In addition, by enriching the study population with well-defined group of asthmatics, this design has increased our confidence that we could detect any difference between asthmatics and non asthmatics. methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects’ homes. == Results == Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1(mite p = 0.001, cat p = 0.0001, dog p = 2.95 10-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 10-8, cat p = 3.93 10-10, dog p = 3.03 10-15, grass p = 2.95 10-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control). == Conclusions == In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR. Keywords:IgE, atopy, quantitative assay, lung function, airway hyperresponsiveness == Background == The association between reduced lung Rabbit polyclonal to BCL2L2 function and allergen sensitisation (mainly to inhalant allergens) has been clearly documented, both among children[1-7] and adults[8], often in the context of high allergen exposure[1,8]. A similar association has also been demonstrated for increased airway hyperresponsiveness amongst atopic individuals compared to those not sensitised[7-13]. Most of the studies investigating the relationship between allergen sensitisation and lung function or airway hyperresponsiveness (AHR) considered atopy as a simple dichotomous variable, assigning individuals as atopic or non-atopic based on arbitrary and differing cut-off points, either for IgE measurement or skin prick testing. [1-5,8-11]. Similar is the case for the studies reporting on the association between atopy and wheeze or other symptoms of allergic disease[14,15]. Analysing sensitisation quantitatively has been shown to improve the specificity of these tests. For example, the level of specific IgE may predict the likelihood of individuals having symptomatic food allergy[16] and the size of the skin prick test wheal can be used in a similar way[17]. We have previously demonstrated related quantitative relationship between specific serum IgE levels to CEP dipeptide 1 common inhalant allergens and the presence and persistence of child CEP dipeptide 1 years wheezing and reduced lung function[6]. We have also shown a similar association between increasing levels of sIgE or size of pores and skin test wheal to inhalant allergens and the presence of child years allergic rhinitis[18]. However, very few studies in adults have investigated a quantitative relationship between atopy and lung function. A study in the US has shown that AHR increased significantly amongst adult asthmatics with increasing size of pores and skin test wheals to inhalant allergens[11]. A significant association was also reported amongst non-asthmatic individuals with increasing level of mite specific IgE[12]. We targeted CEP dipeptide 1 to investigate the associations between the quantification of atopy (using specific IgE levels and the size of pores and skin test wheal to a range of common inhalant allergens) and lung function guidelines (FEV1, FVC) and AHR inside a human population of adults with and without asthma, evaluating this in the context of smoking practices and interior allergen exposure. == Methods == == Study Population == Detailed phenotyping which included info on symptoms and assessment of lung function, airway reactivity and atopy was carried out amongst parents of children enrolled in a population-based birth cohort study (Manchester Asthma and Allergy Study) [19,20]). We enriched the study human population with cautiously phenotyped asthmatics fulfilling the following criteria: (1) physician-diagnosed asthma; (2) asthma symptoms (wheeze, cough, chest tightness, or breathlessness) in the previous 12 months; (3) currently using asthma treatment; and (4) no asthma exacerbation or respiratory illness within 4 weeks before the study.[8]. Only subjects of mixed Western origin were.