Histamine and indirect bronchoprovocation with adenosine monophosphate in asthma

Abstract

Bucchioni and colleagues1Bucchioni E. Csoma Z. Allegra L. et al.Adenosine 5′-monophosphate increases levels of leukotrienes in breath condensate in asthma.Respir Med. 2004; 98: 651-655Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar examined the concentrations of cysteinyl-leukotrienes and histamine in exhaled breath condensate following bronchoprovocation with methacholine and adenosine monophosphate in healthy controls and asthmatic patients. Although the findings showing the lack of change in either histamine or cysteinyl-leukotrienes concentrations in breath condensate following methacholine bronchial challenge was not surprising, the absence of an increase in histamine concentration following adenosine monophosphate challenge was unexpected. Methacholine acts directly on airway smooth muscle cells leading to bronchoconstriction whereas adenosine monophosphate acts indirectly on surface A2-purinoceptors on primed mast cells triggering the release of pro-inflammatory mediators such as prostaglandins, cysteinyl-leukotrienes and histamine. Modern histamine H1-receptor antagonists such as desloratadine, fexofenadine, and levocetirizine at clinically recommended doses as either monotherapy or add-on therapy to inhaled corticosteroids have been shown to attenuate bronchial hyperresponsiveness leading to significant improvement in the provocative concentration of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1s compared to placebo.2Lee D.K. Bates C.E. Currie G.P. et al.Comparative in vivo bioactivity of modern H1-antihistamines on AMP challenge in atopic asthma.J Allergy Clin Immunol. 2003; 111: 337-341Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 3Lee D.K. Jackson C.M. Haggart K. et al.Repeated dosing effects of mediator antagonists in inhaled corticosteroid-treated atopic asthmatic patients.Chest. 2004; 125: 1372-1377Crossref PubMed Scopus (19) Google Scholar, 4Lee D.K. Gray R.D. Wilson A.M. et al.Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma.Br J Clin Pharmacol. 2004; 58: 34-39Crossref PubMed Scopus (25) Google Scholar Therefore, although the study serve to strengthen the fact that adenosine monophosphate acts indirectly by releasing cysteinyl-leukotrienes from primed mast cells, the findings of the authors should not be interpreted as casting doubt as to the involvement of histamine in mediating the response following indirect bronchial challenge testing. The study should thus act as a catalyst for future research into this area rather than providing definitive proof of mediators involved in the response following both direct and indirect bronchial challenges. Histamine levels following adenosine monophosphate challengeRespiratory MedicineVol. 99Issue 4PreviewIn commenting the results of our study on cysteinyl-leukotrienes and histamine following metacholine and AMP bronchial challenge Lee et al. are correct in pointing out that our findings do not rule out involvement of histamine in mediating the response following adenosine monophosphate (APM) challenge. The failure to detect increases in histamine following AMP challenge is probably due to the sensitivity of the assay or factors that may reduce the concentration of histamine in exhaled breath condensate. Full-Text PDF Open Archive