Bronchoconstriction triggered by breathing hot humid air in patients with asthma: role of cholinergic reflex

Am J Respir Crit Care Med. 2012 Jun 1;185(11):1190-6. doi: 10.1164/rccm.201201-0088OC. Epub 2012 Apr 13.


Rationale: Hyperventilation of hot humid air induces transient bronchoconstriction in patients with asthma; the underlying mechanism is not known. Recent studies showed that an increase in temperature activates vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit reflex bronchoconstriction.

Objectives: This study was designed to test the hypothesis that the bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through cholinergic reflex resulting from activation of these airway sensory nerves.

Methods: Specific airway resistance (SR(aw)) and pulmonary function were measured to determine the airway responses to isocapnic hyperventilation of humidified air at hot (49°C; HA) and room temperature (20-22°C; RA) for 4 minutes in six patients with mild asthma and six healthy subjects. A double-blind design was used to compare the effects between pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA challenge in these patients.

Measurements and main results: SR(aw) increased by 112% immediately after hyperventilation of HA and by only 38% after RA in patients with asthma. Breathing HA, but not RA, triggered coughs in these patients. In contrast, hyperventilation of HA did not cause cough and increased SR(aw) by only 22% in healthy subjects; there was no difference between their SR(aw) responses to HA and RA challenges. More importantly, pretreatment with ipratropium completely prevented the HA-induced bronchoconstriction in patients with asthma.

Conclusions: Bronchoconstriction induced by increasing airway temperature in patients with asthma is mediated through the cholinergic reflex pathway. The concomitant increase in cough response further indicates an involvement of airway sensory nerves, presumably the thermosensitive C-fiber afferents.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Airway Resistance / drug effects
  • Analysis of Variance
  • Asthma / diagnosis*
  • Asthma / physiopathology
  • Bronchoconstriction / drug effects*
  • Cholinergic Antagonists / administration & dosage
  • Cholinergic Fibers / physiology*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Hot Temperature / adverse effects*
  • Humans
  • Humidity / adverse effects
  • Hyperventilation / physiopathology*
  • Ipratropium / administration & dosage*
  • Male
  • Middle Aged
  • Reference Values
  • Reflex
  • Reflex, Abnormal / physiology*
  • Respiratory Function Tests
  • Risk Assessment
  • Treatment Outcome
  • Young Adult


  • Cholinergic Antagonists
  • Ipratropium