Nonacid reflux in patients with chronic cough on acid-suppressive therapy

Chest. 2006 Aug;130(2):386-91. doi: 10.1378/chest.130.2.386.


Background: It is generally accepted that extraesophageal gastroesophageal reflux disease (GERD) symptoms and their persistence despite acid-suppressive therapy are poor prognostic factors for antireflux surgery. Recent studies indicating that cough can be temporally associated with reflux episodes of pH 4 to 7 (ie, nonacid reflux) reinvigorates the need for a more careful workup in patients with cough suspected to be due to GERD.

Aim: To evaluate the frequency of chronic cough associated with nonacid reflux and the response of these patients to laparoscopic Nissen fundoplication.

Methods: We retrospectively reviewed data from patients with persistent cough despite twice-daily proton pump inhibitor (PPI) with or without the use of nighttime regimens of histamine-2 receptor antagonist (H2RA), who had undergone combined multichannel intraluminal impedance and pH monitoring. The association of cough and reflux was evaluated by calculating the symptom index (SI) [positive if > or = 50%]. A subset of patients with positive SI values for impedance-detected reflux with therapy was referred for laparoscopic Nissen fundoplication.

Results: Of 50 patients (38 female patients; mean age, 43 years; age range, 6 months to 84 years) who were monitored while receiving therapy, 13 patients (26%) had a positive SI for cough. The SI-positive group had a lower percentage of female patients and patients of younger age compared to the SI-negative group. Laparoscopic Nissen fundoplication was performed in six SI-positive patients who became asymptomatic and stopped receiving acid-suppressive therapy during follow-up evaluations (median time, 17 months; range, 12 to 27 months).

Conclusion: Impedance pH monitoring should be performed while receiving therapy in patients with persistent symptoms who are receiving PPI therapy. A positive SI for nonacid reflux may be helpful in selecting patients who will benefit from antireflux surgery.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Ulcer Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cough / etiology*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Fundoplication
  • Gastric Acidity Determination
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / metabolism
  • Gastroesophageal Reflux / therapy
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Hydrogen-Ion Concentration
  • Infant
  • Male
  • Middle Aged
  • Proton-Translocating ATPases / antagonists & inhibitors*
  • Retrospective Studies
  • Treatment Outcome


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Proton-Translocating ATPases