Hi, my name is MeiLan Han. I’m a professor of pulmonary medicine at the University of Michigan in Ann Arbor. This is a recap of a recent presentation I gave for ATS 2020, which was virtual this year.
Early COPD is something that many of us who do work in COPD have been really interested in. If you think about it, many of the studies that we have that help us understand risk factors for development of the disease are convenient samples and largely look at patients that are already diagnosed. The mean age is usually somewhere in 60s, but some of the patients are even older. But if you think about it, if we’re looking at say a 70- or 80‑year‑old with pretty mild disease, they’re probably never going to get very severe disease, so that’s not a great person to be studying if we really want to understand what can help us identify patients who truly progress, which I think ultimately is really important if we want to arrest disease and study to develop disease‑modifying therapies.
So the question really is whether imaging can be used to help identify some of those patients. There is some data from some of the larger NIH‑sponsored cohort studies that I’ve had the opportunity to be involved in that suggest, yes, there’s actually quite a bit of imaging abnormality in patients, even before they develop spirometric obstruction.
So if we look at data from COPDGene for instance, we know that a good percentage of patients had either small airways disease, emphysema, or even airway wall thickening on CT scan. If we look at data from the SPIROMICS study, we demonstrated that patients without airflow obstruction but who had symptoms actually had airway wall thickening on their CAT scans. So it looks like that is a potential measure, or at least one potential measure, for identifying early disease. In the SPIROMICS Study, we actually did some additional analysis and demonstrated that there were increased mucin concentrations in the sputum of these patients who were symptomatic and having frequent exacerbations and airway wall thickening. So I think this chronic bronchitis subgroup may be a group that will be really interesting to look at.
Another imaging metric that can be really important is simply emphysema.
We know from several other cohort studies including the NELSON trial, which was a large lung cancer study that was done in Europe, as well as the MESA Lung Study, which was another large population-based cohort done here in the United States, that if we see emphysema on patients, this actually helps to predict future lung function decline. MESA Lung also showed a relationship between airway wall thickening measured by the Pi10 and development of COPD.
Yet another metric that we’ve been looking at is something that I’ve been working on with my colleagues here at the University of Michigan. This involves something called dynamic image registration where we compare an inspiratory image to an expiratory image, and we match them up using a computer algorithm so that we can understand what happens at a voxel‑by‑voxel level between inspiration and expiration. It turns out that using this, we can indirectly get a small airways disease.
The super small airways are too small to pick up directly on CT imaging, but we think they’re really important with respect to being the genesis point for development of emphysema. If we can figure out how to identify those, we think that that might be the linchpin to identifying patients who are going to progress.
We’ve actually demonstrated that using this technique that we call Parametric Response Mapping, that we were able to identify small airway abnormality even in patients who don’t have spirometric obstruction. We’re able to identify people who were at greater risk for lung function decline. Also, we saw that these areas of small airway abnormality over time turned over into areas of emphysema, at least, based on CT scan.
One of the cool things that I’ve been working in the last couple of years is we were able to do tissue validation studies to actually demonstrate using human lung tissue that the areas that we think are small airway abnormality on the Parametric Response Mapping Technique really are.
So I would say in summary, I think that there’s reasonable evidence to show that emphysema, airway wall thickening, and small airways disease likely are associated with symptoms, exacerbations, and lung function decline and may be really helpful for helping to identify patients at risk for more rapid progression.
One question you might have is, “Well, how does this influence my practice now?” Certainly, wall thickening and emphysema is something we can pick up visually. If you’re looking at that—particularly if you’re seeing a CT scan of a patient who is younger—that would definitely hit my radar screen as something to think about.
The ability to look at quantitative CT metrics in terms of exact percent of emphysema and small airway abnormality are currently in process. More and more hospitals are obtaining the software to do that. As we move now into the future, then that’s going to be information that’s going to be more and more available for people.
For me, one of the exciting areas of research—and that I hope we can continue and get even more information—will be some of the newer cohorts that are being examined, particularly within the NIH, to get imaging data on younger individuals. That’s really a gap in our data right now, and I think the more data we get on that the better.
Like I said, in the meantime, I think that there are some things that we can get at least from a visual perspective and, hopefully, more and more quantitative data will be more readily available for physicians in the upcoming years.
Thank you for joining me.
