Pepsin and bile acids in induced sputum of chronic cough patients

Respir Med. 2011 Aug;105(8):1257-61. doi: 10.1016/j.rmed.2011.04.015. Epub 2011 May 17.


One of the theories which explain, why gastroesophageal reflux disease (GORD) may provoke cough, is the occurrence of aspiration of gastric content into the airways. The aim of the study was to assess the presence of aspiration markers: pepsin and bile acids (BA) in induced sputum in gastroesophageal reflux-related (GOR-related) chronic cough (CC) patients. Forty-one CC patients and 20 healthy controls were enrolled in the study. GORD as cause of CC was diagnosed by presence of GORD-related symptoms, gastroscopy and/or improvement of cough upon treatment with proton pump inhibitors (PPI). Patients were divided into two groups based on the response to PPI treatment. In all patients and healthy controls induced sputum was obtained and differential cell counts were calculated. Levels of pepsin and BA were measured in sputum supernatants. Pepsin was detectable in 48.8% samples in CC patients and in 60% healthy controls (p = NS). In pepsin positive samples no significant difference in pepsin concentration could be found between CC patients and control subjects. Pepsin levels in pepsin positive samples were significantly decreased in patients treated with PPI compared to non-treated patients. BA were detectable in 56% samples of CC patients and in 70% healthy controls (p = NS). BA concentration in BA positive samples in CC group was not different from healthy controls. There was also no difference when comparing patients who took PPI and those who did not. Patients characterized as PPI-responders and PPI-non-responders had similar pepsin and BA concentrations. Airway cellularity was not significantly different between groups of patients with or without pepsin or BA in induced sputum. Our results demonstrated the lack of differences in gastric content aspiration between patients with probable GOR-related CC and healthy control subjects. This might imply that the reflex cough theory may be more relevant than the reflux-associated aspiration theory in the pathophysiology of GORinduced chronic cough.

MeSH terms

  • Adult
  • Aged
  • Bile Acids and Salts / analysis*
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Case-Control Studies
  • Chronic Disease
  • Cough / drug therapy
  • Cough / etiology*
  • Female
  • Gastroesophageal Reflux / complications*
  • Gastroesophageal Reflux / drug therapy
  • Humans
  • Male
  • Middle Aged
  • Pepsin A / analysis*
  • Pneumonia, Aspiration / metabolism*
  • Proton Pump Inhibitors / therapeutic use
  • Sputum / chemistry*
  • Young Adult


  • Bile Acids and Salts
  • Biomarkers
  • Proton Pump Inhibitors
  • Pepsin A