title: Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort.
abstract: BACKGROUND
  The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.
  
  
  METHODS
  Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.
  
  
  RESULTS
  GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George's Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.
  
  
  CONCLUSIONS
  In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Medical Center Drive, 3916 Taubman Center, Box 0360, 1500 E, Ann Arbor, MI 48109-0360, USA. carlosma@umich.edu.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Martinez
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okajima
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatabu
authors.forename: MeiLan K
authors.initials: MK
authors.lastname: Han
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D057566:Self Report / Q000592:standards*