Reply to Bush: Low Lung Function in Young Adult Life Is Associated with Early Mortality

From the Authors:

We appreciate the cogent comments by Dr. Bush and agree that a possible explanation for the association we reported between early FEV₁ impairment and subsequent mortality risk may be related to a common comorbidity predisposition (1). We propose that a scenario in which FEV₁ deficits per se may have a direct effect on mortality risk is also possible. In our study, participants in the low lung function group had FEV₁ levels that were on average 18% lower than those of participants in the highest tertile. Although subclinical, the magnitude of these FEV₁ deficits may have been sufficient to make participants with low lung function more susceptible (or susceptible at a younger age) to cardiopulmonary risk factors, leading to an increased risk for early mortality. Indeed, we argue that these two scenarios are to some extent complementary because it is likely that adverse social and environmental factors in early life, on a background of genetic susceptibility, may alter normal developmental trajectories and predispose to a variety of adverse outcomes in adult life, which may ultimately affect and worsen each other. These outcomes are almost invariably associated with chronic systemic inflammation and accelerated organ function decline during senescence. Therefore, we definitely agree with Bush on the importance of targeting early life and childhood as critical developmental windows for an effective prevention not only of chronic obstructive pulmonary disease but also its comorbidities.