Age and Small Airway Imaging Abnormalities in Subjects with and without Airflow Obstruction in SPIROMICS

Rationale: Aging is associated with reduced FEV1 to FVC ratio (FEV1/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 (PRMFSA) and emphysema (PRMEMPH) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRMFSA 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, PRMFSA increased 2.7% per decade, ranging from 3.6% (ages 40–50 yr) to 12.7% (ages 70–80 yr). PRMEMPH 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 PRMFSA in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV1 (P = 0.94), yielding lower FEV1/FVC ratios (P < 0.001). Although emphysema was also significantly associated with lower FEV1/FVC (P = 0.04), its contribution relative to PRMFSA 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.