The most common side effects reported with use of COMBIVENT RESPIMAT include infection of the ears, nose, and throat, runny nose, cough, bronchitis, headache, and shortness of breath.
Click here for full Prescribing Information and Patient Instructions for Use.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
SPIRIVA RESPIMAT, 2.5 mcg, and SPIRIVA HANDIHALER are long-term, once-daily, prescription maintenance medicines used to control symptoms of chronic obstructive pulmonary disease (COPD) by relaxing your airways and keeping them open. COPD includes chronic bronchitis and emphysema. SPIRIVA RESPIMAT and SPIRIVA HANDIHALER also reduce the likelihood of flare-ups (COPD exacerbations).
SPIRIVA RESPIMAT, 1.25 mcg, is a long-term, once-daily, prescription maintenance treatment of asthma for people 6 years and older.
SPIRIVA is not a treatment for sudden symptoms of asthma or COPD.
Important Safety Information for SPIRIVA RESPIMAT
Do not use SPIRIVA RESPIMAT or SPIRIVA HANDIHALER if you are allergic to tiotropium, ipratropium, atropine or similar drugs, or any ingredient in these medicines.
SPIRIVA RESPIMAT or SPIRIVA HANDIHALER are not rescue medicines and should not be used for treating sudden breathing problems. Your doctor may give you other medicine to use for sudden breathing problems.
SPIRIVA RESPIMAT or SPIRIVA HANDIHALER can cause allergic reactions. Symptoms can include raised red patches on your skin (hives), itching, rash and/or swelling of the lips, tongue, or throat that may cause difficulty in breathing or swallowing. If you have any of these symptoms, stop taking the medicine and seek emergency medical care.
Before using SPIRIVA HANDIHALER, tell your doctor if you have a severe allergy to milk proteins.
SPIRIVA RESPIMAT or SPIRIVA HANDIHALER can cause your breathing to suddenly get worse (bronchospasm). If this happens, use your rescue inhaler, stop taking SPIRIVA, and call your doctor right away or seek emergency medical care.
SPIRIVA RESPIMAT or SPIRIVA HANDIHALER can increase the pressure in your eyes (acute narrow-angle glaucoma) which can cause the following symptoms: eye pain, blurred vision, seeing halos or colored images along with red eyes. If you have any of these symptoms, stop taking your medicine and call your doctor right away.
Dizziness and blurred vision may occur with SPIRIVA RESPIMAT or SPIRIVA HANDIHALER. If you experience these symptoms, use caution when engaging in activities such as driving a car, or operating appliances or machinery.
SPIRIVA RESPIMAT or SPIRIVA HANDIHALER can cause new or worsened urinary retention. Symptoms of blockage in your bladder and/or enlarged prostate may include difficulty passing urine and/or painful urination. If you have any of these symptoms, stop taking your medicine and call your doctor right away.
The most common side effects reported with SPIRIVA RESPIMAT in patients with COPD include sore throat, cough, dry mouth, and sinus infection.
The most common side effects with SPIRIVA RESPIMAT in adult patients with asthma were sore throat, headache, bronchitis, and sinus infection. The side effect profile for adolescent and pediatric patients was comparable to that observed in adult patients with asthma.
The most common side effects reported with SPIRIVA HANDIHALER in patients with COPD include upper respiratory tract infection, dry mouth, sinus infection, sore throat, non-specific chest pain, urinary tract infection, indigestion, runny nose, constipation, increased heart rate, and blurred vision.
Do not swallow SPIRIVA capsules. The contents of the capsule should only be inhaled through your mouth using the HANDIHALER device.
Do not spray SPIRIVA RESPIMAT into your eyes, as this may cause blurring of vision and pupil dilation.
Tell your doctor about all your medical conditions including kidney problems, glaucoma, enlarged prostate, problems passing urine, or blockage in your bladder.
Tell your doctor all the medicines you take, including eye drops. Ask your doctor if you are taking any anticholinergic medicines because taking them together with SPIRIVA can increase side effects. Do not use SPIRIVA RESPIMAT and SPIRIVA HANDIHALER together.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
Click here for full Prescribing Information and Patient Instructions for Use for SPIRIVA RESPIMAT.
Click here for full Prescribing Information and Patient Instructions for Use for SPIRIVA HANDIHALER.
CL-SVR-0048 2.15.2017
STIOLTO RESPIMAT (tiotropium bromide and olodaterol) Inhalation Spray
APPROVED USE FOR STIOLTO RESPIMAT STIOLTO® RESPIMAT® (tiotropium bromide and olodaterol) Inhalation Spray is a prescription medicine used long term, 2 puffs 1 time each day, in controlling symptoms in adults with chronic obstructive pulmonary disease (COPD). COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both.
STIOLTO is not for treating sudden symptoms of COPD. Always have a rescue medicine with you to treat sudden symptoms.
STIOLTO is not for asthma.
Important Safety Information for STIOLTO RESPIMAT
Do not use STIOLTO if you have asthma. People with asthma who take long-acting beta2-agonist (LABA) medicines, such as olodaterol, (one of the medicines in STIOLTO), without also using a medicine called an inhaled corticosteroid, have an increased risk of serious problems from asthma, including being hospitalized, needing a tube placed in their airway to help them breathe, or death.
Do not use STIOLTO if you are allergic to tiotropium, ipratropium, atropine or similar drugs, olodaterol, or any ingredient in STIOLTO.
Call your healthcare provider or get emergency medical care if you experience symptoms of a serious allergic reaction including: rash, hives, itching, swelling of the face, lips, tongue, throat, and difficulties in breathing or swallowing.
Get emergency medical care if your breathing problems worsen quickly or if you use your rescue inhaler but it does not relieve your breathing problems. Call your healthcare provider if breathing problems worsen over time while using STIOLTO.
Do not use STIOLTO more often than prescribed by your doctor. Do not use STIOLTO with other LABAs or anticholinergics.
Do not use STIOLTO for treating sudden breathing problems. Always have a rescue inhaler with you to treat sudden symptoms.
Tell your doctor about all your medical conditions including heart problems, high blood pressure, seizures, thyroid problems, diabetes, kidney problems, glaucoma, enlarged prostate, and problems passing urine.
STIOLTO can cause serious side effects, including sudden shortness of breath that may be life threatening, fast or irregular heartbeat, increased blood pressure, chest pain, tremor, headache, nervousness, high blood sugar, or low blood potassium that may cause muscle weakness or abnormal heart rhythm. If any of these happens, stop taking STIOLTO and seek immediate medical help.
STIOLTO can cause new or worsening eye problems including narrow-angle glaucoma, and can increase the pressure in your eyes, which can cause the following symptoms: eye pain, blurred vision, seeing halos or colored images along with red eyes. If you have any of these symptoms, stop taking STIOLTO and call your doctor right away.
STIOLTO can cause new or worsened urinary retention. Symptoms of urinary retention may include difficulty passing urine, painful urination, urinating frequently, or urinating in a weak stream or drips. If you have any of these symptoms, stop taking STIOLTO and call your doctor right away.
The most common side effects of STIOLTO are runny nose, cough, and back pain.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, eye drops, vitamins, and herbal supplements. STIOLTO and certain other medicines may affect each other. STIOLTO is for oral inhalation only.
The STIOLTO cartridge is only intended for use with the STIOLTO RESPIMAT inhaler.
Do not spray STIOLTO into your eyes. Your vision may become blurred and your pupils may become larger (dilated).
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatchor call 1-800-FDA-1088.
Read the step-by-step patient Instructions for Use for STIOLTO RESPIMAT before you use your inhaler.
Striverdi® Respimat® (olodaterol) Inhalation Spray is a prescription medicine used long term, 2 puffs, 1 time each day, in controlling symptoms in adults with chronic obstructive pulmonary disease (COPD). COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both.
STRIVERDI RESPIMAT is not for treating sudden symptoms of COPD. Always have a rescue medicine with you to treat sudden symptoms. Striverdi is not for asthma.
Important Safety Information for STRIVERDI RESPIMAT
Do not use STRIVERDI if you have asthma. People with asthma who take long‐acting beta2‐agonist (LABA) medicines, such as STRIVERDI RESPIMAT, without also using a medicine called an inhaled corticosteroid (ICS), have an increased risk of serious problems from asthma, including being hospitalized, needing a tube placed in their airway to help them breathe, or death.
Get emergency medical care if your breathing problems worsen quickly or you use your rescue medicine but it does not relieve your breathing problems. Call your healthcare provider if breathing problems worsen over time while using STRIVERDI.
Do not use STRIVERDI RESPIMAT more often than prescribed for you by your doctor. Do not use STRIVERDI RESPIMAT with other LABAs.
Do not use STRIVERDI for treating sudden breathing problems. Always have a rescue inhaler with you to treat sudden symptoms.
Tell your doctor about all of your medical conditions, including heart problems, high blood pressure, seizures, thyroid problems, and diabetes.
STRIVERDI RESPIMAT can cause serious side effects including sudden shortness of breath that may be life threatening, fast or irregular heartbeat, increased blood pressure, chest pain, tremor, headache, nervousness, high blood sugar, or low blood potassium that may cause muscle weakness or abnormal heart rhythm. If any of these happen, stop taking STRIVERDI and seek immediate medical help.
Call your healthcare provider or get emergency medical care if you get any symptoms of a serious allergic reaction including: rash, hives, itching, swelling of the face, lips, tongue, throat, and difficulties in breathing or swallowing.
The most common side effects are runny nose, sore throat, upper respiratory tract infection, bronchitis, urinary tract infection, cough, dizziness, rash, diarrhea, back pain, and joint pain.
Tell your doctor about all the medicines you take, including prescription and non‐prescription medicines, vitamins, and herbal supplements. STRIVERDI and certain other medicines may affect each other.
STRIVERDI is for oral inhalation only.
The STRIVERDI cartridge is only intended for use with the STRIVERDI RESPIMAT inhaler.
Do not spray STRIVERDI into your eyes.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch, or call 1‐800‐FDA‐1088.
Read the step-by-step patient Instructions for Use for STRIVERDI RESPIMAT before you use your inhaler.
Please see accompanying full Prescribing Information, including Patient Information, and Instructions for Use for STRIVERDI RESPIMAT.
CL-STRR-100001 6.5.2019
Media Contact: Michele Baer Human Pharma Communications [email protected]
Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition.1 A phenotype is generally considered to be the physical appearance or biochemical characteristic resulting from an interaction between your genotype and the environment. In COPD, where the underlying genes are mostly unknown or poorly characterized, phenotype has become almost synonymous with clinical subgroup.2
Phenotyping allows selecting a uniform group of patients and evaluating the most important outcome measures in this group for therapeutic clinical trials.3 The Spanish guide to chronic obstructive pulmonary disease (GEsEPOC) recognizes 3 phenotypes: emphysema, chronic bronchitis and asthma associated with COPD.4 The differences between the three phenotypes are not precisely known.
The forced oscillation technique (FOT), also referred to as respiratory oscillometry, is a non-invasive method able to provide a detailed analysis of the respiratory system resistance and reactance.5 This method has high potential to increase our understanding of the differences between phenotypes, as well as in their differential diagnosis.
Individuals with COPD exhibit multiple systemic manifestations, including a direct association between the decline in respiratory and peripheral muscle strength and their physical performance and overall functionality. The measurement of the respiratory pressures represent an important procedure for the functional evaluation of the respiratory muscles.6 In addition, peripheral muscle strength may be evaluated by the handgrip test. It is recognized for its cost-effectiveness, simplicity, and a robust correlation with morbidity in chronic diseases.7–11
Exercise intolerance is a common feature in patients with COPD, contributing to reduce the ability to perform activities of daily living.12 These abnormalities may be evaluated by the ADL-Glittre test, which proved to be valid, reliable and capable of reflecting the perception of functional limitation.13
In this context, the current study has two main objectives (1) use respiratory oscillometry to investigate the differences among the COPD phenotypes, and (2) evaluate the association between these abnormalities and the decrease in the functional performance of these patients.
Materials and Methods
Study Design
The present work was developed at the Biomedical Instrumentation Laboratory of the State University of Rio de Janeiro. This research is a cross-sectional study that was approved by the Ethics Committee of the Pedro Ernesto University Hospital (protocol 456 - CEP/2018/HUPE). All individuals signed an informed consent form before performing the tests. The study was carried out in accordance with the Declaration of Helsinki and all measurements were performed on the same day. The subjects carried out respiratory oscillometry and spirometry measurements before and after using the BD. Manovacuometry test, palmar grip and ADL–Glittre, were also performed, in that order.
Subjects
The number of volunteers was calculated using the MedCalc version 12 using preliminary results.14 It were assumed type I and type II errors of 5%, which are usual values in the literature. For the control group, individuals with normal spirometry, non-smokers, without previous pulmonary diseases, and with BMI within the normal range were included. Our study involved individuals who were diagnosed in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD)1 criteria and were aged 40 years or older. All studied subjects had no recent history of respiratory infections within the preceding thirty days at the time of the examinations, and they also had no past history of cardiovascular, orthopedic diseases or COVID-19.
The emphysema phenotype,4,15–17 the chronic bronchitis phenotype18 and the ACOS phenotype19 were diagnosed according to previous studies. Before conducting the tests, all patients continued their regular medications, excluding bronchodilators, in order to prevent any interference in the evaluation, as recommended by the American Thoracic Society/European Respiratory Society (ATS/ERS).20
Spirometry
For spirometry, a computerized system (nSpire Health, Inc., 1830 Left hand Circle, Longmont, CO 80501) was used according to standard protocols.20,21 The parameters analyzed were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and the ratio between forced expiratory flow (FEF) between 25% and 75% and FVC (FEF/FVC). These parameters were quantified in both absolute values and as a percentage of predicted values, with reference values derived from Pereira et al.22 Lung function data were acquired following post-bronchodilator testing.
Respiratory Oscillometry
The used instrument has been previously described23 and was employed in accordance with current recommendations.5 Pressure oscillations were applied in the frequency range of 4 to 32 Hz, with an amplitude of 2 cmH2O produced by a loudspeaker coupled to the respiratory system through a mouthpiece. The resulting flow and pressure signals were measured near the mouth by a pneumotachograph and a pressure transducer, respectively. During the exams, the volunteers remain seated, with their heads in a neutral position, use a nose clip, maintain spontaneous breathing through the mouthpiece and firmly supporting their cheeks and chin to minimize the shunt. A total of three acceptable tests, each comprising 16 seconds, were carried out, and the outcome considered was the average score. To eliminate any outlier values, only measurements with a coefficient of variation of respiratory resistance at the lowest frequency (4 Hz) equal to or less than 10% for all three tests were retained. Additionally, only examinations with a coherence function of 0.9 or greater across the entire frequency range were accepted, aiming to minimize the impact of spontaneous breathing.
The resistive properties were interpreted through the resistances at 4 Hz (R4), 12 Hz (R12), 20 Hz (R20) and the difference between R4 and R20 (R4-R20). The reactance results were interpreted using the mean (Xm), dynamic compliance (Cdyn), resonance frequency (fr) and area under the reactance curve (Ax). Cdyn is directly associated with the overall compliance of the respiratory system, and was computed using the reactance at 4 Hz (Cdyn=1/2πfX4). The resonance frequency, where respiratory reactance becomes zero, is an indicator of the homogeneity of the respiratory system. The parameter Ax was assessed by the area under the curve formed by the lowest frequency (4 Hz), the corresponding reactance (X4), and the resonance frequency (fr). To analyze the total mechanical load of the respiratory system, the impedance module at 4 Hz (Z4) was investigated, encompassing both the resistive and elastic components of the respiratory load.22
Manovacuometry
The maximum inspiratory pressure (MIP) and the maximum expiratory pressure (MEP) were measured. Measurements were performed five times, until three values were obtained with a variation of less than 5%, the highest value being considered for analysis. Predicted values were calculated using the formulas described in Black & Hyatt.6
Handgrip Test
The handgrip test was conducted using a handheld hydraulic dynamometer (Saehan, SH 5001). Participants were evaluated seated, with their elbows flexed at a 90° angle, holding the dynamometer in their hand in a neutral position. Three trials were performed with each hand, with a one-minute interval between measurements, and the highest value was used for analysis.24 Predicted values were derived from Novaes et al, 2009.25
ADL–Glittre
The ADL–Glittre test was performed as described in Skumlien et al 2006.26 Heart rate (HR), peripheral oxygen saturation (SpO2) and dyspnea index (Modified Borg Scale)27 were measured at the beginning, at each lap and at the end of the test. No verbal stimulus was offered throughout the test. The results obtained from patients with COPD were compared to reference values.28
Statistical Analysis
Data were initially tested for normality using the Shapiro–Wilk test (OriginLab® 8.0, Microcal Software, Inc. Ostend, Belgium), and when the sample showed a normal distribution behavior, the Two-Sample t-Test was used to analyze the groups. On the other hand, when the distribution presented a non-normal characteristic, the Mann–Whitney test was used to analyze the groups. The value of p < 0.05 was used to consider the statistically significant differences.
Correlation analyses were conducted using Pearson correlations for data that exhibited a normal distribution and Spearman correlations for data that did not adhere to a normal distribution. This analysis was carried out using Prism 5.03 (GraphPad Software, La Jolla CA, USA). The classification of these associations followed the guidelines proposed by Dawson and Trapp.29
The accuracy of oscillometry in distinguishing COPD phenotypes was assessed using receiver operating characteristic (ROC) analysis. Optimal prediction cut points were identified based on the optimal trade-off between specificity and sensitivity. The area under the curve (AUC) was computed to quantify the diagnostic accuracy, and AUC values greater than 0.80 were deemed suitable for diagnostic purposes.30 These results were presented as mean ± 95% of the confidence interval (CI). We evaluated oscillometry parameters pre and post bronchodilator, as well as the variations associated with the use of this drug (Δ=values post BD-values pre BD).
Results
The study included a cohort of 83 participants, comprising 20 control subjects and 63 patients with COPD (Table 1). Among these groups, no significant alterations were observed in terms of height, body mass, and body mass index (BMI). However, there was an increase in both age and pack-years within the COPD group.
Table 1 Biometric and Spirometric Parameters of the Studied Groups
Spirometric pre-bronchodilator (pre-BD) parameters exhibited significant reductions in individuals with COPD compared to the control group, as indicated in Table 1. Considering the BD effect, we observed a significantly higher change in ACOS in comparison with EMP and CB groups and that the EMP and CB groups presented similar modifications.
Oscillometric Parameters
Figure 1 depicts changes in resistive parameters. The values of R4 and R12 (Figures 1A and B, respectively) before BD use were significantly higher than those observed in the control group in all studied phenotypes. The use of the bronchodilator resulted in a significant reduction of R4 and R12 in patients with emphysema and ACOS, but not in patients with CB.
Figure 1 Resistive oscillometric parameters in patients classified according to the studied phenotypes. (A) R4, resistance at 4Hz; (B) R12, resistance at 12Hz; (C) R4-R20, resistance difference between 4 and 20Hz; ACOS, asthma COPD overlapping syndrome; The top and the bottom of the box plot represent the 25th- to 75th-percentile values while the circle represents the mean value, and the bar across the box represents the 50th-percentile value; ns, not significant; *p <0.05; **p <0.01; ***p<0.005; ****p<0.001.
R4-R20 values (Figure 1C) before BD use were significantly higher than those observed in the control group in all studied phenotypes. Bronchodilator use resulted in a significant reduction of R4-R20 in patients with ACOS, but not in patients with emphysema or CB.
Considering the comparisons among the phenotypes, higher values of R4 before BD were observed in the ACOS group in comparison with the group with emphysema (Figure 1A). The ACOS group showed significantly higher values of R4-R20 before using BD than that observed in EMP and CB groups (Figure 1C).
Figure 2A–D, shows that fr, Cdyn, Ax, and Z4 (respectively) values were significantly different from that observed in the control group before BD use. These parameters showed no observable differences following bronchodilator administration in patients with CB. In contrast, patients with emphysema and ACOS exhibited significant changes following bronchodilator administration.
Figure 2 Reactive oscillometric parameters in patients classified according to the studied phenotypes. (A) fr, resonance frequency; (B) Cdyn, dynamic complacency; (C) Ax, area under the reactance curve; (D) Z4, respiratory impedance module; (E) Xm, mean reactance; ACOS, asthma COPD overlapping syndrome; The top and the bottom of the box plot represent the 25th- to 75th-percentile values while the circle represents the mean value, and the bar across the box represents the 50th-percentile value; ns, not significant; *p <0.05; **p <0.01; ****p<0.001.
Xm values before BD use were more negative in all studied phenotypes than in the control group (Figure 2E). Bronchodilator administration resulted in significant increases in Xm in groups of patients with emphysema and ACOS. Patients with CB, however, do not present significant changes.
Functional Analysis Tests
Figure 3 describes predicted and measured values of handgrip test in each one of the studied subgroups of patients. Significant reductions were observed in all groups, both considering the dominant hand (Figure 3A) and the non-dominant hands (Figure 3B).
Figure 3 Predicted and measured handgrip values in the studied COPD phenotypes evaluated in the dominant (A) and non-dominant hands (B). ACOS, asthma COPD overlapping syndrome; The top and the bottom of the box plot represent the 25th- to 75th-percentile values while the circle represents the mean value, and the bar across the box represents the 50th-percentile value; ns, not significant; *p <0.05; **p <0.01; ***p<0.005; ****p<0.001.
Similar comparisons considering the respiratory pressures are showed in Figure 4. Significant changes were observed in all groups, both in MIP (Figure 4A) and MEP values (Figure 4B). Considering the comparisons among the phenotypes, higher values of MIP after BD were observed in the CB group in comparison with the group with emphysema (Figure 4A).
Figure 4 Predicted and measured maximum inspiratory pressure (MIP, (A) and maximum expiratory pressure (MEP, (B) values in the studied COPD phenotypes. ACOS, asthma COPD overlapping syndrome; ns, not significant; the top and the bottom of the box plot represent the 25th- to 75th-percentile values while the circle represents the mean value, and the bar across the box represents the 50th-percentile value; * p <0.05; ** p <0.01; **** p<0.001.
Figure 5 depicts the results of the AVD-Glittre test. The performed time significantly increased in all studied subgroups of patients when compared to predicted values.
Figure 5 Predicted and measured values of Glittre-ADL test in the studied COPD phenotypes. ACOS, asthma COPD overlapping syndrome; the top and the bottom of the box plot represent the 25th- to 75th-percentile values while the circle represents the mean value, and the bar across the box represents the 50th-percentile value; ns, not significant; ***p<0.005; ****p<0.001.
Correlation Analysis
Considering all COPD patients subgroups, almost all studied oscillometric parameters were associated with ADL-Glittre test time and handgrip analysis (Table 2). The exception was due to R4-R20. As can be seen in Table 2, no associations were observed among oscillometric parameters and respiratory pressures.
Table 2 Correlation Analysis Between Total Glittre-ADL Test Time, Handgrip Analysis, Respiratory Pressures and Oscillometric Parameters in the Whole Group of Patients with COPD
Considering only the emphysema phenotype (Table 3), Cdyn and Z4 showed significant inverse or direct associations, respectively (p < 0.05) with the ADL-Glittre test. There was no relationship between oscillometry and the palmar grip test in the dominant hand. With respect to the non-dominant hand, significant inverse correlations (p < 0.05) were observed between the resistive (R4) and reactive (fr) oscillometric parameters. There was no relationship between oscillometric parameters and manovacuometry.
Table 3 Correlation Analysis Between Total Glittre-ADL Test Time, Handgrip Analysis, Respiratory Pressures and Oscillometric Parameters in the Emphysema Group
When the correlation analysis included only CB patients, there was no relationship between the oscillometric parameters and the ADL-Glittre test (Table 4). No relationship was found with the palmar grip test in the dominant hand, and an inverse correlation was observed with R12 (p < 0.05). There was no relationship between oscillometric parameters and manovacuometry.
Table 4 Correlation Analysis Between Total Glittre-ADL Test Time, Handgrip Analysis, Respiratory Pressures and Oscillometric Parameters in the Chronic Bronchitis Group
Similar analysis considering only patients with the ACOS phenotype showed no relationship between the oscillometry and the ADL-Glittre test (Table 5). Concerning the palmar grip test, we do not observed associations with the dominant hand, while, significant inverse correlations (p < 0.05) were observed between R4 and R12 with the non-dominant hand. There was no relationship between oscillometric parameters and manovacuometry.
Table 5 Correlation Analysis Between Total Glittre-ADL Test Time, Handgrip Analysis, Respiratory Pressures and Oscillometric Parameters in the ACOS Group
Oscillometry Discriminating the Different Phenotypes
Oscillometric parameters pre and post bronchodilator do not present adequate values of AUC in discriminating the studied phenotypes (AUC < 0.80). The variations of R4-R20 due to the use of BD, on the other hand, provided an accurate discrimination of ACOS from emphysema (Figure 6A, AUC = 0.82, CI = 0.69±0.95) and chronic bronchitis (Figure 6B, AUC = 0.84, CI = 0.71±0.97).
Figure 6 Analysis of receiver operator characteristic (ROC) for the best parameter observed in the discrimination of ACOS from emphysema (A) and chronic bronchitis. (B) AUC, the area under the ROC curve; Δvariations of R4-R20 due to the use of bronchodilator; R4-R20, resistance at 4Hz minus at 20Hz.
Abbreviation: CI, confidence interval.
Discussion
In this study, four major findings were obtained: 1) initially, that oscillometry provided a detailed and consistent description of the COPD phenotypes; 2) BD response was different among the studied phenotypes; 3) The study revealed an association between oscillometry and functional capacity, especially within the emphysema phenotype; and 4) ROC curve analysis showed that ΔR4-R20 effectively discriminated ACOS from chronic bronchitis and emphysema phenotypes.
Table 1 displays the biometric parameters of the groups under investigation. Although there was a significant difference in age and body mass between the control group and the ACOS group, the analysed groups can be considered homogeneous, since height is the most important parameter for defining impedance values, age and BMI do not significantly alter respiratory oscillometry parameters.31 This parameter did not exhibit statistically significant differences among the studied groups (Table 1).
In general, the observed increases in R4 and R12 described in Figure 1A and B may be associated with inflammation of the mucous glands due to high tobacco consumption, which results in airway obstruction.32,33 Considering the specific characteristics of the phenotypes, the increased values in emphysema in comparison with the control group may be explained by the destruction of the small airways and loss of the parenchymal tissue that keeps the airways open.33 The increase in resistance found in the CB group may be associated with the worsening of airflow obstruction, a result of the excess mucus caused by the increase in goblet cells in the small airways in these individuals.34 The similar increase observed in ACOS can be explained by the typical increased bronchial secretion and, consequently, greater narrowing of the airways.
The comparisons among phenotypes showed that ACOS presented higher R4 values before BD use than the group with emphysema predominance. This is in line with the results of Van Noord et al, which showed that airway resistance was significantly higher in asthma and chronic bronchitis than in emphysema.35 Further support to this finding is provided by 3D CT analyses in the third to sixth generation central bronchus, which showed that the ACOS had greater airway narrowing compared with COPD.36
R4-R20 is associated with the respiratory system homogeneity of ventilation.37 The results of the present study provide evidence of reduced ventilation homogeneity in all studied phenotypes (Figure 1C). In close agreement with these results, Su et al, showed associations between variations in resistance and the degree of morphological abnormalities of the small airways evaluated with endobronchial optical coherence tomography in COPD and heavy smokers.38
R4-R20 increased in ACOS in comparison with emphysema and CB (Figure 1C). This result agrees with that obtained using 3D computed tomography analyses of the airways in COPD and ACOS in the study of Karayama et al.36 This difference may be explained, at least in part, by the addition of the pathophysiological characteristics of asthma in these patients. In this disease, bronchial obstruction may result from bronchospasm, mucosal oedema and hypersecretion.39 Thus, the presence of these additional factors seems to introduce greater non-homogeneities in the ventilation of these patients than those caused in patients with predominance of emphysema or CB.
Some authors claim that bronchodilation in patients with COPD causes an increase in the diameter of the airways.40,41 In line with previous studies,41,42 we found a reduction in respiratory resistance (Figures 1A and B) in individuals classified as having emphysema and ACOS after using a bronchodilator. It was interesting to observe that similar alterations did not occur in the group with a preponderance of CB. This indicates that the smooth muscle relaxation introduced by BD use do not result in significant changes in this group. Since the main mechanism of respiratory obstruction in these patients refers to excessive mucus production, which is not influenced by BD use, this result seems to be reasonable. Important structural changes in CB includes airway wall thickening due to remodeling. This phenomena make airways difficult to “open”, reducing response to bronchodilator agents.43 Baldi et al suggested that airway distensibility is reduced in COPD and that airway smooth muscle contributes to the increased airway stiffness in COPD subjects with prevailing bronchitis,44 but not in those with more emphysema.
Bronchodilator use decreased the value of R4-R20 in patients with emphysema and ACOS (Figure 1C), revealing an improvement in the ventilation homogeneity.45 Although R4-R20 was reduced with the BD use, this parameter still presented increased values compared to healthy individuals. This indicates that not all imbalances in the time constants were eliminated with the BD use.46 In a similar way to what was observed in R4 (Figure 1A) and R20 (Figure 1B), the R4-R20 values did not change with the use of the bronchodilator. We can speculate that the same reasons described earlier for the lack of response in terms of R4 and R20 may also be involved in these results.43,44
A comparative analysis of the reactive parameters before BD use with the control group showed significant changes in all studied parameters and phenotypes (Figure 2). This can be explained by the increased ventilation non-homogeneity in the respiratory system of these patients, which occurs due to the increase in imbalances in the time constants of the different regions of the lungs of patients with COPD.47 These changes may also be associated with abnormalities in lung tissue, chest wall, airway distensibility and increased resistance,47 as well as with the reduction in the apparent compliance.48
The use of bronchodilator medication significantly improved almost all reactive parameters in the emphysema and ACOS groups (Figure 2). The bronchodilator use relax the smooth muscles of the bronchi, improving the compliance of the airway wall.49 A previous study showed an increase in Cdyn after the use of salbutamol in patients with obstruction due to asthma and COPD.50 The increase in compliance reflects the improvement in lung expansion, associated with a reduction in the peripheral airways resistance resulting in an improvement in lung homogeneity and a decrease in hyperinflation after drug inhalation.50 The cited factors explain the improvements observed in Cdyn, AX, Z4 and Xm (Figure 2).
In contrast, the use of BD did not result in discernible changes in patients with CB (Figure 2). Although persistent airflow limitation occurs in patients with COPD, ACOS and asthma, the flow limitation phenomena may have distinct characteristics, resulting in different responsiveness to bronchodilators.51 Chronic bronchitis is caused by the hypersecretion of mucus by the goblet cells, which leads to the worsening of resistance to airflow by obstructing the lumen of the small airways. The presence of inflammation in the epithelium of the central airways is another important characteristic, which may introduce epithelial remodelling.52,53 On the other hand, the main characteristic of emphysema refers to the destruction of the lung parenchyma, leading to loss of elastic recoil.54 Previous works hypothesize that an inflamed and thick airway may appear more rigid than an airway subjected to the devastation of proteases.55,56 This factor could explain, at least in part, observed differences between CB and emphysema, since relaxation in the airways smooth muscles could have lesser effects in more rigid airways, such as those present in CB than in the airways of patients with emphysema.
Asthma is characterized by bronchial muscle contraction and airway narrowing that is highly reversible using BD medication.35 The greater response to BD observed in patients with ACOS compared to those with CB (Figure 2) is probably related to this characteristic.
Respiratory abnormalities represent only one aspect of the multifaceted complications associated with this COPD. In this context, muscle dysfunction emerges as a primary anomaly linked to diminished functionality.57 The evaluation of peripheral muscle strength in COPD patients carries paramount importance due to its correlation with various factors, including exercise intolerance, challenges in performing daily activities, and a diminished quality of life.57 This study observed substantial reductions in manual grip strength for both the dominant (Figure 3A) and non-dominant hands (Figure 3B) within the emphysema, chronic bronchitis, and ACOS groups when contrasted with predicted values for each respective group. The etiology of muscle dysfunction and exercise impediments observed in COPD patients is explicable through systemic inflammation originating from the pulmonary system and a reduction in the bulk of musculature within the lower extremities.10 Musculoskeletal dysfunction, characterized by the loss of muscle strength and endurance, is principally attributed to diminished muscle area, reduced lean body mass, compromised muscle stamina, and an augmented susceptibility to fatigue.58,59 Holden et al described a relation between reduced handgrip strength and diminished quality of life, heightened vulnerability to exacerbated COPD morbidity and increased risk of mortality.58
Significant reductions in manometry were observed for PiMax (Figure 4A) and PeMax (Figure 4B) in the emphysema, chronic bronchitis, and ACOS groups. Muscle fatigue resulting from the detrimental effects of COPD not only affects peripheral muscles but can also compromise respiratory muscle function.60 Another explanation is associated with airway obstruction and pulmonary hyperinflation, which position the diaphragm at a mechanical disadvantage, resulting in a chronic decrease in contact area, leading to reduced respiratory muscle efficiency in these individuals.61
Significant increases in the time taken to complete the Glittre-ADL test were observed in the emphysema, chronic bronchitis, and ACOS groups compared to predicted values (Figure 5). These limitations are associated with several factors, including gas exchange inefficiency, ventilatory limitation, peripheral muscle weakness, alterations in metabolism, and peripheral muscle composition.62 Dynamic hyperinflation may contribute to these findings, potentially worsening when respiratory demand increases during exercise and creating a sensation of dyspnea as respiratory work intensifies.63
Table 2 shows that functional capacity was more sensitive to changes in airway obstruction (R4 and R12) and elastic properties (fr, Cdyn, Ax and Z4) than changes in ventilation heterogeneity (R4-R20). The moderate to good correlations observed among oscillometry with ADL-Glittre test and Handgrip analysis reinforce the notion that oscillatory indices are associated with physical performance and are valuable for predicting reduced exercise tolerance in individuals with COPD.64 The results are also consistent with that obtained recently using the 6-minute walking distance65,66 and during cycle ergometer tests.67 These associations agree with the involved physiology, describing an increase in ADL-Glittre test time with airway obstruction and Cdyn reduction. This reflects the systemic effects due to lung abnormalities, including the presence of airflow limitation and dynamic hyperinflation.
Considering the analysis performed specifically in the studied COPD phenotypes, it was interesting to note significant relationships in the emphysema group (Table 3) describing a decrease in ADL-Glittre test performance with reductions in Cdyn and increases in Z4. These associations agree with the typical changes observed in COPD, describing abnormalities in elastic properties (Cdyn), and respiratory work (Z4). The inverse associations observed among resistive properties (R4) and ventilation heterogeneity (fr) with Handgrip analysis are also consistent with the cited principles.
A recent review points out that oscillometry adds insight into the pathophysiology of COPD, and that we still need more data to assess how this method relates to clinical phenotypes of COPD.37 COPD phenotypes should be able to classify patients into distinct subgroups that provide prognostic information and allow us to better determine the appropriate therapy that alters clinically significant outcomes.3,37 In this sense, the current study provides evidence that oscillometry may help to accurately discriminate ACOS from emphysema and chronic bronchitis (AUC>0.80). This high performance probably reflects the higher impact of bronchodilator use in the ventilation heterogeneity of the ACOS group due to the asthmatic component of this phenotype.
The differential diagnosis between groups of emphysema predominance and chronic bronchitis predominance are likely to be complex, and their clarification needs further investigation. It is important to emphasize that promising values of AUC were observed in these analyses, with values around 0.65. Previous studies from our research group have demonstrated that the application of artificial intelligence methods can enhance the accuracy of oscillometry parameters in the early diagnosis of smoking-induced respiratory changes68 and in the diagnosis69 and classification70 of COPD. In this manner, the application of these methods for the proper discrimination between emphysema and chronic bronchitis is one of the upcoming steps planned by our research group in this line of investigation.
A thorough examination of potential limitations of the current study is necessary. Firstly, the study concentrated on whole-breath impedance measurements and did not evaluate within-breath analysis.71 In future research, it is advisable to explore similar analyses focusing on within-breath impedance parameters. This avenue represents a promising research direction. Another noteworthy point; plethismographic exams were not feasible in all patients due to their clinical condition or inability to cooperate during the test. This resulted in the loss of important information that could have helped to clarify the differences between the phenotypes. Lastly, this is a single-center study, thus the outcomes may lack broad applicability to the entire patient demographic. This emphasizes the necessity for future investigations with a higher number of volunteers. Despite these limitations, this preliminary analysis significantly contributes to a critical discussion concerning the use of oscillometric parameters to evaluate COPD phenotypes.
Conclusion
In conclusion, this study set out to examine COPD phenotypes in-depth via respiratory oscillometry. It has been shown initially that oscillometry provided a description of the COPD phenotypes consistent with the involved physiopathology. The use of BD medication introduced clear changes in ACOS and Emphysema, but not in patients with predominance of CB. The correlation analysis unveiled a clear relationship between oscillometry and functional capacity, notably within the emphysema phenotype. ROC analysis further indicated that oscillometric parameters displayed sufficient accuracy in discriminating ACOS from Emphysema and CB. These findings offer evidence that oscillatory indices have the potential to enhance our understanding and identification of COPD phenotypes.
Acknowledgments
The research presented in this study received support from the Brazilian Council for Scientific and Technological Development (CNPq), the Rio de Janeiro State Research Supporting Foundation (FAPERJ), and was partially funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES) under Finance Code 001.
Disclosure
The authors report no conflicts of interest in this work.
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Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder characterized by progressive airflow limitation and persistent respiratory symptoms. It presents a substantial global health burden and is a leading cause of morbidity and mortality.1 The development of COPD involves a complex interplay between genetic factors, such as predisposition, and environmental factors, including smoking, air pollution, and respiratory infections. Despite the diverse causes of COPD, current diagnostic and therapeutic approaches are limited, highlighting the need for a deeper understanding of its underlying mechanisms.2
In recent years, there has been growing interest in the role of the gut microbiota, which has been found to influence various aspects of human health, including immune regulation and systemic inflammation.3 Accumulating evidence suggests a potential link between the dysbiosis of the gut microbiota and the development of COPD.4,5 Observational studies have identified gut microbiome dysbiosis in COPD patients, and rodent models have demonstrated its contribution to COPD development.6,7 Furthermore, there have been reports on the associations between gut microbial dysbiosis and a decline in lung function in individuals with COPD.8–10
However, establishing a causal relationship between the gut microbiota and COPD remains challenging. The dynamic nature of the gut microbiome introduces challenges when attempting to characterize it through a single cross-sectional study design.11 This is due to the potential variability in microbial sequencing results, which can be influenced by various confounders and covariates. It is crucial to acknowledge that factors such as the use of inhalers, particularly inhaled corticosteroids (ICS), and antibiotics can act as confounding variables in these studies.12
Mendelian Randomization (MR) is an innovative and robust analytical approach that can provide insights into causal relationships between exposures and outcomes using genetic variants as instrumental variables (IV).13 By leveraging naturally occurring genetic variations unaffected by confounders, MR analysis circumvents some limitations of traditional observational studies, including confounding factors and reverse causality, and provides more reliable evidence for causal inference. The utilization of naturally occurring genetic variations in MR analysis offers a valuable approach to overcome limitations commonly encountered in traditional observational studies. MR analysis can effectively sidestep confounding factors and mitigate the issue of reverse causality.13
MR studies have been employed to establish genetic evidence supporting the causal link between gut microbiota and respiratory diseases.14–16 In a recent study conducted by Wei et al, they employed MR analysis to examine the causal connection between the gut microbiome and COPD. They identified 9 bacterial taxa associated with the risk of COPD. However, none of their MR results were found to be statistically significant after applying multiple testing corrections. This lack of significant findings may potentially be attributed to the relatively small sample size of the Genome-Wide Association Study (GWAS) utilized in their analysis.15 Additionally, while several observational studies have previously reported associations between the gut microbiota and lung function in COPD,8–10 the causal relationship involving the interplay between the gut microbiota, lung function, and COPD remains uncertain. Therefore, the objective of this study is to investigate the causal relationship between the gut microbiota, lung function, and COPD within the framework of MR analysis. To achieve this, we have incorporated the latest GWAS datasets, allowing for a more comprehensive analysis. By utilizing an extensive dataset and employing the MR approach, this research aims to shed light on the intricate causal relationships between these variables, providing insights into the pathogenesis and potential intervention strategies for COPD.
Method
Study Exposures
The summary statistics for gut microbiota abundance were obtained from a comprehensive GWAS conducted by the MiBioGen consortium. This study involved the analysis of host genetic variations in 18,340 participants from 24 cohorts, primarily of European descent. The study combined 16S rRNA gene sequencing profiles and human genotyping data from the participants. The dataset included a total of 211 taxa, encompassing 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera, identified through 16S rRNA gene sequencing techniques (Supplementary Table S1).
Study Outcomes
The GWAS summary statistics for the outcomes were extracted from the large-scale biomedical databases of UK biobank and FinnGen biobank, both of which contain comprehensive health and genetic information from a large population of participants. The summary statistics for lung function, including FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and percentage of predicted FEV1, were extracted from the second analytical round of the UK biobank database. This extraction was performed on July 2, 2023. The GWAS summary statistics for COPD were obtained from the eighth analytical round of the FinnGen biobank database, accessed on April 29, 2023. It is worth noting that there was minimal overlap between the individuals included in the exposure and outcome samples. Supplementary Table S1 provides details about the GWAS summary statistics for reference.
Selection of Instrumental Variables
Human SNPs that were associated with the abundance of gut microbiota, which demonstrated genome-wide significance with a p-value of less than 1×10−5 were included. To assess potential confounding factors associated with the identified SNPs, we employed the Phenoscanner. SNPs found to be linked to confounding factors or outcomes were excluded from our analysis. (Supplementary Table S2) Clumping of these variants was performed to ensure the independence of the IVs. A clumping window of 10,000 kb and a pairwise linkage disequilibrium (LD) threshold of r2 < 0.001 were used for this purpose. To avoid weak instrument bias and ensure the strength of the IVs, we calculated the F-statistic. SNPs with an F-statistic below 10 were excluded from the analysis. Harmonization of variants was undertaken by aligning the effect alleles of different studies to the same reference allele using the TwoSampleMR package in R. Given the variability in genotyping platforms utilized in GWAS, it is possible that certain SNPs associated with the gut microbiota may not be present in the outcome dataset. Consequently, these missing SNPs were excluded from this study’s analysis.
Mendelian Randomization Analyses
The primary method used for causal inference in this study was the inverse variance weighted (IVW) method. This method combines the ratio estimates obtained from each genetic instrument in a meta-analysis model.17 To ensure the robustness of our findings, we employed additional analysis methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. MR-Egger detects violations of MR assumptions, such as horizontal pleiotropy, and provides an effect estimate that is not affected by these violations.18 The weighted median method combines the ratio estimates from genetic instruments using a median-based approach, which can provide reliable estimates even if up to 50% of the instruments are invalid. The simple mode and weighted mode methods consider the majority or weighted majority of genetic instrument estimates, respectively, to determine the direction and strength of the causal relationship.17 MR-PRESSO, a general test for the presence of outliers, was used to identify and remove genetic variants that significantly contributed to heterogeneity through a simulation approach.19 By incorporating these supplementary analysis methods, we can evaluate the consistency of the results and gain a more comprehensive understanding of the causal associations while considering potential violations of MR assumptions. For associations with an IVW-MR p-value < 0.05, we applied the Benjamini-Hochberg (BH) correction for multiple testing to reduce the likelihood of false-positive findings. Additionally, we conducted reverse analysis to examine the reverse causal association. All statistical analyses were performed using R version 4.2.3.
Sensitivity Analyses
In order to ensure the robustness of our primary causal estimate for associations with an IVW-MR p-value < 0.05, we performed sensitivity analyses. Cochran’s Q statistic was utilized with both the IVW and MR-Egger methods to assess the heterogeneity of effects. Additionally, we employed the MR-Egger intercept and MR-PRESSO Global test to evaluate the presence of horizontal pleiotropy. If any of these tests indicated the presence of pleiotropy with a significance level of p < 0.05, the corresponding results were excluded.18,19 Furthermore, a leave-one-out analysis was conducted to identify outliers and assess the stability of the results. These sensitivity analyses were crucial in ensuring the reliability and robustness of our findings.
Result
The purpose of this MR study was to investigate the causal effects of specific gut microbial taxa on lung function and COPD. (Figure 1) There are three main assumptions of MR analysis. First, the IVs should be strongly associated with the exposure. To address this assumption, we selected only exposures that had at least three independent genetic instruments at minimum p-value < 1×10−5. Additionally, we have excluded SNPs with mean F statistics < 10. The SNPs were then clumped by LD to ensure the independence of the IVs. Second, the genetic variants used as IVs are independent of any confounding factors that may influence both the exposure and outcome. Thus, we utilized the Phenoscanner to examine potential confounding factors associated with the SNPs. Any SNPs found to be related to confounding factors or outcomes were excluded from our analysis. The third assumption requires that the IVs only affect the outcome through their effect on the exposure and not through any alternative pathways. In order words, no pleiotropy should be presented. Any causal relationships that were detected to have pleiotropy would be excluded. After selecting SNPs according to the above criteria, we proceeded to harmonize the effect sizes of these variants on the exposure and the outcome for consistency and comparability. Among the MR results we obtained (Supplementary Table S3), a total of 64 potential associations were identified. These findings are summarized in Supplementary Table S4.
Figure 1 Overall MR framework and workflow of this study.
Effect of Gut Microbial Abundance on Lung Function
Fifteen potential causal relationships were identified between the genetically predicted abundance of gut microbial taxa and FEV1 in the IVW analysis. Six relationships remained significant after conducting multiple correction. (Figure 2) (Table 1) Order Erysipelotrichales (β = 0.031, CI = 0.009–0.053, p = 0.032), order Desulfovibrionales (β = 0.029, CI = 0.010–0.049, p = 0.031), order Clostridiales (β = 0.037, CI = 0.015–0.060, p = 0.020), class Clostridia (β = 0.044, CI = 0.020–0.067, p = 0.003), class Deltaproteobacteria (β = 0.034, CI = 0.015–0.053, p = 0.003) and class Erysipelotrichia (β = 0.031, CI = 0.009–0.053, p = 0.026) were positively associated with FEV1. No significant horizontal pleiotropy was detected in the MR-Egger intercept and MR-PRESSO analysis (p>0.05). (Supplementary Tables S5 and S6) Results from Cochrane’s. Q test showed no significant heterogeneity in the relationships (p>0.05). (Supplementary Table S7) All the results remained robust after excluding the SNP one by one in leave-one-out analysis. (Supplementary Table S8) The reverse analysis did not reveal any reverse correlations. (Supplementary Table S9)
Table 1 Causal Relationships Between Gut Microbiota and FEV1
Figure 2 Forest plot for the causal effects of genetically predicted abundance of gut microbial taxa on lung function and COPD.
In the IVW analysis, we identified sixteen potential causal relationships between the abundance of distinct gut microbiota and FVC. Following multiple correction, a significant association remained for four out of sixteen relationships. (Figure 2) (Table 2) Family Desulfovibrionaceae (β = 0.034, CI = 0.013–0.054, p = 0.033), order Desulfovibrionales (β = 0.032, CI = 0.013–0.051, p = 0.016), class Clostridia (β = 0.035, CI = 0.013–0.058, p = 0.016) and class Deltaproteobacteria (β = 0.034, CI = 0.016–0.053, p = 0.003) were all positively correlated with FVC. No significant heterogeneity and horizontal pleiotropy were detected in MR-Egger intercept, MR-PRESSO and Cochrane’s Q tests. (Supplementary Tables S5–S7) Leave-one-out analysis revealed that some single SNPs might dominate the positive effects of class Clostridia. (Supplementary Table S8) No reverse correlations were found through reverse analysis. (Supplementary Table S9)
Table 2 Causal Relationships Between Gut Microbiota and FVC
IVW analysis unveiled eighteen potential causal relationships linking the abundance of gut microbiota and percentage of predicted FEV1. After conducting multiple corrections, two of these relationships remained statistically significant. (Figure 2) (Table 3) Order Selenomonadales (β = −0.073, CI = −0.120 – −0.026, p = 0.044) and class Negativicutes (β = −0.073, CI = −0.120–0.0026, p = 0.035) were negatively correlated with percentage of predicted FEV1. MR-Egger intercept, MR-PRESSO and Cochrane’s Q tests indicated no evidence of horizontal pleiotropy and heterogeneity. (Supplementary Tables S5–S7) Furthermore, the stability and robustness of the results were confirmed through the leave-one-out analysis. (Supplementary Table S8) The reverse analysis indicated no reverse correlations. (Supplementary Table S9).
Table 3 Causal Relationships Between Gut Microbiota And percentage of Predicted FEV1
Effect of Gut Microbial Abundance on COPD
Our Mendelian randomization analysis revealed that genetically predicted abundance of fifteen microbial taxa exhibited potential causal effects on COPD. After implementing multiple corrections, two of these relationships remained statistically significant. (Figure 2) (Table 4) The abundance of genus Holdemanella (OR = 1.176, CI = 1.082–1.278, p = 0.015) were positively correlated with the risk of COPD, while FamilyXIII. (OR = 0.750, CI = 0.629–0.894, p = 0.042) exhibited a negative correlation with the risk of COPD. MR-Egger intercept, MR-PRESSO, and Cochrane’s Q tests did not detect any significant heterogeneity or horizontal pleiotropy in the analysis. (Supplementary Tables S5–S7) The robustness and stability of the results were confirmed by the leave-one-out analysis. (Supplementary Table S8) The reverse analysis provided confirmation of the causal direction of the results. (Supplementary Table S9)
Table 4 Causal Relationships Between Gut Microbiota and the Risk of COPD
Discussion
To our knowledge, this study is the first to explore the causal relationship between gut microbiota, lung function, and COPD. Following a rigorous analysis that included sensitivity analysis, reverse analysis, and multiple corrections, a total of fourteen robust and stable causal relationships were identified. There was no overlap found between the microbial taxa influencing lung function and those impacting COPD. However, several microbial taxa were discovered to have a positive causal correlation with lung function, offering potential insights into the development of probiotics. Furthermore, the presence of microbial taxa negatively correlated with lung function and positively correlated with COPD emphasized the potential impact of gut microbiota dysbiosis on lung function and COPD development. This contributes to the expanding understanding of the gut-lung axis.
Based on our research, we found that our findings reinforced the existing body of observational evidence, lending further support to the established knowledge in this domain. In our results, the bacterial taxa that were positively associated with lung function were family Desulfovibrionaceae, order Erysipelotrichales, Desulfovibrionales, Clostridiales, class Clostridia, Deltaproteobacteria and Erysipelotrichia. On the other hand, order Selenomonadales and class Negativicutes were negatively correlated with lung function. Interestingly, various pulmonary disease states have been associated with the elimination of these taxa. Upon treating influenza-infected mice with either the Chinese herb formula GeGen QinLian or fecal microbiota transplantation, the intestinal flora was restored. This restoration led to an increase in the abundance of Desulfovibrio_C21_c20 and a subsequent decrease in both mortality and lung inflammation.20 Long-term consumption of allium tuberosum reduced inflammatory cell count, interleukin (IL)-5 and IL-13 in bronchoalveolar lavage fluid in asthmatic mice. This consumption also improved pulmonary histopathology. Additionally, Desulfovibrionaceae was revealed as a biomarker indicating the effectiveness of the treatment.21 Clinical observational studies have revealed a decrease in Clostridia within the gut microbial composition of adult asthma patients.22 Interestingly, among asthmatic patients, those with lower specific IgE levels to mites and Ascaris exhibited an enrichment of various members from the order Clostridiales.23 In a MR study, it was found that class Negativicutes and order Selenomonadales exhibited a notable association with COVID-19 hospitalization, susceptibility, and severity.14
Previous studies have provided evidence of the impact of gut microbiota on immune regulation, suggesting a potential mechanism by which dysbiosis of gut microbiota could affect lung function. Among the various mechanisms investigated, the role of short-chain fatty acids (SCFAs) has received significant attention. SCFAs are produced through the fermentation of dietary fibers and are released into the lumen and peripheral circulation. The binding of SCFAs to free fatty acid receptors on immune cells such as neutrophils and macrophages allows them to exert anti-inflammatory effects.24,25 This protective role of SCFAs has been observed in both animal models and clinical studies. In a mouse model of emphysema, SCFAs demonstrated notable preventive potential by reducing the progression and severity of emphysema.26–28 Furthermore, a comprehensive study revealed that individuals who consumed dietary fibers over a long term had a 30% reduced risk of developing COPD.29 Previous observational studies have also reported associations between changes in the gut microbiome and a decline in lung function in individuals with COPD. These associations may be linked to the loss of protective microbial taxa that are involved in SCFA pathways.8–10 In addition to the immune regulatory mechanisms associated with the secretion of SCFAs, the beneficial microbiota may be associated with the homeostasis of the gut microbiome, which attribute to the colonization of a more diverse microbiome, preventing the dominance of one potentially pathogenic microbiota. Furthermore, the maintenance of gut microbial homeostasis allows beneficial intestinal microorganisms to play a protective role. Therefore, the gut microbiota that exhibited positive associations with lung function in our study may potentially act as protective bacteria through similar mechanisms.
It is noteworthy that the bacterial taxa correlated with lung function in our study have not only been associated with pulmonary diseases in previous observational studies, but they have also been linked to inflammatory bowel diseases (IBD). In dogs with IBD, the abundance of Erysipelotrichia and Clostridia were notably diminished.30 Similarly, individuals with Crohn’s disease displayed a significant decrease in the abundance of Erysipelotrichales and Clostridiales within their gut microbial profile, which strongly correlated with their disease status.31 Interestingly, it has been reported that patients with COPD exhibit reduced integrity and function of the intestinal barrier, as well as a higher prevalence of IBD.32–35 Therefore, our results have offered insights into the intricate relationship between the gut and lungs, known as the gut-lung axis. The bacterial taxa that demonstrated positive causal correlations with lung function may potentially confer protective effects through this gut-lung axis.
In our MR results, the abundance of genus Holdemanella were positively correlated with the risk of COPD, while FamilyXIII exhibited a negative correlation with the risk of COPD. It is worth noting that previous findings have shown a intriguing negative correlation between the abundance of Holdemanella and propionate levels, one of the SCFAs, in individuals with diabetes and cognitive impairment.36 Furthermore, a recent MR analysis has observed a causal correlation between Holdemanella and the risk of developing asthma.16 These findings indicate that the genus Holdemanella could potentially play a role in the development of pulmonary diseases, possibly through the SCFA pathways. However, Holdemanella biformis, a specific strain belonging to the genus Holdemanella, has exhibited protective effect in mouse colitis.37 Therefore, it is important to note that different species within the same genus can have distinct impacts on health, though microbial taxa can only be classified up to the genus level when using 16S rRNA sequencing. As far as our knowledge goes, there have been no previous associations reported between FamilyXIII and either pulmonary or bowel diseases in animal or clinical studies. Therefore, the causal correlation we observed between FamilyXIII and COPD necessitates additional investigation. All in all, the causal relationships uncovered in our study likely involve intricate interactions between specific microbial taxa and host factors. To fully understand the mechanisms through which dysbiosis of the gut microbiota impacts lung function and COPD, future studies employing metagenomic and metabolic sequencing techniques are warranted. Further validation of the potentially beneficial bacteria we identified can be conducted in subsequent experiments. For instance, Lai et al conducted a study where they constructed a murine model of COPD, analyzed the intestinal bacterial profiles of COPD rats and normal rats, isolated a strain called Parabacteroides goldsteinii from the differing bacteria, and demonstrated that preparations of this strain had a beneficial effect in mitigating COPD. Thus, investigations into the functional capabilities of specific microbial taxa are necessary to gain further insights.
The inclusion of a MR design presents an advantage in our study. Through selection of SNPs significantly associated with the exposure, while excluding SNPs correlated with the outcome or potential confounders, we establish the validity of the IVs, thereby enhancing the reliability of our results. By conducting sensitivity analysis, multiple testing, and reverse analysis, we confirm the stability, robustness, and direction of the identified causal relationships in our MR results. Consequently, we overcome limitations commonly encountered in traditional observational studies, including confounding factors and reverse causality, and provide genetic evidence for causal inference. Furthermore, our study benefits from utilizing the largest publicly available GWAS datasets, ensuring a comprehensive and robust analysis. Incorporating these extensive datasets significantly enhances the statistical power of our MR analysis, enabling accurate estimation of causal effects.
It is important to acknowledge certain limitations in our study. Firstly, our analysis utilized GWAS data for microbiota that did not specifically target the complete 16S rRNA gene. This limitation poses a challenge in differentiating between microbial taxa with the desired taxonomic resolution. It is worth noting that within the same genus, microbial taxa can have opposing effects on the host, thus the absence of complete 16S rRNA gene sequencing data restricts our ability to identify potential therapeutic targets accurately. Furthermore, since 16S rRNA sequencing is not designed to target viruses and fungi, the impact of such microbiota components was not investigated in our study. Secondly, given the dynamic and complex nature of the gut microbiota, it is an exposure phenotype that influenced by numerous variants with relatively small effect size. To address this complexity and increase statistical power, we have used a less stringent p-value threshold of 1 × 10−5, thus incorporating a larger number of IVs into our analysis, consequently facilitating the use of sensitivity analysis and bolstering statistical power. However, this approach carries the risk of including false-positive variants. By only including SNPs with a F statistic above 10 and performing multiple correction, we have reduced the possibility of false-positive results. Thirdly, our study predominantly focused on European populations due to the availability of suitable genetic data. This limits the generalizability of our findings to other ethnic groups, and further investigations involving diverse populations are warranted. Lastly, our results only establish a limited causal relationship between one specific flora and the outcome. The intricate biological mechanisms, including the impact of short-term or long-term changes in this flora on the overall gut microbiome and the influence on microbial metabolites and host immunity remain unclear. These aspects require more comprehensive mechanistic studies to be conducted in the future.
In summary, our MR analysis presents genetic evidence supporting a causal link between alterations in gut microbiota, lung function, and COPD. Our findings highlight the potential involvement of the gut microbiota in the development and advancement of COPD. The findings of this study provide potential insights for future research, including the investigation of therapeutic approaches such as probiotics to modulate the gut microbiota and alleviate COPD progression. Further investigations, particularly utilizing metagenomic and metabolomic sequencing approaches, are warranted to elucidate the underlying mechanisms and enhance our understanding of the complex interplay within the gut-lung axis.
Summary statistics for the studies used for analysis were composed and obtained from published studies. All studies have received prior approval from their respective institutional review boards (IRBs). The institutional Review Board of Zhongshan Hospital approved the protocol for this study, and as per their guidelines, this study exclusively utilized publicly available data without using any individual-level data. Therefore, no additional IRB approval was necessary.
Acknowledgments
We would like to extend our appreciation to the participants and investigators involved in the MiBioGen Consortium, UK biobank, and FinnGen study. Their invaluable contributions to the large-scale GWAS studies have significantly advanced our knowledge of the gut microbiome and its connection to lung function and COPD. We would also like to extend appreciation to Dr. Xicheng Gu from Huashan Hospital, Fudan University, for providing invaluable advices on code writing.
Funding
This work is supported by the Shanghai Science and Technology Committee (Project number 19DZ1920104).
Disclosure
The authors declare that they have no competing interests in this work.
References
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Asthma and chronic obstructive pulmonary disease (COPD) are both common diseases diagnosed by the presence of chronic symptoms such as cough, sputum, shortness of breath, and airflow obstruction. Several clinical/inflammatory factors are commonly associated with the risk of developing asthma or COPD or with important clinical outcomes such as reduced lung function, exacerbations, reduced quality of life and mortality.1,2 They are characterized by their complex and heterogeneous nature, both clinically and in their molecular pathogenesis. Endotype is a dynamic molecular network that arises when an individual’s genetic factors interact with various environmental factors, such as infections, air pollution, tobacco smoke, antibiotics, and lung flora, driving the phenotype in a particular patient. Given the clinical and biological complexity and heterogeneity of the diseases, the development of therapeutic strategies targeting individual endotypes could help us enable early identification of disease risk with a high degree of accuracy and implementation of preventive strategies.3
Numerous genetic studies, including genome-wide association studies (GWAS), have found a number of loci that influence the development of asthma and COPD, and several genetic factors are common to both diseases. Genetic contribution of individual common variants to disease susceptibility is very small, especially in isolation, and the small proportion of heritability explained by these variants makes it difficult to predict disease onset in a practical clinical setting. At present, the more important significance of GWAS, however, is not to estimate individual risk, but rather to discover the biological pathways underlying complex diseases.4 The pathophysiological pathways identified by GWAS for a disease have important implications not only for carriers of a particular genetic polymorphism, but also in the origins of the disease itself.
This review describes representative endotypes indicated by genetic and molecular data to be commonly involved in both asthma and COPD, including chronic non-type 2 inflammation, type 2 inflammation, increased susceptibility to viral infections, and impaired lung development and repair/remodeling. Advances in genomic medicine in asthma and COPD are critically important for achieving precision medicine, allowing a departure from the current one-size-fits-all medicine according to disease labels or clinical symptoms, and population approach to disease incidence prevention that does not consider individual disease susceptibility.5
Overlap Between Asthma and COPD
Dutch hypothesis was proposed more than 50 years ago.6 In this hypothesis, asthma and COPD are two phenotypes of a syndrome called chronic nonspecific lung disease (CNSLD), where CNSLD is defined as the result of an interaction between intrinsic genetic factors and extrinsic factors such as viral infection, air pollution, tobacco smoke exposure, and allergen exposure. The timing of this interaction during an individual patient’s life stage determines which clinical syndrome develops (ie, asthma or COPD) or whether characteristics of both asthma and COPD appear. Thus, a particular genetic factor may combine with a particular environmental factor to cause asthma, or the same genetic factor may combine with another genetic or environmental factor to cause COPD.7 Several genes and loci have been reported as common factors in susceptibility to asthma and COPD.7,8 We performed a PubMed database search published through September 2012 for asthma, COPD, tuberculosis, and essential hypertension, respectively. For each disease, pathway-based analysis was performed to determine how the identified genes interacted with each other.8 In at least two independent reports, a total of 108 genes were found to be associated with asthma and 58 with COPD. These genes were grouped into multiple networks according to functional annotation. Twelve networks were found in asthma and 11 in COPD, and the overlapping network between the two diseases formed one complex network consisting of 229 common molecules (Figure 1). These overlapping molecules were significantly associated with aryl hydrocarbon receptor (AhR) signaling, the role of cytokines in mediating information transfer between immune cells, glucocorticoid receptor signaling, and pathways involved in IL-12 signaling and production in macrophages. At the network level, the Jaccard similarity index for asthma and COPD was 0.81, with an odds ratio of 3.62 for asthma/COPD pair in comparison to tuberculosis/essential hypertension pair. The overlap in the asthma and COPD gene networks indicated a high degree of pathobiological similarity between these two diseases.
Figure 1 Overlapping networks between asthma and COPD. The Ingenuity Pathway Analysis software program identified 229 overlapping molecules between 12 asthma networks and 11 COPD networks, and merged them into a single larger network. In total, 229 genes were common to both diseases, and 190 and 91 genes were unique to asthma and COPD, respectively. Each network is represented by a colored rectangle, and is labeled with its corresponding network number. Adapted with permission from Dove Medical Press. Kaneko Y, Yatagai Y, Yamada H, et al. The search for common pathways underlying asthma and COPD. Int J Chron Obstruct Pulmon Dis. 2013;8:65–78.8
Common Pathogenesis Characterized by Chronic Non-Type 2 Airway Inflammation
As discussed in the section above, AhR signaling is implicated in common pathologies of asthma and COPD; AhR acts as a regulator of mucosal barrier function and affects lung immunity by inducing changes in gene expression, intercellular adhesion, mucin production, and cytokine expression.9 Although the binding of this receptor to different ligands leads to what seems to be variable responses, AhR-regulated neutrophils and Th17 cells are involved in the responses to pro-inflammatory stimuli, including tobacco smoke and air pollutants.10 The AhR-ROS-NLRP3 inflammasome functional axis, which regulates Muc5ac expression and airway inflammation, may also be involved in airway inflammation in asthma and COPD.11
We performed a GWAS of adult-onset asthma that developed over the age of 40 and identified the HCG22 gene as a susceptibility gene.12 This gene was also associated with diffuse panbronchiolitis (DPB) and COPD. DPB is a chronic neutrophilic bronchiolitis with chronic cough, sputum, and shortness of breath on exertion as the main symptoms, and its prevalence increases after the age of 40 years. HCG22 is a novel mucin-like gene13 located at 6p21.3, the DPB susceptibility gene region. Furthermore, HCG22 has been reported to be associated with tree-in-bud pattern identified on chest computed tomography in asthmatic patients and with steroid refractoriness requiring high doses of corticosteroids.14 Based on its amino acid sequence, HCG22 has a chitin-binding protein-like structure.15 YKL-40, a chitinase-like protein similar to HCG22, has been reported to be associated with phenotypes characterized by neutrophilic inflammation in asthma and COPD.16,17 Chitin is a pathogen-associated molecular pattern found in mites and fungi, and it is of interest due to its involvement in infection immunity in the airway mucosa, and its association with the pathogenesis of middle-age-onset asthma, COPD, and DPB. Recently, the new disease category of muco-obstructive lung disease has been proposed, and it includes COPD, primary ciliary dyskinesia, and bronchiectasis.18 Mucus-derived obstruction is characterized by altered airway microbiota, mucociliary dysfunction, neutrophilic inflammation, and airway destruction, which are also important features in DPB and a subgroup of patients with non-type 2 asthma.
We have found a gene encoding HA synthase 2 (HAS2) as associated with asthma.19 HAS2 is a glycosaminoglycan found in the extracellular matrix and is highly expressed in the lung. Asthma-associated single nucleotide polymorphisms (SNPs) affected the expression levels of HAS2 mRNA. Hyaluronic acid (HA) is involved in many physiological and pathological processes, including cell migration, morphogenesis, tissue regeneration, wound repair, and tumor cell proliferation and invasion, and increased levels of HA in sputum have been reported in COPD patients.20 Patients with higher levels of hyaluronan had impaired lung function than patients with patients with normal hyaluronan levels. In addition, influx of neutrophil and levels of interleukin-8 and soluble tumor necrosis factor (TNF) receptors were higher in COPD patients with elevated HA levels. Decreased Has2 expression in mice enhanced ovalbumin (OVA)-induced airway inflammation, including increased neutrophils and eosinophils, airway hyperresponsiveness, and attenuated CD44 and transforming growth factor (TGF)-β signaling.21 CD44 is an HA binding protein and decreased CD44 downregulates TGF-β. In addition, lung mRNA sequencing and pathway analysis identified enriched terms “IL-17A signaling in fibroblasts”, “NRF2-mediated oxidative stress response”, and “glucocorticoid receptor signaling”. These terms were thought to be associated with severe asthma and COPD. Furthermore, in a chronic OVA sensitization and challenge-induced asthma model,22 IL-17A levels in lung homogenates were higher in Has2 heteroknockout OVA mice than in wild-type mice, and Has2 heteroknockout OVA mice showed goblet cell hyperplasia and excessive mucus production. Thus, chronic OVA stimulation induced a characteristic phenotype of airway remodeling through Has2-mediated attenuation of IL-17 and TGF-β signaling.
Taken together, neutrophil inflammation is recognized as an important pathogenic factor in asthma as well as COPD.
Common Pathogenesis Characterized by Type 2 Inflammation
Eosinophilic airway inflammation is found in patients with COPD as well as asthma, and the presence of eosinophilic inflammation is associated with exacerbations and responsiveness to inhaled corticosteroids. Overall, 612 (56%) of 1094 Japanese COPD patients had an absolute eosinophil number of 150 cells/mm3 or greater, and 902 (69%) of 1304 Japanese patients had an eosinophil fraction of 2% or greater23 (Figure 2). In a study comparing the comprehensive gene expression in the airway epithelial cells of asthma and COPD patients, the gene expression levels associated with type 2 inflammation were increased not only in asthma patients, but also in COPD patients.24 In particular, the expression of type 2-related genes in COPD patients was associated with stronger airflow limitation, airway eosinophil infiltration, and even the responsiveness to inhaled corticosteroid (ICS).
Figure 2 The distribution of blood eosinophil levels in a Japanese COPD clinical trial database. Distribution of (A) absolute blood eosinophil count and (B) percentage blood eosinophils among Japanese patients with COPD. Reprinted with permission from Dove Medical Press. Barnes N, Ishii T, Hizawa N, et al. The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world. Int J Chron Obstruct Pulmon Dis. 2018;13:433–440.23
In a large GWAS of 8068 patients with the overlapping asthma and COPD pathology in the UK Biobank and 4301 patients with the overlapping pathology from other cohorts, eight loci were identified,25 including the thymic stromal lymphopoietin (TSLP) gene. These eight loci were not clearly associated with smoking habits, but they were strongly associated with the peripheral blood eosinophil counts, immunoglobulin (Ig) E sensitization and asthma, suggesting the importance of type 2 inflammation in the overlapping pathology. Elevated TSLP protein and TSLP mRNA levels have been reported in bronchial epithelium in COPD patients.26 Multiple factors related to exacerbations of asthma and COPD, including respiratory viruses, cigarette smoke, and inflammatory cytokines, have been associated with increased TSLP production.27–30TSLP gene was also identified as a potential susceptibility locus for impaired lung function in non-COPD, non-asthmatic healthy subjects, which supports the idea that TSLP is a genetic determinant of lung function that influences the risk of developing asthma and COPD.31
The ORMDL3/GSDMB gene located on chromosome 17q has been consistently associated with childhood-onset asthma, and most asthma patients associated with this gene are atopic. In addition, an association of the region with overlap between COPD and asthma without rhinitis has been reported.32 Susceptibility to rhinovirus (RV) infection is associated with this genetic region that affects transcription and protein expression of intercellular adhesion molecule 1 (ICAM1), a major receptor for human RV (HRV).33ORMDL3/GSDMB has also been implicated in the development of childhood asthma related to indirect exposure to smoking at home.34 Furthermore, the importance of ORMDL3/GSDMB was indicated in susceptibility to early-onset adult asthma in Japanese. While the region was not associated with allergic sensitization, it was strongly associated with increased serum total IgE levels,35 and therefore, the region appears to act as a stress sensor in the airways caused by viral infections and smoking, and promotes airway inflammation through an enhanced innate type 2 immune response.
Common Pathogenesis Characterized by Increased Susceptibility to Viral Infections
HRV is an important risk factor for exacerbations both in asthma and COPD. RV induces several cytokines including IFNα, IFNγ, TNFα, CXCL10/11, and CC chemokine ligand 5 (CCL5) in airway epithelial cells. The airway epithelial cell responses to RV was overlapped with gene expression signatures reported in patients with asthma or COPD.36
We previously found that the gain-of-function −28G allele of a promoter SNP (rs2280788) in the CCL5 gene was a risk factor for adult-onset asthma who developed the disease at age 40 years or older, and also for COPD who had less emphysema lesions.37,38 Given that the CCL5 gene is a pathway involved in both the pathogenesis of older-onset asthma and COPD with less emphysema, it is interesting that CCL5 is shown to contributes to tissue-resident T cell-associated T1 neutrophilic inflammation in asthma and correlates with T2 inflammation and sputum eosinophilia as well.39
The CDHR3 gene, which was identified in GWAS of childhood asthma with frequent severe exacerbations, was found to encode a receptor for RV type C.40 We confirmed that the functional variant at CDHR3 has a significant genetic influence in Japanese adult asthma patients with onset by age 10 years, and that the association is stronger when restricted to allergen sensitization-positive individuals.41 In addition, a 10-year observational study was conducted to examine the genetic impact of the CDHR3 gene on the newly development of asthma or COPD in 1523 healthy adults with no pulmonary disease who had health checkups in 2008. During the 10-year period, a total of 79 cases and 25 cases newly developed asthma and COPD, respectively. The CDHR3 gene had a genetic influence on the development of asthma or COPD, especially in adults with allergen sensitization in 2008.42 A molecular network (endotypes) derived from the susceptibility to RV infection and allergen sensitization was found to be responsible not only for childhood-onset allergic asthma, but also for adult-onset asthma or COPD.
Common Pathogenesis Characterized by Impaired Lung Development and Repair/Remodeling in Asthma and COPD
The primary risk factor for COPD is smoking. However, there is growing evidence to suggest that lung disease in adults may originate from prenatal or early-life exposures to harmful stimuli.43 A whole genome sequencing study44 that compared 3181 moderate/severe asthmatics with 3590 non-asthmatic controls showed that asthma risk is genetically correlated with lung dysfunction. This genetic factor associated with asthma development was shown to be independent of genetic factors associated with eosinophilic inflammation that also contribute to asthma. The polygenic score for impaired lung function was also associated with early-onset of asthma. Thus, genes that influence lung development in utero and in early childhood, in combination with environmental exposure such as cigarette smoke and viral infections, all contribute to both childhood asthma and future COPD development.
Asthma and COPD are heterogeneous and complex diseases, because they are caused by multiple factors, and the impact of individual risk factors is small. A genetic risk score (GRS) has been applied to address the heterogeneity and complexity of these diseases.45 We developed a quantitative GRS according to genotypes at 16 SNPs implicated in impaired lung function in both Japanese and non-Japanese individuals.46 The modest effects of 16 SNPs were combined into a single variable, which was calculated as the weighted sum of the number of high-risk alleles at each SNP. The GRS with a reduced forced expiratory volume/forced lung capacity ratio was consistently associated with asthma or COPD in two independent Japanese populations. Clustering of patients with asthma according to their lung function GRS indicated that elevated GRS may be associated with the development of distinctive phenotype of asthma (early onset, atopy, and severe airflow obstruction). Analysis of the functional relevance of these 16 genes showed that lung function GRS is associated with molecular pathways involved in tissue repair and remodeling induced by lung injury. In addition, a study using UK Biobank data to examine the association of 391 genes known to regulate lung development and lung function in adults47 found that 55 genes were significantly associated with four biological categories including growth factors, transcriptional regulators, intercellular adhesion, and extracellular matrix. These results together showed the importance of lung growth-related genes in regulating lung function and influencing airflow obstruction in adults. Thus, respiratory function measurements from infancy through adolescence may facilitate early identification of individuals prone to lung growth failure, leading to early intervention and prevention of asthma and COPD development.
Several GWAS have indicated the hedgehog signaling pathway as an important pathway underlying lung function and COPD; hedgehog-interacting protein (HHIP) is a negative regulator of the hedgehog pathway and patched 1 (PCTH1) is a receptor that activates the pathway.48 In older adults with asthma, the PTCHD4 gene has recently been associated with the responsiveness to ICS, as indicated by the presence of oral corticosteroid bursts.49PTCHD4 encodes patched domain-containing protein 4, which represses hedgehog signaling.50 Increased PTCHD4 mRNA expression was associated with aging, and enrichment of methylated CpG sites in the PTCHD4 gene was associated with COPD.51,52 Furthermore, COPD patients with larger lesion with airway smooth muscle cell of bronchial tissue responded better to ICS than those with smaller lesion with airway smooth muscle cell, suggesting that a detailed histological classification of COPD patients may reflect differences in endotypes and help determine treatment strategy.53 These results suggest that responsiveness to ICS in asthma and COPD patients may be strongly influenced by specific patient endotypes, and that patients with specific endotypes related to lung growth abnormalities or impaired injury repair may be less responsive to ICS.
Treatable Traits Approach in Patients with Asthma and COPD
Given the complexity and heterogeneity of chronic inflammatory pulmonary diseases, including asthma and COPD, their appropriate management requires a new approach that includes multidimensional assessment. Patients with chronic inflammatory pulmonary diseases should not be treated according to disease labels such as asthma, COPD, or asthma COPD overlap, but rather on what endotypes play a critical role in individual patients.54 In 2015, I had proposed a plausible approach for positioning ICSs and long-acting β2-agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) in the treatment of COPD based on both the extent of airflow obstruction and the presence of type 2 airway inflammation55 (Figure 3). Thereafter, a management strategy based on the so-called treatable traits was proposed.56,57
Figure 3 Approach to COPD treatment based on the degree of airflow obstruction and peripheral blood eosinophil counts. This proposal for positioning ICSs and bronchodilators for the treatment of COPD in clinical practice follows a personalized medicine approach that is not based on the stratification of patients into subgroups, but rather is based on individual characteristics that consider the heterogeneity and complexity of the disease in patients. Reprinted with permission from Dove Medical Press. Hizawa N. LAMA/LABA vs ICS/LABA in the treatment of COPD in Japan based on the disease phenotypes. Int J Chron Obstruct Pulmon Dis. 2015;10:1093–1102.55
We attempted to identify a group of patients who were more prone to exacerbations beyond the name of the diseases using multiple risk factors common to asthma and COPD exacerbations.58 As a result, we identified five distinct clusters, each characterized by high eosinophil counts, smokers with reduced lung function, gastroesophageal reflux, non-allergic women, or allergic rhinitis with high total IgE levels. Clinical heterogeneity of disease exacerbations was shown to possibly indicate the presence of exacerbation-prone endotypes common to asthma and COPD, supporting the benefit of a trait-based approach for exacerbation prevention in patients with chronic inflammatory pulmonary disease.
Recently, it was reported that in COPD patients with type 2 inflammation, in whom both blood eosinophil counts and FeNO are elevated, dupilumab, an antibody against the IL4 receptor alpha chain, leads to a reduction in exacerbation frequency, improvement in lung function and quality of life, and even improvement in respiratory symptoms compared to placebo.59 Considering that patients with currently diagnosed asthma or a history of asthma were excluded from the study, these results appear to support the usefulness of a treatable trait approach.
Conclusion
Both asthma and COPD are syndromes with highly variable clinical manifestations (phenotypes), including severity and course over time, and are caused by complex interactions between individual genetic factors and various environmental factors such as viral infection, allergen exposure, and tobacco smoke exposure (endotype). In this review, I have described four representative endotypes common to asthma and COPD (Figure 4). These endotypes are involved in patient pathogenesis in varying proportions. Furthermore, while the interactions of individual endotypes shape each patient’s pathology, the relative contribution of each endotype in an individual patient may change over time. Clinical traits or biomarkers could be used to identify the presence of each endotype. We must consider that it is not one endotype per patient, but rather the interaction of multiple endotypes that drives individual patient pathologies. With the advancement of genomic medicine, our understanding of endotypes will advance, new therapeutic agents will be developed, and the diseases will be reclassified according to specific phenotypes and biomarkers that reflect differences in molecular pathobiology, ushering in an era of precision medicine that targets the molecular mechanisms underlying the diseases in individual patients.
Figure 4 Common endotypes underlying asthma and COPD. Asthma and COPD are syndromes caused by complex interactions between individual genetic factors and various environmental factors. At any given time, the interaction of multiple endotypes drives individual patient pathologies and phenotypes.
Disclosure
The author has received speaker fees and/or research funding from AstraZeneca, Boehringer Ingelheim, Kyorin Pharmaceutical, GlaxoSmithKline, Novartis, and Sanofi.
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(MENAFN- Straits Research) A spirometer measures the air volume inhaled and exhaled during a single breathing cycle. The device facilitates the occupational diagnosis of various respiratory problems, such as chronic obstructive pulmonary disease, emphysema, asthma, and other respiratory diseases. Spirometers are one of the respiratory laboratories and clinics' most commonly observed tools. Spirometers can create a profile of a user's lung health. Clinicians, therefore, utilize spirometers as both a diagnostic and monitoring tool. Numerous benefits are associated with personalized spirometers for patient use outside the clinic. Regular spirometry can detect a decline in lung health or the progression of the disease considerably earlier. This allows the patient and physician to prevent or treat the condition before it worsens. The global growth in the prevalence of chronic obstructive pulmonary disease (COPD) is ultimately pushing higher demand for spirometers. According to the World Health Organization (WHO), around 300 million people worldwide have asthma, and 250,000 have died. In 2019, around 65 million people globally had COPD, including approximately 16 million Americans; this figure is projected to rise in the coming years. In addition, chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality in the United States. Numerous studies indicate that the general public is primarily uninformed of COPD. However, many individuals with respiratory symptoms are unaware that they require a diagnosis, which hinders the use of spirometers for identifying respiratory devices. Market Dynamics Growing Prevalence of Respiratory Diseases to Drive the Global Spirometer Market Respiratory illnesses are one of the leading causes of death and disability worldwide. Several causes, including filthy air, outdoor and indoor pollution, tobacco usage through smoking, and dangerous particles emitted from workplaces, contribute to the increase in the prevalence of respiratory illnesses in the population. The incidence of cases ending in respiratory failure and death has climbed dramatically in recent years. The World Health Organization reported that around 65 million individuals suffered from chronic obstructive pulmonary disease in 2017, and approximately 3 million died as a result. Asthma is the most prevalent chronic disease affecting children, impacting 14% of children worldwide. It affects nearly 334 million people. As effective healthcare solutions, such as spirometers, are readily available, enhancing respiratory health through early identification and diagnosis can prevent, manage, and treat various illnesses. Hence, with the growing prevalence of respiratory illnesses, the worldwide spirometer market is predicted to rise rapidly in the upcoming years. Moreover, spirometers can identify chemical exposure in the workplace, shortness of breath, medicine side effects, lung performance assessment before surgery, and the progression of illness treatment. Thus, it is projected that such spirometers' advantages will help expand the global spirometer market. Furthermore, lifestyle behaviors such as smoking and alcohol consumption have led to respiratory issues and are among the key drivers driving the growth of the worldwide spirometer market. As spirometers aid in the early detection of several respiratory disorders, it is anticipated that the prevalence of these conditions would rise, hence driving demand. In addition, an increase in the older population, susceptible to a variety of respiratory diseases, stimulates the expansion of the spirometer market. In addition, technological developments in spirometry and an increase in regulatory approvals contribute to the growth of the spirometer market. Regional Insights North America will command the market with the largest share and a CAGR of 3.2% during the forecast period. Increasing asthma, COPD, and cystic fibrosis incidences are primarily accountable for the region's predominance. The American Lung Association reports that COPD is the third leading cause of death in the United States. Additionally, around 20.4 million people in the United States have asthma. As a result, there is a growing preference among Americans and physicians for pulmonary function testing for the early detection of lung illnesses to avoid future expensive medical expenses. In addition, technical advancements in the production of user-friendly and portable spirometers and greater patient awareness are expected to fuel the growth of the U.S. spirometer market throughout the forecast period. In addition, North America is considered an early adopter of new medical innovations. This is mainly attributed to raising awareness of the numerous respiratory medicines in hospitals and expanding government and non-governmental organization (NGO) programs. Consequently, it is projected that the need for spirometers will increase among individuals afflicted with various respiratory illnesses. Asia-Pacific will hold the second-largest share of USD 539 million with a CAGR of 4.5%. Due to its large population, multiple chronic and lifestyle disorders, and rapid increase in the frequency of respiratory diseases, the Asia-Pacific region provides market participants in the spirometer industry lucrative opportunities. During the forecast period, the market for spirometers is likely to be propelled by an increase in the proportion of geriatric patients susceptible to a variety of respiratory disorders and an increase in the use of spirometers in general healthcare settings, such as hospitals. Moreover, using artificial intelligence (AI) in spirometers will create opportunities for key market participants. Increasing demand for modern medical devices, healthcare reforms, and the prevalence of chronic respiratory diseases like asthma, COPD, cystic, and pulmonary fibrosis all lead to the expansion of the spirometer market. In addition, an increase in programs, grants, and initiatives connected to the availability of medical equipment in the region is anticipated to propel further the growth of the spirometer market in the region. Key Highlights
The global spirometer market had a share value of USD 1,221 million in 2021, which is expected to grow to USD 1,608 million with a CAGR of 3.5% during the forecast period. Based on type, the segment of table-top spirometer is expected to hold the largest share with a CAGR of 3.7% during the forecast period. Based on technology, the segment of flow measurement is estimated to have the largest market share with a CAGR of 4.1% during the forecast period. Based on end-user, the segment of hospitals & clinics is expected to have the largest market share with a CAGR of 3.9%. Based on regional analysis, the North American region is expected to command the market with the largest share and a CAGR of 3.2%.
Competitive Players in the Market
SCHILLER Hill-Rom, Inc. Midmark Corp. FutureMed COSMED Srl MGC Diagnostics Corporation Smiths Medical Vyaire Medical Teleflex NSPIRE HEALTH INC.
Market News
In 2022, Midmark Corp. announced a strategic partnership with Bien-Air Dental SA. In 2022, Midmark Corp. announced the launch of its Synthesis Wall-Hung Cabinetry to provide animal health teams with enhanced visibility and access to supplies. In 2022, MGC Diagnostics Corporation announced the global distribution agreement with BedfontÒ Scientific Ltd.
Global Spirometer Market: Segmentation By Type
Hand-Held Tabletop
By Technology
Volume Measurement Flow Measurement
By Application
COPD Asthma Others
By End-User
Hospitals & Clinics Home Care Settings Others
By Region
North America Europe Asia-Pacific LAMEA
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Coleen Nolan quits smoking after terrifying health scare credit:Bang Showbiz
Coleen Nolan has finally quit smoking after a terrifying health scare.
The 'Loose Women' star - who was a smoker for over 40 years - revealed she gave up cigarettes in December after being left unable to breathe.
She told The Mirror: "“I literally couldn’t walk a few feet without stopping to catch my breath. It was the scariest thing, feeling constantly winded. After 'Loose Women' one day, our warm-up guy Lee insisted on taking me to see a doctor, who put me on antibiotics. Being a typical woman and mum, I kept saying I’d be fine.
"I met [partner Michael Jones] outside the hotel and by the time we’d gone up in the elevator and walked a few paces to my room, I was gasping and trying to say that I couldn’t breathe. I had a full-scale panic attack and the more stressed I got and the more I cried, the less able I was to breathe.
"I genuinely thought ‘I’m going to die in my hotel room, away from home’. It was really frightening. The whole thing lasted two minutes but it felt like an hour.”
Coleen, 58, made an appointment with her doctor the following day.
She said: "He knows I smoke and told me I could be looking at COPD and emphysema. The message was, if you carry on smoking, this is what will happen. I thought: ‘What the hell am I doing?’ I want to be around for as long as I can for my kids.
"I was going to bed at night, saying to Michael, ‘I’ve got COPD or lung cancer... what an idiot!’ When I went back to get the results and was told my X-ray had come back clear, it was a massive relief. My chest will probably never recover but hopefully quitting will mean it won’t get any worse. I felt like the universe was saying ‘This is your last chance’.”
Coleen shares daughter Ciara, 22, with former husband Ray Fensome, and sons Shane, 34, and Jake, 31, with her first husband Shane Richie.
Breathing+ by Breathing Labs has passed peer review in a randomized controlled clinical trial that was recently published in SCI Q2 journal Pediatric Pulmonology. Research done by @bezmialem Full text is available in a link here: https://www.breathinglabs.com/clinical-trials/research-breathing-labs-and-nintendo-clinical-trial-is-published-in-journal-pediatric-pulmonology-sci-q2-impact-factor-3/?fbclid=IwAR2wNhSgurdbrrf3gzOOkHthgiWfXJ1x8RWvnMhkSo6fi33QPZEGzxzd6jM
BREAKING: @breathinglabs and @Nintendo clinical trial is published in journal Pediatric Pulmonology (SCI Q2, Impact Factor > 3), full text: https://breathinglabs.com/Nintendo%20&%20Breathing%20Labs%202022 #telemedicine #telehealth #mhealth
Clinical mouthpieces 10pcs packages are now available at 45€/50USD (shipping cost not included). Learn more: https://www.breathinglabs.com/latest-news/announcement-breathing-mouthpieces-for-clinical-and-professional-use-are-now-available/
BREATHING VR: Lately we are sourcing this VR headset for use in Breathing VR application. It allows easiest installation of both breathing+ headset cable, and USB charging cables, which is essential in professional use: https://www.banggood.com/VR-SHINECON-G5-VR-Glasses-3D-Virtual-Reality-Glasses-VR-Headset-For-iPhone-XS-11Pro-Mi10-p-1679808.html?rmmds=myorder&cur_warehouse=CN
Update: Each purchase of Breathing+ will now include three machine washable mouthpieces. Previous buyers will be supplied with those by their country representatives but will have to cover shipping costs. Please be patient while we arrange distribution. https://www.breathinglabs.com/latest-news/announcement-breathing-mouthpieces-for-clinical-and-professional-use-are-now-available/
Update: We moved servers + relocated all our games to our servers, please be patient while google reviews all that (showing unsafe website atm). Use duckduckgo or non-chromium browsers to reach our pages in the meantime. Everything ok + new product addons coming out in a month!
Registration and all functionalities at http://breathinglabs.com (and in our iOS and Android games) are fixed and fully working. If you find any issues -> [email protected]
We are back in stock with Breathing+, currently searching for VR supplier, and setting up mass production for toys and tens stimulation + in November we will be signing up new erasmus traineeships, research projects, bilateral, FP(eu), and asia-pacific ->[email protected]
BREAKING: Nintendo Co. Ltd (Japan) is implementing Breathing Games by @breathinglabs in FDA approved clinical trial for children with bronchiectasis: https://clinicaltrials.gov/ct2/show/NCT04038892
Notice to b2b partners: we are running late with some minor upgrade-> briefly running out of stock -> retail and b2b sale is closed until early october. To get a list of partners with stock to sell contact us at [email protected] Thanks, we'll go strong again in winter 💪