Rationale: Gastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes to the progression of COPD as measured by lung function or computed tomography. Objective: To determine the impact of GERD on longitudinal changes in lung function and radiographic lung disease in the COPDGene cohort. Methods: We evaluated 5728 participants in the COPDGene cohort who completed Phase I (baseline) and Phase II (5-year follow-up) visits. GERD status was based on participant-reported physician diagnoses. We evaluated associations between GERD and annualized changes in lung function [forced expired volume in 1 s (FEV1) and forced vital capacity (FVC)] and quantitative computed tomography (QCT) metrics of airway disease and emphysema using multivariable regression models. These associations were further evaluated in the setting of GERD treatment with proton-pump inhibitors (PPI) and/or histamine-receptor 2 blockers (H2 blockers). Results: GERD was reported by 2101 (36.7%) participants at either Phase I and/or Phase II. GERD was not associated with significant differences in slopes of FEV1 (difference of - 2.53 mL/year; 95% confidence interval (CI), - 5.43 to 0.37) or FVC (difference of - 3.05 mL/year; 95% CI, - 7.29 to 1.19), but the odds of rapid FEV1 decline of ≥40 mL/year was higher in those with GERD (adjusted odds ratio (OR) 1.20; 95%CI, 1.07 to 1.35). Participants with GERD had increased progression of QCT-measured air trapping (0.159%/year; 95% CI, 0.054 to 0.264), but not other QCT metrics such as airway wall area/thickness or emphysema. Among those with GERD, use of PPI and/or H2 blockers was associated with faster decline in FEV1 (difference of - 6.61 mL/year; 95% CI, - 11.9 to - 1.36) and FVC (difference of - 9.26 mL/year; 95% CI, - 17.2 to - 1.28). Conclusions: GERD was associated with faster COPD disease progression as measured by rapid FEV1 decline and QCT-measured air trapping, but not by slopes of lung function. The magnitude of the differences was clinically small, but given the high prevalence of GERD, further investigation is warranted to understand the potential disease-modifying role of GERD in COPD pathogenesis and progression. Clinical trials registration: NCT00608764.
Bibliographical noteFunding Information:
This work was supported by NIH National Heart, Lung, and Blood Institute (NHLBI) grants U01 HL089897 and U01 HL089856, and NIH NCATS grant UL1TR002494. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprised of AstraZeneca, Boehringer-Ingelheim, GlaxoSmithK-line, Novartis, and Sunovion.
The views expressed in this article are those of the authors and do not reflect the views of the United States Government, the Department of Veterans Affairs, the funders, the sponsors, or any of the author’s affiliated academic institution. This research was also supported by the National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS), grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH NCATS.
© 2020 The Author(s).
- Chronic obstructive
- Computed tomography
- Gastroesophageal reflux
- Longitudinal study
- Pulmonary disease
- Respiratory function tests