Fog-induced Respiratory Responses Are Attenuated by Nedocromil Sodium in Humans

Abstract

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.