Low Lung Function in Young Adult Life Is Associated with Early Mortality

To the Editor:

The Tucson data showing early sustained and increased mortality from the second and third decade of life in those with the lowest tercile of FEV₁ are truly challenging (1). There is no biological plausibility for such a minor impairment of lung development of itself to translate into early death. The only possible explanation is that FEV₁ is the canary in the mine (2), warning of the early onset of the premature multimorbidity that is characteristic of later chronic obstructive lung disease (3). Supporting this concept is a recent study of birth weight, itself an important determinant of FEV₁ (4), which demonstrated that 15% of birth weight variance was genetically determined. Pathway analyses demonstrated that genes within birth weight–associated regions were enriched for processes likely important in long-term mortality risk, including type 2 diabetes, fasting glucose, triglycerides, total cholesterol, coronary artery disease, and systolic, mean, and diastolic blood pressure (5). The next step is to perform a similar genetic analysis for FEV₁. The implications of the Tucson findings are profound. First, it is not merely the airway disease of chronic obstructive lung disease that has its origins in early life (6) but also the comorbidities, and it is in early life that the remedies must be found. Second, there is a strong case for performing spirometry at early school age, as well as the routine of measuring weight and height, to identify and target a high-risk population for not just airway but also systemic disease.