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Involvement of the Cholinergic Pathway in Airway Response to Hyperthermia in Mild Asthmatics FREE TO VIEW

Don Hayes, Jr., MD; Ruei-Lung Lin, MS; Lu-Yuan Lee, PhD
Chest. 2011;140(4_MeetingAbstracts):971A. doi:10.1378/chest.1119167
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PURPOSE: The activation of transient receptor potential vanilloid type 1 (TRPV1) channels has an important role in hyperthermia-induced airway constriction in anesthetized guinea pigs. Our preliminary data have shown that airway hyperthermia generated by breathing warm humidified air induced transient and reversible bronchonconstriction in asthmatics. We hypothesized that TRPV1 channels, expressed on bronchopulmonary C-fiber vagal afferents, are activated by increasing the temperature in the lower airways, which elicits bronchoconstriction via the cholinergic pathway. This study was designed to test this hypothesis.

METHODS: Airway resistance (Raw) measurements were performed after isocapnic hyperventilation (40% MVV) of both humidified warm air (49°C) (HWA) and humidified room air (21°C) (HRA) for 4 minutes in 6 patients (2 male, 4 female) with mild asthma. The HWA hyperventilation challenges were repeated in the same subjects after inhalation of ipratropium bromide (500 µg/2.5 ml) and placebo (sterile saline) in a double-blind manner. Only one test was performed each day to ascertain a full recovery in each subject.

RESULTS: Raw was significantly increased after isocapnic hyperventilation of HWA in asthmatics: baseline Raw = 2.18 ± 0.12 cmH2O/L/sec (mean ± SEM); after HWA challenge, peak Raw = 4.13 ± 0.45 cmH2O/L/sec (p<0.05; n=6). Furthermore, airway hyperthermia also triggered cough, wheezing, and dyspnea in the asthmatics. In contrast, hyperventilation of HRA did not cause the bronchoconstrictive effects in the same asthmatic subjects. More importantly, the HWA-induced bronchoconstriction was prevented in the asthmatics by the inhalation of ipratropium bromide (peak Raw = 1.65 ± 0.17 cmH2O/L/sec), but not by placebo (peak Raw = 4.03 ± 0.62 cmH2O/L/sec; p<0.05; n=6), indicating an important role of the cholinergic reflex.

CONCLUSIONS: These data clearly indicate the involvement of airway sensory nerves and cholinergic mechanisms in the manifestation of symptoms in asthma triggered by breathing HWA, which further implies the involvement of TRPV1 as a possible contributing factor. Additional studies are warranted to better define the role and mechanism of TRPV1 activation in triggering asthma exacerbation related to exposure of patients to warm humid conditions.

CLINICAL IMPLICATIONS: Activation of airway sensory nerves contributes to bronchoconstriction accompanied by cough, wheezing, and dyspnea in mild asthmatic patients breathing warm humid air.

DISCLOSURE: The following authors have nothing to disclose: Don Hayes, Jr., Ruei-Lung Lin, Lu-Yuan Lee

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