EFFECT OF MAGNITUDE OF AIRWAY RESPONSIVENESS AND THERAPY WITH INHALEDCORTICOSTEROID ON HISTAMINE TACHYPHYLAXIS IN ASTHMA

Histamine challenge testing is used to measure airway responsiveness i n asthma. Histamine tachyphylaxis has been demonstrated after repeated challenges in mild asthmatics not using inhaled corticosteroid. Other studies, using subjects with variable severity of asthma, have not de monstrated histamine tachyphylaxis. Forty patients with stable asthma were studied and stratified according to severity of airway hyperrespo nsiveness and use of inhaled corticosteroid, to examine the effects of these factors on histamine tachyphylaxis. Airway responsiveness was m easured as the histamine provocative concentration causing a 20 percen t fall in FEV(1) (PC20). Twenty subjects had mildly increased airway h yperresponsiveness (PC20 >1 mg/ml), of whom 10 were using inhaled cort icosteroid. Twenty subjects had moderate to severely increased airway hyperresponsiveness (PC20 <1 mg/ml), of whom 10 were using inhaled cor ticosteroid. On each of two study days, 1 week apart, two histamine ch allenges were performed 1 h apart. Histamine tachyphylaxis was found f or the entire group on both study days. The geometric mean PC20 increa sed from 1.0 mg/ml (percent SEM 1.2) to 1.3 mg;/ml (percent SEM 1.2) 1 h later on day 1(p<0.0005), and 1.1 mg/ml (percent SEM 1.2)to 1.3 mg/ ml (percent SEM 1.2) 1 h later on day 2 p<0.05). Subgroup analysis dem onstrated that tachyphylaxis only occurred consistently in subjects wi th mildly increased airway hyperresponsiveness not receiving inhaled c orticosteroid. In this group, the PC20 increased from 2.2 mg/ml (perce nt SEM 1.2) to 3.2 mg/ml (percent SEM 1.2) on day l(p<0.001), and from 2.5 mg/ml (percent SEM 1.3) to 3.4 mg/ml (percent SEM 1.2) on day 2 ( p<0.05). This study confirms that histamine tachyphylaxis occurs in as thmatics, but is consistently present only in mild, noncorticosteroid- dependent asthmatics,