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

As the duration of bronchoconstriction induced by inhaled histamine phosphate is greater than five minutes, a study was carried out to determine whether this leads to a cumulative effect when histamine is inhaled at five minute intervals as in standardised procedures. Fourteen clinically stable adult asthmatic subjects were studied. In the first 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 seven subjects and 15% in forced expiratory volume in one second for seven others). After functional recovery the last concentration of histamine was nebulised on two more occasions, allowing for functional recovery after each nebulisation. In the second part of the study (the cumulative stage) subjects inhaled, depending on their responsiveness, three to eight consecutive doses of the histamine concentration last administered in the non-cumulative stage, these doses being administered at five minute 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 less than 0.01) correlations were obtained and the slopes were positive, thus showing a cumulative effect. It is concluded that histamine has a cumulative bronchoconstrictor effect if inhaled at five minute intervals once appreciable bronchoconstriction has been reached.