Histamine phosphate has a cumulative effect when inhaled at five minute intervals.

Abstract
As the duration of bronchoconstriction induced by inhaled histamine phosphate [used to detect asthma] is greater than 5 min, it was determined whether this leads to a cumulative effect when histamine is inhaled at 5 min intervals as in standardized procedures. Fourteen clinically stable adult asthmatic subjects were studied. In the 1st part of the study (the noncumulative stage) they inhaled doubling concentrations of histamine until appreciable bronchoconstriction occurred (changes close to 50% in lung resistance for 7 subjects and 15% in forced expiratory volume in 1 s for 7 others). After functional recovery the last concentration of histamine was nebulized on 2 more occasions, allowing for functional recovery after each nebulization. In the 2nd part (the cumulative stage) subjects inhaled, depending on their responsiveness, 3-8 consecutive doses of the histamine concentration last administered in the non-cumulative stage, these doses being administered at 5 min intervals, without recovery. The cumulative effect was assessed by linear regression analysis of the changes in the specific functional indices, all the values obtained during the non-cumulative stage being given the score 0 and those obtained during the cumulative step scores of 1, 2, etc. In all but one instance significant (P < 0.01) correlations were obtained and the slopes were positive, thus showing a cumulative effect. Histamine has cumulative bronchoconstrictor effect if inhaled at 5 min intervals once appreciable bronchoconstriction has been reached.