Loss of FEV1 and the pathogenesis of COPD

Posted by • July 8th, 2015

Insight-picture-7-8-15For years, the dominant model for the pathogenesis of chronic obstructive pulmonary disease (COPD) has been that exposure to particulate matter (usually tobacco smoke) leads to a rapid decline in lung function, i.e., more than 40ml of FEV1 per year. This paradigm has recently come into question, but a careful study to test this model has yet to be performed.

In this week’s issue of NEJM, Lange et al. report the results of an analysis of three longitudinal cohort studies in which there was an initial spirometry assessment performed at around age 40-the “baseline”- and at least one subsequent measurement. The authors stratified the patients into two groups: those with a FEV1 below 80% at baseline (657 individuals) and those with baseline FEV1 greater than or equal to 80% (2207). In the former group, 26% had COPD after 22 years, while in the latter group 7% had COPD (P<0.001). Of the 332 individuals with COPD at the end of observation, about half had a normal FEV1 at the beginning of the trial and subsequently experienced a rapid decline of FEV1 (mean loss of 53 ml/year), while the other half had a reduced FEV1 at the start of the trial and a reduced rate of lung function decline (mean loss of 27 ml/year), despite similar rates of smoking between these two groups.

These results suggest that our current understanding of COPD may be neglecting another subtype of the disease. While some patients do indeed experience a rapid decline in lung function, it appears that others may have lower lung function at baseline, and experience a slow decline in lung function resulting in slower onset of COPD. However, these results do not rule out the possibility that a rapid decline in FEV1 occurred in the individuals with low FEV1 at baseline before the commencement of the trial. Thus, as Frank Speizer, MD, and James Ware, PhD, point out in an accompanying editorial, the ideal trial design would involve tracking lung function measurements from soon after birth through old age.

Another interesting question that arises is, if indeed there are subtypes of COPD, does this distinction reflect differences in the underlying pathogenesis, and would these patients respond differently to treatment? Although further studies will be needed to answer these important questions it will be a long time before we can get data about the lifetime changes in FEV1. As always the message for patients is that they are better off not smoking- that we know now.

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