Background: Epidemiologic and physiologic studies suggest an association between gastroesophageal refl ux disease (GERD) and chronic cough. However, the benefi t of antirefl ux therapy for chronic cough remains unclear, with most relevant trials reporting negative fi ndings. This systematic review aimed to reevaluate the response of chronic cough to antirefl ux therapy in trials that allowed us to distinguish patients with or without objective evidence of GERD. Methods: PubMed and Embase systematic searches identifi ed clinical trials reporting cough response to antirefl ux 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 identifi ed (eight used proton pump inhibitors [PPIs], one used ranitidine). Datasets from two crossover studies showed that PPIs signifi cantly 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 benefi t 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 refl ux 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. CHEST 2013; 143(3):605-612Abbreviations: GERD 5 gastroesophageal refl ux disease; LPR 5 laryngopharyngeal refl ux; PPI 5 proton pump inhibitor

The therapeutic gain with PPIs over placebo or comparator agents for the relief of regurgitation is modest, and considerably lower than for heartburn. Thus, regurgitation is likely to be an important factor for determining incomplete response to PPI treatment in GERD. Future trials would benefit from using regurgitation as a primary end point, applying an unambiguous definition of the symptom and of a positive treatment response, and using a validated patient-reported instrument for regurgitation assessment.

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Unexplained chest pain in patients with endoscopic or pH-monitoring evidence of GORD tends to improve, but not resolve, with PPI therapy, whereas GORD-negative patients have little or no response. Heartburn was a poor predictor of whether patients with chest pain were GORD-positive or GORD-negative by objective testing.

BACKGROUND: Patient satisfaction is increasingly regarded as an important aspect of measuring treatment success in individuals with gastroesophageal reflux disease (GERD).OBJECTIVE: To review how satisfied patients with GERD are with their medication, and to analyze the usefulness of patient satisfaction as a clinical end point by comparing it with symptom improvement.METHODS: Systematic searches of the PubMed and EMBASE databases identified clinical trials and patient surveys published between 1966 and 2009.RESULTS: Twelve trials reported that 56% to 100% of patients were ‘satisfied’ or ‘very satisfied’ with proton pump inhibitor (PPI) treatment for GERD. Patient satisfaction levels were higher for PPIs than other GERD medications in two trials. The sample-size-weighted average proportion of patients ‘satisfied’ with their PPI after four weeks of treatment in trials was 93% (95% CI 87% to 99%), with 73% (95% CI 62% to 83%) being ‘very satisfied’. In four surveys, the average proportion of patients ‘satisfied’ with their PPI treatment was 82% (95% CI 73% to 90%) and 62% (95% CI 48% to 75%) were ‘very satisfied’. Seven trials found a positive association between patient satisfaction and symptom improvement, and two surveys between satisfaction and improved health-related quality of life. Three trials found that continuous treatment yielded higher rates of satisfaction than on-demand therapy.CONCLUSIONS: More than one-half of patients were satisfied with their PPI medication in trials, and more patients were satisfied with PPIs than other medication types. An association between patient satisfaction and symptom resolution was found, suggesting that patient satisfaction is a useful end point for evaluating GERD treatment success.