title: Therapy with proton-pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD.
abstract: Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD.
  
  
  
  A total of 638 patients with stable COPD for ≥6 weeks, ≥10 pack-years of smoking and Global Initiative for Chronic Obstructive Lung Disease II-IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death.
  
  
  
  A total of 85 (13.3%) of COPD patients were on anti-GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF-36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6-min walking distance (P = 0.0004) and a higher adjusted Charlson score (P < 0.0001). Anti-GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37-3.08). Using three multivariable Cox-regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26-2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04-2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04-2.53).
  
  
  
  These findings suggest that patients with stable COPD receiving acid-suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations.
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Luzia
authors.initials: L
authors.lastname: Baumeler
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Eleni
authors.initials: E
authors.lastname: Papakonstantinou
authors.affiliation: Faculty of Medicine, University of Belgrade; Clinic for Pulmonary Diseases, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Milenkovic
authors.affiliation: Department of Microbiology, CIBER Enfermedades Respiratorias, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lacoma
authors.affiliation: Department of Pneumology, CHU Liege, GIGAI Research Group, University of Liege, Liege, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.affiliation: Department of Pneumology, Amphia Hospital/Erasmus MC, Breda, The Netherlands.
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
authors.affiliation: Department of Pneumology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Pneumology, University of Thessaly, Medical School, Larissa, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostikas
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Department of Pneumology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Boersma
authors.affiliation: Department of Pneumology, Hospital Clinic, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Gernot G U
authors.initials: GG
authors.lastname: Rohde
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Boeck
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Janko
authors.initials: J
authors.lastname: Rakic
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherr
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
mesh_terms: D000368:Aged; D015897:Comorbidity; D005060:Europe; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D011788:Quality of Life; D012306:Risk; D011795:Surveys and Questionnaires
chemical_list: D054328:Proton Pump Inhibitors
keywords: anti-gastroesophageal reflux disease therapy; chronic obstructive pulmonary disease; chronic obstructive pulmonary disease exacerbations; gastroesophageal reflux disease; proton pump inhibitors