Rationale

The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.

Objectives

We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.

Methods

We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping.

Measurements and main results

Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM(fSAD) but not PRM(emph) was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRM(fSAD) and PRM(emph) were associated with FEV1 decline (P < 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM(fSAD) and PRM(emph) in GOLD 1/2 and 3/4, respectively.

Conclusions

CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).