Comparison of the tussive effects of histamine and methacholine in humans

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Abstract
The tussive and bronchoconstrictive effects of histamine inhalation in 7 normals, 7 asthmatics, and 24 patients with chronic cough (PCC) were measured by counting coughs during a standard histamine inhalation challenge. All PCC had a tussive response. Fifteen PCC exhibited significant linear correlations between cough count and either the change in forced expiratory volume at 1.0 (delta FEV1) or conductance-volume ratio (sGaw) (delta sGaw). Normals and asthmatics had little or no cough. Metaproterenol pretreatment in seven PCC reduced both the FEV1 and cough response to histamine without changing the relationship between cough and delta FEV1. The tussive and bronchoconstrictive effects of methacholine inhalation were also measured in 7 asthmatics and 16 PCC. One asthmatic coughed. Fifteen PCC coughed. There were significant linear correlations between cough count and delta FEV1 or delta sGaw in 10 PCC. At comparable delta FEV1 and delta sGaw, histamine produced more cough than methacholine. These data indicate that during inhalation of histamine or methacholine by PCC cough is related to, and may be caused by, bronchoconstriction. Histamine also causes cough by an additional mechanism not related to bronchoconstriction.