Maximal Airway Narrowing in Humans in vivo

Maximal airway narrowing to inhaled nonsensitizing stimuli is limited to a mild degree in nonasthmatic and mildly asthmatic subjects. We investigated whether this limitation is due to a nonspecific inhibitory mechanism (with regard to the agonist) by comparing the maximal response plateaus of histamine and methacholine dose-response curves. Twenty subjects (15 nonasthmatics, 5 asthmatics) were selected in order to cover a wide distribution of airway responsiveness from the normal into the mildly asthmatic range. The subjects inhaled doubling doses of either histamine (up to 54 nmol) or methacholine (up to 340 μmol), delivered to the mouth during tidal breathing, on 2 separate days. The response was measured from volume-history-standardized, partial expiratory flow-volume curves as the flow at 40% of the control vital capacity (40p), and expressed as the percentage fall from baseline value. Sixteen subjects demonstrated a plateau for both histamine and methacholine. The maximal response on the plateau was ...