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Original Research: Signs and Symptoms of Chest Diseases |

Chronic CoughMicroaspiration and Chronic Cough: Relationship Between Microaspiration, Gastroesophageal Reflux, and Cough Frequency

Samantha Decalmer, PhD; Rachel Stovold, PhD; Lesley A. Houghton, PhD; Jeff Pearson, PhD; Chris Ward, PhD; Angela Kelsall, PhD; Helen Jones, MPhil; Kevin McGuinness, PhD; Ashley Woodcock, MD; Jaclyn A. Smith, PhD
Author and Funding Information

From the Respiratory Research Group (Drs Decalmer, Houghton, Kelsall, McGuinness, Woodcock, and Smith and Ms Jones), Faculty of Medicine and Human Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, England; the Applied Immunobiology and Transplantation Research Group (Drs Stovold, Pearson, and Ward), Institute of Cellular Medicine, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, England; the Division of Gastroenterology and Hepatology (Dr Houghton), College of Medicine, Mayo Clinic, Jacksonville, FL; and the National Institute for Health Research Translational Research Facility in Respiratory Medicine (Drs Kelsall and Woodcock), University Hospital of South Manchester, Manchester, England.

Correspondence to: Jaclyn A. Smith, PhD, University of Manchester, ERC Bldg, Second Floor, Wythenshawe Hospital, Manchester, M23 9LT, England; e-mail: jacky.smith@manchester.ac.uk


Funding/Support: This study was funded by a grant from the Moulton Charitable Trust. Dr Smith was funded by a Stepping Stones Fellowship from Manchester University followed by a Medical Research Council Clinician Scientist Fellowship [Grant G0701918].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(4):958-964. doi:10.1378/chest.12-0044
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Background:  Microaspiration is often considered a potential cause of cough. The aim of this study was to investigate the relationship between microaspiration, the degree and type of gastroesophageal reflux, and the frequency of coughing in patients with chronic cough.

Methods:  One hundred patients with chronic cough (mean [± SD] age, 55.8 years [± 11.0 years]; 65 women) and 32 healthy volunteers (median age, 43.5 years [interquartile range (IQR), 30-50.8 years]; 16 women) were recruited. Patients with chronic cough performed 24-h objective cough frequency with simultaneous esophageal impedance/pH monitoring and measurement of pepsin concentrations in sputum and BAL. Twelve healthy volunteers underwent bronchoscopy/BAL, and 20 underwent impedance/pH monitoring.

Results:  Patients with chronic cough had significantly more reflux episodes than healthy volunteers (median, 63.5 reflux episodes [IQR, 52.5-80.0] vs 59.0 [IQR, 41.8-66.0]; P = .03), although the absolute difference was small, and there was no difference in numbers of events extending into the proximal esophagus (median, 17.2% [IQR, 8.0%-26.0%] vs 20.3% [IQR, 5.1%-32.1%]; P = .36). BAL pepsin levels were also similar in chronic cough to control subjects (median, 18.2 ng/mL [range, 0-56.4 ng/mL] vs 9.25 ng/mL [range, 0-46.9 ng/mL]; P = .27). Sputum but not BAL pepsin weakly correlated with the number of proximally occurring reflux events (r = 0.33, P = .045) but was inversely related to cough frequency (r = −0.52, P = .04). Sputum pepsin was, therefore, best predicted by combining the opposing influences of cough and proximal reflux (r = 0.50, P = .004).

Conclusions:  Proximal gastroesophageal reflux and microaspiration into the airways have limited roles in provoking chronic cough. Indeed, coughing appears to be protective, reducing pepsin concentration in the larger airways of patients with chronic cough.

Trial registry:  ISRCTN Register; No.: ISRCTN62337037; URL: www.isrctn.org

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