PURPOSE: We recently reported that increasing airway temperature induced a transient airway constriction in anesthetized guinea pigs with activation of transient receptor potential vanilloid type 1 (TRPV1) channels being primarily responsible (J. Appl. Physiol. 106: 1917-24, 2009). TRPV1 channels expressed on bronchopulmonary C-fiber vagal afferents are polymodal sensors and can be activated by increasing temperature in the airways. Stimulation of these sensory nerves is known to elicit bronchoconstriction via the cholinergic pathway. This pilot study was designed to confirm these observations made in the animal study and to test our hypothesis that airway hyperthermia-induced bronchoconstriction in asthmatics is mediated through the cholinergic pathway.
METHODS: Airway resistance measurements were performed after isocapnic hyperventilation (40% MVV) of both humidified warm air (49°C) and humidified room air (21°C) for 4 minutes in 4 patients (2 male, 2 female) with moderate, controlled asthma. The same protocols were repeated in the same subjects after inhalation of ipratropium bromide (500 μg/2.5 mL) and placebo (sterile saline) prior to the hyperventilation maneuver. Only one test was performed each day to ascertain a full recovery in each patient.
RESULTS: Bronchoconstriction (ΔRaw = 57.2 ± 15.9%, p < 0.05) was induced after isocapnic hyperventilation of humidified warm air. Furthermore, airway hyperthermia also triggered cough, wheezing, and dyspnea. In contrast, hyperventilation of humidified room air did not cause any of these effects in the same patients. More importantly, bronchoconstriction was prevented by the inhalation of ipratropium bromide but not by placebo, indicating an important role of the cholinergic pathway.
CONCLUSION: These preliminary data indicate the involvement of airway sensory nerves and cholinergic mechanisms in the manifestation of symptoms in asthma triggered by breathing humidified warm air, which further suggests the potential involvement of TRPV1 over-expression as a possible contributing factor.
CLINICAL IMPLICATIONS: Activation of airway sensory nerves contributes to bronchoconstriction, coughing, wheezing, and sensation of dyspnea in asthmatic patients exposed to a warm humid environment. Further study is warranted to better define the cholinergic mechanisms involved in asthma under these conditions.
DISCLOSURE: Don Hayes, Jr., No Financial Disclosure Information; No Product/Research Disclosure Information