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

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.

To determine if chest computed tomography (CT)-assessed functional small airway would increase with age, even among asymptomatic individuals.

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).

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 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 PRM^FSA in those without airflow obstruction was limited by its low burden.

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.