title: Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease.
abstract: BACKGROUND
  Epidemiologic and physiologic studies suggest an association between gastroesophageal reflux disease (GERD) and chronic cough. However, the benefit of antireflux therapy for chronic cough remains unclear, with most relevant trials reporting negative findings. This systematic review aimed to reevaluate the response of chronic cough to antireflux therapy in trials that allowed us to distinguish patients with or without objective evidence of GERD.
  
  
  METHODS
  PubMed and Embase systematic searches identified clinical trials reporting cough response to antireflux therapy. Datasets were derived from trials that used pH-metry to characterize patients with chronic cough.
  
  
  RESULTS
  Nine randomized controlled trials of varied design that treated patients with acid suppression were identified (eight used proton pump inhibitors [PPIs], one used ranitidine). Datasets from two crossover studies showed that PPIs significantly improved cough relative to placebo, albeit only in the arm receiving placebo fi rst. Therapeutic gain in seven datasets was greater in patients with pathologic esophageal acid exposure (range, 12.5%-35.8%) than in those without (range, 0.0%-8.6%), with no overlap between groups.
  
  
  CONCLUSIONS
  A therapeutic benefit for acid-suppressive therapy in patients with chronic cough cannot be dismissed. However, evidence suggests that rigorous patient selection is necessary to identify patient populations likely to be responsive, using physiologically timed cough events during reflux testing, minimal patient exclusion because of presumptive alternative diagnoses, and appropriate power to detect a modest therapeutic gain. Only then can we hope to resolve this vexing clinical management problem.
authors.affiliation: Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: p-kahrilas@northwestern.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kahrilas
authors.affiliation: Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Howden
authors.affiliation: Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, England.
authors.forename: Nesta
authors.initials: N
authors.lastname: Hughes
authors.affiliation: Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, England.
authors.forename: Michael
authors.initials: M
authors.lastname: Molloy-Bland
mesh_terms: D002908:Chronic Disease; D003371:Cough / Q000188:drug therapy* / Q000453:epidemiology*; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000453:epidemiology*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D018579:Patient Selection; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D011899:Ranitidine