EFFECTS OF INHALED HISTAMINE, METHACHOLINE AND CAPSAICIN ON SPUTUM LEVELS OF ALPHA(2)-MACROGLOBULIN

Background - Plasma exudation-derived proteins and peptides contribute significantly to inflammation in the airway mucosa in vivo. In the gu inea pig trachea both histamine and the neurogenic stimulant capsaicin produce acute mucosal tissue distribution and luminal entry of bulk p lasma, whereas cholinergic agonists fail to produce this effect. Of th ese agents, only histamine induces mucosal exudation of plasma in huma n nasal airways. The exudative effect of the above agents on human bro nchi remains unknown. Methods - The bronchial exudative responses to i nhalation of histamine, methacholine, and capsaicin were examined in t wo groups of healthy volunteers. Sputum was induced an three occasions in each study group by inhalation of hypertonic saline (4.5%) given a s an aerosol for 40 minutes using an ultrasonic nebuliser. The second and third occasions were preceded by histamine and capsaicin challenge s in the first study group, and by histamine and methacholine challeng es in the second study group. Histamine and methacholine were given in cumulative doses (total doses 3160 mu g, respectively) or until a 20% reduction in forced expiratory volume in one second (FEV1) was achiev ed. Cumulative doses of capsaicin were inhaled until coughing prevente d the subjects from drawing a full breath. Sputum levels of alpha 2-ma croglobulin (720 kDa) were measured as an index of mucosal exudation o f bulk plasma. Results - Histamine increased mean (SE) sputum levels o f alpha(2)-macroglobulin from 2.72 (1.01) mu g/ml (95% confidence inte rval (CI) 0.49 to 4.94) to 18.38 (8.03) mu g/ml (95% CI 0.49 to 36.27) in the first group, and from 1.66 (0.84) mu g/ml (95% CI -0.18 to 3.4 9) to 9.43 (3.63) mu g/ml (95% CI 1.59 to 17.27) in the second group. In contrast, capsaicin evoked no exudation (sputum levels of alpha(2)- macroglobulin 1.21 (0.28) mu g/ml (95% CI 0.59 to 1.83)) and methachol ine produced a minor increase in sputum levels of alpha(2)-macroglobul in (2.90 (0.92) mu g/ml (95% CI 0.90 to 4.89)). Conclusions - These re sults indicate that histamine is a useful agent for studying bronchial exudative responsiveness in man and that exudative effects are only o f marginal importance in the cough and bronchoconstriction produced by capsaicin and methacholine.