Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Air pollutant exposure has been linked to a rise in wheezing illnesses. Clinical data highlight that exposure to mainstream tobacco smoke (MS) and environmental tobacco smoke (ETS) as well as exposure to diesel exhaust particles (DEP) could promote allergic sensitization or aggravate symptoms of asthma, suggesting a role for these inhaled pollutants in the pathogenesis of asthma. Mouse models are a valuable tool to study the potential effects of these pollutants in the pathogenesis of asthma, with the opportunity to investigate their impact during processes leading to sensitization, acute inflammation and chronic disease. Mice allow us to perform mechanistic studies and to evaluate the importance of specific cell types in asthma pathogenesis. In this review, the major clinical effects of tobacco smoke and diesel exhaust exposure regarding to asthma development and progression are described. Clinical data are compared with findings from murine models of asthma and inhalable pollutant exposure. Moreover, the potential mechanisms by which both pollutants could aggravate asthma are discussed

[Contribution of epidemiology to the study of allergic response in children].

International audienceAllergy is the conjunction of hereditary predisposition and risk factors encountered in the environment, phenomenon which can be observed very early in individual life. The aim of this review is to present the contribution of epidemiology in the study of allergic response in childhood, from sensitization to clinical manifestations as eczema, asthma and rhinitis. The first contribution of epidemiology has consisted in estimating the scatter of the allergic response, the presence of circulating antibodies against allergens (IgE and IgG), the evaluation of immediate hypersensitivity (such as the response to skin prick tests) and the prevalence of clinical manifestations. Then, knowledge of allergic response has been improved by the contribution of aetiological epidemiology. Various risk factors have been described according to the different stages during life in which their effects are observable. In prenatal life, potential risk factors are maternal immunity and smoking during pregnancy. Later in perinatal or neonatal life they are perinatal complications, month of birth and maternal smoking. Lastly, in infancy a role can be played by feeding, immunological deficiencies, infections, parental smoking and early exposure to allergens or pollution. Perceiving these risk factors helps to determine strategies to prevent allergy occurrence

In utero exposure to parental smoking, cotinine measurements, and cord blood IgE.

International audienceThe relationship between parental smoking and cord blood IgE has been studied in a survey conducted in 99 unselected newborn infants with a sensitive tests for IgE and cotinine as a biologic marker to validate smoking data. For both cord blood cotinine and maternal urine continine creatinine ratio (CCR), significantly higher levels were observed for smokers compared to nonsmokers. Furthermore, among nonsmokers, passive smokers had significantly higher cotinine levels than true nonsmokers, which demonstrates that cord blood may be used to assess active as well as passive maternal smoking. No association was observed in this study between cord blood IgE and maternal smoking assessed by questionnaire (geometric means of cord blood IgE levels were 0.11 IU/ml for newborn infants of smoking mothers and 0.12 IU/ml for newborn infants of nonsmoking mothers). The same observations were drawn from the analysis of cord blood IgE and cotinine levels, with correlation coefficients of -0.005 for cord blood CCR and 0.003 for maternal CCR. Additional studies are needed to determine whether maternal smoking is causally related to cord blood IgE and by which mechanisms

[Contribution of epidemiology to the study of allergic response in children].

International audienceAllergy is the conjunction of hereditary predisposition and risk factors encountered in the environment, phenomenon which can be observed very early in individual life. The aim of this review is to present the contribution of epidemiology in the study of allergic response in childhood, from sensitization to clinical manifestations as eczema, asthma and rhinitis. The first contribution of epidemiology has consisted in estimating the scatter of the allergic response, the presence of circulating antibodies against allergens (IgE and IgG), the evaluation of immediate hypersensitivity (such as the response to skin prick tests) and the prevalence of clinical manifestations. Then, knowledge of allergic response has been improved by the contribution of aetiological epidemiology. Various risk factors have been described according to the different stages during life in which their effects are observable. In prenatal life, potential risk factors are maternal immunity and smoking during pregnancy. Later in perinatal or neonatal life they are perinatal complications, month of birth and maternal smoking. Lastly, in infancy a role can be played by feeding, immunological deficiencies, infections, parental smoking and early exposure to allergens or pollution. Perceiving these risk factors helps to determine strategies to prevent allergy occurrence

Relationship of upper airway disease to tobacco smoking and allergic markers: a cohort study of men followed up for 5 years.

International audienceData derived from a cohort study of 191 men, seen 5 years apart, were used to investigate the involvement in allergic as well as in nonallergic upper airway disease (UAD) of two risk factors, immediate hypersensitivity and tobacco smoking, the roles of which have been well established in lower airway disease. At both surveys, UAD and smoking habits were assessed by an extended version of the BMRC/ECSC questionnaire. UAD consisted of usual or chronic rhinitis, seasonal allergic rhinitis and perceived nasal hyperresponsiveness (PNHR) to tobacco smoke, cold air or exercise. Immediate hypersensitivity was determined either in vivo (skin prick test, SPT, positivity) or in vitro (total IgE). UAD prevalence and smoking habits did not vary significantly over 5 years. On the contrary, SPT positivity increased significantly between the two surveys. At both surveys, SPT positivity for common aeroallergens (grass pollens overall) was significantly related to seasonal allergic rhinitis but not to usual or chronic rhinitis and to PNHR. Similarly, the total IgE level was increased in seasonal allergic rhinitis, but never significantly. Current smoking was always a habit significantly more frequent in men reporting chronic rhinitis (odds ratios of 5.3 and 4.9 in 1985 and 1990, respectively). The relationship was of the dose-response type: the more the subjects smoked, the more they reported chronic rhinitis. In contrast, seasonal allergic rhinitis was more associated with exsmoking, either in 1985 or in 1990. These results were confirmed longitudinally and after exclusion of asthmatics. Further investigations are needed to support the hypothesis raised by our data according to which immediate hypersensitivity, as assessed by SPT positivity for common aeroallergens, and tobacco smoking might intervene alternatively in UAD, probably because of the 'healthy smoker effect'

Coffee drinking and prevalence of bronchial asthma.

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The relation between snoring and smoking, body mass index, age, alcohol consumption and respiratory symptoms.

International audiencePotential risk factors for snoring were studied in a population of 457 middle-aged men. Eversnoring was reported by 60% of the men and snoring with an age of onset before or equal to 20 years by 13%. Eversnoring was significantly related to older age, higher body mass index and smoking habits. Alcohol consumption, estimated by questionnaire and gamma-glutamyl transpeptidase was unrelated to a history of snoring. Logistic regression showed that snoring was independently associated with age, body mass index and smoking habits. An exposure-effect relationship clearly appeared between tobacco consumption and snoring. After adjustment for smoking habits, none of the upper or lower respiratory symptoms was significantly related to snoring

Cat sensitization according to cat window of exposure in adult asthmatics

P>Background In adults, there is limited information on tolerance to cat, which may be reflected by high IgG(4) without IgE sensitization. Early exposure to cat may play a critical role. Objective The aim was to assess among adults the association of Fel d 1 IgG(4), Fel d 1 IgE, skin prick test (SPT) response to cat and pet-related symptoms in relation to exposure to cat considering the period of exposure. Methods SPT response to cat, specific IgE and IgG(4) to Fel d 1 were assessed in 167 asthmatics recruited in chest clinics (40 years of age in average) from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Childhood and/or current exposure to cat were studied retrospectively. Results IgG(4) was higher in relation to current cat exposure (0.53 vs. 0.09 ng/mL; P <0.001) and higher in women than in men. The period of cat exposure was significantly related to Fel d 1 IgE, the IgE/IgG(4) pattern and cat weal size. The lowest values of Fel d 1 IgE, cat weal size, pet-related nasal or respiratory symptoms were observed in those with both childhood and current exposure as well as the highest proportion of the IgE <SU- </SU/IgG(4) <SU+ </SU pattern observed in 1.4%, 4.0%, 38.1% and 12.5% of those with -/-, +/-, +/+, -/+ childhood/current exposure, respectively. Conclusions Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG(4) and low IgE. Continuous exposure may maintain a state of immunological tolerance to ca

Relationships of active smoking to asthma and asthma severity in the EGEA study. Epidemiological study on the Genetics and Environment of Asthma.

International audienceThe role of smoking as potential risk factor, selection factor ("healthy smoker" effect) and modifying factor (severity) of asthma was studied in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The analysis involved 200 adult asthmatic cases recruited in chest clinics, 265 nonasthmatic controls and 586 relatives of asthmatics (147 with asthma). Asthma in childhood was not associated with a reduced take-up of smoking (odds ratio (OR)=1.06 in males and 0.98 in females), but smoker asthmatic cases quit more often than controls (OR = 2.20 (95% confidence interval (95% CI) 1.11-4.34) in males and 2.76 (1.19-6.42) in females). Adult onset asthma was unrelated to ever smoking (OR 1.07 in males and 1.02 in females). In asthmatic cases, active smoking was associated with asthma severity. Current smokers, compared to never and exsmokers, had more asthma symptoms, more frequent (> or =1 attack x day(-1)) asthma attacks (OR 2.39 (95% CI 1.06-5.36)) and higher asthma severity scores. No clear pattern regarding the relationships of smoking habits with asthma was observed in first degree relatives. It is concluded that active smoking is not a risk factor for asthma in adulthood, but that smoking increases asthma severity