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

Abstract

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 (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 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.

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.

Keywords: aging; geriatrics; imaging analysis; lung function; spirometry.

Figure 1.

Flow of participants in SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). CT = computed tomography.

Figure 2.

Changes in FEV₁/FVC ratio across varying levels of computed tomography–defined small airway abnormality (parametric response mapping with functional small airways abnormality [PRM^FSA]) and emphysema among subjects without airflow obstruction. Increasing percentage of PRM^FSA (x-axis) is associated with decreasing FEV₁/FVC ratio (y-axis), an effect that persists at any degree of emphysema severity, as shown by the similar slope of the lines describing the burden of emphysema.

Figure 3.

Distribution of parametric response mapping–determined small airway abnormality (PRM^FSA, top) and emphysema (PRM^EMPH, bottom) by age and presence of airflow obstruction. At any age, those without airflow obstruction (represented by group No) have significantly less small airway abnormality (y-axis, top) and emphysema (y-axis, bottom) than subjects of similar age with mild airflow obstruction (Yes).