COPD: What are the Available Guidelines and Agents?

Peter L. Salgo, MD: You’ve got to morph this, also, into, what can we do about it? It does you no good to make a diagnosis unless you’ve got something to offer, right? This brings us to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) and the COPD Foundation treatment algorithms. Fernando, can you run through those?

Fernando J. Martinez, MD: Yes. It’s clear that there has been nihilism in this disease. There’s no question about it. There’s been a pejorative component, in terms of the exposure history. All of that is correct. But having dealt, personally, in my family with severe COPD, it is also important to realize something that all 3 of my colleagues have said—in contrast to even the previous “definitions” for COPD, the definitions have been changed and have been changed to incorporate 2 important concepts. It’s preventable and it is treatable across the spectrum of disease. And so, when you look at what’s occurred, in terms of the multi-specialty guidelines, whether it’s the COPD Foundation or work of the GOLD group, which is an international group, all of those have worked under the same paradigm—preventable and treatable. The complexity of treatment is there because it’s a heterogeneous disorder. There’s a very rigorous approach that has been taken by all of those recommendations to point out that, at every stage of COPD, no matter where you diagnose the patient, you have therapeutic interventions that clearly can make the patient feel better and can have implications in terms of what occurs in their disease over time. Those are crucial concepts.

Peter L. Salgo, MD: So, you can address the progression of disease? You can address exacerbations?

Frank C. Sciurba, MD, FCCP: Yes. One of the factors that bridges that last question to this is that it’s not just the symptoms that they say. You have to probe the discussion with these questionnaires. Some of these folks are still smoking. They don’t want to have that lecture. They know what’s coming next, and often what happens is they suppress, even in their own heads, that they have symptoms. They start withdrawing from activity. They do less and less. If you just say, “Do you have symptoms?” they may say, “No.” And you say, “What are you doing?” “Well, I sit on the couch all day.”

Peter L. Salgo, MD: It’s like claudication, right? “I don’t have claudication.” “How much do you walk?” “I stopped doing that.”

Frank C. Sciurba, MD, FCCP: Exactly. And if you don’t find out what they’ve withdrawn from, or what happened to their quality of life, you’re not going to elucidate that they have an impairment. It’s not just shortness of breath and cough.

Fernando J. Martinez, MD: Capture is just one of several instruments that have been developed. I don’t know if you had noticed the same thing when you developed that type of a simple approach, 5 questions, something simple for primary care. You included primary care clinicians and patients, but patients said that, “You’re not asking this correctly.” You need to be asking the questions the way Frank just said.

Peter L. Salgo, MD: What strikes me is a paradigm from the aviation industry. Somebody at Boeing finally woke up and said, “Why don’t we ask pilots what they’d like in a cockpit?” They got a vastly different answer than what the engineers were providing.

You were talking about therapy, and everyone has been alluding to the point that we finally have something that works. We have a whole class of things that do work. We’ve got all kinds of drugs. There are short-acting bronchodilators, long-acting bronchodilators, muscarinic receptor antagonists, and inhaled corticosteroids. Why don’t we start, in a very organized way, by running down this list? The short-acting bronchodilators? Can you give me an overview of this class?

James F. Donohue, MD: Something that has changed is the phrase “partially reversible.” In the past, we used to think it was inexorable and irreversible. So, finally, people have actually looked at the patients and have made some measurements. There is a component. It’s not asthma, but it’s a little bit like asthma. The short-acting agents can be used in COPD, first, as rescue therapy, and that’s what the GOLD guidelines say. And, there’s beta agonists like albuterol, and antimuscarinic, short-acting ones, like ipratropium. Those agents also, as opposed to asthma, can be used regularly. If you want to use them regularly, although there’s no reason to because we have better, long-acting agents.

Peter L. Salgo, MD: For the sake of this discussion, we’ll call the short-acting bronchodilators “SABA,” as opposed to long-acting bronchodilators, “LABA.”

James F. Donohue, MD: Correct. The LABAs will last for either 12 or 24 hours, by the FDA definition of a long-acting agent, and we have many of them. For the muscarinics, the first one was tiotropium. Now, we have umeclidinium, aclidinium and glycopyrronium. So, there is a whole variety of them. They’re all fairly similar in efficacy.

Peter L. Salgo, MD: In other words, there are long-acting bronchodilators, which are LABAs.

James F. Donohue, MD: These are the muscarinics.

Peter L. Salgo, MD: There is a distinction there, between the long-acting muscarinics?

James F. Donohue, MD: Right. The muscarinics block the cholinergic system. The long-acting beta agonists are stimulatory. The beauty of these 2 systems is that they work together. There’s crosstalk. There’s synergy. One presynaptically enhances the other. So, the beauty of a long-acting beta agonist and the long-acting muscarinic is you can put them together with a single inhaler and have a very large effect on lung function and, hopefully, symptoms.

Peter L. Salgo, MD: So, there are 2 receptors? One is the beta receptor and one is the muscarinic receptor?

James F. Donohue, MD: Correct.

Fernando J. Martinez, MD: As you said, Peter, there are 2 different receptors that we’re targeting: the beta receptor and the muscarinic receptor. Then, there are short-acting preparations that can target either of those or combinations of those. Those are drugs that have relatively rapid effects but relatively short duration effects. So, there are short-acting agents that include beta agonists, antimuscarinics, that can be combined. And if the person has persistent symptoms, then you can look at long-acting versions of targeting those 2 receptors—the long-acting beta agonists. And then, there are long-acting antimuscarinics, which we call the LAMAs, and those can also be combined. One advantage is, where we used to have only 1 or 2 agents in this class, we now have agents that you can choose from, that can be dosed twice-a-day, or once-a-day—a whole series of devices. Is that, you think, a practical approach to looking at it?

James F. Donohue, MD: Actually, that’s spot-on. The short-acting one lasts 4 to 6 hours. Then, it’s gone. The long-acting one lasts 24 hours, and there’s still an effect when you wake up in the morning. When I was a young doctor, and you can relate to this because of working, the rest of you, in pulmonary critical care, we used to do surgery on chest patients in the afternoon. I did a couple of rotations at Columbia when I was in medical school and was a house officer. The surgery was done in the afternoon because patients did so poorly in the morning. With this trough effect, which is about 100 cc’s, or 140 cc’s, somewhere in that range, you wake up and you don’t feel great. Don’t get me wrong, I’m not going to underestimate it, but you feel much better than if you just took short-acting agents that wore off in the middle of the night.

Peter L. Salgo, MD: There’s a class of drugs that nobody has mentioned—the inhaled corticosteroids. Have they fallen off a cliff? Are they still out there?

James F. Donohue, MD: They were in the process of falling off the cliff, but I think they may be resurrected with the new onset of what’s called “triple therapy.” For years, because of the fear of missing asthma, we knew that one of the drug classes for asthma, the long-acting beta agonists, had some increased side effect profile. So, you never gave them by themselves. You always gave the combination of an inhaled steroid and a LABA. COPD is a steroid-resistant disease for a variety of reasons. But, again, with marketing and a “one shoe fits all” marketing approach, they led the marketplace, even more than monotherapy, with a LAMA.

Now, that’s too much. A very brilliant discussion from Canada shows that with inhaled steroids, there’s a pneumonia signal with the more important ones. If you just use bronchodilators without steroids, you probably will reduce hospitalizations due to exacerbations. But if you use the steroid, you might have some hospitalizations due to pneumonia. That’s the debate. So, there has been, and I think we’re going to talk about it as we go along today, a lot of studies trying to decrease the use of corticosteroids in COPD by using LABA/LAMA. But there are people for which you must still use them in—people with so-called asthma/COPD overlap, people with frequent exacerbations, those with eosinophils greater than 300 and maybe people with very severe disease.

Transcript edited for clarity.