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International audience; Anaphylaxis during anaesthesia is a life-threatening conditionwith an estimated incidence of approximately 1:10,000.1 Broncho-spasm during general anaesthesia is classically associated with anIgE-mediated reaction but other underlying mechanisms havebeen described during general anaesthesia.2 It is well known thatbeing overweight is associated with an increased risk of airwayhyperresponsiveness (AHR). The aim of this study is to determinewhether being overweight is associated with an increased risk ofbronchospasm or non-IgE-mediated bronchospasm during generalanaesthesia and describe the clinical characteristics of patientswith bronchospasm

International audience; Multiple drug hypersensitivity syndrome (MDHS) is defined as confirmed drug hypersensitivity (DH) to at least 2 chemically and pharmacologically unrelated drugs. Reports of MDHS are scarce and poorly specified, and studies that diagnose MDHS on the basis of positive allergy test results are lacking.Objective: To evaluate retrospectively the frequency and characteristics of patients with MDHS in a large database.Methods: We included all patients who consulted and were tested in our Allergy Unit between September 1996 and February 2018 for a suspicion of DH. Clinical history and allergy workup results compiled in our Drug Allergy and Hypersensitivity Database were reviewed, and data of patients with a diagnosis of MDHS were retrieved and analyzed.Results: During this period a total of 9250 patients were explored and 1819 tested positive for at least 1 drug. Forty-five cases, 30 female and 15 male patients cumulating 92 DHs, were confirmed as having MDHS. An immunologic mechanism, as demonstrated by positive skin testing, accounted for 59 DHs. Drug provocation tests were performed to confirm the diagnosis for the remaining 33 DHs. Of the 92 DHs in this series, 38 were classified as type IV and 21 as type I allergies; 33 remained of undetermined mechanism. Drug class occurrences seem to differ from those in monoallergic patients.Conclusions: Our data support the concept of MDHS as a distinct and rare subgroup of DH. The prevalence in our database was 2.5% in the total DH alleged patient population and 0.5% of the demonstrated DHs. Skin testing and drug provocation tests are mandatory for confirming the diagnosis.

International audience; BACKGROUND: Although the negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known, the effect of ETS on allergic sensitization is still debated. OBJECTIVE: To evaluate how maternal allergies modulate the effect of tobacco exposure on allergic sensitization in childhood. METHODS: Of 9000 children in grades 4 and 5 selected in 6 cities in France, 7798 participated in a survey that consisted of an epidemiologic questionnaire, skin prick testing to common allergens, and skin examination for eczema. Tobacco exposure was obtained from parent questionnaires. RESULTS: Twenty-five percent of the children had allergic sensitization, 25.2% had eczema, 11.6% had allergic rhinitis, 9.9% had asthma, and 8.3% had exercise-induced asthma. Twenty percent of the children were exposed to tobacco in utero. Maternal exposure had a greater impact than paternal exposure on children's allergic sensitization. Prenatal exposure was more associated with sensitization than postnatal exposure. Children with maternal allergies and exposure to maternal ETS during pregnancy were at higher risk for sensitization to house dust mite (25.7% vs. 14.0%; odds ratio, 1.95; 95% confidence interval, 1.19-3.18; P = .006). In contrast, sensitization to food allergens was not associated with tobacco exposure. CONCLUSIONS: Children exposed to maternal smoking had a higher risk of sensitization to house dust mite, especially when the mothers were allergic.

International audience; Since December 2009, chest physicians and allergologists in Burgundy have been able to call upon a medical indoor environment counsellor (MIEC). The consultations are free for the patient and are undertaken following a medical referal after systematic cutaneous prick tests. To describe the indications, the distribution of prescriptions and to measure the impact of the counsellor's visits on the first 100 patients at 6 months and on the physicians at 18 months. Telephone interviews with the 67 physicians (whether prescribers or not) concerning their motivation and/or expectations, and with the first 100 patients concerning follow up of the recommendations. Seventy percent of the physicians replied (n=47). The satisfaction of prescribers (n=22) was 8.42/10. The indications were rhinitis and a poorly controlled asthma. The requests concerned the search for dust mite (50%) and moulds (46%). Eighty-four percent of the physicians discussed the MIEC's report with the patients. The patients' symptoms were rhinitis (79%), asthma (57%) and conjunctivitis (33%). The Acarex test(®), performed in cases of positive prick tests to house dust mites (n=72), was strongly positive for 67 patients. Sixteen mould samples out of 21 were above the standard concentrations. Sixty-nine patients had followed the recommendations of the MIEC. The impact of the MIEC visits was perceived as positive by the physicians and the patients. The medico-economic impact warrants further evaluation.

International audience; We report the case of a 7-yr-old girl with no previous history ofatopic disease who developed abdominal pain with vomitingand anaphylactic reaction few minutes after ingestion of cow’smilk and cereals containing barley malt. Arrival to ouremergency pediatric hospital took only 5 min where a gradeIII shock had been detected, according to the classification ofRing and Messmer. After adrenaline IV and anti-histaminicadministration, her condition gradually improved.

International audience; This study aimed at investigating whether the efficiency of the leishmanin skin test (LST) to evaluate the immune status of individuals exposed to Leishmania (L.) infantum is age-related. It was conducted in two districts of the governorate of Kairouan, an endemic region for L. infantum infection in Tunisia. Healthy individuals (n = 119) were selected according to two criteria: no current or past history of visceral or cutaneous leishmaniasis, and their age range: 1-6 years (group I), 7-14 years (group II), and 20-66 years old (group III). Assessments comprised LSTs, in vitro lymphoproliferative response, and interferon-gamma (IFN-gamma) productions induced by soluble leishmanial antigens (SLA). LST recorded an overall of 89.07% and 89.9% concordance with T cell proliferation and IFN-gamma production induced by SLA, respectively. Using in vitro tests as gold standards, LST was found more sensitive for screening individuals from group I (96% and 100%, considering T cell proliferation and IFN-gamma production results, respectively), than group II (91% and 97%) and group III (70% and 74%,). Conversely, LST was less specific in group I (84% and 77%) than group II (100% and 94%) and group III (100% for both in vitro tests). Our results suggested that the strength of LST resided in its higher sensitivity, to unravel asymptomatic injections and cell mediated immunity to L. infantum parasite in infants and its higher specificity for screening adult individuals. Negative LST in adults and positive LST in children < 5 years, the population at risk of developing visceral leishmaniasis, remain the weaknesses of LST and should be interpreted with caution.; Le but de cette étude a été de voir si l'efficacité du test cutané à la leishmanine (TCL) à évaluer l'im-munité des individus exposés à Leishmania (L.) infantum dépend de l'âge du sujet testé. Nous avons conduit notre étude dans deux délégations du gou-vernorat de Kairouan, région endémique pour la transmission de L. infantum. Des individus sains (n=119) ont été sélectionnés selon les critères d'ab-sence d'antécédents de leishmaniose viscérale (LV) ou cutanée (LC) ainsi que leurs âges:1 à 6 ans (Groupe I); 7 à 14 ans (Groupe II); et 20 à 66 ans (Groupe III). Les évaluations ont compris le TCL, les réponses lymphoprolifératives et la synthèse de l'in-terféron-gamma (IFN-γ) induits in vitro par les antigènes leishmaniens solubles. Les résultats du TCL ont concordé globalement à 89.07% et 89.9% avec ceux des proliférations cellulaires T et de pro-duction d'IFN-γ, respectivement. Considérant les tests in vitro comme «gold standards», le TCL s'est avéré plus sensible pour examiner les individus du groupe I (96% et 100% de concordance avec les proliférations cellulaires T et la production d'IFN-γ, respectivement), que ceux du groupe II (91% et 97%), et ceux du groupe III (70% et 74%). Inversement, il s'est avéré moins spécifique pour l'évaluation du groupe I (84% et 77%), que du groupe II (100% et 94%) et que du groupe III (100% pour les deux tests in vitro).Ces résultats indiquent que la puissance du TCL réside, grâce à une sensibilité élevée, dans sa capacité à identifier une infection asymptomatique et l'acquisition d'une immunité à médiation cellulaire chez l'enfant, et une plus haute spécificité à examiner une population adulte. Un TCL négatif chez l’adulte ou positif dans la population à risquede développer une VL, enfants de moins de 5 ans, constituent les points faibles de ce test et devraient être pris avec précaution.

International audience; PURPOSE: Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics. METHODS: We searched for potential cases of DRESS with fluindione reported in the French pharmacovigilance database since 2000. RESULTS: Thirty-six cases of DRESS were included and concerned 17 women and 19 men. The mean age was 65 years (median: 68 years, range: 28-95 years). Kidneys and liver were the most frequent organs involved. Thirty-five cases were serious. In 5 cases, the effect was life-threatening. Most of the patients recovered. Fluindione was the only medicine suspected in 26 cases. Skin patch tests, performed in 10 cases, were positive with fluindione in 9 cases. CONCLUSIONS: Fluindione is not known to be a frequent cause of DRESS. However, the number of reports found is probably underestimated. The seriousness of DRESS, as all immuno-allergic adverse effects, contraindicates fluindione reintroduction. Coumarinic derivatives are the alternatives in patients who need oral anticoagulant treatment.

International audience; BACKGROUND: Allergic sensitization to Alternaria has been related to asthma in various studies, but its association with allergic rhinitis is still controversial. OBJECTIVES: The aim of this study was to assess at the population level the relationships in childhood between Alternaria sensitization and 'past-year rhinoconjunctivitis' (PYRC), 'ever hay fever' (EHF) and 'ever allergic rhinitis caused by allergens other than pollens' (EAR) according to the presence or the absence of asthma. METHODS: This study is part of the Six Cities Study, the French contribution to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II. Children underwent skin prick test (SPT) to Alternaria and parents filled a standardized medical questionnaire. RESULTS: Some 6726 children with a mean age of 10 years were examined. The overall prevalence of Alternaria sensitization was 2.8%, 0.8% for monosensitization. Prevalences of symptoms in sensitized children were 27.7% for PYRC, 27.0% for EHF and 30.4% for EAR. Adjusted Odds Ratios (OR) between Alternaria sensitization and allergic rhinitis phenotypes were 2.34 (95% confidence interval: 1.51-3.63) for PYRC, 2.40 (1.65-3.50) for EHF and 2.95 (2.05-4.23) for EAR. The relationship still remained in the case of monosensitization to Alternaria for both PYRC and EAR when excluding the asthmatic children [OR = 3.87 (1.54-9.78) and 2.88 (1.10-7.55) respectively]. CONCLUSION: In our population-based sample of children, we found a link between Alternaria sensitization and allergic rhinitis, independently of asthma, which is compatible with the mechanisms of deposition of Alternaria in the upper airways.

According to a 2000 estimate based on workforce data and the CAREX (Carcinogen Exposure) database 1 there were 386,000 deaths worldwide due to non-cancer respiratory diseases (asthma: 38,000; chronic obstructive pulmonary disease (COPD): 318,000; pneumoconioses: 30,000) and nearly 6.6 million disability-adjusted life years (DALYs) (asthma: 1,621,000; COPD: 3,733,000; pneumoconioses: 1,288,000) attributable to occupational exposure to airborne particulates. The same figures for Europe were 52,700 deaths (asthma: 6,200; COPD: 39,300; pneumoconioses: 7,200) and 868,000 DALYs (asthma: 139,000; COPD: 468,000; pneumoconioses: 261,000). Respiratory diseases rank as the third most prevalent occupational disease category (after ergonomic and stress-related diseases) according to a survey of occupational diseases in the European Union (EU). The prevalence of respiratory diseases was 296 per 100,000 population, with the highest proportion found in the mining industry. This amounts to almost 600,000 persons in the former 15 member states. Many of these diseases, though induced while working, are chronic, thus explaining the highest prevalence among older workers (0.5% aged 55–64 yrs). Traditional high-risk occupations, such as mining, farming, manufacturing and service work ( e.g. hairdressers), are among the professions with a high prevalence of occupational lung diseases. However, high rates of occupational lung disease are also seen in newer professions, such as public administration, education 2 and occupational cleaning; the latter could be a reflection of problems related to new cleaning procedures, as found by the European Community Respiratory Health Survey (ECRHS) 3, or to problems with indoor air in public spaces. The pneumoconioses induced by exposure to mineral and other dusts at high concentrations were the dominating occupational lung diseases in the early industrialisation era. Their prevalence has been decreasing during the past decades. At the same time the obstructive lung diseases have gained increased importance, first because these diseases are widespread in the population, hence even small occupational contributions …

International audience; The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

International audience; BACKGROUND: A close relation between asthma and allergic rhinitis has been reported by several epidemiological and clinical studies. However, the nature of this relation remains unclear. We used the follow-up data from the European Community Respiratory Health Survey to investigate the onset of asthma in patients with allergic and non-allergic rhinitis during an 8.8-year period. METHODS: We did a longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461 participants, aged 20-44 years, without asthma at baseline. Incident asthma was defined as reporting ever having had asthma confirmed by a physician between the two surveys. Atopy was defined as a positive skin-prick test to mites, cat, Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed. Participants were classified into four groups at baseline: controls (no atopy, no rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox proportional hazards models were used to study asthma onset in the four groups. FINDINGS: The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49), respectively; p

International audience; BACKGROUND/PURPOSE: Studies about the adaptation of ethnic types of skin to an environment radically different from their original environment are rarely found in the literature. We have evaluated the differences in the skin surface properties of three ethnic groups: Black, African or Caribbean Mixed-race and Caucasian women living in defined climatic conditions. METHODS: Biometrological evaluations of barrier function were made by measurements of transepidermal water loss (TEWL), skin hydration and skin dryness. To approach the skin protective coating we evaluated cutaneous lipid index (LI), cutaneous pH, skin frictional properties and skin wettability. RESULTS: The TEWL, cutaneous hydration, dryness and LI show no significant difference. Volunteers were given a self-assessment questionnaire regarding their hygiene and cosmetic practices. The results show that 100% of Black and 92% of African or Caribbean Mixed-race women use a hydrating product daily vs. only 16% of Caucasian women. They justify this practice by the 'dry skin' sensation that they feel if they do not use a moisturizer. We tried to assess objectively to the protective coating surface of the human skin: the hydrolipidic cutaneous film, by measurements of pH, frictional properties and wettability which show significant differences. We may suppose that the hydrophilic/lipophilic balance of the skin in these three ethnic groups is different. CONCLUSION: To interpret these results as accurately as possible, it would be interesting, in future investigations on the ethnic types of skin, to evaluate the sweat secretion, and to analyse each element of the sebaceous secretions quantitatively as well as qualitatively.

International audience; The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.

International audience; BACKGROUND/PURPOSE: The Reviscometer RVM600 that measures resonance running time (RRT) has been shown to be inversely related to the skin stiffness. However, very few publications describe the use of this instrument for testing the effect of cosmetic products. METHODS: Slight xerotic skin condition was induced by using an alkaline soap for 1 week. Skin has then been rehydrated with a lotion or further dehydrated and dried with sodium lauryl sulfate (SLS). Skin condition at the different stages of the study was evaluated by visual assessment for dryness and redness and by non-invasive methods (Corneometer, Cutometer, Reviscometer, Evaporimeter and squamometry). RESULTS: All methods showed highly significant changes after the slight drying phase with the soap usage. They illustrated skin repair after lotion treatment and further skin impairment after SLS application. Nevertheless, the Reviscometer was able to better statistically discriminate between the treatments (water, lotion, SLS) than the Cutometer . Measurement of the RRT along the transversal axis of the forearms was the most sensitive for differentiating between normal and dry skin and between the treatments on the basis of skin mechanical properties. CONCLUSION: The Reviscometer RVM600 is a sensitive instrument able to detect slight skin surface effect of cosmetics. Combined with published literature on the interpretation of RRT measurements on polymeric gel or in different skin conditions (elderly skin and photoaged skin), the Reviscometer looks to be a recommendable instrument to measure slight changes in SC stiffness/suppleness induced by cosmetic products.

online supplement; International audience; BACKGROUND: Delineating asthma subphenotypes is of interest to understand the cause of the disease. Few studies have addressed the interrelationships of quantitative asthma-related traits. OBJECTIVE: We sought to study the interrelationships of allergy markers and FEV(1) in relation to asthma and sex in children and adults. METHODS: Total IgE levels, skin prick test (SPT) positivity, eosinophil counts, and FEV(1) were assessed in 299 asthmatic cases (children and adults) recruited in chest clinics and 309 nonasthmatic population-based control subjects in the French Epidemiological Study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy. RESULTS: Allergy parameters were significantly higher in asthmatic cases than in control subjects for children and adults and for both sexes. Sex and age modified the pattern of concordance of high IgE levels, SPT positivity, and eosinophilia among asthmatic cases, with the greatest overlap in male children (64%) and the lowest in male adults (18%). Patterns of change over the lifespan of IgE levels, eosinophil counts, and FEV(1)/height(2) varied, with the acceleration of FEV(1) decrease being particularly evident in asthmatic adults. In adult cases and control subjects, SPT positivity (particularly to indoor allergens) was significantly related to IgE levels but not to eosinophil counts. The association of eosinophil counts with IgE levels was evident only in children. Environmental factors (smoking, pets, and country living) did not alter the patterns observed. CONCLUSIONS: Each allergy-related phenotype showed a distinct relation with asthma, with the role for eosinophils being different than that for IgE levels and SPT responses. CLINICAL IMPLICATIONS: Taking age and sex into account is essential for understanding the interrelationships of the various allergy-related phenotypes to asthma status.

online supplement; International audience; BACKGROUND: Delineating asthma subphenotypes is of interest to understand the cause of the disease. Few studies have addressed the interrelationships of quantitative asthma-related traits. OBJECTIVE: We sought to study the interrelationships of allergy markers and FEV(1) in relation to asthma and sex in children and adults. METHODS: Total IgE levels, skin prick test (SPT) positivity, eosinophil counts, and FEV(1) were assessed in 299 asthmatic cases (children and adults) recruited in chest clinics and 309 nonasthmatic population-based control subjects in the French Epidemiological Study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy. RESULTS: Allergy parameters were significantly higher in asthmatic cases than in control subjects for children and adults and for both sexes. Sex and age modified the pattern of concordance of high IgE levels, SPT positivity, and eosinophilia among asthmatic cases, with the greatest overlap in male children (64%) and the lowest in male adults (18%). Patterns of change over the lifespan of IgE levels, eosinophil counts, and FEV(1)/height(2) varied, with the acceleration of FEV(1) decrease being particularly evident in asthmatic adults. In adult cases and control subjects, SPT positivity (particularly to indoor allergens) was significantly related to IgE levels but not to eosinophil counts. The association of eosinophil counts with IgE levels was evident only in children. Environmental factors (smoking, pets, and country living) did not alter the patterns observed. CONCLUSIONS: Each allergy-related phenotype showed a distinct relation with asthma, with the role for eosinophils being different than that for IgE levels and SPT responses. CLINICAL IMPLICATIONS: Taking age and sex into account is essential for understanding the interrelationships of the various allergy-related phenotypes to asthma status.

International audience; Among early-life environmental factors, parental smoking (ETS) has been associated with adverse respiratory outcomes in children. The aim of the study was to evaluate whether parental smoking might lead to asthma and allergies taking into account family history of asthma, personal atopy, breast feeding as confounders and owing pets and day-care during the first 6 months of life as modifiers. About 9000 children of fourth and fifth grade were selected in six cities of France. About 7798 answered an epidemiological questionnaire, underwent a medical examination including skin prick test positivity to common allergens, skin examination for eczema, and run test to assess exercise-induced asthma (EIA). Prevalence of allergies was, respectively, 25.2% for eczema, 12.9% for rhinitis, 9.9% for asthma and 25% for atopy. About 8.3% had an EIA. About 21.6% of children were exposed to maternal tobacco smoking during pregnancy. Maternal smoking, in utero and later, was significantly related to lifetime wheezing (odds ratio (OR): 1.24[1.10-1.56]) and asthma (OR: 1.22[1.04-1.66]). There was no association between atopy, rhinitis, eczema and parental smoking, respectively. ETS remains a risk factor of wheezing in childhood. Counselling parents of children to quit smoking still remains a public health policy.

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International audience; BACKGROUND: The impact of air pollution on asthma and allergies still remains a debate. OBJECTIVE: Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren. METHODS: Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O3) were calculated at children' schools using measurements of background monitoring stations. RESULTS: After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O3. The adjusted odds ratios (aOR) per increase of 5 microg/m3 of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 microg/m3 of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2. CONCLUSIONS: A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.

International audience; BACKGROUND: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5 q 33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. OBJECTIVE: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. METHODS: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. RESULTS: One 15-bp insertion/deletion in exon 4 of TIM 1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07--1.45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12--1.47]; P=.0003). SNPs in the 5' genomic region in ITK, which show moderate linkage disequilibrium with those in TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. CONCLUSION: Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.

International audience; AIMS AND METHODS: Long term effects of air pollution on mortality were studied in 14,284 adults who resided in 24 areas from seven French cities when enrolled in the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox proportional hazards models controlling for individual confounders (smoking, educational level, body mass index, occupational exposure) were applied, and frailty models used to take into account spatial correlation. Indicators of air pollution were the mean concentration. RESULTS: Models were run before and after exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb). After exclusion of these areas, analyses showed that adjusted risk ratios (95% CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to 1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10 microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was associated with increased mortality over 25 years in France.

International audience; BACKGROUND: Exhaled nitric oxide (eNO) has attracted increasing interest as a non-invasive marker of airway inflammation in asthma. However, little evidence exists on the influences exerted on eNO by the interrelations among atopic status, asthma and rhinitis. METHODS: Among the 1156 children who participated in a large-scale epidemiological survey on asthma and allergies (ISAAC II: International Study of Asthma and Allergies in Childhood Phase II) in the city of Clermont-Ferrand, 53 asthmatics without corticosteroid treatment and 96 non-asthmatics were invited to perform eNO and skin prick tests (SPTs) to 12 common allergens. RESULTS: Atopic asthmatic children had higher eNO than non-atopic asthmatic children (28.9+/-9.1 vs. 17.1+/-13.1 p.p.b.; P=0.0004) with a significant increase when one SPT or more are positive (26.5+/-7.8 vs. 17.1+/-13.1 p.p.b.; P=0.03). Similarly, non-asthmatic, atopic subjects had higher eNO than non-atopic subjects with a significant increase when two SPTs or more are positive (19.4+/-9.8 vs. 11.7 +/-6.7 p.p.b.; P=0.003). In the case of equal levels of positive SPTs (0, 1, >/=2), asthmatic children always had higher eNO than non-asthmatic ones. Furthermore, among non-asthmatic children, the eNO level increased only in atopics who had rhinitis (20.7+/-13 vs. 12.5+/-6.4 p.p.b. in atopic controls (subjects without rhinitis and asthma) and 12.3+/-6.6 p.p.b. in non-atopic controls; P=0.001), whereas among asthmatic children, eNO level increased in atopics independently of rhinitis (28.2+/-9.5 p.p.b. in those with rhinitis and 30.9+/-8.1 p.p.b. in those without) as well as in non-atopics with rhinitis (22.5+/-17.2 p.p.b.). CONCLUSIONS: Our data suggest that besides atopy and asthma, allergic rhinitis should also be taken into account in the assessment of eNO.

International audience; BACKGROUND: Although allergy is highly associated with childhood asthma, it is not well known if there is a relationship between the intensity of allergic sensitization and asthma severity. OBJECTIVE: The objectives of the study were to examine the relationships between several markers of allergy and asthma severity in asthmatic children included in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA). METHODS: The population comprised 216 asthmatic children below 16 years of age. Total IgE and blood eosinophil counts were measured and skin prick tests to 11 aeroallergens were performed. The intensity of the allergic sensitization was assessed by the number of positive skin prick tests and by skin weal sizes. Asthma severity was measured with four criteria: a clinical severity score, history of hospitalization for asthma, FEV1% predicted and inhaled steroid use in the last 12 months. RESULTS: Most of the children were sensitized to at least one aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for a tendency for a more severe clinical score in non-atopic children. The type and intensity of the allergic sensitization were not associated with any criteria of asthma severity. Total IgE was significantly increased in children treated with inhaled corticosteroids and in children ever hospitalized for asthma (P-values 0.009 and 0.04, respectively). Eosinophil counts were not related to asthma severity. CONCLUSION: Our results suggest that severe childhood asthma may be related to a high level of total IgE but not to blood eosinophil counts. The lack of positive relationships between both atopy and the intensity of allergic sensitization with asthma severity supports the hypothesis of different risk factors being associated with asthma and with the severity of asthma.

Purified protein derivative (PPD) skin testing is used to identify persons infected withMycobacterium tuberculosis(Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and itsin vitrocorrelates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and/or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly,in vitrostimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-γ and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.

International audience; BACKGROUND: No validated assessment of allergic rhinitis (AR) is presently available that can be used in population studies in the absence of medical diagnosis and of objective measurements of allergy. To compensate for this lack, a quantitative Score For Allergic Rhinitis (SFAR) ranging between 0 and 16 has been developed by experts. METHODS: The SFAR, encompassing eight features of AR, was validated in three different ways: 1) among 269 outpatients taking the specialist's diagnosis of AR and skin prick tests (SPT) positivity as a gold standard (diagnosis validation); 2) using psychometric methods (internal validation); and 3) in a random population-based sample of 3001 individuals by telephone interview (population acceptability). RESULTS: A SFAR value > or = 7 allowed satisfactory discrimination between the outpatients with AR from those without (sensitivity = 74% [95% confidence interval CI: 0.69,0.79], specificity = 83% [0.79, 0.87], positive predictive value = 84% [0.80, 0.88], negative predictive value = 74% [0.69, 0.79] and Youden's index = 0.57, respectively). Internal consistency of the score was also high (among others, Cronbach's alpha coefficient = 0.79). On average, it took only 3 min for the individuals interviewed on the phone to complete the questionnaire, the questions of which were well understood. Among these subjects, the prevalence of AR was 21% [95% CI: 19.5%, 22.5%], which is comparable to other determinations in France. CONCLUSIONS: The newly a priori proposed Score For Allergic Rhinitis (SFAR) is easy to use and can be useful to estimate prevalence and to study causation of AR in population settings.

International audience; The relative influence of early life events in the development of IgE-mediated allergy is still undetermined. We investigated early life factors in relation to skin-prick test positivity (SPT) and clinical manifestations of atopic disease in a population-based sample of 201 Italian children (3 months-5 years), after considering their interactions with known determinants of allergy. Among them, 143 children had SPT performed to common allergens. Threatened abortions, general anesthesia at delivery, prematurity, birthweight < 2500 g, maternal smoking, dampness and gas heating exposure were all significantly related to an increased risk of frequent rhinitis in the absence of cold (18%). In utero smoking, threatened abortions, fetal health complications, infantile colic, maternal smoking in childhood (satisfactorily correlated with maternal expired CO during the survey) and respiratory infections were all independent determinants of frequent wheezing (23%). Doctor's diagnosis of asthma (3%) was related to in utero smoking, being born in spring, infantile colic and respiratory infections. A simultaneous exposure to in utero smoking and infantile colic put the infants to a fourfold higher risk of frequent wheezing and to a ninefold risk of asthma, respectively. Having a pet and washing blankets at < 60 degrees C were inversely related to frequent wheezing. Data confirmed also that maternal phenotype influences the inheritance of atopic disease. No event, except a low intake of fruit (< 3/week), was significantly associated with positive SPT (20%) or eczema. Besides allergic sensitization, other events, which occur early in life, seem critical to the development of IgE-mediated allergy.

International audience; The increase of total IgE in relation to active smoking has been shown in the general population, but little is known about subjects with a personal or family history of asthma. The objective of this report is to analyze the relationships of active and passive smoking to total IgE in the Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). The sample studied includes 122 asthmatic probands, 430 first-degree relatives, and 190 control subjects, age 25 to 54 yr. As expected, first-degree relatives had total IgE intermediate between cases and control subjects and men had higher values than women. Current smokers had significantly higher IgE than never smokers. The relationship was statistically significant restricting the analysis in asthmatic probands. In a model taking into account gender, personal and familial history of asthma, socio- occupational class, and the nonindependence of subjects from the same family, IgE were in current smokers, ex-smokers, and never smokers 128, 61, and 76 IU/ml and 77, 41, and 55 IU/ml in men (p = 0.01) and women (p = 0. 05), respectively. The relation was independent of skin test response. Some increase in IgE was observed in both men and women first-degree relatives in relation to passive smoking. That relation was statistically significant in women only (adjusted for asthma values: 103 IU/ml versus 48 IU/ ml, p = 0.02). Results show that an increase in total IgE in relation to active smoking may be evidenced even in asthmatics despite the healthy smoker effect. Susceptible subjects, such as women who are first-degree relatives of asthmatics, may increase total IgE in relation to passive smoking.

International audience; BACKGROUND: A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. OBJECTIVES: To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. METHODS: Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. RESULTS: In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm, respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). CONCLUSIONS: Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.

International audience; Allergy 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.

International audience; Epidemiologic data relating total circulating immunoglobulin E (IgE), an objective marker of allergy, to cross-sectional and longitudinal FEV1 as well as to methacholine bronchial hyperresponsiveness were obtained from 310 French adult men surveyed five years apart. Skin prick test responses to common aeroallergens, IgE level, and bronchial hyperresponsiveness were assessed at the end of the follow-up. IgE level was not associated with PD20 to methacholine. Cross-sectionally, age and height-adjusted FEV1 score was inversely related to total IgE level (regression coefficient of FEV1 score on Log[IgE] beta = -.20; p = 0.02). Stratified analysis showed that IgE level was associated with FEV1 score only in nonsmokers (beta = -0.52; p less than 0.001), an association that remained after exclusion of asthmatics. Longitudinally, five-year FEV1 decline was related to IgE in nonsmokers (regression coefficient of FEV1 decline on Log[IgE] beta = 19.9; p = 0.03) and exsmokers (beta = 18.9; p = 0.06) but not in current smokers. The relationship persisted, even if with lesser significance, among exsmokers after exclusion of asthmatics (beta = 17.2) and further exclusion of skin prick test-positive men (beta = 18.8). Whether IgE production also reflects factors other than allergy, possibly nonallergic inflammation, needs further investigations.

International audience; A previous cross-sectional analysis of 1980 data from a population of working men in the Paris area has shown a significant relationship of blood eosinophilia to a reduced FEV1 among nonsmokers, remaining after excluding men with a history of asthma. In the present report, we reexamine this relationship, after taking into account asthma, bronchial hyperresponsiveness, and positive skin prick tests, using data collected in 1985 in a subsample of 363 men from the initial population. Blood eosinophilia, defined by 5% or more eosinophils or by 250 or more eosinophils per cubic millimeter appeared to be associated with a lower FEV1, primarily in nonsmokers. A difference of approximately 0.40 L was observed in never-smokers with eosinophilia (greater than or equal to 5% of eosinophils) compared with those without. This association persisted after exclusion of subjects with atopy, asthma, and bronchial hyperresponsiveness. Longitudinally, no significant association was observed between 1980 eosinophilia and the annual FEV1 decline between 1980 and 1985, even in nonsmokers. The results of our cross-sectional analyses suggest that asthma or asthma-like disorder does not explain the association between eosinophilia and FEV1. The role of eosinophil in respiratory disorders may go beyond its intervention in allergy. Further longitudinal studies are needed to better understand discrepancies between cross-sectional and longitudinal data and whether eosinophilia is a risk factor for chronic air-flow limitation.

International audience; Five-year FEV1 decline in 329 working men was shown to be significantly related only among eversmokers to methacholine bronchial hyperresponsiveness (assessed at the end of follow-up), allergic rhinitis and rhinitis induced by cold air, independent of asthma and FEV1 level. Positive skin prick test was not associated with FEV1 decline.

International audience; When a vaccine in three different concentrations (non-diluted, half-strength and one-third strength) was used on a study population of 159 students, six weeks after the vaccination only the vaccine at one-third strength showed small vaccination lesions in comparison with those of the other two concentrations. There is no evidence of any significant difference between them with respect to the positive reaction to the tuberculin testing. After one year, the number of subjects with a positive vaccination scar is drastically reduced in the case of the vaccine at one-third strength. As regards the tuberculin reaction, even if the difference in the number of positive values is not significant, the reaction size for the one-third and one-half strength dose diminishes significantly with respect to that observed at six weeks.

International audience; A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.