Abstract
RATIONALE: Aging is associated with reduced FEV(1) to FVC ratio (FEV(1)/FVC), hyperinflation, and alveolar enlargement, but little is known about how age affects small airways. OBJECTIVES: To determine if chest computed tomography (CT)-assessed functional small airway would increase with age, even among asymptomatic individuals. METHODS: We used parametric response mapping analysis of paired inspiratory/expiratory CTs to identify functional small airway abnormality (PRM(FSA)) and emphysema (PRM(EMPH)) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRM(FSA) and age in subjects with or without airflow obstruction. We subdivided participants with normal spirometry based on respiratory-related impairment (6-minute-walk distance <350 m, modified Medical Research Council ≥2, chronic bronchitis, St. George's Respiratory Questionnaire >25, respiratory events requiring treatment [antibiotics and/or steroids or hospitalization] in the year before enrollment). MEASUREMENTS AND MAIN RESULTS: Among 580 never- and ever-smokers without obstruction or respiratory impairment, PRM(FSA) increased 2.7% per decade, ranging from 3.6% (ages 40-50 yr) to 12.7% (ages 70-80 yr). PRM(EMPH) increased nonsignificantly (0.1% [ages 40-50 yr] to 0.4% [ages 70-80 yr]; P = 0.34). Associations were similar among nonobstructed individuals with respiratory-related impairment. Increasing PRM(FSA) in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV(1) (P = 0.94), yielding lower FEV(1)/FVC ratios (P < 0.001). Although emphysema was also significantly associated with lower FEV(1)/FVC (P = 0.04), its contribution relative to PRM(FSA) in those without airflow obstruction was limited by its low burden. CONCLUSIONS: In never- and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms.