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Jeffrey J. Swigris, DO: Welcome to Medscape InDiscussion on the topic of idiopathic pulmonary fibrosis, or IPF. I'm Dr Jeff Swigris. Today we'll be discussing the use of supplemental oxygen in patients with IPF. How and how often should we test for oxygen needs? Is supplemental oxygen beneficial to our patients, and if so, how? With me today to answer these and other questions is Anne Holland. Anne is professor of physiotherapy and head of respiratory research at Monash University and Alfred Health in Melbourne, Australia, and she is a leadership fellow at the National Health and Medical Research Council, or NHMRC. Her own research focuses on supportive therapies for individuals with chronic obstructive pulmonary disease (COPD) as well as pulmonary fibrosis. She's currently leading a multinational trial of ambulatory oxygen for people with fibrotic lung disease. She is also a chief investigator for the NHMRC Centre of Research Excellence in Pulmonary Fibrosis. Anne, welcome, all the way from Melbourne, Australia. And thank you for taking the time to be with us today.
Anne E. Holland, BAppSc (Physiotherapy), PhD: Thank you very much for inviting me. It's a pleasure to be here.
Swigris: Fantastic. Your research has focused largely on nondrug therapies for patients with chronic lung disease. Those therapies have included predominantly physical exercise and supplemental oxygen. You're clearly a leader in our field and in these two modalities. How did you become so committed to this work, and what keeps you going today?
Holland: Thank you for the question. I trained as a physical therapist, so I had been involved in pulmonary rehabilitation programs here in Australia for some time. I was really struck by how little we knew about the role of rehabilitation and other nondrug therapies for people with pulmonary fibrosis. At that time, which was many years ago now, there really wasn't an accepted role for rehabilitation in people with pulmonary fibrosis. It was at the time when there weren't drug treatments available such as the antifibrotics we have now. There was a sense of nihilism around pulmonary fibrosis care. There's a bit of a disconnect for me in terms of some of the benefits I was seeing in the patients coming through my rehabilitation program and this lack of enthusiasm for these treatments. But by the same token, I also had experiences in which we had some patients who were coming close to the end of their lives, and participating in something like rehabilitation was a huge burden to them — those burdens might not be outweighed by the benefits. So, I was motivated to work out what the role of this treatment was and how we could deliver it to patients who'd benefit in a way that would be meaningful for them in their lives. That's rolled into the examination of other nondrug treatments such as oxygen, and there's so much we still need to learn about these treatments. Clinical observations tell you that there are some patients who, for instance, desaturate a lot on a 6-minute walk test but have almost no symptoms. For them, the thought of oxygen is difficult. But you have other patients with a lot of symptoms associated with that desaturation. You can see a measurable benefit for oxygen in those patients. These are really challenging clinical scenarios in which to figure out what would work best for patients and give them treatments that would improve their lives. What keeps me going today is trying to find meaningful treatments for these patients.
Swigris: I hearken back to the time you were referring to. You're exactly right. Practitioners weren't thinking about pulmonary rehabilitation and exercise for their patients with pulmonary fibrosis. The programs were predominantly targeted for patients with COPD. Now it really is standard of care. As you mentioned, it's one of the few modalities we can use that leads to substantial improvements in how patients feel and function in their daily lives.
Holland: Absolutely. It's been one of the biggest changes I've seen over my clinical and research career — the fact that rehabilitation is now a very well-accepted treatment. It's in guidelines as an important treatment for people with pulmonary fibrosis. I still get a buzz out of the improvements patients experience and can tell you about in terms of their breathlessness and quality of life. So, it's a very meaningful treatment for many patients.
Swigris: Let's shift gears now to supplemental oxygen. Tell us your thoughts and practices around testing your patients with IPF for the need for supplemental oxygen. How do you do it? How should we do it? How should we think about assessing supplemental oxygen needs in our patients?
Holland: Thank you. That's a great question. Evaluating for supplemental oxygen is something that happens when we see a patient for the first time in our clinic. We have a specialist interstitial lung disease (ILD) clinic. When a patient first presents to our clinic, it's something we would consider at that time. Our philosophy around testing is that a 6-minute walk test provides very useful information about exertional desaturation. Of course, if a patient has hypoxemia at rest, that's a different story that might point you in the direction of long-term oxygen therapy. With exertional desaturation, I'm not sure we've yet found a better and more robust option than a 6-minute walk test. In fact, we've recently done some work here in which we've evaluated people's desaturation walking around in daily life when we put an oximeter on them for 48 hours at a time. What we found is that what we see in the 6-minute walk test for desaturation does reflect what happens in daily life. It's a bit worse in daily life, but we don't miss desaturation if we evaluate patients using a 6-minute walk test. We will detect that desaturation. That assessment is only the first part of the equation, though. Then there's the discussion with the patient about the benefits vs the burdens of those sorts of treatments, which might be different across different patients. And then, of course, as you indicated, there's the reevaluation. We're fortunate that we can do 6-minute walk tests often at 6-month intervals or, at the most, yearly intervals. So, we get to reevaluate patients at that point. But there's a role for reevaluation when there is a change in the clinical status of the patient. If they're reporting more symptoms than they've had previously, in which there might be a step change in their symptomatology, I think that's a really good time to consider reevaluation, as well.
Swigris: Let's move on now to the actual use of supplemental oxygen. You brought up
long-term oxygen therapy. There was a large trial conducted in patients with COPD who desaturated with activity but were not hypoxemic at rest. This trial showed that supplemental oxygen had no beneficial effects on the outcomes that were assessed whether it was survival, hospitalization, lung function, or disease-specific quality of life. Should those data shape how we think about supplemental oxygen use in our patients with IPF?
Holland: If we start first with the question of long-term oxygen therapy, it is a treatment for people with hypoxemia at rest. There's little debate in the community that this is something that should be treated and that these patients get benefit from treatment. Although we don't have a lot of direct evidence in pulmonary fibrosis, in that situation, it is reasonable to use some of the older COPD evidence regarding a survival benefit. This is a group of patients who are often highly symptomatic, as well. Treatments that can support the advanced stages of disease are well accepted, and there's a strong recommendation for this in the American Thoracic Society oxygen guideline. Where it gets more complicated, as you've indicated, is when people have isolated exertional hypoxemia. What we saw in the trial in COPD were no convincing benefits in a large-scale trial in the group who only had hypoxemia when they were exercising. We can note those findings. There are lots of differences in patients with pulmonary fibrosis. First and foremost, the magnitude of the desaturation with exercise tends to be more dramatic in the patient with IPF than in the patient with COPD — often really dramatic. So, I'm not sure we can take those findings and apply them directly, but we can certainly learn from them and not assume that providing oxygen to correct somebody's hypoxemia during exercise will necessarily make a difference. It makes us think harder about what the relevant outcomes are for patients that might make this treatment worthwhile. We need pulmonary fibrosis–specific research to evaluate those questions.
Swigris: Right. You hit the nail on the head. Our clinical experience is similar, and the literature would certainly support that. IPF is a completely different condition from COPD in terms of supplemental oxygen needs. Patients with IPF tend to need more oxygen — in many cases, much more oxygen — and desaturate quite profoundly and more so than patients with emphysema.
Tell me your thoughts on AmbOx, a relatively small trial of patients with IPF on supplemental oxygen. A crossover design was used — 2 weeks on oxygen and 2 weeks off oxygen with no placebo control. In that trial, supplemental oxygen was shown to improve quality of life as assessed by a patient-reported outcome called the King's Brief Interstitial Lung Disease (K-BILD) questionnaire. What's your takeaway from those results, and how should we use those data?
Holland: The results with K-BILD in AmbOx are encouraging in terms of improvements in quality of life with oxygen for people with pulmonary fibrosis. As you mentioned, it is a 2-week trial and a crossover trial. Of course, when we're talking about using ambulatory oxygen in pulmonary fibrosis, we're not talking about 2 weeks. We're essentially talking about lifelong use by the time we start using it. While that is cause for some optimism, it doesn't give us the information we need about the longer term benefits for patients using this therapy, which is quite burdensome for many patients. We do a lot of qualitative research in our program, so we have the privilege of interviewing patients about what happens in their lives. The burden of oxygen is something that comes up very often. These are not easy devices to manage. They have an associated stigma with using them in the community, and both patients and caregivers talk about how difficult they can be to manage. So, while some improvement over 2 weeks is good, we probably need information over the longer term. We also need information that can help patients make informed decisions about the benefits in terms of their disease progression — what might happen in the future, such as whether they'll develop pulmonary hypertension or need long-term oxygen therapy. We still need information that can help us have discussions with patients about whether oxygen is a meaningful therapy for them.
Swigris: I think that's the key here: meaningful therapy for patients who are not hypoxemic at rest. It's repeated "n-of-1" trials where you're trying to get a sense of patients' goals and share with them the possible benefits of supplemental oxygen therapy on how they feel and function but also be transparent. As you mentioned, oxygen therapy is not without its burdens. It takes away a patient's ability to live as carefree as they would like, with the stigma of being out in public with supplemental oxygen. There's a lot to unravel there with an individual patient.
Holland: I agree. I would love to be able to put my hand on my heart and say to a patient, "If you use this therapy, your disease will not progress, or it will not progress as quickly. And you won't go on to need long-term oxygen therapy, and things will be much better." Unfortunately, right now, we don't have the data to support that conversation, but hopefully we will in the future. As you say, it's talking with patients about the potential benefits for them in their unique situation, weighing those benefits vs the burdens, and accepting that this is not a one-time conversation. At this point in time, perhaps the benefits don't outweigh the burdens for a patient who's very active in the community. But that might change over time. We need to be prepared to have that conversation again as their circumstances change.
Swigris: Exactly. In the care of patients with IPF, we really have to be mindful that this is a longitudinal conversation — whether we're talking about going on an antifibrotic, monitoring disease progression with physiologic variables or a 6-minute walk test, the need for nonpharmacologic therapy, or the desire to participate in pulmonary rehab or use supplemental oxygen. I share with my patients, "You don't have to decide today. It's not like you're on the clock and you have 5 minutes to decide. And then once you decide, it's set in stone and we'll never revisit it. It's not like you don't have the right to change your mind." It is important to have a longitudinal discussion in which we ask these really important questions about how patients are doing and how they're responding to whatever it is we're doing or not doing — whether it's the right thing for them at that time. Circumstances change, and our approach in our therapies and the way we monitor patients need to change along with these circumstances.
Holland: Yes. Absolutely. You've done some lovely work on the meaning of oxygen therapy and the touchpoints for patients. Qualitative work suggests that patients see the prescription oxygen of as a very significant moment in their journey. They often see it as a sort of harbinger of the end. So it is an important conversation to be having, to be talking about what these therapies are for — particularly for ambulatory oxygen, which is really about quality of life and activity in the community. Addressing that with patients is important but also addressing it with ourselves. Our work shows that clinicians often see ambulatory oxygen use that way — that is, they see it as a marker of disease progression and a marker of the end getting closer more quickly. We also must examine our own attitudes and feelings toward supplemental oxygen, particularly in the ambulatory space, to be able to have meaningful conversations about potential benefits.
Swigris: That's a great lead into my next question. If you have a patient who's sitting there in front of you saying, "Professor Holland, just don't let me go on oxygen and I'll be okay. I can live with things the way they are now." You've done your 6-minute walk test in this patient who is desaturating to, let's say, 78% SpO2, and their dyspnea rating is a seven on a scale of one to 10. You might be saying to yourself or saying to the patient, "I think supplemental oxygen could play a role here." How do you talk with that patient? Can you give us some specific examples of lines you would use and how you would approach that discussion?
Holland: For that patient, you would really want to have that discussion, wouldn't you? Because that's a patient who not only has bad numbers — they desaturate a lot — but also has significant symptoms. In my head, I'd be thinking this is somebody in whom it might be worth giving oxygen a go. But there's already some suggestion that to this individual, oxygen has a meaning that is not a positive one. I'd want to understand that a little bit first. I'd want to understand why it is that this patient particularly wants to be kept off oxygen. I'd have that conversation around expectations and what the patient expects both negatively and positively about oxygen therapy, so I can understand and address some of those things. People often feel that oxygen is addictive. They feel it is a marker that people have given up on them, and they're very concerned about what people will think of them in public. It's important to understand and acknowledge these things and be able to articulate some of the expected benefits you might see.
The way I try and frame ambulatory oxygen and the way we've tried to frame it in a trial for patients is to say, "This is a treatment to help you be more active with fewer symptoms. It's a 'doing' treatment. It's not a treatment for your numbers — for your desaturation. It's a treatment to help you be more involved in the things in your community you would like to be involved in, and to be able to do this in a way that you have fewer symptoms and it's less distressing for you." Understanding what the things are that people want to be involved in is important because that will also guide what type of oxygen prescription might be given.
Again, as you've alluded to, this is not a one-time decision. I'd absolutely be saying, "This might be worth having a go and seeing how you experience it — if it's something that's giving you benefits you can feel and experience and helps you do more things you want to do. But if it doesn't, let's have another conversation about that. If you're not ready for it today, let's have the conversation about how we might make it work for you the next time you come back."
Swigris: I love that approach, and I'm going to steal it now — the "doing therapy." I really like how you refer to oxygen in that way. You mentioned a trial that's ongoing. I know we weren't slated to talk about this, but can you share with the audience a bit about the trial you're conducting now on supplemental oxygen?
Holland: Absolutely. The trial is called the PFOX trial or the Pulmonary Fibrosis Oxygen Trial. It's a randomized controlled trial running in Australia and Sweden comparing ambulatory oxygen with a sham device in people with pulmonary fibrosis. We're keen to use the sham because that hasn't been done previously in pulmonary fibrosis. We really wanted to know whether it was the oxygen that caused the benefits or whether it was the device itself. We're randomizing people for a period of 6 months. The primary outcome in our trial is physical activity in daily life using an activity monitor. So again, that's tackling that "doing therapy." Is this something that helps a patient get out and about and do more of the things they'd like to do? And then we are measuring, of course, other important outcomes in terms of dyspnea and quality of life, as well.
Swigris: Such a great trial. I love that design. You know, the AmbOx trial we referred to earlier is shorter — only 2 weeks and then a 2-week crossover without a sham device. So, it was using a tank and then not using a tank. Clearly, there's potential for significant bias in the AmbOx trial. Your design with the sham is incredibly bold and absolutely needed in our field. I'm really looking forward to that trial answering some key questions we've all tussled with for a long time.
Holland: Absolutely. There's so much we don't know about oxygen therapy and pulmonary fibrosis. Hopefully this trial will start to give us some of the answers that can then inform those discussions with patients when we're trying to help them decide whether this treatment is right for them.
You know, we haven't touched so much today on different devices, but there are different devices out there for ambulatory oxygen therapy, and trying to find the best match for the patient and their activity is part of that conversation, as well. There are a range of devices available to deliver ambulatory oxygen therapy, and the device may be different for individual patients depending on their needs. There are, of course, oxygen cylinders that come in a variety of sizes. There are some very small cylinders patients can carry on their backs — for instance, in a backpack that might be useful for patients who are very active. There are also portable concentrators that can be carried in a bag over the shoulder or put in a backpack that are much lighter than cylinders. The concentrators have the disadvantage that often, they can't deliver very high levels of oxygen, and that can be limiting for patients with pulmonary fibrosis who have a lot of desaturation. But there'll be some patients for whom those are useful. There is absolutely a need for new and novel devices. And I'm really hoping there is good collaboration out there between engineers, clinicians, and patients to come up with devices that are fit for purpose for people with pulmonary fibrosis that deliver high oxygen levels in a way that's truly portable with lightweight devices.
Swigris: If somebody needs a high flow and can get away with a smaller cylinder, I tell them to take their cylinder to the nearest outdoor store and go to the backpack section. I talk to them about the specific backpack I want them to get. I want it to obviously fill their cylinder, but I want the weight on their iliac crest — on what patients refer to as their hips — rather than on their shoulders because I think patients feel as if they will have these heavy straps on their shoulders. So, I say, "Take your cylinder, go into the backpack section, and make sure you get a nice backpack with a comfy weight strap and a chest strap that takes the weight off your shoulders." I think patients find that helpful.
Holland: Absolutely. I think that's a great approach. The other thing patients often talk about is the need for information and education about how to use the devices. For devices such as cylinders and portable concentrators, the way to use them often seems obvious to us because we've been doing it for such a long time, but they can be intimidating devices for patients and caregivers. Some early education on how to use these devices is very important in terms of people adopting them in their daily lives and feeling comfortable using them.
Swigris: Anne, we've about come to the end of our time. In the couple of minutes left, give me two bullet points you would like our audience to take away from our conversation.
Holland: The first one would be that the discussions around ambulatory oxygen with people with pulmonary fibrosis are an opportunity for shared decision-making. There is an opportunity for really meaningful discussion about whether this is a treatment that is worthwhile for patients at this point, and that puts the onus on us as clinicians to be able to articulate those potential benefits and also hear the benefit vs the burden of those sorts of treatments, which might be different across patients.
Because of my background, I'd also like to give a plug for not forgetting other nondrug treatments as well in terms of managing symptoms and helping people to be active. This is pulmonary rehab and other symptom management techniques such as handheld fans to increase air flow. These are any other things that can give patients not only symptom relief but a greater feeling of control over what's happening in their lives. Those things are also important.
Swigris: Absolutely. It has been a real pleasure and a delight to have you here today. Thank you so much for getting up early there in Melbourne, and for sharing your expertise and your thoughts with us.
Holland: Thank you very much for having me. I've really enjoyed the conversation.
Swigris: Wonderful. And to the audience, thank you for listening to this conversation on idiopathic pulmonary fibrosis with our guest, Professor Anne Holland. There's much more ahead in the coming episodes, so be sure to check out the Medscape app, and share, save, and subscribe if you enjoyed this episode. I'm Dr Jeff Swigris for Medscape InDiscussion.