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Published online before print March 1, 2006, 10.1183/09031936.06.00142905
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Eur Respir J 2006; 27:1152-1159
Copyright ©ERS Journals Ltd 2006

Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge

E. Ihre1, P. Gyllfors1, L. E. Gustafsson2, M. Kumlin3 and B. Dahlén4

1 Division of Respiratory Medicine, Dept of Medicine, Karolinska University Hospital Solna, 2 Dept of Physiology and Pharmacology, and 3 Division of Physiology, The National Institute of Environmental Medicine, and 4 Division of Respiratory Medicine and Allergy, Dept of Medicine, Centre for Allergy Research at Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

CORRESPONDENCE: B. Dahlén, Division of Respiratory Medicine and Allergy, Dept of Medicine, C1 88, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Fax: 46 87117306. E-mail: barbro.dahlen{at}ki.se

Keywords: Adenosine 5'-monophosphate, airway hyperresponsiveness, allergic asthma, exhaled nitric oxide, leukotrienes, prostaglandins

Received: December 14, 2005
Accepted February 14, 2006

Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (Fe,NO) and urinary biomarkers of airway inflammation.

Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and Fe,NO and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine.

Despite no change in pulmonary function (forced expiratory volume in one second mean±SEM fall 0.3±0.7 versus 0.6±1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in Fe,NO (up to a doubling from baseline) and a small increase in the mast cell marker 9{alpha}11ß-prostaglandin F2 after adenosine challenge.

In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.




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H. Meurs, R. Gosens, and J. Zaagsma
Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models
Eur. Respir. J., August 1, 2008; 32(2): 487 - 502.
[Abstract] [Full Text] [PDF]




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