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Sure. Yeah. I am happy to join. I am a Professor of Medicine in the Pulmonary Division at the University of Alabama at Birmingham. I have a clinical COPD practice, where I run a COPD clinic for advanced COPD, and I also have a research interest in COPD, where I do clinical trials in COPD, and I also direct the Center for Lung Analytics and Imaging Research, where we do AI-based imaging research in COPD.

Sure, yeah. So both of these are chronic airway diseases. Asthma usually can occur during any age. Usually, can sometimes occur in childhood. Sometimes they grow out of it, sometimes it continues into adult life. Some people get late onset asthma in their 20s and 30s. Oftentimes, the symptoms overlap, so most people are short of breath, either episodically or on a daily basis. They have wheezing, coughing, so these symptoms are overlapping symptoms. The diagnosis and the differentiation is mainly based on certain characteristic features. Asthma is characterized by reversible airflow obstruction and high responsiveness to bronchodilators. So if you give a bronchodilator, the lung function markedly improves. There is significant variability. For example, if you measure lung function either with peak flow or spirometry at multiple times during the day or week, it fluctuates quite a bit. So that is the hallmark of asthma.

In contrast, COPD is more later in life. Usually, it can happen in the 30s, but usually after the age of 40, that is when the onset is because the primary risk factor is still cigarette smoking, although we recognize that more often in non-smokers as well. The hallmark of this is, despite the overlapping symptoms, it is characterized by fixed or partially irreversible airflow obstruction, meaning when you give a bronchodilator, there is minimal response, and certainly the low FEV1/FVC ratio, which is what we use for diagnosis, does not get reversed with the bronchodilator.

Sure, yeah. An acute exacerbation is every patient has fluctuating symptoms on a daily basis, depending what is going on around them, pollution, heat, humidity, and so on. If the symptoms get markedly worse than usual, that is what we call an exacerbation. There are three grades of severity. One is mild, where the patient kind of roughs it out, takes some additional bronchodilators at home, does not really report it, and this, I think, amounts to about half of the exacerbations. The other half are more severe in intensity, something we call moderate exacerbations, where patient seeks medical attention, gets antibiotics and/or steroids. That could be, if it is treated on an outpatient basis, meaning at home, that is considered a moderate exacerbation. But if they happen to be severe enough to come to the emergency room or to get hospitalized especially, that is considered a severe exacerbation.

The definitions are a little limited in that we make these post hoc determinations as to where they receive their care to determine the severity of these exacerbations. The moderate exacerbations that are treated at home, patients usually get about five days worth of steroids and/or antibiotics, and sometimes longer, depending on response. They usually symptomatically feel better in about seven to 10 days, and it takes a couple of weeks for them to feel like their usual, but their lung function often does not return back to normal, even up to five to six weeks out. In about one-fifth of the people, if you measure peak respiratory flow every day, it stays low below the baseline for up to five weeks out. Severe exacerbations seem to be much more of concern.

These patients can stay in the hospital, usually for about 3 days, and they start feeling reasonably better that they can be sent home, but sometimes they stay in the hospital for 10 to 14 days or even longer sometimes. It is not just an inconvenience for the patients, but these severe exacerbations are associated with more inflammation and likely more lung damage to the point that they lose a lot of lung function. It does not return back to normal after they are discharged home. When we discharge patients, we usually try to bring them back in a couple of weeks to see a specialist or a primary care doctor. May or may not happen often, always, but that is our goal. But certainly the recommendations are to bring them back in 2 to 4 weeks.

Again, these patients usually do not feel back to their usual for about 3 to 4 weeks. They feel quite debilitated, highly symptomatic, very high risk of having another exacerbation again in the first 30 to 90 days post-exacerbation. I hope I covered most of it. With the severe exacerbations, the treatment is again giving steroids and antibiotics, more often IV rather than oral. Then in some people who retain carbon dioxide, they may need additional treatments like non-invasive ventilation. Some of them need oxygen therapy, which they may be discharged home on for short-term or long-term.

Yeah. I think these treatments have been quite limited. The exacerbation treatment paradigm has not changed in almost 5 decades now. It has always been steroids, either by mouth or IV. The outcomes, not surprisingly, have not changed much immediately after an exacerbation. We know that a single moderate exacerbation increases the risk of another exacerbation by about 70%. Severe exacerbations are much more concerning, like I said earlier, because it is also associated with about a 20% risk of hospital admission again within the next 30 days. Within about 90 days, about 35%-40% of patients get admitted again. Or they could get another exacerbation resulting in the same downstream consequences. About 25% of people die within the hospitalization event.

I think it's very high morbidity and mortality, so we don't have great treatments that have altered the course of this, even in the short term, during an exacerbation, for example, length of stay and so on, or during the first 30 days, where they're very likely to bounce back with another exacerbation or long-term in terms of mortality. I don't think we made a dent in any of those with the previous usual status quo of antibiotics and steroids.