While smoking is a known risk factor for chronic obstructive pulmonary disease (COPD), heavy smokers can exhibit a series of respiratory symptoms without developing airflow blockage – one of the criteria to diagnose COPD – a study reports.
The findings, which are based on the long-term follow-up of participants of the SPIROMICS clinical trials, suggest lung disease may go undiagnosed and untreated in chronic tobacco users.
“A large proportion of tobacco smoke-exposed persons without airflow obstruction have a persistent, symptomatic nonobstructive chronic airway disease that is distinct from COPD,” Prescott Woodruff, MD, chief of pulmonology at the University of California, San Francisco (UCSF) and the study’s senior author, said in a university news release.
According to Woodruff, who led the SPIROMICS studies, “although tobacco-exposed persons with preserved spirometry are currently categorized as having pre-COPD by the COPD guidelines, the data from the current study emphasize that the definition of smoking-related lung disease needs to be broadened so new treatments can be developed.”
The study, “Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry,” was published in JAMA.
Smoking with, without respiratory symptoms
COPD is a chronic inflammatory lung disease marked by respiratory symptoms that include shortness of breath, persistent cough, and wheezing. A definite diagnosis requires evidence of airflow blockage, which is usually assessed using a spirometry, which measures how much and how quickly air can flow into and out of the lungs.
Doctors assess the ratio of two measurements — the volume of air that can be breathed out in one second (FEV1) by the volume of air that can be forced out of the lungs after taking the deepest breath possible (FVC). A FEV1 to FVC (FEV1/FVC) ratio below 0.7 suggests COPD.
Smoking is a known risk factor for COPD, but people with a heavy history of it may have respiratory symptoms without airflow obstruction. This means they don’t get a COPD diagnosis and may not get appropriate treatment.
A team led by UCSF researchers evaluated the outcomes of people who smoked one pack of cigarettes a day for 20 years (20 pack-years) and had respiratory symptoms, but with “preserved spirometry,” enrolled in the SPIROMICS II trial, an extension study of the SubPopulations and Intermediate Outcome Measures in COPD Study I, or SPIROMICS I (NCT01969344).
The group was called the symptomatic TEPS (tobacco exposure and preserved spirometry). Their outcomes were compared to those with the same features but without symptoms, or asymptomatic TEPS. Those without a long history of smoking (one pack-year or less) and with a normal spirometry served as controls.
A total of 1,397 patients were analyzed, or which 226 had symptomatic TEPS (mean age, 60.1 years; 59% women) and 269 had asymptomatic TEPS (mean age, 63.1 years; 50% women). Those in the symptomatic group were more likely to be Black, current smokers, and have a longer pack-year history (median, 40 vs. 38 pack-years). They also had more respiratory exacerbations, or episodes when symptoms suddenly worsened, during the 12 months before enrolling.
After a median follow-up of 5.76 years, the data revealed the rate of lung function decline assessed by FEV1 in the symptomatic TEPS group was similar to the asymptomatic TEPS group — less 31.3 mL per year in the symptomatic group and less 38.8 mL/y in the asymptomatic one.
The participants diagnosed with symptomatic mild to moderate COPD had a significantly more rapid FEV1 decline than the symptomatic TEPS participants (less 42.3 mL/y).
Incidence of COPD
The cumulative incidence of COPD was similar in the two groups — 33% in the symptomatic TEPS group and 31.6% in the asymptomatic group — after adjusting for several potential confounding factors.
Among the group of symptomatic TEPS, Black participants were at risk of developing COPD at a rate 2.15 times higher than the white participants. Current smokers in the symptomatic TEPS group had a 1.95 times higher risk of COPD than nonsmokers.
The rate of respiratory exacerbations during up to 10 years of follow-up was significantly higher with symptomatic TEPS (mean, 0.23 exacerbations per person-year) over asymptomatic TEPS (mean, 0.08 exacerbations per person-year) and the control group (0.03 exacerbations per person-year).
More than half the symptomatic TEPS participants (51.3%) required medications for their exacerbations, with the same percentage reported by patients with asymptomatic COPD, and in contrast to 29.7% of asymptomatic TEPS.
Severe exacerbations that required emergency assistance or hospitalizations were reported by 31.4% of those with symptomatic TEPS, surpassing those with asymptomatic mild to moderate COPD (21.2%), but not those with symptomatic COPD (41.6%). This was reported by 6.3% of participants in the asymptomatic TEPS group.
Overall, “this extension study of SPIROMICS found that participants with symptomatic TEPS had similar rates of FEV1 decline and similar incidence of COPD diagnosed by spirometry as participants with asymptomatic TEPS over a median follow-up of 5.8 years. However, participants with symptomatic TEPS had increased pulmonary symptoms, higher rates of respiratory exacerbations, and increased activity limitation compared with those with asymptomatic TEPS,” the researchers said.
Regarding smoking, “even in persons with no respiratory symptoms and normal breathing tests, smoking continues to harm their lungs,” said James Kiley, PhD, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, which funded the study. “The study results highlight the importance of smoking cessation, underscore the need for regular follow-up of smokers with and without symptoms, and call for more research to treat respiratory symptoms due to smoking.”