Amir A. Zeki, MD: Biomarkers in Asthma, COPD & ACO Overlap


Biomarkers are a fairly uncharted territory in asthma and chronic obstructive pulmonary disease (COPD), but adding asthma-COPD overlap (ACO) into the mix can make it all the more confusing.

While at the 2018 CHEST Annual Meeting in San Antonio, TX, Amir A. Zeki, MD, associate professor of medicine at The University of California, Davis, specialist in pulmonary and critical care medicine, sat down with MD Magazine® to go over the known and unknown regarding biomarkers in asthma, COPD, and ACO.

MD Mag: What data is available on biomarkers in asthma, COPD, and ACO?

Zeki: It’s really an area that needs a tremendous amount of research. There is a lot more to be done, and we have to agree on the definition of a biomarker. What is a biomarker?

Are you measuring something in the blood, in the sputum, is it in the exhaled breath, is it a [computed tomography] CAT scan, is it a lung function parameter? There are a lot of ‘biomarkers.’ Most people are referring to a blood test of course.

Pulmonary diseases are complex though. The problem—or the reality will be—is some kind of combination of exhaled breath and blood testing that we will put together to enhance diagnostic accuracy. That’s still an area that needs a lot of work.

The best thing I can tell you that I have seen from the literature is if you put together exhaled nitric oxide and blood eosinophil counts, your positive predictive value increases for asthma-COPD overlap relative to COPD—let’s say as an example. There is decent data for that.

There is still much more that needs to be done. Other things that have been reported, like interleukin 6, NGAL [neutrophil gelatinase-associated lipocalin], and others, are still in the realm of research. We don’t have any specific cutoffs to say, ‘Oh, if you’re above this level or below that level, you have asthma or you have COPD.’ That still needs a lot of work and validation.

The first stage is to identify the biomarkers that, on average, can allow you to distinguish between these disorders. The higher-level work is what are the cutoffs, and are they actually predictive? Can these change your diagnostic thinking between those 3 disorders—ACO, COPD, and asthma?

MD Mag: What are the next steps that need to be taken in order to establish biomarkers for asthma, COPD, and ACO?

Zeki: If you’re talking about asthma and COPD, the answer is easier. However, if you’re talking about asthma, COPD, and ACO overlap, I think the first thing that needs to happen is we need to come up with a consensus [on the] definition for asthma-COPD overlap that everyone agrees on.

Once we agree on that [the definition], then the research will move forward much more rapidly. Right now, we’re still stuck in the realm of taxonomy, classifying, and trying to understand where it fits in.

I think the lowest hanging fruit is to just accept the latest description we have—which is from GINA, the Global Initiative for Asthma—which is really a description of asthma-COPD overlap. It’s not really a diagnostic criteria, but people have used it. For the time being, if people can agree to use that until we come up with a consensus [on the] definition, then research can move forward in that area as well.

I think it will be still be dubious until we all agree on a definition globally because there is a lot of research coming out from all over the world on overlap. That makes it challenging.

Another way to answer the question is to just take what we’re using in the clinic now—IgE [Immunoglobulin E] levels, testing for atopy, exhaled nitric oxide, peripheral blood eosinophils, etc. Use those tests and follow patients over time to then look back and see if you can correlate it to 1 disease type or another.

It’s not that simple, but these are simple answers to a very complicated question.

The right way to do it is to agree on the definitions and move forward with the proper studies that are longitudinal and that are done periodically so that you can correlate it to the various clinical parameters—lung function when they exacerbate and the various diagnostic criteria.

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