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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, Improving Clinical Inertia, and Integrating Personalized Approaches to Care. I'm Dr. Stephanie Christensen, Associate Professor of Medicine at the University of California, San Francisco. I'm joined today by my esteemed colleague, Dr. Felix Reyes, Clinical Director, COPD Program Northwest Medical Center. For full financial disclosure information, please see the landing page for this activity.
This educational activity is supported by an independent educational grant from GlaxoSmithKline. We would like to thank them for their support for this initiative. The learning objectives for this program are to summarize the concept of patient phenotyping in COPD, focusing on treatable traits and applying this approach to tailored interventions.
ensuring a more precise and personalized management plan for individual patients and discuss how to engage patients in the management of COPD, recognizing the pivotal role patients play in their own care and wellbeing. I would like to start by discussing personalized strategies in the management of COPD. Can you introduce COPD phenotypes and the treatable traits strategy? Before we talk about phenotypes, let's define what a phenotype is. A phenotype is the physical.
or biochemical appearance that results from the interaction of a genome or genotype with the environment. Phenotypes help us in guiding prognosis questions and guiding management questions for our patients with COPD. There are widely accepted COPD phenotypes. First, the classical chronic bronchitic type and emphysemitic type. But over the years of taking care of patients with COPD, we learned that there's patients who have
a history that would resemble asthma, but they have the fixed obstruction of a COPD patient. And that's how the asthma COPD overlap syndrome came to be, which is a distinct clinical entity. We've also learned that we could classify our COPD patients based out of how frequently they need medical care as frequent exacerbators or rare exacerbators and frequent exacerbators being defined differently in different literatures. But most of the definitions
come down to either two or three exacerbations per calendar year. There's emerging COPD phenotypes. The most interesting ones, at least in my take, are the pulmonary cacaxia phenotype, which is those patients who have a lot of muscle wasting and not another explanation rather than their own pulmonary disease. And the molecular mechanisms that lead to that are being unraveled currently. There's an overlap of COPD and bronchiectasis, which is its own challenge in management.
and we have other phenotypes that are evolving, the fast-decliner, and those who have systemic disease. Alpha-1 antitreatsome deficiency is the most common genetic cause of COPD, and all patients should be screened for Alpha-1 antitreatsome deficiency, regardless of their smoking status. And unfortunately, patients who never smoke can't develop COPD. They're rare, but they're out there, and they're in everybody's patient panel.
but the treatment for them doesn't vary a lot from the more common phenotypes. As the research evolved on patients with COPD and the different phenotypes, more interest was placed on how could genetic information and changes in the environment give us such a varied patient population. And that's how we identified that some patients do have specific treatable traits.
phenotypical manifestations of COPD for which we can offer a direct intervention. There's two phases to this approach. Phase one, which we should consider in the first encounter, is determining the degree of airflow, which can be done through a pulmonary function test or in-office spirometry, exercise tolerance, which can be assessed by a six-minute walk test, chronic bronchitis, which we would assess by determining how many episodes of
or requirement of antibiotics or systemic steroids the patients had in a calendar year. Aeosinophilic airway inflammation and alpha-192-3-sim deficiency can be evaluated by a simple blood draw at the time of office visit. And the other freeze-worn treatable traits can be evaluated during our clinical interview with the patient. If the patient is obese or malnourished, that will be part of the initial intake of vital signs. How much you're able to get done in a day will tell us their
degree of physical activity, their smoking status, it's a classic question in any of a new or known COPD patient, and then evaluating their inhaler compliance issues with inhalers leading to polypharmacy, they're confused when to use what inhaler and who's there in their support network. If we notice that our patients are becoming more symptomatic or are having more exacerbations or not controlled with the initial guideline directed therapy for
patients with COPD, we would go on to phase two, treatable traits. And here it's when we're looking at the more chronic ailments that come with COPD. If our patients have chronic hypoxia, chronic hypercapnia, we would assess that through an AVG. We would also look at comorbidities. We would be thinking of getting a CAT scan to make sure that our patients don't have bronchiectasis, upper lobe emphysema, evidence of pulmonary hypertension and imaging, considering then
a cardiovascular evaluation through an echocardiogram, which would also give us more information about both cardiovascular disease and pulmonary hypertension. And as we were discussing before, we could start screening for alpha-1 and detrital deficiency in the first encounter. However, we could also do that in the second encounter. And after we know that the patient is not improving, we could look at more silent aggravators, such as obstructive sleep apnea, OSA, highly prevalent in patients with COPD.
regardless of your weight, patients should be screened for it if they're reporting symptoms of extreme fatigue and also determining if they have anxiety and depression, which is always really hard to tease out because so many things are going on in the life of our patients. Now I'd like to move into personalized strategies for the management of COPD. Dr. Reyes, could you share a few strategies you use? Great numbers of patients with COPD actually have
poor knowledge of what COPD is and a misunderstanding of the different therapies that are available or what adherence to these therapies would mean. This slide reflects the importance of an educational intervention. We can see that after two face-to-face interventions, both 30 minutes in which in the first intervention, the patients were educated on what COPD is, what is the diagnosis, what is the role of PFDs and what are the different treatment strategies.
And on the second visit, inhaler compliance and inhaler technique was reviewed, plus treatable traits were further identified. We can see that patients had improvement in their knowledge score based out of a 20 question survey. They had improved inhaler technique, but also they had a statistical significant difference in their symptoms of anxiety and depression. So educating our patients has a big impact. It's a challenge in the time of
more limited face-to-face time with our patients, but the evidence is there. And even trying to do small interventions within 30-minute time slots has an impact in our patients with COPD. Regarding strategies to promote the adherence to COPD management protocols, before we address those, what is adherence? Adherence is defined by the World Health Organization
as the extent to which a patient will change either behavior, following a diet, lifestyle changes, or using a medication following the guidance of a clinical provider. The big challenge with adherence in COPD is that there's no consistent method to evaluate adherence in patients with COPD. There's two ways of addressing it, either through direct methods with the patient or
indirect methods. And within these two methods of doing it, there's either subjective, in which in an indirect way, we do so by having patients complete diaries and questionnaires, objective ways in which we can monitor their adherence, either by looking ourselves and seeing how patients use their inhalers or in an indirect manner, having patients bring their inhalers to their appointments with us.
and looking at the dose count of the inhaler. Another objective way, but through electronic means is by evaluating directly the deployment of the inhaler therapies through different devices and different brands that are available for different inhaler mechanisms that will tell us at what time of the day, how frequently and how effectively our patients are using our inhalers. And biochemical monitoring in COPD adherence
It's being used in the research setting. It's how we document how our patients use their inhalers and how we prove it, but it's prohibitively expensive in clinical practice. To improve the care of our patients with COPD and their adherence and their holistic management, we tried to expand the chronic care model by providing all care that the guidelines will require in different interventions, which is the patient center medical home.
The patient center medical home is trying to bring some of the interventions to the patient home by bringing the delivery systems to their house, by empowering patients to have access to clinical information systems or decision support systems that would help guide them to avoid exacerbations or mismanagement of their COPD, all with the goal of trying to keep them outside of the hospital. The other side of that coin is
empowering our patients to take care of their own COPD. This is a chronic illness with which they're gonna live for the rest of their life. However long that is, some patients are gonna be diagnosed really early on in their life, 40s, 50s, 60s, and they're gonna have an expected lifespan of 70 plus. So they're gonna have to live with COPD for two to three decades. So empowering them and helping them to self-determine.
how their disease trajectory should play out. It's an important role, especially in the patients that we meet early in their COPD trajectory. And a four step approach in which in different consults, we're trying to address different aspects of self-determination has been proven to be helpful and feasible in patients with COPD. In the first appointment, we would focus on understanding where the patient is coming from.
How is COPD affecting their life? How is COPD affecting their ability to do the things that they would like to do? In their second appointment, we would still explore how COPD affects their life, but we would prompt the patient to give us their values, give us their habits, and what do they look for in their life? Then once we know where the patients are coming from and what they're looking for, the third time we're seeing this patient, we know them well.
We've done the workup to understand if they have treatable traits. We've done the workup to understand what phenotype they have. And now we understand them as human beings and we can create a plan of change for them to follow. If they still smoke, we can look at the different options that they would have to explore smoking cessation. If they do not smoke or they need extra help at home with carrying their daily activities, we could maybe
get care management involved and see if we could get them extra help at home. And in the fourth appointment, we will talk about how they felt about these changes, if there's new strategies that we can explore, and if their goals or their intentions have changed based on what they're able to get done now. Thank you so much for that, Dr. Reyes. Let's move on to discuss a patient, John.
Sean is a 62 year old man who was recently hospitalized for a severe COPD exacerbation. He has a history of smoking and a history of occupational exposure to dust. His current medications include a short-acting bronchodilator as needed. He presents with shortness of breath, chronic cough and frequent respiratory infections. So I'm really interested to hear
What are your initial thoughts when you see this patient case and how you might tackle kind of initially thinking about them? Thank you for your question, Stephanie. This is definitely a patient that it's quite representative of something we see often in any pulmonary clinic or even in a bread and butter primary care clinic, which is a patient that probably just had a really bad respiratory episode and maybe
they're seeking care for the first time or they've never had optimized care. So the first question I would have for John is, where is he sat from a symptoms perspective? Because that will help us understand where he would fall in symptom severity classification based out of the goal report. And also it will help me understand where we're at in the exacerbation continuum. We know that our patients are treated for an exacerbation
Sometimes they leave the hospital and still symptomatic just because a time quota has to be met. And some of these patients we want to avoid a bounce back. And depending on how symptomatic he is, I might consider different strategies. If he's really symptomatic and he presents to clinic wheezing and really short of breath and coughing, I would still offer nebulizer therapy for him at home in that scheduled basis.
with some systemic steroids with either Medrol or Prednisone depending on what's available in his pharmacy. And depending on the symptoms that he's telling me, I would also consider a citric amycin or any other macrolide depending on what sputum characteristics he's telling us. However, if he comes to the clinic and he's reporting better symptom control, he's back to his baseline. He's back to what his normal life looks like.
That's when I would address trying to figure out what are his treatable traits, who he is, where he has been. And he has already the risk exposure that we would expect from a patient with a informal diagnosis with COPD. But I would work towards getting the formal diagnosis of COPD. If he's from far out of town and drove two hours to meet us, I would do an in-office spirometry.
has a shorter commute, I would consider getting a full PFD within the next couple of weeks while his symptoms are better controlled. Depending on where he's at, again, symptoms wise, salva or as needed bronchodilator might be enough at that time, or it might be the time since he had a recent exacerbation to consider a longer acting therapy. that's where, depending on how we determine his profile to be, we would consider
a lava llama or a llama lava ICS triple therapy. On the first visit, definitely I would be doing a blood draw, especially if he's off steroids and have been off steroids for a couple of days, just so can understand that inflammation a little bit better. See if there's an oceanophilic component. I don't usually send CRPs or pro calcitonins for this kind of patients, because they tend to be just awash. They don't give me a lot of information.
But definitely I would offer at that time, or I would start the discussion of also if he's the only person with emphysema in his family and if this is his first event and then consider triaging him also to undergo the evaluation for opal-1 antitreps deficiency. So at least we would cover the first stages of treatable traits. However, if he's really symptomatic, that's where the treatable traits
become a little bit murky. We should address both treatable traits, phase one and two. If I hear from him, well, this is my second flare up within two months. I'm still on oxygen, not doing better. That's when I would look for in-hospital AVGs, look at doing an AVG in the office just to determine, this hypoxia just an episodic thing or is it chronic? And we already have to talk about oxygen supplementation. And obviously the other questions that we would be
doing during our initial meeting, which is documenting inhaler compliance and adherence technique, identifying financial barriers, identifying potential insurance barriers. Sometimes these exacerbations occur because patients change jobs or their insurance won't cover their previously covered inhaler and we need to find an alternative. And third, I would start
with just a simple interview, just asking the impact of this exacerbation in his life. For example, is he still working? How many days he missed from work? How is that impacting him emotionally? And I would start going into a segue of the other dimensions of COPD care that we spoke about and see how we can help him in his self-determination pathway.
You know, I really like how you're thinking about that as kind of this multifaceted approach. And one of those things being, hey, actually patients in the hospital relapse and some of that actually ends up being back in the hospital or sometimes they may just come back to you in the clinical setting. And you may actually end up having to treat them for a relapse or even re-exacerbation depending on where, know, what timeframe has gone and that some of these patients may not feel better after a severe exacerbation for
weeks to months. And so you may actually be treating them for an acute event, even long-term. And then kind of really getting on top of like, you know, how bad these severe exacerbations really are and that you really need to be working on prevention, but taking this multi-pronged approach. So working on their symptoms, working on exacerbation prevention with, you know, our inhaled therapies and potentially working on some of these other oxygen supplementation.
Do they have alpha one that's often goes very much under diagnosed, right? That it oftentimes people don't get diagnosed with that. Do they have sleep apnea? Do they have cardiovascular disease, depression, those things that really need to be addressed separately or other treatable items that really need their own intervention. So I think that's really great.
I think the one kind of question I had is, is when you think about things like, when we're, you know, kind of talked about some of the inhaled therapies, but what do you, when you think about, okay, this patient continues to have symptoms, continues maybe to have exacerbations that you might kind of consider, you know, alternative options to treatment. So more of the, more kind of advanced therapies like reflumulaster, azithromycin, when do you start to think about those things?
recommended and being shown to have clinical significance in patients with recurrent exacerbations. So if this is a first time episode, I wouldn't be necessarily considered them at that time. But if they tell me, hey, this is month eight of the calendar year, and I've been to the emergency department three times, I would first always make sure that inhaler compliance and adherence, it's there because that's one of the criteria from where that evidence came from.
And if that's there and they still have an issues with COPD and there's no environmental trigger, meaning they've gone through their smoking cessation, there's no other smokers in the household, they don't have unstable housing or they're not in a setting, in an environmental setting that would trigger a COPD flare up. That's when I would start already talking with them about either rough lumilase, as it reminds me and the dreaded chronic steroid therapy.
while we figure things out. And hopefully in the coming months as new data surfacing, we'll have new tools in the armamentarium for our patients with eosinophilic profile, endo-inflammation and COPD as a diagnosis. Yeah, I like that approach. And I think, as you were talking about, it's really nice to like understand kind of where our patients are coming from and what is potentially causing adherence problems and realizing,
sometimes they may not be able to stop smoking. That's actually very common. And so it's a thermos and may not be a great option for them. We still might be able to try reflumulase, but it may, you know, we may, we may have other barriers in thinking about how do we work, work with some of their barriers and are there ways to do that because we know that it's going to be so potentially harmful. So to summarize, there are widely accepted and emerging COPD phenotypes.
And the treatable trait strategy has two approaches, the broad approach and kind of a phased approach. So tailoring treatment plans and engaging patients in management as Dr. Reyes has done kind of so well in his case example. We've reached the end of this episode. I want to thank Dr. Reyes for this engaging discussion. We would also like to thank GSK for their support of the program. Be sure to claim your CME credit by filling out the evaluation and post-test. This is part
three of a four part series. Be sure to follow Iridium on socials to see the corresponding remaining episodes and meta-ed threads.