Effect of histamine and adenosine 5′-monophosphate provocation on sputum neutrophils and related mediators in atopic patients

Background Airway hyperresponsiveness and inflammation can be noninvasively studied by bronchial provocation using direct (histamine) or indirect (adenosine 5′-monophosphate [AMP]) stimuli and induced sputum. Objective To report on the immediate effects of histamine and AMP challenge on induced sputum neutrophil counts and related mediator levels. Methods We performed a single-masked, randomized, placebo-controlled, 3-way, crossover, methodological study in 14 atopic patients (median age, 25 years; 8 males; mean ± SD forced expiratory volume in 1 second, 99% ± 5%) without anti-inflammatory medication use. At baseline, sputum induction was performed. Bronchial challenges with AMP, histamine, or placebo were performed 48 hours later. Thirty minutes after challenge, sputum induction was performed again. Challenge periods in each patient were separated by more than 2 weeks. Sputum cells and the mediators leukotriene B 4 , interleukin 8, myeloperoxidase, and albumin were quantified. Results Comparing median challenge-induced relative changes in cells and mediators, neither histamine nor AMP challenge altered the induced sputum neutrophil counts (histamine, 2.7%; AMP, 2.95%; placebo, −2%; P > .07 for all), interleukin 8 levels (histamine, 2.4 ng/mL; AMP, −3.8 ng/mL; placebo, −0.2 ng/mL; P > .06), leukotriene B 4 levels (histamine, −4.8 pg/mL; AMP, 3 pg/mL; placebo, 6 pg/mL; P > .08), or myeloperoxidase levels (histamine, 0.16 μg/mL; AMP, 0 μg/mL; placebo, −0.03 μg/mL; P > .07). Sputum albumin levels were increased after histamine challenge compared with AMP and placebo challenge ( P Conclusions Histamine and AMP provocation have no major effects on induced neutrophil counts and related mediator levels in atopic patients, whereas histamine challenge induces plasma leakage. Potential interactions of noninvasive methods to evaluate airway reactivity and inflammation should be carefully considered.