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"From Lab to Life" is a cutting-edge podcast that bridges the gap between groundbreaking medical research and real-world clinical practice. Hosted by leading experts in the healthcare field, each episode delves into the latest innovations in medicine, offering insights on how scientific discoveries translate into practical solutions for patient care. From emerging therapies to case-based discussions, this podcast equips healthcare professionals with the knowledge they need to bring the future of medicine into their daily practice. Join us as we explore the journey from the lab to life.
Welcome to Leveling Up COPD Care, Closing Critical Gaps in Vaccination Guideline Adoption, Approving Clinical Inertia and Integrating Personalized Approaches to Care. My name is Bobby Burkes. I'm an Assistant Professor of Pulmonary Medicine at the University of Cincinnati. I'm joined today by my esteemed colleague, Dr. Stephanie Christensen, Associate Professor of Medicine at the University of California, San Francisco. For full financial disclosures, please see iridiumce.com landing page for this activity.
This educational activity is supported by an independent educational grant from GlaxoSmithKline, who would like to thank them for their support in this initiative. Their learning objectives for this program are to review the factors contributing to delays in initiating therapy for COPD and implement measures to minimize such delays, ensuring prompt and effective intervention, and to discuss the importance of escalating therapy after symptomatic events in COPD management. Dr. Christensen, let's discuss tackling delayed diagnosis and treatment escalation.
Can you discuss issues with delayed diagnosis in COPD? Absolutely. So I think this is actually a major issue and certainly a major issue to getting patients treated, feeling better, so symptomatically improved, but also to prevent exacerbations, which we know are highly morbid and potentially even mortal events.
Some of the literature around this suggests that up to 70 % of COPD patients may be under diagnosed and diagnosis is often delayed with a medium delayed time to diagnosis of 230 days. One in four patients, however, wait five years for diagnosis, even though many of them have had missed opportunity for diagnosis during that time, like other healthcare interventions where potentially this could have come up. From a survey of
primary care clinicians, the most common barriers were multiple chronic conditions and you know we're trying to tackle many things all at once. So having a CPD come in on top of multiple other conditions, there's only so much time in a patient encounter to be tackling all these chronic conditions. There's a failure of patients to recognize and report dyspnea. You know, oftentimes symptoms, including dyspnea kind of come on slowly. And so what often happens is that patients kind of adapt.
to what's happening by potentially doing less. So that can lead to failure as well. And then just lack of knowledge or training both on the part of patients that they don't understand that this could be one of their conditions, but then also on the part of physicians. So I think all of those are potential barriers that I have certainly seen. We can talk next about what should you be looking for in these patients? So certainly history of COPD risk factors, either a history of smoking or current smoking.
but then we also talked about other types of pollutants, being a risk factor for COPD, wood fuel or other combustible products, particularly in developing countries. Other things that we can think about are for lung development. So if they've had issues as a child with lung development or being born prematurely, issues with asthma throughout the life cycle, recurrent pneumonias can also put you at risk. So those are some of the.
risk factors, but then also we think about other things that might make us think, hey, is this person actually have COPD, recurrent lower respiratory tract infections, so they keep getting pneumonias, chronic cough, recurrent wheezing, dyspnea that is progressive over time, worse with exercise and persistent. And I think as we kind of talked about, you have to ask them really about exercise limitations as well as the dyspnea. And we can talk a little bit about
how delaying a diagnosis impacts outcomes, because I think this is a really important piece. We do actually see increased rates of exacerbations in patients with delayed diagnosis. So in one study, they found 108.9 exacerbations over three years for a late diagnosis versus 57.2 for early diagnosis. And if you have a diagnosis that decreases time to first exacerbation. So 14.5 months,
for a late diagnosis and 29 months for early diagnosis. So important because we do have therapies. In fact, it's one of our mainstays of therapies to prevent exacerbations. If you delay giving those therapies, then we also increase your odds of any exacerbation by 11 % with each 30 day delay. So pretty important to be thinking about because not only can we maybe
improve patient symptoms earlier, so getting them feeling better, so maybe they can increase their exercise capacity, which also has a lot of important health outcome effects, but also preventing exacerbations, which can cause worse outcomes overall. So important for those reasons. Dr. Christensen, can you summarize what clinicians need to know about when to escalate therapy in patients with COPD? We're really treating patients.
either because they're having symptoms or they're having exacerbations. So we can think about escalation in terms of those two things. I'm also thinking about other non-medical managements, but if we are thinking about medical management, the GOLD report is now suggesting that you're on a dual inhaler to start out with, LABA, long-acting beta agonist, plus the long-acting anti-muscarinic. However, many of our patients are just on one or the other, or sometimes they're on something like an inhaled steroid.
but either way, wherever you're starting from, oftentimes what I will do for dyspnoic patients, I'll usually try to ensure that they're on the combo inhaler if they were just on one. And I might actually consider switching up inhaler devices. And then I also may actually be considering, they have other things like asthma overlap where we're needing to treat the asthma symptoms with an inhaled steroid as well, although that's not the first thing I'm necessarily thinking about for dyspnea.
Now for exacerbation, so again, I'm thinking about that LABA/LAMA first time therapy. However, oftentimes now we're checking a biomarker, so eosinophils, and I'm oftentimes thinking about whether to add an inhaled corticosteroid. If I can have all those in a single inhaler, I try to combine them and that's mostly for adherence. And then oftentimes if I still am having problems, I may try reflumelast or azithromycin.
Ruflumelast being for a patient with chronic bronchitis and a very low FEV1, so less than 50%. And I do find that it works in some patients, but it can also cause side effects like GI upset. So I may not consider this in a patient that's kind of frail and malnourished where I'm worried about those things. Azithromycin is another one that I might try in former smokers. And again, I just kind of think of some of the potential adverse.
effects in relation to those things like the potential for arrhythmias, the potential for hearing loss, and then potential for antibiotic resistance, which is tough in a patient with pneumonia. So those are certain things that I am checking in on around these patients. We have summarized and simplified the GOLD guidelines for escalating therapy. However, there's still some patients that will not respond to the therapies that were discussed. And you describe some of the emerging therapies.
that those who take care of COPD may find useful in these patients that may help fill this gap. Absolutely. So I think, you know, we are in an interesting era where we're starting to think about biologics for COPD patients. We're going to talk about three drugs. First, let's talk about methylizumab. So methylizumab targets IL-5, a cytokine that works on eosinophils. And it has had two randomized controlled trials.
metrics and metrio. Those were done in COPD patients with a history of moderate or severe exacerbations while taking an inhaled steroid plus the lava and the llama. And they found that in their overall study, so when they combine data, that the point values were promising that it looks like there was a trend towards a
decrease in exacerbation, but that that did not quite meet statistical significance. So I think again here, they are looking at targeting a higher eosinophil count. And so some of those studies again are ongoing to look at this drug in COPD with high eosinophil counts. And some of those studies I think we'll read out soon. The next drug we're talking about is the IL-5 receptor blocker.
Benrelizumab. So there were two studies done on that, Galathea and Terra Nova studies. And really what they found was that in one of the studies, the 30 milligram dose did not really seem to reduce exacerbations in a statistically significant way. And the 100 milligram dose looked like it might have.
but in the other, the 30 milligram dose didn't and maybe the 10 milligram dose was getting closer. So really kind of mixed results on how well Benrelizumab did versus placebo for exacerbations at the different doses. The final one is Dupilumab. And so there are two phase three studies for Dupilumab, the Boreus and Notus studies. And in both of these, Dupilumab decreased the rate of exacerbations.
as compared to placebo. They also saw an improvement in lung function as a secondary outcome across both forious and notice. So I think that those are kind of some of where we're at. And I think there's, like I said, there's actually a lot of interest in this space, which is wonderful that we may have new drugs with new mechanisms of action for these patients. So Stephanie, even with these guidelines in place, new therapies on the horizon, therapeutic inertia,
issues with escalating care, adding, kind of folding in these new therapies, de-escalating care sometimes, is a widespread problem that occurs when a patient's treatments, you know, aren't working for them and are not working in a timely manner and the patient's goals are not met. Do you have any strategies for overcoming this? Yeah. So acting on exacerbations would be one thing reviewing what happened to cause the exacerbation and trying to figure out
are there modifiable risk factors? So if it sounded like it was a virus, have they been vaccinated? If it sounds like they were exposed to smoke or something else that caused an uptick, were they having problems with their adherence? Did they change over medications? Did something get missed here? So we're always kind of looking through those things. And that's also true of hospital discharges, particularly at the time of exacerbations, but also...
for other things, making sure they didn't get their medication switched. But also one of the major thing I'm always harping on is making sure when they are on prednisone that they don't get just taken off all their inhalers and don't have those restarted because that can be an issue for some of our patients. And then thinking about, do they need things like pulmonary rehabilitation? Do they need us to upscale their inhaler therapy going from?
you know, a single inhaler to a dual inhaler or a dual inhaler to a triple inhaler. And then I think we should really be making sure that in all healthcare settings that people understand what an exacerbation is and our patients understand what it is. A patient doesn't necessarily talk about an exacerbation. They might say that their symptoms feel different. They all talk about it quite differently. So really understanding.
when they actually had an exacerbation asking probing questions so we can really get more information. And then making sure they're getting referred for to pulmonary appropriately if they're having escalating needs or seeing respiratory therapy to make sure their inhalers are used appropriately or to go get vaccines at their pharmacy. So really working across all those things.
And then acting on those predictors of risk for exacerbation. So really working on treatable traits as soon as possible, working on comorbidity as soon as possible. So I think that there's several things that we can do here and really making sure we're teaching our patients and our colleagues on how to recognize and what we can do for them. I could not agree more with that. There's a Swiss cheese model almost. There's multiple times you can catch these folks. It's just that they're colliding.
The GOLD guidelines also kind of advocate for some active case finding, looking for patients who might have COPD using questionnaires, because we know that in certain communities, spirometry is not always available. So we're not gonna send every single patient to go get spirometry. And there's different types of small handheld spirometry devices that can be used and using kind of a combination of some of these tools in patients.
who look like they might have risk factors, then we can figure out who might be a better candidate. So if you're particularly for a primary care physician who's having difficulty in understanding, who are the patients who are at risk using some of these kind of combined tools might help you decide who's better to go on for spirometry and get that limited resource. There are four strategies.
to overcome therapeutic inertia, act on an exacerbation, act on hospital discharge and follow-up, act on recognition and recording of these events, and act on predictors that may suggest further exacerbations. We've reached the end of this episode. I would like to thank Dr. Stephanie Christensen for this engaging discussion. We'd also like to thank GSK for their support of this program. Be sure to claim your CME credits by filling out the evaluation and post-test.
This is part two of our four part series. Be sure to follow Iridium on the socials to see the remaining episodes and other med-ed threads.