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 (F(e,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 F(e,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 F(e,NO) (up to a doubling from baseline) and a small increase in the mast cell marker 9alpha11beta-prostaglandin F(2) 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.