Back to the Box: Using Lung Volumes to Predict Susceptibility to Develop Chronic Obstructive Pulmonary Disease among Smokers.

BACKGROUND: Abnormal lung volumes that represent air trapping are common in chronic obstructive pulmonary disease (COPD). However, their clinical significance in those without spirometrically defined COPD (normal forced expiratory volume in 1 s [FEV1 ] to forced vital capacity [FVC] ratio) is unclear.

METHODS: Using the Veterans Administration Informatics and Computing Infrastructure (VINCI) database, we identified 7,479 patients at risk for COPD (smokers > 40 years of age without restrictive lung disease) who had preserved spirometry (FEV1 /FVC and FEV1  ≥ lower limit of normal) and also had concomitant lung volume measurements by plethysmography across 37 Veterans Affairs Medical Centers in the United States between 1985 and 2017, and examined their subsequent health records for clinical diagnoses of COPD, respiratory exacerbations, healthcare utilization, spirometry, and mortality. We then estimated the association of lung volumes representing air trapping (residual volume [RV], functional residual capacity [FRC], inspiratory capacity [IC], and their ratios to total lung capacity [TLC]) with health outcomes and changes in spirometry using mixed-effect linear (and logistic) regression modeling with inclusion of follow-up time as random effects, and Cox proportional hazards and Poisson regression modeling as indicated ( 1 ). Predicted values and ranges for lung function measurements were calculated using Crapo predicted formulas ( 2 - 4 ), except for FRC/TLC, IC, and IC/TLC, for which data from Francisco and colleagues ( 5 ) and Quanjer and colleagues ( 6 ) were used. Data from other VA Medical Centers were not used because of lack of availability of coded pulmonary function testing data that were obtainable through VINCI ( 1 ).

RESULTS: Air trapping was prevalent, with 30.8% of patients having RV/TLC greater than the upper limit of normal. RV/TLC varied widely, spanning 46% ± 13% and 38% ± 11% across the increments of FEV1 /FVC and FEV1 , respectively. Patients with RV/TLC greater than the upper limit of normal were more likely to receive subsequent clinical diagnoses of COPD (odds ratio [OR], 1.47 ± 0.08; P < 0.001) and had higher all-cause mortality (hazard ratio [HR], 1.41 ± 0.06; P < 0.001). They had higher numbers of respiratory medication prescriptions and hospital and intensive care unit admissions. Other air-trapping indices showed similar associations with health outcomes ( 1 ). Inclusion of baseline airflow indices (FEV1 /FVC, FEV1 , FEV1 reversibility, and forced expiratory flow, midexpiratory phase) in the multivariate analysis did not significantly affect the observed associations ( 1 ). In addition, high-normal RV/TLC was associated with intermediate adverse health outcomes compared with low-normal and abnormal RV/TLC. Abnormal RV/TLC predicted higher likelihood of progression to spirometric COPD (OR, 1.27 ± 0.15; P = 0.044).

CONCLUSIONS: These findings indicate the predictive usefulness of lung volume measurements in those at risk for COPD and argue for their use as an additional dimension for COPD risk stratification. Smokers with abnormal lung volumes representing air trapping are at higher risk to develop adverse respiratory outcomes and COPD. Understanding physiological and biological mechanisms underlying this susceptibility could lead to discovery of novel therapeutic strategies.