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Acute Sustained Hypoxia Suppresses the Cough Reflex in Healthy Subjects

Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park; School of Molecular and Biomedical Science, Discipline of Physiology, University of Adelaide, Adelaide; and Department of Medicine, Flinders University, Bedford Park, South Australia, Australia

Correspondence and requests for reprints should be addressed to Danny Eckert, B.Sc. (Hons), Adelaide Institute for Sleep Health, Repatriation General Hospital, Daw Park, South Australia, Australia, 5041. E-mail: danny.eckert{at}rgh.sa.gov.au

Rationale: An intact cough reflex is important to protect the lung from injurious substances and to clear excess secretions. A blunted cough reflex may be harmful or even fatal in respiratory disease. Hypoxia is common in respiratory disorders and has been shown to have depressant effects on respiratory sensation and ventilation. We hypothesized that it might also suppress the cough reflex.

Objectives: To determine if acute hypoxia increases cough threshold and cough tachyphylaxis to inhaled capsaicin.

Methods: On two occasions, 16 healthy subjects inhaled a saline control followed by doubling doses of capsaicin aerosol (range, 0.49–500 µM) every minute for 15 s during controlled ventilation ( 190% baseline) with isocapnic hypoxia (Sp_O2, 80%) or isocapnic normoxia, in random order. When a subject responded to a dose with five or more coughs, the next doubling dose of capsaicin was administered continuously for 60 s to assess acute tachyphylaxis.

Main Results: The capsaicin concentration required to elicit five coughs was significantly higher during isocapnic hypoxia compared with normoxia (29.6 ± 16.0 vs. 23.4 ± 15.6 µM, p = 0.01). During continuous capsaicin inhalation, significantly more coughs were evoked in the first 10 s compared with the last (2.3 ± 0.3 vs. 1.3 ± 0.3, p < 0.01), indicating cough tachyphylaxis. However, the decrease was the same during hypoxia and normoxia (–1.3 ± 0.4 vs. –0.9 ± 0.6, p = 0.54).

Conclusions: Acute isocapnic hypoxia suppresses cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex may be impaired during acute exacerbations of hypoxic-respiratory disorders.

Key Words: capsaicin • cough reflex • tachyphylaxis

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