Wha-Yong Lee1, Thomas Southworth, Steven Booth, Dave Singh. 1. Manchester Academic Health Science Centre, Manchester, UK; University Hospital South Manchester NHS Foundation Trust, Manchester, UK; NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Medicines Evaluation Unit, The University of Manchester, Manchester, UK.
Abstract
AIMS: The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. METHODS: Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day(-1) ) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. RESULTS: The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1 ) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1 , but had no effect on FEV1 at 24 h after challenge or sputum measurements. CONCLUSIONS: The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.
AIMS: The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. METHODS: Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day(-1) ) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. RESULTS: The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1 ) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1 , but had no effect on FEV1 at 24 h after challenge or sputum measurements. CONCLUSIONS: The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.
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