title: Adenosine 5'-monophosphate increases levels of leukotrienes in breath condensate in asthma.
abstract: Hyperresponsiveness (AHR) is a key physiological abnormality in asthma. In clinical and research studies AHR is measured bronchial challenge, with methacholine (MCh), but more recently with adenosine-5'-monophosphate (AMP). In the search for markers of airway inflammation in asthmatic patients, we measured the concentrations of histamine and cysteinyl-leukotrienes (cys-LTs) before and after MCh and AMP challenges in the exhaled breath condensate of 13 patients with mild asthma (FEV1 78.5%pred) and nine healthy non-smokers, using specific enzyme immunoassays. With methacholine challenge we did not find any differences between asthmatics and normal subjects in the pre- and post-challenge concentrations of cys-LTs: 27.2+/-1.4 vs. 29.2+/-1.2 pg/ml and 26.3+/-2.2 vs. 27.5+/-4.2 pg/ml, respectively or histamine: 5.1+/-0.4 vs. 5.1+/-0.6 nM and 4.5+/-0.4 vs. 4.4+/-0.3 nM; P>0.05). In asthmatic patients cys-LT levels were significantly higher after AMP challenge (56.2+/-9.7 vs. 31.7+/-6.9 pg/ml; P<0.05); but there was no difference in healthy subjects (27.2+/-4.6 vs. 30.3+/-4.7 pg/ml). There was no difference in histamine concentrations in asthmatic (5.9+/-1.8 vs. 4.5+/-0.5 nM), or healthy subjects (5.5+/-0.4 vs.5.7+/-0.9 nM) after AMP challenge. In conclusion, our results show that the cys-LTs are increased in exhaled breath condensate after AMP challenge, which may indicate that the AMP acts indirectly by releasing cys-LTs from primed mast cells. The detection of LTs and histamine in exhaled breath condensate may be useful in monitoring asthma.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
authors.forename: E
authors.initials: E
authors.lastname: Bucchioni
authors.forename: Z
authors.initials: Z
authors.lastname: Csoma
authors.forename: L
authors.initials: L
authors.lastname: Allegra
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: S A
authors.initials: SA
authors.lastname: Kharitonov
mesh_terms: D000249:Adenosine Monophosphate; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests / Q000379:methods; D003545:Cysteine / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D016210:Methacholine Chloride; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D003545:Cysteine