Healthcare stakeholders recognize the large prevalence and burden of chronic obstructive pulmonary disease.

 One of the things I’m curious about, to try to understand as we go through this conversation, is what’s the prevalence of COPD [chronic obstructive pulmonary disease]? And then what does that mean in terms of the economic burden of disease?

 Sixteen million diagnosed. Thirty million, probably, total in this country. Many of them are undiagnosed. Over 300 million around the world. This is a major health issue, and one which is not going away. It’s a disease that impacts every level. It’s not just a disease of older adults. The majority of people with COPD are in the workforce, which as Maria knows, leads to issues of absenteeism and presenteeism. It has tremendous financial burden, beyond the $50 billion a year in medical costs.

 Absolutely. Yeah, and just to add to what Byron was saying, on the health-cost side we’re seeing over 400,000 admissions a year responsible for this condition. Often, these patients can be readmitted. ER [emergency department] visits, antibiotic use—not to mention PCP [primary care physician] visits, pulmonologist visits, and other specialists&mdash;as well as imaging. We also now have low-dose CT [computed tomography] for screening, and hopefully for early detection of lung cancer for patients who are smokers. There is a lot of focus and effort, and certainly it has not only direct cost impact on the health system, but as Byron alluded to, it leads to absenteeism, presenteeism, symptoms that often lead to additional costs, and a major health economic problem. Actually, COPD is second only to heart failure in readmission rates, so it is important to keep that in mind.

 Maria, you might want to stress the presenteeism issue. It’s easier for businesses if someone doesn’t show up. If they have work to be done, they can find someone to replace them. If someone shows up but is not well enough to work to the level you’re used to, which is what presenteeism is, it’s much more difficult for businesses to understand that, and it makes defining the impact of that much more complicated.

Yes. It’s challenging, though, to measure. I think most payers would have a hard time…. Obviously, if it’s their own employee, that may be important, because we’re all consumers of healthcare. But for a large employer, what that may mean not only in terms of absenteeism but also, you’re absolutely right, presenteeism—how much more productive somebody could be if they were fully functional. Absolutely.

COPD Disease Burden

Key considerations in distinguishing chronic obstructive pulmonary disease from other conditions.

 Hello, and thank you for joining this American Journal of Managed Care® program titled “COPD Treatment Updates: Impact on Daily Life.” Chronic obstructive pulmonary disease, COPD, is a progressive and debilitating disorder. While COPD is associated with a significant medical and financial burden, COPD symptoms also present a severe burden on patient quality of life. Our panel of experts will review the latest therapeutic developments in the treatment of COPD and address the impact of the progression of disease and exacerbations on a patient’s life.

I’m Dr Neil Minkoff, the founder of FountainHead HealthCare and the former medical director of pharmacy and network medical management for Harvard Pilgrim Health Care in Wellesley, Massachusetts, and an instructor of medicine at the Harvard Medical School, in Boston, Massachusetts.

Joining me today are Dr Maria Lopes, the former chief medical officer from Magellan Rx in Cresskill, New Jersey, and the current medical director of AMC Health; Dr Frank Sciurba, a professor of medicine at the University of Pittsburgh School of Medicine, the medical director of the pulmonary physiology laboratory and the director of the [Emphysema] COPD Research Center in the Division of Pulmonary, Allergy, and Critical Care Medicine in Pittsburgh, Pennsylvania; and Dr Byron Thomashow, a professor of medicine at Columbia University Medical Center, the medical director of the Jo-Ann LeBuhn Center for Chest Disease, and the medical co-director of the lung reduction program and Emphysema Clinic at Columbia University Medical Center in New York, New York. He is also the chief medical officer of the COPD Foundation.

Thank you all for being here. Let’s begin.

Just to level set and make sure everybody who’s watching and participating is starting from the same place, let’s start simply and ask: What is COPD, or chronic obstructive pulmonary disease, and how do you look for it?

 That answer has become more complicated than easy to answer, but I’m going to start with the straightforward answer as we classically define disease. That’s based on obstruction to airflow. COPD actually represents many different diseases that result in expiratory airflow obstruction. You can’t get the air out, and then there’s trapping of that air, so it limits your space to breathe in. We classically define it using a simple test called spirometry, in which you blow hard, and you see how much air comes out during that first second and the total air that comes out. If you get less than 70% of your total air out in that first second, that classically defines the disease as COPD.

 Yeah. Spirometry and some of those results, and barriers to getting those, is something I’m going to want to come back to in a little while. But I wanted to see if you wanted to add anything to that definition, or other ways of looking for or diagnosing?

 Well, as Frank has said, we’re at a time now when a number of studies are suggesting that people with symptoms may not have obstruction on spirometry, and therefore there may be a need to broaden the way we think of this disease, because people often will have symptoms before they develop obstruction. And the possibility exists that if we could diagnose them earlier, perhaps we could make more of a difference. But that’s a work in evolution as well.

COPD Defined

Common symptoms and triggers of disease that may suggest chronic obstructive pulmonary disease versus other conditions such as asthma.

 What are the common signs and symptoms that you’re looking for when you see a patient and suspect COPD [chronic obstructive pulmonary disease]? And what do you anticipate as triggers to exacerbate it?

 The initial presentation in COPD often occurs in individuals who are still smoking. In COPD, over 80% of the cases in this country, not necessarily around the world, are related to tobacco smoking. When they’re smoking, they often don’t say, “I’m short of breath” or “I have symptoms,” because they know what the next response is: “You need to quit smoking.” And they recognize that. But also, patients often don’t even recognize it themselves. If they cough, they think it’s a smoker’s cough. They begin withdrawing from activities rather than saying they’re short of breath. They don’t challenge themselves. They stop doing things. When they go to the mall, they drive around until they find a parking place right next to the door rather than walk across the parking lot.

Often 1 of the first things you need to ask is not just, “How are you doing? Are you short of breath?” But instead, “What are you doing? Are you just withdrawing from activity? Are you sitting on the sofa? You’re no longer golfing. You’re no longer getting out with your children. You’re starting not to shop on your own.” And that, often, is the first sign. Once it is recognized and they can no longer deny it, shortness of breath, cough, sputum production. Often, not all the symptoms together. Often, individuals will present differently. Chest tightness. Wheezing actually isn’t all that common in COPD, except during flare-ups. But these are the types of classic things that can be experienced in these patients. Chest tightness.

 I want to stress what Frank said, because you asked before, Neil, about spirometry, and I know we’re going to come back to that. But if you look at the recommendations, the repeated recommendations of the United States Preventive Services Task Force stress that spirometry is indicated only for those people who are at risk and have symptoms. And the problem with that is what Frank just said: Many people self-diagnose and self-treat. They say to themselves, “I’m getting old. I’m out of shape. I’m overweight,” and they cut back on their activity level. In that 5-, 6-, 7-, 8-minute visit you have with your primary care provider, where there are multiple medical issues you need to discuss, if they ask 1 question about the breathing and say, “How’s your breathing, Frank?” Frank might say, “It’s not bad, doc,” because he’s not doing anything.

 So when he says it’s not bad, you’re looking further out than he is, right, from your example? And so what are you concerned about in terms of long-term complications? And then, also, systemic manifestation beyond just shortness of breath?

 I can certainly give you some thoughts on that. I would stress with you, Neil, that it comes down to—as it often does in medicine&mdash;asking the right questions. Because if you don’t ask the right questions, you’re going to get the wrong answers. A better question than, “How are you breathing, Jack?” might be, “How’s your breathing compared with a year ago? Can you do what you could do a year ago? Can you do what you want to do?” Those sort of things give you a much broader issue and much more of a take of where you are. As far as your question is concerned, COPD, like many chronic diseases, is associated with multiple other systemic manifestations. I’m sure that Frank and Maria would agree. You can’t treat a patient with COPD by just treating their COPD. You have to treat the person who has that disease, because otherwise you will not get to where you need to go.

 Let me ask you a question. In your clinical experience—not you personally, but what you see the fellows do, other pulmonologists do, and so on&mdash;are people asking, “What can’t you do this year that you could do at our last visit?” or “What have you withdrawn from?” Do you think that’s part of the work-up yet?

 Is it commonly practiced? Probably not. Part of it is private practitioners. Primary care doctors are so busy that somebody says, “That’s not a problem.” They don’t dig and discover that. I can’t tell you how many patients I’ve picked up who I know have had their disease for years and years and years. They come in with advanced-level disease, and you know they had it 5 years ago. And they’ve been seeing primary care doctors or, in some cases, other specialists, and it hasn’t been discovered. Or they’ve gone to a cardiologist who focuses on their minimal coronary artery disease and doesn’t recognize that they have significant COPD that needs to be treated and may be the primary problem and the reason they present to the cardiologist.

Characteristics That Help Diagnose COPD

Healthcare professionals comment on the progressive nature of chronic obstructive pulmonary disease and highlight considerations for stratifying patients and navigating through limitations when managing patients.

 The question I was going to ask is: Define the impact on patients’ lives, which I think you’ve all done to a great extent. How bad does it get? How withdrawn do these patients get? How immobile do these patients get, in your experience, as the kind of people who are probably treating some of the most complicated patients?

 Most of the time people live with their disease, and most of the time they live with their disease for a very long time. It is usually a gradually progressive disease. There is a subset who tend to be more rapidly progressive. That’s the exception rather than the rule, but we certainly do see that. And point of fact, 1 of the things that has certainly been a concern for many of us for many years is that we have tended to lump all COPD [chronic obstructive pulmonary disease] as the same and have treated it all the same. All COPD is not the same. Just as we have moved, in recent years, away from treating all cancers the same, we need to start moving away from treating all COPD the same.

There are certainly some recent data that have come out from a very large study that both Frank Sciurba and I have been involved in, called COPDGene, that suggests that COPD progresses in different ways. There’s a group that does progress that tends to have more of an emphysematous phenotype, if you will, through the classic gets more and more severe obstruction. But there’s another group that tends to go to a more restricted pattern, and then more rapidly down to progression, that perhaps we need to view in a different fashion. This is all that’s changing in front of us, but I think we all recognize the need to move away from treating and dealing with it all the same.

 Let me ask a question. Let me bring what you just said over here. Are there ways for you, as a clinician or for you as someone who’s looking at it in an aggregate from the claims point of view, to try to identify who those rapid progressors are versus the slower progressors? And do you stratify their care differently?

 This is actually an important question, but it’s not a question we would target differently right now. Right now, our therapies are not convincingly effective in preventing progression. They’re to optimize a given person’s lung function at a given time and to improve their quality of life. We can affect exacerbations, and I’m sure we’ll get into that in a little bit. But as far as the gradual decline that we know happens in these individuals over time, we’ve not convincingly proven that we have therapies that can affect that.

 Although there is some suggestion that if we did it earlier, maybe we could make a difference.

 Certainly with smoking cessation that’s the case.

 With the drugs we have early suggestions, but I think we need better therapies.

Yeah, I think we tend to follow guidelines as well as US Preventive Services Task Force measures. Certainly smoking cessation is a huge opportunity. Fifty percent of our chronic conditions are driven by bad behaviors.

Smoking cessation is 1 of them. Particularly in this disease, it can make a big impact and have an impact on cancer prevention as well. Going back to the diagnosis, even just making the diagnosis with spirometry you see so much variation. Patients may be labeled and not have the disease or have restrictive lung disease and not have COPD. So getting the right diagnosis in play to hopefully have the right treatment approach that follows is important.

Other opportunities in terms of pulmonary rehab, as a health plan covering pulmonary rehab and how many patients avail themselves to the benefit that exists. And then I also think that clinical inertia, the adherence, even better training with devices, and strategies related to technique and inhalation. Because obviously that matters. The best drug, unless it’s taken appropriately, is not going to have the desired impact. Also, prevention in terms of flu vaccination, pneumococcal vaccines. These are the things on a macro level we tend to be focused on. They impact our rating scores and our quality metrics and have a major impact on cost of care as well.

 I think we all agree with everything you just said. I know we’re going to talk a lot more about the medications, but I do want to stress, and I’m sure Frank feels this as well, that pulmonary rehabilitation and exercise programs, in general, are tremendously underutilized in this population. There are some data suggesting that somewhere between 2% and 5% of the 30 million people in this country with COPD ever complete pulmonary rehabilitation. In New York City, where I practice, there may be at most half a dozen pulmonary rehab programs for a population of millions of people. For a therapy that clearly is very effective, that’s really just not acceptable. And it’s gotten progressively worse, actually, since the national reimbursement policy went into place, because the reimbursement rates are just not sustainable. I assume it’s similar in Pittsburgh, Frank?

 One of the problems with pulmonary rehab is that it’s almost never accessible in rural populations, and there are incredible variations even in cities. The 

review on pulmonary rehab said, “We’re not doing this anymore because it’s convincingly effective in improving quality of life and exercise tolerance. So just do it.” Unfortunately, it’s not being done—3% to 5%, as Byron said.

 Frank mentioned rural America. There are a tremendous amount of data that have come present in recent years that reveal that people who live in rural America are at far greater risk of having COPD and progressive COPD than those who even live in an urban environment. It’s an area that is really difficult because that’s an area where the number of practicing pulmonologists is frighteningly small. And the number of rehab programs is even smaller.

Progressive Nature of COPD

An overview of current challenges in achieving an early, accurate diagnosis of chronic obstructive pulmonary disease and considerations surrounding referral to pulmonologists.

 Let me jump ahead, and then I’m going to come back to a question I have on spirometry. One is this disconnect that you’re mentioning. One of the things we struggle with at different parts of our careers, whether on the provider side or the payer side, has been this early-versus-late diagnosis and when the PCP [primary care physician] should be pushing the patient to someone with more COPD [chronic obstructive pulmonary disease] experience. I’d like to get your sense on a couple of things. When should you or your colleagues be consulted? And why are PCPs not accurately diagnosing? Why are they resistant to doing spirometry? Not to load up the whole boat here, but I feel like those all kind of go together as 1.

 As pulmonologists, we often feel that our touch matters in almost every case. Let’s start with the easy question. In folks who have persistent symptoms and are headed in a more severe direction, especially when some of the more advanced therapies are indicated, I think at that point a pulmonologist has to at least weigh in. When the usual therapy that a primary care doctor is used to seeing affect the patient is not working, then maybe something unusual is going on that a specialist may have seen more often, and we may have to get them involved.

But I would argue, even at an earlier stage of COPD, for a specialist to weigh in just once. Because often, patients who are diagnosed with many other things are first diagnosed with COPD because it’s so common. Patients present with cough and sputum production, so interpreting the complexities of pulmonary function testing and imaging sometimes can lead us in other directions. A specialist should weigh in once if somebody has a recognized pulmonary disease. As far as long-term management, I think it’s the more resistant, more severe patient. Primary care doctors are more than capable, in most cases, of managing these patients.

 Maria, from your point of view in trying to manage the system—and referral is a part of that, and medication management is part of that&mdash;do you have any limitations on access to pulmonologists? Is it based on certain clinical criteria, or is it more open than that?

 It’s more open. I think that certainly there are limitations in your geographic area. Who is it that you can see? In rural areas, how much access to a pulmonologist or a pulmonary clinic is there? Those are some regional limitations, particularly in rural areas. I think what would be interesting is, especially now with telehealth, to have that ability to check in remotely with a pulmonologist who can weigh in on setting the stage, if you will, in terms of diagnosis, treatment approach, and maybe be part of an annual evaluation that hopefully raises all tides, including what the PCP can do and is able to do and is considering, because you’re absolutely right.

In a world where you have a patient who may have 4 or 5 other comorbid conditions and you’re focused on HEDIS [Healthcare Effectiveness Data and Information Set], Medicare Star [Rating System] measures, A1C [glycated hemoglobin] control, blood pressure, and often the checkoff box with smoking cessation, and there’s not enough time to address all the symptoms, the disease itself becomes important to have a multidisciplinary approach weigh in.

I want to follow up on that thought if it’s OK, Neil. I agree with what both of you guys have said, but it’s complicated because most of the people who are sent to pulmonologists tend to be frequent exacerbators. They’re sick that often. They’re calling their doctors a lot of times. With that constant need for attention, they’re often referred. We see far less of the people who are not the frequent exacerbators but who are gradually deteriorating. You could certainly make an argument that it would be nice to see some of those patients a little earlier on, before they reach the point that they can’t go from here to the wall without getting short of breath. Maybe there might be some things we could add. We don’t see a lot of those.

 The way your practices are set up, you might not know the answer to this question, but do you feel that a fair number of patients are self-referring? Or they’re waiting for their PCP to say you need more help?

 With advanced disease, yes. But with up to even moderate or early severe disease, rarely.

 I think our resources are almost the opposite of what they should be. The opportunity is perhaps to manage this early on, and we do have disease-management programs, usually led by nurses and case managers. But as you get sicker and as you become a higher cost burden, that’s where the tendency is to be able to then focus on that individual. Perhaps there are opportunities early on to be able to control the disease and do a better job?

I don’t want to suggest that COPD is a disease that can’t be managed in primary care. Most of it lives in primary care, and I don’t think Frank is suggesting that we take over the management of all these people. I just think that it potentially provides a little bit of additional guidance when necessary, and it would be nice not to see them at the end stages of their disease.

Accurately Diagnosing COPD

Experts in the field of chronic obstructive pulmonary disease define the role of pulmonary function tests such as spirometry for a diagnosis.

 Let me ask 1 last question before we move over to different forms of therapy, which we have touched on but haven’t really explored: The differences between how you, as clinical experts, use pulmonary function tests and spirometry as opposed to ways that PCPs [primary care physicians] may or may not be using them; and the complexity that they may feel about FEV1 [first expiratory volume in the first second of breath] and forced vital capacity?

 I think Frank would agree with most of what I’m going to say. Attempts to get spirometry widely used in primary care have generally failed in this country. It’s been more successful in Great Britain, for example.

 But mostly it failed. There’s limited time. Oftentimes, we need to have an office staff that’s capable of it. Perhaps even worse, when you’ve looked at the data, they suggest that even those offices that have spirometry stop doing them after a period of time. If you look at the quality of the spirometry that’s done, it generally doesn’t meet the ATS [American Thoracic Society] criteria. So it’s complicated.

Some 12 years ago now—it’s been 12 years that we’ve been working on this&mdash;the COPD Foundation co-sponsored a workshop with the NHLBI [National Heart, Lung, and Blood Institute] on case findings in COPD [chronic obstructive pulmonary disease]. And out of that, over this long period of time, came the development of the technique called CAPTURE [COPD assessment in primary care to identify undiagnosed respiratory disease and exacerbation risk], which is the development of a very short questionnaire&mdash;5 questions&mdash;tying it to a mechanical peak-flow device that is very inexpensive and is widely used in primary care in asthma, for example.

And the publications of several of the studies we’ve done, including 1 in the “Blue Journal” [

American Journal of Respiratory and Critical Care Medicine

] within the last couple of years, are really very impressive and suggest that we might be able to use CAPTURE as a way of better defining who needs spirometry. We’re now in the process of doing another NHLBI study in primary care. We are recruiting 5000 people in primary care to see how this works in a primary care setting. And the potential exists that it could better define for us where we go.

There’s even some interest from the World Health Organization, for example, in areas where there is less medical technology available, where you could envision CAPTURE, potentially using it as a way of defining COPD. This is in part because the majority of people right now are not being diagnosed with spirometry. There is both, therefore, as Maria was mentioning, the issue of both underdiagnosis and overdiagnosis, and therefore the issues of undertreatment and potentially overtreatment. Figuring out a better way to do this, which is what this 12-year process has really been involved in, should be helpful for us going forward.

Pulmonary Function Testing in COPD

Factors to consider when establishing treatment goals for patients with chronic obstructive pulmonary disease.

 I’m going to try to switch to the next section here and move on. We’ve covered a lot on the diagnosis and the basics and have talked about the goals of therapy and escalation strategies. One of the things we have been talking about are nonmedical ways of doing this. We’ve touched on pulmonary rehab, exercise programs, vaccinations, and so on. But now let’s talk about medical therapies. When you’re treating a patient, what is your goal of therapy? And how do you escalate that strategy?

I think the goals of therapy need to be targeted at what is bothering that person in front of you at that time, and they have to be customized. It’s not 1 treatment fits all. We’re hoping we can make even more progress with personalized medicine. But even now, we have different approaches that ought to be uniquely applied to an individual. If somebody has a lot of flare-ups and that’s their major problem—flare-ups are two-thirds of the cost of healthcare in COPD [chronic obstructive pulmonary disease] patients, so they’re really important. Not only do the individuals struggle with it, but it burdens the healthcare system and the providers. That’s 1 thing.

The other is symptoms: shortness of breath with exertion, disability, withdrawal from activity, cough, sputum production. With that I have a line I often ask my patients, that gives me some guidance, because everybody starts at a different level. I ask, “What is the last thing you lost?” We’re going to target to try to get that back. Because in some more extreme cases it’s, “I can’t leave the house anymore to go shopping.” In others it’s, “I can’t do 18 holes without a cart anymore,” and they’re still golfing. So you have to target the individual. What is their limitation? And then it also gives you, as a practitioner, a sense of whether your treatment is effective.

 Let me just restress that, because I think what Frank just said is really unbelievably important. Far too often in the respiratory world, and I do think in medicine in general, we as providers try to set goals. We need to do a much better job of listening to the individual patient and finding out what goals are important to them. Whether they’re the ones Frank talked about, or it’s being able to dance at your daughter’s wedding, or being able to play ball with your grandchildren in the backyard, we need to define what the goals of that individual person are. And then we need to work with them to try to attain those goals. That’s what our job is, and it has gotten lost somewhere in the mix.

Establishing Goals of Therapy in COPD

Considerations for tracking patients’ responses to treatment and achieving treatment goals.

 We’ve been discussing the goals of therapy and escalation strategies, but I know it’s important to you: Tell us the importance of lifestyle modifications and self-management strategies and why you find that important. And then how lung function impacts people’s ability to go through their daily lives.

 The lower the FEV1 [forced expiratory volume during the first second], the worse the lung function, the more symptomatic someone will be, and oftentimes the more limitations there are. The problem is that there’s a tremendous amount of variability. You can have 2 people with the exact same FEV1, and some people function better than other people do. Some of that has to do with their other comorbid conditions. If you have someone with the same FEV1, but 1 person has arthritic limitations in their legs, they’re going to be able to do less than someone else. No one cares. I don’t have a single patient who cares what their FEV1 is. They care about how they breathe and how they function. And our job is to maximize what they’re doing with their lives. Part of that is improving the FEV1 if we can. Much of that is improving their level of function, which can be partly medicines and partly exercise programs and other things.

 You can actually objectively measure FEV1, which is important but isn’t everything. And you can objectively measure the air trapped in their lungs at the end of a breath. And while FEV1 often reflects, when that improves, less hyperinflation and less air trapping, there are many circumstances and well-done studies that show that you can get deflation in the absence of improvement in FEV1.

That winds up that degree of hyperinflation. The barrel chest overinflated, and not being able to exhale completely, correlates with shortness of breath more closely than FEV1. So FEV1 is relevant, but it is not everything. If we get improvement in quality-of-life parameters independent of FEV1 or disproportionate to FEV1, it’s probably meaningful.

 Are you able to get access to any of this data, in terms of trying to make formulary management decisions—whether it’s in the whole or it’s patient by patient&mdash;in terms of whether they can escalate therapy?

 I think now with the apps and the newer tools, it will be interesting to see in heart failure, we’ve been tracking patients. With telehealth, we can track their weights and symptoms, and that comes together into an algorithm that is more timely, meaningful, and actionable in terms of a protocol. It will be interesting, as we start gathering data from apps, to see how this can integrate with care managers, for example, and respiratory therapists, so that between office visits maybe there’s a better assessment. But if this can tie to a protocol or even a referral process, as needed, to a pulmonologist, I think that’s the exciting part.

I have to believe that in the end, as we look at new therapies that are coming forward, pharmacotherapies, it is more than FEV1. FEV1 is objective. But how patients are feeling, and shortness of breath that ultimately leads to… It’s the tip of the iceberg with everything underneath—shortness of breath, how they’re functioning&mdash;so it’s going to escalate to resource utilization, ER [emergency department] visits, and ultimately total costs of care.

Monitoring Response to Therapy in COPD

An overview of treatment algorithms for chronic obstructive pulmonary disease and implications for standardized therapy versus a personalized approach.

 Let me raise what seems to me to be somewhat of a conundrum. I talk to specialists and subspecialists, like yourselves, and there’s a tremendous amount of concern about the patient not being treated as a patient and their goals not being adjusted to. Yet when I go to any of the fancy buildings in Washington with 3-letter acronyms that want to measure healthcare and so on, everything comes back to how closely you followed the guideline, right? And so the plans, the payers—many of them have adopted either the goals or the COPD [chronic obstructive pulmonary disease] Foundation treatment guidelines because that’s what they have to fall back on and that’s what they’re being pushed to use…

I’m going to ask you, Maria, how you’re using those algorithms. And then, where do we need to follow the algorithms for a basic patient, and when do we know to veer away from them? Because we’re having this sort of head butting between personalizing therapy and standardizing therapy, and both are actually quite strong movements.

 And also, the payer is usually not in the role of practicing medicine. And this may have been tied to the formulary—what drugs are available, how onerous we create barriers in terms of using certain drugs or not. But I think the point is a good one. As a payer, this is a disease that has incredible importance in terms of the implications for total cost of care. For the most part, wanting to have access to agents and classes of agents that, according to the guidelines, should be used&mdash;and, if anything, generics are on the lowest tier. We want patients to use them.

But to the extent that there’s clinical inertia, that’s where hopefully data [help] to assist in closing gaps in care or being able to provide meaningful and actionable data to clinicians. They could see that even though they wrote the prescription, that patient never picked it up. Or they’re using the wrong combinations or more rescue inhalers, etc. The payer is an incredible position with data to be able to look at not only variations in care but also gaps in care that hopefully have a meaningful impact on how we can not only personalize but perhaps keep people out of the hospital or ER [emergency department].

 Let me just follow up on that, Maria, because I find it very interesting. Part of the problem, as we mentioned before, is that patients with chronic diseases like COPD have so many other comorbid conditions.

 So it’s not at all unusual for a patient with COPD to have 5, 6, 7 other conditions and to be on 10 to 15 different medications. Anyone who believes that those patients take 10 or 15 different medicines are drinking something. It just doesn’t happen. Even if you’ve got a drug plan, once you start adding 5, 10, 15 different drugs with your co-pays, you’re talking about hundreds and hundreds of dollars a month. It’s an impact with all the things we do in medicine, but it’s particularly an impact in patients who have COPD because of what Frank said from the beginning: People frequently will cut back on their activity level. It’s the reason why there are a lot of data suggesting that even though we have medicines that oftentimes can help, only 30% of people refill a prescription for many of these medicines, because there’s a cost issue as you start adding these 15 different drugs. It’s 1 of the major differences between asthma, for example, and COPD. There are many, but most young asthmatics just have asthma. Most COPD patients, as they go along, have multiple other issues with multiple other medicines. I don’t have a simple answer to that, but it is a problem.

 So let me ask you a question about trying to pull this together. We, as payers, and a lot of provider organizations spend their time bringing the GOLD [Global Initiative for Chronic Obstructive Lung Disease] guidelines, as an example, out to their primary care doctors and so on. When do you deviate from those? And is it based on exacerbations? Is it based on symptoms? Is it based on patient to patient? How do you decide when the deviation from the algorithm is justified?

 One good thing about the COPD-based guidelines—both with the COPD Foundation that Byron has a heavy hand in and the GOLD guidelines&mdash;is they actually do have components of personalized medicine in those. So they do acknowledge that 1 size doesn’t fit all. They’re also not just based on the traditional definer of disease severity, FEV1 [forced expiratory volume in 1 second]. They acknowledge symptoms and exacerbation frequency, and they stratify different therapies based on those. And so those guidelines do allow for some granularity.

As specialists, we don’t worship the guidelines. We recognize there’s even more granularity and make decisions that—I mean, I don’t know when I follow or I don’t follow the guidelines, because as a specialist, I think the guidelines are thoughtful. They help guide therapy, but I feel that there needs to be more flexibility. And so I don’t make a decision to follow or not follow the guidelines. I treat the patient in front of me. The reality is that my treatment is consistent with the guidelines, but there are some variations, I think, as a specialist.

 What Frank said is probably true with most of us. I think the problem is complicated because, for example, if you look at GOLD, and you can make a strong argument that GOLD is the most important program in the COPD world over the last several decades—they deserve a tremendous amount of credit from moving away from FEV1 alone to include issues like exacerbations and symptoms, and I think they provide a wealth of information&mdash;I think their impact has predominantly been on the academic world&mdash;on clinical research trials in academic centers&mdash;with much less of an impact in the primary care world, where I suspect most people don’t know what GOLD is. And that’s problematic when most of your people live in primary care.

I know we’re going to be talking more about the medications that are available. And there are medicines that are available, but I think the data are suggesting that in the primary care world, most of these people are being treated with a combination of a long-acting beta-agonist and inhaled corticosteroid as if they have a variation of asthma. That’s probably not the best approach.

Utilization of Treatment Guidelines for COPD

An overview of the medication classes available for the treatment of chronic obstructive pulmonary disease and recommendations for how to utilize and in whom.

 Let’s use that as a segue to jump into some of these medication classes. So thank you for that nice segue. We have a class of the short-acting bronchodilators. An example of that would be albuterol. But then we have 3 types of maintenance classes: the LABAs [long-acting beta-agonists], and an example would be salmeterol; the LAMAs [long-acting muscarinic antagonists], where an example would be tiotropium; and the inhaled corticosteroids [ICS therapy], where you might see fluticasone. What I’m curious about isn’t so much how you look at those drugs individually but, based on what you just said, the use of those in combination. Where do you see the use of those, and where do you think dual combination makes the most sense?

 The first, most important point that I would like to get across to primary care providers—and databases tell us that we have a lot of progress we need to make&mdash;is that COPD [chronic obstructive pulmonary disease], with rare exception, should be treated with long-acting maintenance drugs, OK? Now, which of the 2 or 3? We’re going to have further discussions. But what that means is it’s not an as-needed albuterol or as-needed Combivent [ipratropium/salbutamol]. These drugs are gone in 3 to 6 hours, and patients rarely take enough to cover them throughout the day. That impacts not only their symptoms but exacerbation frequency. We have proven that long-acting inhalers, meaning twice-a-day or once-a-day inhalers&mdash;and the 3 classes are long-acting muscarinic antagonists, long-acting beta agonists, and inhaled corticosteroids in various combinations&mdash;all have proven to decrease flare-ups, which impact their lives and impact the cost of healthcare. So No. 1, long-acting bronchodilators. Everything else is an important nuance, but that’s climbing the mountain.

 I agree with what Frank says. There are, as Frank says, guidelines that are available to us, and there are nuances that differ between guidelines. Their overall approach is the same, with the concept that short-acting beta-agonists, which are a mainstay in the treatment of asthma, for example, are not the mainstay in the treatment of COPD. COPD should be treated with maintenance therapies. Most of us start, in more mild disease, with the long-acting muscarinics that Frank was talking about. And GOLD tends to suggest that you start with 1 and add as you go.

 That was my next question. Is that really what you’re doing?

 I think Frank and I do the same thing. If I’ve got a patient with significant disease and significant symptoms, I’m actually starting them on a LAMA and a LABA at the same time. I think the evidence demonstrates that those drugs are more effective than either of the agents alone. And thankfully there’s no evidence that there is increased risk of those agents alone. And the data on the third group of drugs that we have, the ICS, suggests that predominantly, if not completely, they are for those patients who have more frequent exacerbations.

All this may change as we go along. Part of the problem is we all understand that in many people, particularly with the airway disease, with the bronchitic component, there’s a major inflammatory component. And steroids may not ultimately be the best choice for that—inhaled corticosteroids. These are things that we talk about, but I think the mainstay of therapy are LAMAs and LABAs, and then we add on from there. I assume you agree with that?

 Let me ask you a question as just a lowly internist here. Who gets the LABAs and LAMAs, and who gets the LABAs with corticosteroids? Which types of patients end up on which therapies?

 In asthma, I always says you lead with the inhaled corticosteroid to shut down the symptoms. And often, those patients no longer have obstruction. They don’t even need bronchodilators, except for, as Byron said, as-needed short-acting for symptoms. In COPD, they are incompletely reversible by definition. Even when you maximally treat them, you can’t completely reverse them. And that often is associated, regardless of how well you treat them, that you can improve symptoms but you can’t eliminate symptoms.

So we lead with the long-acting bronchodilators. And Byron and I both feel similarly that in patients who often present—certainly to pulmonologists but often even to primary care doctors&mdash;they’re in the more moderate to severe stage. You could slowly work your way up to maximal treatment, but in almost all cases, they’re all going to be on both the LABA and the LAMA. And so very often we’ll start the LABA and LAMA, which means that a LABA/ICS is almost never the right thing to start with.

In somebody who has symptoms and is frequently exacerbating, or some of us are looking at eosinophil counts as a guidance. We’ll go with a LABA/LAMA and the inhaled corticosteroid right out of the gates. But in almost all cases, we work our way up to LABA/LAMA. That is fundamental to patients with moderate to severe disease with persistent symptoms across the board. The ICS—I’ll let Byron begin to describe the nuance, and when we want an ICS and when we don’t. But I think the bronchodilators maximally bronchodilated is fundamental to all patients who have persistent symptoms.

 Yeah, I would agree with that completely. The interesting thing is that not only is the LAMA/LABA oftentimes very effective in their symptoms, but there’s evidence suggesting they’re reasonably good for exacerbations as well. Now, if you have someone with ongoing exacerbations, then you would think about adding the ICS component. If you have somebody with really quite severe disease, I would suggest that many of us have pathways in our hospitals on how to deal with that. I think that if you have someone who’s been bad enough with bad enough disease to be hospitalized, you could make a pretty strong argument based on some of the data existing now that they should be discharged on a triple regimen. I think that is a possibility.

The only other thing I want to bring up—and I’m not trying to confuse anybody, but it does come up in primary care a lot&mdash;is the confusing issue of an overlap between asthma and COPD. What is the difference between it? And I’m sure, Maria, you deal with this a lot from your standpoint. It’s complicated because for a primary care doctor, even for a pulmonologist who’s been in practice for many years, as Frank and I have, it’s sometimes not completely clear. That’s a subset that primary care might look at and say, “I don’t know for sure what it is. I know it’s important to have an inhaled corticosteroid in the asthmatic population, so it’s just easier for me to use that.” That comes, again, to education and defining the nature of the diseases you’re dealing with.

COPD Treatment Selection

A payer perspective regarding the utilization and coverage of combination therapies for the treatment of chronic obstructive pulmonary disease.

 I want to address some of the things we’ve been talking about here, in terms of a lot of payer formularies are based on guidelines. In this case, GOLD [Global Initiative for Chronic Obstructive Lung Disease] is the most common. So how does the GOLD guideline or anything else affect your formulary in terms of stepwise management, and going from 1 to 2 to 3? And do you even approve triple therapy?

 We try to be evidence based. The role of national guidelines plays a role to the extent that they outline what categories—what LAMA/LABA [long-acting muscarinic antagonist/long-acting beta-agonist] combinations or ICS [inhaled corticosteroid] combinations based on mild, moderate, and severe disease. Obviously that’s overarching. When we’re in a P&T [Pharmacy and Therapeutics] committee and we’re looking at a drug, we’re starting with: What’s the category? What’s the mechanism of action? But we’re also looking at what the efficacy is in clinical trials, particularly around exacerbations.

We’ve moved beyond FEV1 [forced expiratory volume in 1 second], and we really are looking at what the impact is on exacerbations. In the end, that’s also the big impact on total cost of care. We’ll certainly also look at safety, including black box warnings. Obviously, if 1 drug has a black box warning and another does not, that’s an area of differentiation. We do have pulmonologists who are practicing, also part of that committee, to give us exactly the kind of feedback that we’re getting here in this discussion. In the end, generally speaking, in the area of COPD [chronic obstructive pulmonary disease], it’s about choice. And 1 of the things I heard from both the thought leaders here is there needs to be choice to be able to individualize what that patient needs based on symptoms. Although not everything is tier 2, unrestricted—tier 2 is typically nonpreferred&mdash;there are usually options on a preferred tier that satisfy, if you will, the need for some individualized choice across different classes.

Some payers are actually covering the triple combination. I think we all recognize that for some patients—and probably those who are most severe, in order to keep them out of the hospital, out of the ER [emergency department], and better controlled&mdash;that convenience and adherence may tie together. That’s what success is going to look like if we’re going to manage to total cost of care. Others may put some more restrictions or perhaps move the triplet to a nonpreferred tier, which has cost-share implications for patients, but I think you’re seeing some also recognize there’s value in choice and maybe also an opportunity for contracting. That said, I think we’ve recognized the importance of managing COPD [chronic obstructive pulmonary disease] and doing a better job in choice and access to remove barriers to patient adherence.

 Let me just throw out 1 thing, which is 1 of the things we found across a number of my roles. A lot of times when these switches happen, it wasn’t that the plan was switching. It was that the employer was carving out to a new pharmacy manager. There was nothing we could do. They made a business decision. I know that from your point of view, it’s all just the insurance company, right? I understand that, but sometimes it’s taken away from us.

Wherever the decision is made in the pathway, we’re all in this to try to improve the care of the people we’re taking care of. I think it’s just really important to understand that if you don’t know how to use the devices you’re using, that’s problematic.

It’s also, by the way, extremely frustrating when we get a request to say that this LAMA/LABA isn’t available and 1 of the choices is Combivent [ipratropium/albuterol], which is a short-acting LAMA/LABA but is not part of a maintenance therapy. It doesn’t provide many of the other things. When you get the request form from wherever it’s coming and it says you can switch to, and this is 1 of your options, it suggests a lack of understanding, which is problematic.

 Yes. But also, like Byron said, I think it is our problem when we’re paying for a drug and patients aren’t taking it correctly. So [we go] back to the point of training. And if there is a switch, what can we do? We have disease management. We have clinical pharmacists. We now have technology that can do maybe a Skype video to help train patients appropriately. I would actually put the onus on us, collectively, to say, “What are some ways we can overcome some of these training issues?”

And having inhaler videos available within the app or a different portion, perhaps. Potentially getting pharmacists who work in CVS and Walgreens to show the person how to use the different devices. But we have to get away from this issue of somebody has changed their drug and they’re not using it.

Before we leave this issue, I do have a question for Frank. There are data suggesting that, particularly in people who have more severe disease, they don’t have the inspiratory force to get some of these drugs in. Should that play a role in the decisions we’re making?

 I would broaden that a little to say that different patients seem to sync with different devices. Some of it is cognitive related, dexterity related—severe arthritis. Some of it is inspiratory flow rate. To answer your specific question, there has been some discussion that particularly the more severe patients&mdash;small, petite women in particular&mdash;may have trouble activating some of the dry powder inhalers.

I can tell you that there’s truth in that, and it has to be recognized. But as in many things, it may have gone too far and needs to be pulled back. I think some of the patients with more severe disease, especially with variable rates and especially if they’re not educated on how to use the devices, can get below the inspiratory thresholds. In some cases, nebulized therapy is indicated in patients who can’t coordinate with devices in general or who are particularly arthritic.

In general, dry-powder inhaler devices actually are preferred by patients, and they’re the easiest to use. So you have to balance this contradiction. And so the answer to that is, if the medicine doesn’t get down in your lungs because you don’t know how to use the device, it’s not going to do well. And different patients sync with different devices. I’m a big fan of a redundant formulary, and I always make that argument to have at least a couple of choices.

Let me just follow up on that, because I think it’s really important. It’s our job, as providers, at whatever level we’re providing, to provide something that works best for our patients. While we have a limited number of types of drugs that are available, there are a number of different ways they can be delivered. If you find someone who’s struggling, you can often find a different approach that can work with a different variation of the drug using a different device. Over the last year or 2, there have been a couple of nebulized LAMAs that have finally gotten into the formulary. So there are options available. Clearly, a single device—you know, once a day&mdash;would be ideal. It may not be ideal for every one of the patients we’re dealing with.

Coverage of Combination Regimens for COPD

Clinical measures that can be useful in identifying patients appropriate for a recommended chronic obstructive pulmonary disease treatment strategy.

 Let me ask you to hold that thought for 30 seconds, because we’re going to come right back to exacerbations. I have some questions about how we measure those and the proper way of doing so. But before I do that, I want to just finish the last topic with you in terms of—not just you, but as an industry&mdash;do you think this is allowing for a LAMA [long-acting muscarinic antagonist] or LABA [long-acting beta-agonist] to be started together and then add therapies? Does it have to be 1, and then 2, and then 3? What are you seeing out there?

 What I’m seeing is this is a disease with pretty significant consequences and very high costs. I don’t see the appetite for payers to really prior authorize. You know, start with 1, and move to 2, and move to 3, and sequence. I see choice within each category, which I think speaks to the need to be able to somewhat individualize therapy. I see greater opportunities certainly on, “Let’s make the diagnosis,” and the unmet need in terms of even understanding who has the disease and who does not.

I also see that real-world data help us all understand the magnitude of benefit of what triplets may bring, particularly for a moderate to severe population. That’s what I see—the opportunity, and really some of the discussion around maybe an algorithm that cuts through the chase in terms of how you medically optimize someone. That’s what I think the appetite is. It’s around, how do we impact total cost of care as well?

 I’m curious about a number of different things. Can you identify ahead of time who you think is at increased risk? Whose definition of exacerbation are you using? Does the patient have to be hospitalized? Do they have to have gone to urgent care? Can it just be their description of a really bad day at home? How do you define exacerbation as you’re saying things like, “Well, if they have more than X number of exacerbations, we should consider adding an ICS [inhaled corticosteroid].”

 We’ve had these intellectual debates onstage that the COPD [chronic obstructive pulmonary disease] Foundation has sponsored with patients in the audience. If you give the patient the chance to go to the microphone, they’ll say, “You know, you guys can debate all you want what an exacerbation is, but I’ll tell you when I’m having one. I know it.” That’s probably right. When they call in and say, “I’m having a flare-up. I’m more short of breath.” Or “I’m bringing up more sputum and coughing more. What can you do for me?” That’s an exacerbation. It’s a change in symptoms. And the pure definition usually correlates with that—a change in symptoms for at least 2 days that warrants an escalation in therapy.

 There are 2 paths to look at that, right? One is, what is that effect on lung function in terms of clinical progression? But the other is the effect on quality of life. And trying to pair those together. What do you concentrate on and focus on in the office?

 Well, we do understand that exacerbations are bad things. The more frequent they are, the worse it is. They have more airway inflammation, there’s more rapid deterioration of lung function, and in those who are frequently exacerbated—2 or more a year&mdash;there is a mortality risk over the course of time. It’s certainly something we aggressively need to treat. Indeed, we have medicines that are available that can make a difference, whether it’s a combination of bronchodilators and inhaled corticosteroids. Or if you’re continuing to exacerbate, consideration of things like roflumilast, which is an oral drug that’s available, or erythromycin, which potentially is an immune modulator.

It’s important for everyone to understand that we actually have a number of different therapies available. Being aggressive and trying to prevent those exacerbations is really a critical issue, not just from the standpoint of cost—although it’s a critical issue from that standpoint&mdash;but from the issue of quality of life, continued quality of life, and length of life as well.

 We’ve talked about lung function and, in general, quality of life. What is your ability to look at exacerbation rate and things like improvements in activities of daily living with the data that you have in terms of helping to support or deny different types of therapies?

 Well, we have claims data. We have utilization data on the pharmaceutical side. We have claims data on hospitalizations, on ER [emergency department] visits. What I find fascinating is, there’s a lot of interest in patient-reported outcomes [PROs]. Can the PRO, in this case, predict an exacerbation? And if we actually were able to capture this data? Perhaps it’s more real-time tools like mobile apps that can integrate into disease management and, hence, define the protocol or the referral, or when the patient is actually seeing a provider.

 Exactly. I find the elements of PROs that actually have a predictive ability and are meaningful and potentially impactful on what can be done to prevent that exacerbation to be sort of at the forefront of what we can then do to translate these PROs into better care at the right time to prevent that exacerbation.

 Just to reiterate something you said, to make sure we’re getting it, absenteeism is reasonably easy to measure. Productivity is very hard to measure, and presenteeism is very hard to measure.

 And the payer may not have that data at all.

 The employer may, but it’s very hard to merge. They exist with different entities. The health plan, unless it’s their own employee, may not have absenteeism data, for example.

Opportunities to Optimize Care in COPD

Preferences for combination regimens for the treatment of chronic obstructive pulmonary disease and important considerations when selecting an appropriate regimen.

 You guys have covered the whole waterfront, and there are like 1000 follow-up questions I want to ask. Let me just narrow it down to a few of the important ones. One of the things I’ve been trained to do, when we start talking about the benefits of combination therapy, my job is to say, “What are the risks of it? Are there significant risks, and do we need to be concerned about it?” Then I want to come back to you in terms of working your way up to combination therapy and how you manage against the guidelines. But let’s start with the risks and then see if those are impacting these decisions.

 The 1 risk that I take into account lends to asking why even worry to add the ICS [inhaled corticosteroid] on to the double? Because it might help or it might not help. But the fact is that 2% to 3% of patients per year on ICS therapy can get pneumonia. If you’re eliminating 25% of the flare-ups, if you pick the right patient, that may be a risk that the system and the patient is willing to accept. But there is that risk of immune suppression and a minor infection spreading into a pneumonia.

With the long-acting bronchodilators, I’m with Byron. There’s a lot of theoretical literature. Certainly, we know there’s a small signal with regard to cardiovascular disease and sudden death. But I always say that in a baseball stadium, you pick out 3 people in a year and they may not do well. The rest of them feel better. Is that a choice you’re willing to make? Actually, the biggest problem I see with the LAMAs [long-acting muscarinic antagonists] in men who have borderline urinary retention with prostate problems is that we can tip them over. So I’m careful in that situation. Those people weren’t included in the clinical trials, by the way, but they come to my clinic. So I am a little cautious sometimes with the anticholinergics. But in general, the LAMAs and LABAs [long-acting beta-agonists] are extremely well tolerated.

 No. The only thing I would add is that while the pneumonia concern is the greater concern that I have, ICS has been potentially associated with some cataracts and eye-related issues. There’s a potential issue with your bones if you’re using high enough doses. Like any other medicine, you have to balance the risks and benefits of everything that you’re going to use. In general, the medicines we have available in COPD [chronic obstructive pulmonary disorder] are very well tolerated and reasonably effective in what we’re trying to do. That doesn’t mean we don’t need better. We do. We need to define therapies for specific types of disease, but it’s helpful.

I will come back to an issue that we haven’t discussed, and I’d be interested in Frank’s take. We talk a lot about advancing therapy. Going from LAMA/LABA to triple, there are some situations where you might go to triple faster. But if you have someone, for example, Frank, who isn’t a frequent exacerbator, who comes to you and who had gotten stuck on triple therapy, recognizing that we both have some concerns about that, there are potential arguments and there are studies that have suggested that you might be able to cut back on the dose. That’s 1 of those areas in which maybe that eosinophil count that you talked about before might help you a little, isn’t that right?

 Yes. I’m a believer in looking at the CBCs [complete blood counts] that are over their chart. Often, they’re gathered during exacerbations, but you’re describing patients who don’t exacerbate. But it’s a rare patient who, at some point, didn’t get a CBC. If you look at the eosinophil count, that little count that we just kind of ignore—it doesn’t mean a whole lot, and it has something to do with parasites, maybe asthma&mdash;if it’s under 100, then they’re probably not going to benefit a whole lot from inhaled corticosteroids.

Certainly, I would never put anybody who has no history of exacerbations and 100 or fewer eosinophils on an inhaled corticosteroid. And the counter to that, if somebody comes in without a flare-up history, I’m probably going to convert them to a LAMA/LABA if they’re symptomatic and dyspneic.

 Do you guys prefer the fixed-dose combinations, or do you prefer to ramp up with 2 different inhalers?

 You never want to give people 2 different inhalers if you can avoid it. It’s hard enough to get people to learn how to use 1 inhaler. I actually think that’s an area that we need to talk to Maria [Lopes] about, because it’s increasingly an issue.

 What happens is, you train your patients on how to use it. One of the advantages of the mobile app that the COPD Foundation has come up with is that we have all the inhaler videos available for people to look at. But you teach someone, they know how to use an inhaler, and 2 months after you’ve seen them, their insurance company has changed the formulary and they’ve switched them to a new drug that has a different device. If you don’t know how to use the device, you’re wasting your time.

Combination Therapy for COPD

Recommendations for utilizing triple therapy in patients with chronic obstructive pulmonary disease.

 I’d like to start to move us toward the part here where we get to the burden of disease on patients and measuring exacerbations. We’ve covered a tremendous amount of this, but just to bring this together—this discussion about combination therapies and so on&mdash;I have a 2-part question for everybody. When do you consider triple therapy, and what is your advice to PCPs [primary care physicians] who are flirting with the idea of triple therapy?

 I think that the answers to that question are, if you have someone who continues to struggle on a LAMA [long-acting muscarinic antagonist] or LABA [long-acting beta-agonist], with continued exacerbations and continued problems with everything, then moving toward triplet therapy is a perfectly reasonable approach.

 The eosinophil count has greater negative predictive value. With a low one, you’re much less likely to get a benefit from the inhaled steroid.

 Yeah. In somebody who’s just been on short-acting inhalers or on nothing, when do you start it? Or it’s easier to say, when you increment from a double LAMA or LABA, OK?

 That’s somebody who continues to exacerbate, particularly if they have high eosinophil levels. So it’s a no-brainer. You’ve had 3 steroid tapers, or 1 hospitalization, and your eosinophil counts are greater than 200. There’s no controversy. That person needs to be on triple therapy.

If they just had 1 or 2 outpatient exacerbations and they have lower eosinophil levels… Now, in somebody who’s a frequent exacerbator—2 or 3 exacerbations&mdash;with hospitalizations&mdash;1 or 2&mdash;we’re going to give a trial of an ICS [inhaled corticosteroid] on top of the LAMA or LABA to see if we can suppress that. I know we like rigid cutoffs and rigid guideline therapies, but in reality, we’re factoring in multiple different components of this disease in ultimately making that decision.

Right out of the gates, it is a little different of a story. Again, I think for somebody who comes in with frequent exacerbations and high eosinophils, I might start them straight on the triple. But for somebody who’s had a couple of exacerbations and they’ve been on only short-acting bronchodilators, they need to be maximally bronchodilated and may not need the inhaled corticosteroid. Often those folks will start with a dual bronchodilator and then consider the ICS down the line if that doesn’t hold them.

 I think we all agree with that. The 1 issue that is complicated is the person who has not been adequately treated who comes in with a hospitalization. We recognize the power of those hospitalizations, from not just what happens to the quality and indeed the quantity of lives of these people going forward but the cost issues involved as well—the issue of rehospitalization and stuff. Certainly, arguments could be made that in that subset it may be important to think about moving to the triple therapy sooner.

Triple Therapy for COPD

Stakeholders in healthcare consider the implications for treating chronic obstructive pulmonary disease with triple therapy based on data demonstrated in the IMPACT and FULFIL trials.

 One of the things we need to touch on as we have this conversation is that there were a couple of reasonably large studies on treatment of COPD [chronic obstructive pulmonary disease] recently: the IMPACT trial and the FULFIL trial. I was hoping we could walk through those. I’m going to ask you to start with the IMPACT trial and discuss a combination of the patient population, the efficacy, and then, more important, exacerbations and quality of life.

 The IMPACT trial is an interesting trial in part because it’s a very large trial. We’re talking about 10,000 people. That’s not very large in our cardiology study, but it’s a very large study for COPD. There are relatively few studies with that number of people. I think that’s important to start with.

What the IMPACT trial did was it looked at basically 3 groups: People who were on a LAMA [long-acting muscarinic antagonist] or LABA [long-acting beta-agonist], people who were on a LABA or ICS [inhaled corticosteroid], and people who are on triple therapy. In this trial, at least, the triple therapy was clearly better than either of the 2 others, from the standpoint of both exacerbations and symptoms. There was even a suggestion of a mortality benefit. So the results were very powerful.

In this particular trial, it looked like the results from LABA/ICS were a little better than those of LAMA/LABA, which is different from what we’ve seen in other trials. When you see that difference, you need to look at who is being studied, how it’s being studied, and what the washout period was like beforehand. It’s complicated to look at it. It doesn’t necessarily mean that 1 study was good and 1 study was bad. But I think the major take-home point from the IMPACT trial is that there is certainly a subset of patients with COPD who would clearly benefit from triple therapy.

 Were there any concerns about safety that were raised?

 There is always the issue of pneumonia with the addition of the inhaled corticosteroid. It was not a major issue in the IMPACT study. It’s important to recognize that in every study where that has been shown—that there’s a pneumonia signal&mdash;pneumonia doesn’t seem to have impacted the quantity of life. They don’t seem to be carrying a mortality risk. But that doesn’t mean they’re not an issue, and it doesn’t mean they couldn’t. As we’ve discussed before, every time you add a medicine or a combination of medicines, you to need to view it and weigh the benefits and risks of that. But there are certainly data suggesting that in a subset of the COPD population, the triple therapy is beneficial.

 And they looked at both exacerbations and quality of life as well?

 And so if we could, let’s move on to the FULFIL trial.

The FULFIL trial is a little bit of an older trial. What it did was look at the triple therapy, a once-a-day, 1-puff-a-day triple therapy versus a commonly used double LABA/ICS, of which none of us feels that ought to be a primary therapy. In part, it’s influenced by these trials. So it’s comparing LABA/ICS twice a day with LABA/LAMA/ICS once a day.

The way this trial was designed, I recall about 1800 individuals were randomly assigned after measuring them on whatever their usual therapy was. Whatever they came in on—whether they were inappropriately just on short-acting, whether they were on a single anticholinergic, whether they were on a LABA/ICS, or whether they may have been on a triple&mdash;didn’t matter. They were then randomized to either the triple or the LABA/ICS twice a day. And the primary outcomes in this trial were quality of life&mdash;the St. George’s Respiratory Questionnaire&mdash;and FEV1 [forced expiratory volume in 1 second].

The triple outperformed the double in all categories. A secondary outcome measure that wasn’t even the primary, at 6 months, was exacerbation rate, and results also showed a better reduction in exacerbation rates with the triple compared with the LABA/ICS. Both of these studies highlight that LABA/ICS is not the appropriate therapy for patients with this disease.

 Same follow-up question: Any concerns about safety raised by this trial?

In this trial, all patients were on a bronchodilator and received inhaled corticosteroids. The only difference was 1 group had the LAMA. No, there were no safety issues comparing those 2 groups.

Triple Therapy in COPD: IMPACT and FULFIL

The role of assessing and measuring patients’ feedback to improve how chronic obstructive pulmonary disease is managed.

 For both of you, let me ask this question: Because clinical practice and trying to fit patients in while doing research and other things can be challenging and hectic, are you doing PRO [patient-reported outcome] data collection in your clinics or offices?

 With the COPD Foundation, we’re doing it all the time. In my clinical practice, a little less. That’s my honest answer.

 We have incorporated smart tablets in our waiting room, for patients to fill out forms. We sometimes have problems consistently giving a tablet to them and getting it to work, but we’re getting better. But yes, they’re helpful to track it over time to see. This little mobile app that Byron has an easy-to-use CAT [chronic obstructive pulmonary disease assessment test] score. I give it to them often while I’m doing the physical examination, listening to their lungs, and they have to click 8 slots, on a scale of 0 to 5, and you come up with your CAT score. Greater than 10 is a symptomatic patient.

 Let me ask you a question, and I’ll give you a hypothetical based on 1 of the examples you gave earlier. The guy who can do 18 holes of golf only if he used the cart is now feeling well enough that he can do 18 holes again without using the cart, or maybe 9 holes. But he’s showing improvement. You’re not really seeing a lot of difference in his PFT [pulmonary function test] scores. What do you do with him?

 It depends whether they’re maximized or not. I think you do the happy dance and say, “We’ve actually got a marker that says we’ve made progress.” This is management of a chronic disease. You don’t completely eradicate their symptoms or their physiological abnormality, but you optimize their quality of life and their function. You add therapies if they still have residual deficits, until they don’t improve any more, and that’s what we try to do.

Pulmonary rehab is not just exercise. It has breathing techniques. It is a social network. It’s 1 of the issues, Maria, that you were talking about in doing telemedicine. Considering where we are with pulmonary rehab, I think we all agree that we need to figure out a way to get that more into their homes. The 1 concern with that is you lose that social component of pulmonary rehab, which is very important. But pulmonary rehab exercise is really a critical issue going forward. Again, it helps the person in many, many different ways. People need to understand that this is almost always a preventable and treatable disease, and we need to do a better job doing those things.

 Let me ask you a follow-up to that, which is, where are the differences between how your patients perceive improvement versus how you perceive improvement? Are there significant differences?

 It’s all about what the patient perceives. If the patient doesn’t feel they’re doing well enough, then I need to do more. It comes back to, again, the concept of goals. In the mobile app that Frank mentioned before, there’s a provider component to it, but there’s now a patient component to it as well, where they can put in their goals and work toward achieving those goals. But it has much less to do with me than it does with them. If they’re not satisfied, then I need to do more. As Frank can tell you, there are times when there isn’t any more we can do. But before we leave this point…

 I don’t want to leave the point. I want to follow up.

 I think it’s important to understand. We talked a lot about medicine. We talked a lot about exercise programs. There are a couple of other things just to put on the table.

 Just to add a little to the question you asked, what if you think they’re doing better, but the patient says they’re not doing better? Often, the patient is right and you’re looking at the wrong thing. If you’re looking and say, “Well, your FEV

 [forced expiratory volume in 1 second] is a bit improved, and it’s stabilized.” But the patient says, “I don’t sense it. I don’t feel better.” Well, the thing limiting them may not be their lung mechanics at that point. It may be, leading into what Byron said, that they’re desaturating, or they have pulmonary hypertension, or they have cardiac comorbidity. If those are the dominant limiting factors, then improving their lung function a little isn’t going to make a huge difference. Or if it’s the flare-ups with the exacerbations, the day-to-day variability that bothers them the most, and the cough and sputum, that may not be reflected by a little improvement in lung function.

Patient-Reported Outcomes in COPD

Implications for treating chronic obstructive pulmonary disease with combination regimens based on clinical data and how the condition will likely be managed in the coming years.

 We’ve been talking a lot today about all of these different things, but we had a significant section on combination therapy and triple therapy. I’m going to start with you, Maria, and ask, have you felt that there are enough data to support that combination or triple therapy improves health outcomes and has the potential to lessen cough?

 I think there are. There’s no question that pharmacotherapy is having a major impact on not only symptoms but the reduction of exacerbations. We see this from a lot of the studies from when these first drugs even came out, much less than in the real world. I think many have proven themselves to have an impact on exacerbations and, ultimately, our visits as well as hospitalizations. That’s part of what we usually want to see at launch, as well as even in the real world—the ability to understand what that impact is on total cost of care.

 What do you think the patient perspective is on the use of combination and triple therapy, and how it’s affecting them, and whether or not it’s lessening their healthcare utilization?

 There are 2 components. One is, if it makes them feel better, they love it. They’re happy. The other side is, if it reduces risk, they may not immediately perceive that. That’s like treating cholesterol or hypertension. That takes some education to get compliance. If you’re adding an inhaled corticosteroid to a dual bronchodilator, they may not perceive an immediate benefit from that. You need to tell them, “I believe this is going to reduce your flare-ups. It’s going to stabilize your disease.” There has to be an education piece. They have to understand why they’ve added that, including maybe that expense or the need to use a couple of inhalers at times.

 I have to say, this has been a great conversation and a really outstanding dialogue. I think people are going to get a lot out of this. Before we conclude, I’d like to get a final thought, maybe just a couple of sentences—the major point you want to get across, or something like that, or something you found particularly interesting or newsworthy that came out of our conversation today. I’ll ask you to go first, Maria.

 There is tremendous opportunity in COPD, on both the prevention side as well as treatment optimization. I have heard some great comments and feedback from thought leaders around how PROs [patient-reported outcomes] are being instrumental in understanding and assessing what the patient’s symptoms are. But also, how do you individualize goals? Hopefully that not only creates a meaningful impact but really optimizes care and the care delivery as well as impact on total cost.

 It’s important to recognize that we can do something with this disease. Unfortunately, this disease has often been stigmatized to former smokers. It’s been defined as irreversible. But the reality is that many diseases in our society are based on just human errors, human activities. We should not stigmatize these patients.

The data show we can have impact on how they feel, and we can have impact on the cost of the healthcare system and the burden. We need to take them seriously, treat them, do evidence-based therapy, and not treat them as we did 30 years ago with just short-acting bronchodilators and steroids. Those are the wrong treatments.

COPD Treatment Updates: Impact on Daily Life

EP 1: COPD Disease Burden

EP 2: COPD Defined

EP 3: Characteristics That Help Diagnose COPD

EP 4: Progressive Nature of COPD

EP 5: Accurately Diagnosing COPD

EP 6: Pulmonary Function Testing in COPD

EP 7: Establishing Goals of Therapy in COPD

EP 8: Monitoring Response to Therapy in COPD

EP 9: Utilization of Treatment Guidelines for COPD

EP 10: COPD Treatment Selection

EP 11: Coverage of Combination Regimens for COPD

EP 12: Opportunities to Optimize Care in COPD

EP 13: Combination Therapy for COPD

EP 14: Triple Therapy for COPD

EP 15: Triple Therapy in COPD: IMPACT and FULFIL

EP 16: Patient-Reported Outcomes in COPD

EP 17: Treating COPD With Combination Therapy