Search

Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth.Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth.Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth.Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters. [ABSTRACT FROM AUTHOR]

A previous study reported positive associations of maternal urinary concentrations of triclosan, a synthetic phenol with widespread exposure in the general population, with placental DNA methylation of male fetuses. Given the high number of comparisons performed in -omic research, further studies were needed to validate and extend on these findings. Using a cohort of male and female fetuses with repeated maternal urine samples to assess exposure, we studied the associations between triclosan and placental DNA methylation. We assessed triclosan concentrations in two pools of 21 urine samples collected among 395 women from the SEPAGES cohort. We used Infinium Methylation EPIC arrays to measure DNA methylation in placental biopsies collected at delivery. We performed a candidate study restricted to a set of candidate CpGs (n = 500) identified in a previous work as well as an exploratory epigenome-wide association study to investigate the associations between triclosan and differentially methylated probes and regions. Analyses were conducted on the whole population and stratified by child's sex. Mediation analysis was performed to test whether heterogeneity of placental tissue may mediate the observed associations. In the candidate approach, we confirmed 18 triclosan-associated genes when both sexes were considered. After stratification for child's sex, triclosan was associated with 72 genes in females and three in males. Most of the associations were positive and several CpGs mapped to imprinted genes: FBRSL1 , KCNQ1 , RHOBTB3 , and SMOC1. A mediation effect by placental tissue heterogeneity was identified for most of the observed associations. In the exploratory analysis, we identified a few isolated associations in the sex-stratified analysis. In line with a previous study on male placentas, our approach revealed several positive associations between triclosan exposure and placental DNA methylation. Several identified loci mapped to imprinted genes. [Display omitted] • Pregnancy exposure to triclosan assessed from two pools of 21 urine samples per woman. • Triclosan increased placental DNA methylation at several loci. • 18 candidate genes were confirmed in the whole population, 72 in females, three in males. • Placental cell composition mediated part of these associations. • Several identified loci mapped to imprinted genes. [ABSTRACT FROM AUTHOR]

Exposure to phthalates and synthetic phenols is ubiquitous. Some of them are suspected to impact child respiratory health, although evidence still remains insufficient. This study investigated the associations between prenatal exposure to phthalates and phenols, individually and as a mixture, and child respiratory health assessed by objective lung function measures since 2 months of age. Among 479 mother-child pairs from the SEPAGES cohort, 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites were measured in 2 pools including each 21 urine samples collected at the 2nd and 3rd pregnancy trimesters. Lung function was measured at 2 months using tidal breathing flow-volume loops and nitrogen multiple-breath washout, and at 3 years using oscillometry. Asthma, wheezing, bronchitis and bronchiolitis were assessed by repeated questionnaires. A cluster-based analysis was applied to identify exposure patterns to phenols and phthalates. Adjusted associations between clusters as well as each individual exposure biomarker and child respiratory health were estimated by regression models. We identified four prenatal exposure patterns: 1) low concentrations of all biomarkers (reference, n = 106), 2) low phenols–moderate phthalates (n = 162), 3) high concentrations of all biomarkers except bisphenol S (n = 109), 4) high parabens–moderate other phenols–low phthalates (n = 102). At 2 months, cluster 2 infants had lower functional residual capacity and tidal volume and higher ratio of time to peak tidal expiratory flow to expiratory time (t PTEF /t E) and cluster 3 had lower lung clearance index and higher t PTEF /t E. Clusters were not associated with respiratory health at 3 years but in the single-pollutant models, parabens were associated with increased area of the reactance curve, bronchitis (methyl, ethyl parabens) and bronchiolitis (propyl paraben). Our results suggested that prenatal exposure to mixtures of phthalates reduced lung volume in early life. Single exposure analyses suggested associations of parabens with impaired lung function and increased risk of respiratory diseases. [Display omitted] • 457 mother-child pairs with early and objective children's respiratory measurements. • Phenols and phthalate biomarkers measured in 2 pools of 21 urine samples each. • Children were clustered into patterns of prenatal exposure to the chemical mixture. • Prenatal phthalates, parabens and bisphenol S might impact child respiratory health. [ABSTRACT FROM AUTHOR]

Background Asthma is a heterogeneous disease in which age of onset plays an important role. Objective We sought to identify the genetic variants associated with time to asthma onset (TAO). Methods We conducted a large-scale meta-analysis of 9 genome-wide association studies of TAO (total of 5462 asthmatic patients with a broad range of age of asthma onset and 8424 control subjects of European ancestry) performed by using survival analysis techniques. Results We detected 5 regions associated with TAO at the genome-wide significant level ( P < 5 × 10 −8 ). We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD] ) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor–like 1 [IL1RL1] ), 6p21 (HLA-DQA1) , 9p24 (IL33) , and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2] –gasdermin A [GSDMA] ). Conditional analyses identified 2 distinct signals at 9p24 (both upstream of IL33 ) and 17q12-q21 (near ZPBP2 and within GSDMA ). Together, these 7 distinct loci explained 6.0% of the variance in TAO. In addition, we showed that genetic variants at 9p24 and 17q12-q21 were strongly associated with an earlier onset of childhood asthma ( P ≤ .002), whereas the 16q12 single nucleotide polymorphism was associated with later asthma onset ( P = .04). A high burden of disease risk alleles at these loci was associated with earlier age of asthma onset (4 vs 9-12 years, P = 10 −4 ). Conclusion The new susceptibility region for TAO at 16q12 harbors variants that correlate with the expression of CYLD and nucleotide-binding oligomerization domain 2 (NOD2) , 2 strong candidates for asthma. This study demonstrates that incorporating the variability of age of asthma onset in asthma modeling is a helpful approach in the search for disease susceptibility genes. [ABSTRACT FROM AUTHOR]

BACKGROUND: To maximize the likelihood of successful long-term mechanical ventilation (MV) in patients with neuromuscular diseases, ventilator characteristics and settings must be chosen carefully, taking into account both medical requisites and the patient's preference and comfort. OBJECTIVES: To evaluate patients' knowledge about and comfort with their long-term MV; to compare patients' and prescribers' opinions and expectations regarding long-term MV; and to compare the equipment used by the patients to the prescribers' current MV prescription. METHODS: Neuromuscular patients receiving long-term MV, and home MV prescribers in Belgium and France were asked to respond to a questionnaire survey specifically developed for the study. RESULTS: Completed questionnaires were collected from 209 patients (mean age 35.4 ± 15.9 y, range 3-86 y), ventilated since 11 ± 17 year, and 45 MV prescribers. One hundred sixty-three (78%) patients correctly designated their MV mode as a volume or pressure controlled mode. When an inspiratory trigger was available, 92% of the patients were able to use it, but only 69% were satisfied. Prescribers were more prone than patients to use new technologies such as an emergency-release system for the noninvasive interface (1-10 visual analog scale score 9.2 ± 1.5 vs 6.8 ± 3.3, P < .001), a humidification system (8.6 ± 1.4 vs 7.8 ± 2.6, P = .02), a contactor for providing larger inspiratory volumes (8.4 ± 1.7 vs 6.0 ± 3.0, P = .009), a built-in cough assistance mode (9.2 ± 1.4 vs 5.5 ± 3.5, P < .001), new options to improve speech, or new MV modes such as a volume-targeted pressure control. CONCLUSIONS: The opinions of patients and prescribers differed about the ideal home ventilator. Patients were less prone to use new technologies, mainly because of a lack of information, underlining the need for regular MV update in patients receiving long-term MV. [ABSTRACT FROM AUTHOR]

Summary: Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma. Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006–2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1–7) and the generic SF-36 (scores range: 0–100) were used. Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (−1, p = 0.09), borderline significant for the MCS (−1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains. Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology. [ABSTRACT FROM AUTHOR]

Summary: Background: The association between smoking and asthma remains unclear and has mostly been assessed in cross-sectional studies, with potential selection bias (“healthy smoker effect”). Aims: Using a longitudinal approach, the aims were to assess whether 1) childhood asthma modifies smoking initiation, 2) active smoking influences asthma incidence in adults and 3) active smoking among subjects with asthma influences the persistence of the disease or the 12-year evolution in lung function in children and adults. Methods: Subjects (513 children and 1190 adults) were recruited and followed-up for 12 years in the context of the EGEA study (Epidemiological study on the Genetics and Environment of Asthma). Results: Childhood asthma was not associated with a decreased probability of starting active smoking (Hazard Ratio, HR = 0.96; 95% confidence interval (CI): 0.72, 1.27). Smoking at baseline was associated with a higher risk for asthma incidence in adulthood (HR = 1.95, 95% CI: 1.00, 3.77). Among subjects with asthma, smoking was unrelated to lung function evolution; however, among children with moderate to severe asthma at inclusion, smoking tended to slow down the lung function growth (P = 0.04). Conclusion: These findings support the hypothesis that childhood asthma does not prevent smoking initiation and confirm that active smoking has a deleterious role on asthma. Altogether this study emphasizes the importance of active smoking as a serious public health problem particularly for children and women. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic evidence related to asthma control in patients from the general population is scanty. Objectives: We sought to assess asthma control in several European centers according to the Global Initiative for Asthma (GINA) guidelines and to investigate its determinants. Methods: In the European Community Respiratory Health Survey II (1999-2002), 1241 adults with asthma were identified and classified into inhaled corticosteroid (ICS) users and non-ICS users in the last year. Control was assessed in both groups by using the GINA proposal (controlled, partly controlled, and uncontrolled asthma), and it was related to potential determinants. Results: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their asthma under control; individuals with uncontrolled asthma accounted for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%), respectively. Among ICS users, the prevalence of uncontrolled asthma showed great variability across Europe, ranging from 20% (95% CI, 7% to 41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species were associated with poor control in ICS users. About 65% and 87% of ICS users with uncontrolled and partly controlled asthma, respectively, were on a medication regimen that was less than recommended by the GINA guidelines. Conclusion: Six of 7 European asthmatic adults using ICSs in the last year did not achieve good disease control. The large majority of subjects with poorly controlled asthma were using antiasthma drugs in a suboptimal way. A wide variability in asthma control emerged across Europe. Clinical implications: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines. [Copyright &y& Elsevier]

Summary: Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990–94) and ECRHS-II (1998–2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was −2% (95% CI: −9.5, 5.5), 7.5% (−2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08–10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11–3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication. [Copyright &y& Elsevier]

Background: Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. Objective: To evaluate whether prolonged treatment with ICSs is associated with FEV1 decline in adults with asthma. Methods: An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV1 decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. Results: As ICS use increased, the decline in FEV1 was lower (P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction (P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV1 decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. Conclusion: Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. Clinical implications: This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management. [Copyright &y& Elsevier]

Background: Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. Objective: The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. Methods: The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. Results: Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% ± 20% vs 43% ± 12%, P < .05; and 25.02 ± 9.43 ng/mL vs 8.6 ± 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001). Conclusion: Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. Clinical implications: Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction. [Copyright &y& Elsevier]

Summary: Reduced pulmonary function is an important predictor of cardiovascular morbidity and mortality. The mechanisms underlying this association are unknown but may involve systemic inflammation. We assessed the cross-sectional and longitudinal relationships between C-reactive protein (CRP) levels and forced expiratory volume in 1s (FEV1) and its decline in the general population, over a period of 8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37±7 years, 50% women and 42% non-smokers), recruited at two French centers participating in the European Community Respiratory Health Survey. Lung function was expressed as a percentage of predicted FEV1. CRP was measured centrally, by means of a highly sensitive assay. In cross-sectional analysis, FEV1 as a % of predicted values was negatively associated with serum CRP concentration (). Multivariate adjustment did not alter these results (). In longitudinal analysis, annual FEV1 decline tended to increase from the lower to the upper tertile for baseline CRP concentration but the association was borderline significant (). Mean values of annual FEV1 decline were 26±32, 31±32, and 34±32ml/year for the lower, middle and upper tertiles of baseline CRP concentration, respectively, after adjusting for potential confounders (). Changes in CRP levels during follow-up were associated with annual FEV1 decline. The mean annual FEV1 declines in subjects with increasing CRP, in those with stable CRP and in those with decreasing CRP were 36±31, 30±31 and 24±31ml/year, respectively (). These findings were not affected by adjustment for potential confounders (). In conclusion, increases in CRP levels over time were associated with a steeper FEV1 decline. [Copyright &y& Elsevier]

Background: A higher exposure to bacterial compounds is purported to explain the lower prevalence of allergy in farm children, but responsiveness to bacterial compounds is modulated by genetic factors. Objective: To assess whether the protective effect of farm exposure on atopy is influenced by a CD14 promoter functional polymorphism. Methods: We administered a detailed questionnaire on farm exposure in childhood and genotyped the CD14 C-159T polymorphism in 2 French centers participating in the European Community Respiratory Health Survey (ECRHS)–II. Results: Six hundred randomly selected young adults provided blood samples for IgE measurements and had CD14 C-159T genotyped. Exposure to a farming environment in early life was associated with a reduced risk of nasal allergies (odds ratio [OR], 0.54; 95% CI, 0.29-1.00) and atopic sensitization (OR, 0.47; 95% CI, 0.24-0.93) in adulthood. A lower risk of allergic rhinitis and atopy was also observed in carriers of the CD14-159TT genotype compared with −159CC subjects (OR, 0.52; 95% CI, 0.30-0.88; and OR, 0.54; 95% CI, 0.31-0.92, respectively). When farm exposure and CD14 C-159T were considered together, the risk of nasal allergies and atopy was the most reduced in the subjects who combined both an early-life exposure to a farming environment and the −159TT genotype (OR, 0.26; 95% CI, 0.07-0.94; and OR, 0.21; 95% CI, 0.05-0.93, respectively, vs nonexposed −159CC+CT subjects). The results were consistent in the 2 centers, supporting the validity of the results. Conclusion: A gene-by-environment interaction between CD14 C-159T and environmental exposure in childhood may modify the development of atopy. Clinical implications: This polymorphism should be considered in interventions studies that use microbial stimuli to reduce sensitization. [Copyright &y& Elsevier]

Background: The natural history of asthma severity is poorly known. Objective: To investigate prognostic factors of asthma severity. Methods: All current patients with asthma identified in 1991 to 1993 in the European Community Respiratory Health Survey were followed up, and their severity was assessed in 2002 by using the Global Initiative for Asthma categorization (n = 856). Asthma severity (remittent, intermittent, mild, moderate, severe) was related to potential determinants evaluated at baseline and during the follow-up by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios (RRRs). Results: Asthma severity measured at baseline was a determinant of a patient''s severity at the end of the follow-up. At baseline, severe persistent had a poorer FEV1% predicted, a poorer symptom control, higher IgE levels (RRR, 2.06; 95% CI, 1.38-3.06), and a higher prevalence of chronic cough/mucus hypersecretion (RRR, 4.90; 95% CI, 2.18-11.02) than patients with intermittent asthma. Moderate persistent showed the same prognostic factors as severe persistent, even if the associations were weaker. Mild persistent had a distribution of prognostic factors that was similar to patients with intermittent asthma, although the former showed a poorer symptom control than the latter. Remission mainly occurred in patients with less severe asthma and was negatively associated with a change in body mass index (RRR, 0.86; 95% CI, 0.75-0.97). Allergic rhinitis, smoking, and respiratory infections in childhood were not associated with asthma severity. Conclusion: Patients with moderate and severe persistent asthma are characterized by early deterioration of lung function. High IgE levels and persistent cough/mucus hypersecretion are strong markers of moderate/severe asthma, which seems to be a different phenotype from mild persistent or intermittent asthma. Clinical implications: Our results suggest that the evolution of asthma severity is to a large extent predictable. [Copyright &y& Elsevier]

For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values < 0.05). While improved compared to studies that relied on spot samples, Intraclass Correlation Coefficients for the pregnancy were below 0.40 for most metabolites. Spearman correlation coefficients between pooled samples collected in infancy were lower than those observed during pregnancy, and were all below 0.30. Exposure to emerging phthalate substitutes such as DINCH and DPHP seems widespread among pregnant women and infants. Collecting repeated urine samples in pregnant women and infants is feasible. The relatively low correlation across trimesters and between maternal and infant samples highlights the need to collect biospecimens in the assumed sensitive time window. [Display omitted] • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time. Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population. [ABSTRACT FROM AUTHOR]

Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults. We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis. Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO 2 , PM 10 , PM 2.5 , and PM coarse (calculated by subtracting PM 2.5 from PM 10) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used. A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM 10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 μg/m3 increase in PM 10 : for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM 2.5. Higher exposure to NO 2 was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO 2. People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association. [ABSTRACT FROM AUTHOR]

Background The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. Objective We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. Methods A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Results Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). Conclusions The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses. [ABSTRACT FROM AUTHOR]

Background Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. Objective We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. Methods Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. Results Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (−4.6%; 95% CI, −7.0% to −2.1%). The prevalence of sensitization to house dust mite (−4.3%; 95% CI, −6.0% to −2.6%) and cat (−2.1%; 95% CI, −3.6% to −0.7%) decreased more than sensitization to grass (−0.6%; 95% CI, −2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. Conclusion Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years. [ABSTRACT FROM AUTHOR]

Background Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. Objectives Our aim was to assess whether the level of forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF 25-75 ) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV 1 . Methods We studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF 25-75 decreased by 10% of predicted value. Results A reduced level of FEF 25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV 1 and in participants with FEV 1 of greater than 80% of predicted value. A reduced FEF 25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness ( P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation. Conclusion Our analysis is the first to suggest that small-airway obstruction, as assessed based on FEF 25-75 , might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways. [ABSTRACT FROM AUTHOR]

Background: A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) reported strong evidence of linkage of 11p14 to eczema. Objective: Our purpose was to conduct fine-scale mapping of the 11p14 region to identify the genetic variants associated with eczema. Methods: Association analyses were first conducted in the family sample from the French EGEA by using 2 methods: the family-based association method and logistic regression. Replication of the EGEA findings was sought in French Canadian and United Kingdom family samples, which, similarly to EGEA samples, were ascertained through asthma. We also tested for association in 2 German samples ascertained through eczema. Results: We found significant association of eczema with 11p14 genetic variants in the vicinity of the linkage peak in EGEA (P = 10−4 for rs1050153 by using the family-based association method, which reached the multiple testing–corrected threshold of 10−4; P = .003 with logistic regression). Pooled analysis of the 3 asthma-ascertained samples showed strong improvement in the evidence for association (P = 6 × 10−6 for rs293974, P = 3 × 10−5 for rs1050153, and P = 8 × 10−5 for rs15783). No association was observed in the eczema-ascertained samples. Conclusion: The significant single nucleotide polymorphisms are located within the overlapping anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. Several lines of evidence suggest that MUC15 is a strong candidate for eczema. Further investigation is needed to confirm our findings and to better understand the role of the ANO3/MUC15 locus in eczema and its relationship with respect to asthma. [ABSTRACT FROM AUTHOR]

Background: Integrin β3 (ITGB3) and Toll-like receptor 2 (TLR2) are candidate genes for asthma and sensitization to mold allergens. Integrin β3 forms a complex with TLR2, and this biological interaction is required for the response of monocytes to TLR2 agonists such as fungal glucan. Objective: To study whether genetic interaction between single nucleotide polymorphisms (SNPs) in genes encoding the TLR2-ITGB3 complex enhances susceptibility to mold sensitization. Methods: Association analysis was conducted in 1243 adults (524 with asthma) who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma. Allergic sensitization to mold allergens was determined by skin prick testing. Association of mold sensitization with 14 ITGB3 SNPs was tested under an additive genetic model. Interaction between ITGB3 SNPs and TLR2/+596, which was previously shown to be associated with asthma, was studied. Results: A positive skin prick test to mold was found in 115 subjects with asthma (22.0%) and in 61 subjects without asthma (8.5%). The ITGB3 rs2056131 A allele was associated with mold sensitization in subjects with asthma with an odds ratio (95% CI) of 0.60 (0.43-0.83; P = .001). Ten other ITGB3 SNPs were significantly associated with mold sensitization in TLR2/+596TT subjects with asthma (P = .03-.002), whereas much weaker associations were found in carriers of the TLR2/+596 C allele (P = .60-.04). Interaction between TLR2/+596 and these ITGB3 SNPs was statistically significant (P interaction = .05-.001). Conclusion: TLR2/+596 genotype may influence the association between ITGB3 SNPs and mold sensitization in adults with asthma. [ABSTRACT FROM AUTHOR]

Objective: To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia. Study design: A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale. Results: Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child. Conclusions: CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call. [Copyright &y& Elsevier]

Background: Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied. Objectives: The aim was to estimate the distribution and the phenotypic characteristics of asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). Methods: Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use. Results: Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control. Conclusion: Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds). [Copyright &y& Elsevier]

Background: Little is known about factors associated with lung function decline in asthma. Objective: To identify the determinants of FEV1 decline in adults with asthma with and without airflow obstruction at baseline. Methods: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV1 decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV1/forced vital capacity < 0.70) at baseline. Results: In the group of individuals without airflow obstruction (n = 544), a faster FEV1 decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV1 decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV1 decline, whereas weight gain was not associated with decline. Conclusions: The detrimental effect of weight gain on FEV1 decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma. [Copyright &y& Elsevier]