Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 4

Effects of Uncontrolled Severe Asthma

June 14, 2021
Reynold Panettieri, Jr, MD, Robert Wood Johnson Medical School

Sidney Braman, MD, Icahn School of Medicine

Geoffrey Chupp, MD, Yale School of Medicine

Nicola Hanania, MD, MS, Baylor College of Medicine

The panel discusses the effects of uncontrolled severe asthma on patients’ lung function and quality of life and how to determine if worsening symptoms are due to underlying asthma or comorbidities.

Reynold Panettieri Jr, MD: What effect does uncontrolled severe asthma have on patients’ lung function and, more importantly, functional status and quality of life? Geoff, what do you think? Why don’t you start off?

Geoffrey Chupp, MD: The evidence is pretty clear that individuals who are uncontrolled both by chronic symptoms and poor ACT [Asthma Control Test] scores and asthma control scores, and people who flare frequently, have a steeper decline in lung function. The individuals that we see who are middle-aged, who’ve had asthma for 20, 30 years and have never been adequately controlled, really have some of the most impressively low lung function that I’ve seen. I saw a gentleman the other day who has an FEV1 [forced expiratory volume in 1 second] of 22% of predicted. He has never had controlled asthma, has never smoked, and doesn’t have alpha-1 antitrypsin deficiency or anything like that. We’ve checked the patient. You can have really horrible decline in lung function and poor quality of life. That links to functional status very well. You need pulmonary reserve, especially as you get older, to exercise and be active. These things really become limiting for people. I talked to a patient yesterday who’s about 70 years old, and she’s had asthma for about 20 years. She said that she had just been looking at her breathing and how it was going to be bad—and continue to get worse—because she had uncontrolled asthma and was on steroids 3 or 4 times a year. Then she received a biologic drug, and she felt like she got her life back. Instead of looking at the next 10 or 20 years of her life as something that was just going to be in decline, she feels as if the whole world is open to her.

Reynold Panettieri Jr, MD: That’s a really good point. You raised a very interesting angle, and we all need to keep this in mind when we question the patient. The patient will say, “I’m fine,” but that’s because they reacclimate to the severity of their disease and then acceptance. What we can’t lose sight of, maybe by using objective measures, is really to define: What’s your quality of life? People will acclimate to what their life is like the last month or 2 months and assume a new baseline. We shouldn’t accept that. We should try to strive for the best. Nic, do you have comments on this question?

Nicola Hanania, MD, MS: No. The scenario that Geoff mentioned is very familiar to me. There’s definitely an “aha” effect in many patients when we start treating them right. Unfortunately, most uncontrolled asthmatics don’t have severe asthma, but it affects their quality of life and lung function. Actually, most of the uncontrolled disease is mainly due to an adherence problem with taking the medication or even taking it correctly. But whatever the cause of uncontrolled asthma is, whether it’s severe disease or poor compliance or comorbidities, it affects every aspect. When patients come to me, they want to get their life back. They don’t want to keep missing work. They want to participate in gym again. Asthma should not be a disabling disease, but unfortunately in some of these uncontrolled patients, it can be. That’s what we all strive to improve: To get them back to their life. We can’t cure them, but we can get them better controlled.

Reynold Panettieri Jr, MD: It’s a great question. We’re going to finish this segment with the last question. Sid, 1 of the hardest things to understand is an exacerbation of asthma. Is this an exacerbation of a comorbidity that then triggers the asthma attack? How do you define that?

Sidney Braman, MD: Sometimes it’s tough. You need to go over the potential reversible factors. Do they start smoking again? Are they really taking their medications? Did the young man just get a new girlfriend and he’s visiting her home, and she has a cat but he’s allergic to cats? What’s happening in the environment? These are some of the things that will let us know. However, as we’ve discussed, there are other comorbidities that may have the same symptoms: chest tightness, wheezing, shortness of breath, and cough. These are all the symptoms that you’ve mentioned—about asthma and other conditions—that the lungs would be related to. At a minimum, I would do a chest radiograph. I would like to see, especially because you’re getting older, if there may be concomitant cardiac disease. Wouldn’t it be something if you saw cardiomegaly [megacardia] on the x-ray or evidence of congestive heart failure, pleural effusion [excess fluid in the pleural cavity], and other things? Certainly, in asthmatics who may develop severe mucus plugging, atelectasis [collapsed lung] of a lobe may suddenly cause worsening. You think it’s asthma. It’s not asthma. It may just be mucus plugging that can be treated in different ways. These are some of the things that I would certainly consider doing the chest x-ray for.

Next, there should be very careful questioning about their sleep. Are they having difficulty with sleep? There’s a particular association between sleep apnea with those who have been put on oral corticosteroids and have weight gain. Sleep apnea is another thing I would be getting to think about. Lastly, there’s GERD [gastroesophageal reflux disease]. You may want to think about this. Although there’s no good evidence that treatment of GERD will improve your asthma, it will certainly improve your heartburn and your nocturnal awakening from that. Lastly, obviously, chronic rhinosinusitis and investigation into sudden nasal polyps that are obstructing the breathing should be taken into consideration. The patient has a perception that this breathing problem is their asthma. 

Reynold Panettieri Jr, MD: That last aspect is 1 that resonates with me. I can see someone’s nasal polyposis getting worse, and I can see a gradual increase in the upper-airway symptoms. Geoff, you see that also. Predictably down the road, they will have worsening asthma that requires oral steroids. I find that to be 1 of the major comorbidities. Geoff, have you seen similar aspects?

Geoffrey Chupp, MD: Yes, absolutely. We know that with this concept of eosinophilic phenotype, there’s a significant percentage of these people who have nasal polyposis. The upper- and lower-airway diseases tend to track together. We used to think, “Well, if you treated their sinuses, then their asthma would get better and you would have some of that for a time.” But now we recognize that we’re probably treating 1 endotype of disease when we’re doing this with systemic steroids. If you put the patient on steroids for their nasal polyps, then you tend to control their asthma. But the moment you get them off, they deteriorate.

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