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document
Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge . BACKGROUND Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma . However , clinical symptoms are less likely to be induced . Therefore , we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation . METHODS A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days . Pulmonary function and exhaled NO were measured at every visit . Induced sputum was analysed before and after the allergen challenges for cell counts , ECP , IL-5 , INF-γ , IL-8 , and the transcription factor Foxp3 . RESULTS We found a significant decrease in pulmonary function , an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness , as well as a significant induction of eNO , eosinophils , and Th-2 cytokines . Repeated provocation was feasible in the majority of patients . Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms . CONCLUSIONS Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation . The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations . TRIAL REGISTRATION ClinicalTrials.govNCT00677209 .
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Intervention_Educational
repeated high-single-dose allergen challenge
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Intervention_Educational
repetitive high-dose allergen challenges with household dust mites for four consecutive days
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Outcome_Physical
Airway responses and inflammation
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Outcome_Physical
Pulmonary function
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Outcome_Physical
exhaled NO
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Outcome_Physical
Induced sputum
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Participant_Condition
27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma