Early rise in exhaled no and mast cell activation in repeated low dose allergen challenge

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

^* To whom correspondence should be addressed. E-mail: barbro.dahlen{at}ki.se.

	Abstract

Repeated low dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. We performed a controlled study to evaluate the time course of changes in exhaled nitric oxide (F_ENO) and urinary biomarkers of airway inflammation.

Eight subjects with mild allergic asthma completed two seven-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and F_ENO and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine.

Despite no change in pulmonary function (FEV₁ mean fall (±SE): 0.3(±0.7) vs 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 F_ENO (up to a doubling from baseline) and a small increase in the mast cell marker 911-PGF₂ after adenosine challenge.

Serial measurements of F_ENO 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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