ORIGINAL ARTICLE AIRWAY DISEASES The allergen specificity of the late asthmatic reaction M. Hatzivlassiou, C. Grainge, V. Kehagia, L. Lau & P. H. Howarth Infection, Inflammation and Immunology Division, University of Southampton School of Medicine, Southampton General Hospital, SO16 6YD, UK To cite this article: Hatzivlassiou M, Grainge C, Kehagia V, Lau L, Howarth PH. The allergen specificity of the late asthmatic reaction. Allergy 2010; 65: 355–358. Inhaled allergen challenge in sensitized asthmatics induces an early asthmatic reaction (EAR) as a result of IgE-mediated mast cell activation and subsequent bronchial smooth muscle cell constriction (1). This is succeeded by a late asthmatic reaction (LAR) 3–8 h later in some individuals, that is char- acterized by further airway obstruction, airway inflammation and an increase in airways hyperresponsiveness (2). The late reaction is thus considered a better predictor of clinical asthma than the immediate reaction. The mechanisms under- lying the LAR are less clear than the early response but are considered likely to be generated, at least in part, by T cell activation (2–4). The ability of different allergens to induce a LAR may differ; seasonal asthma during the hay fever season is not as common as, and differs from, house dust mite- related perennial asthma, in that it responds well to antihista- mine therapy (5), inferring that this form of asthma may be more dependent on immediate type responses. To evaluate of the allergen specificity of the LAR, we examined the presence and magnitude of the LAR in asthmatics sensitized to both house dust mite and grass pol- len allergens, by examining the airway bronchoconstrictor response, the change in airway reactivity and induced airway inflammation after separate inhalation challenges with these allergens, matched to achieve the same magnitude EAR. Methods Subjects Six volunteers (three male) with mild asthma were recruited. All were nonsmokers and had documented physician diag- nosed asthma, positive skin prick tests to grass pollen and house dust mite, resting FEV 1 > 75% of predicted and a PC 20 to histamine of £10 mg/ml at screening. Subject baseline characteristics are shown at Table 1. Subjects were excluded if they had experienced a respiratory infection within 4 weeks of the study, an exacerbation requiring oral steroids within the preceding three months or deteriorating asthma requiring Keywords allergen challenge; asthma; chitin; house dust mite; late reaction. Correspondence Peter H. Howarth, Infection, Inflammation and Immunology Division, University of Southampton School of Medicine, Mail Point 810, Level F, South Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Accepted for publication 24 July 2009 DOI:10.1111/j.1398-9995.2009.02184.x Edited by: Marc Humbert Abstract Background: Allergen inhalation challenge in asthma may induce both early (EAR) and late (LAR) asthmatic reactions. The EAR is IgE and mast cell dependent. The mechanism of the LAR is less well defined and we have hypothesized may be aller- gen dependent. The aim of this study was to investigate the allergen specificity of the LAR to allergen inhalation in asthma. Methods: In a randomized, double-blind, crossover design six asthmatic volunteers with dual sensitization to house dust mite (HDM) allergen and grass pollen (GP) allergen underwent inhalation allergen challenge with these separate allergens on two occasions separated by 14 days. Lung function changes were followed for 8-h postchallenge. Bronchial reactivity (histamine PC 20 ) and airway inflammation, assessed by induced sputum differential cell count, were measured 24-h pre and postallergen challenge. The allergen inhalation challenges were matched to achieve the same magnitude of EAR. Results: Despite comparable group mean EAR percent falls in FEV 1 (25.8% follow- ing GP and 28.0% following HDM (P = 0.917), the LAR was statistically greater on the HDM challenge day (13.0%vs 22.8% [P = 0.046]) and was associated with a significant airway eosinophil recruitment (mean (SD) of 5.4 (4.8)% to 22.1 (18.2)% (P = 0.028) that was not evident on the GP allergen challenge day. Conclusions: These findings identify the allergen specificity of the LAR and indicate that factors independent of IgE contribute to the LAR. Such findings have relevance both to the understanding of the allergen-induced airway responses in asthma and the need for homogeneity in inhaled-allergen challenge studies in asthma. Allergy Allergy 65 (2010) 355–358 ª 2009 John Wiley & Sons A/S 355