Nonadrenergic bronchodilator mechanisms in normal human subjects in vivo

In seven normal subjects we investigated whether a nonadrenergic bronchodilator nervous system is demonstrable in humans in vivo. After inhalation of leukotriene D4 (LTD4), respiratory resistance (Rrs) increased by 115 +/- 11% (SE). Subsequent inhalation of 2 nmol of capsaicin induced coughing and a fall in Rrs of 22.1 +/- 2% (P less than 0.01). However, inhalation of the diluent of capsaicin, 10% saline-ethanol, decreased Rrs similarly. These bronchodilator responses were not altered by inhaled ipratropium bromide (120 micrograms) and oral propranolol (80 mg). After ipratropium and propranolol, voluntary coughing alone decreased Rrs by 25 +/- 3% (P less than 0.05). We next investigated whether these bronchodilator responses could be blocked by anesthesia of the airways with inhaled lidocaine. After inhalation of lidocaine and LTD4, capsaicin aerosol induced coughing and a transient increase in Rrs of 18 +/- 6% (P less than 0.05) but no bronchodilation. Inhalation of saline-ethanol (n = 4) and a deep inhalation (n = 6) decreased Rrs by 18 +/- 4% (P less than 0.05) and 34 +/- 3% (P less than 0.001), respectively. We conclude that in normal subjects a nonadrenergic, noncholinergic bronchodilator mechanism exists, which can be activated by inhalation of capsaicin and inhibited by local anesthesia.