Summary 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<0·0001). After controlling for country, sex, baseline age, body-mass index, forced expiratory volume in 1 s (FEV1 ), log total IgE, family history of asthma, and smoking, the adjusted relative risk for asthma was 1·63 (95% CI 0·82–3·24) for atopy only, 2·71 (1·64–4·46) for non-allergic rhinitis, and 3·53 (2·11–5·91) for allergic rhinitis. Only allergic rhinitis with sensitisation to mite was associated with increased risk of asthma independently of other allergens (2·79 1·57–4·96). Interpretation Rhinitis, even in the absence of atopy, is a powerful predictor of adult-onset asthma. Funding UCB Institute of Allergy and Agence Nationale de la Recherche.
Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth ...weight. Objective: Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns. Methods: We conducted a case-control study on male malformations of the genitalia nested in two French mother-child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases. Results: Adjusted birth weight decreased by 77 g 95% confidence interval (CI): –129,–25 and by 49 g (95% CI:–86,–13) in association with a 1-unit increase in In-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) In-transformed concentrations were positively associated with weight (26 g; 95% CI:–2 , 54) and head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in In-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonie associations with birth weight. Conclusions: Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight.
•Phenols and phthalates were frequently detected in this recent pregnancy cohort.•Weighted Quantile Sum indexes were associated with child behaviour.•Associations tended to be stronger in ...girls.•Bisphenol A, triclosan, MEP were the main mixture contributors for externalizing score.•MEP, MBzP, MnBP were the main mixture contributors for internalizing score.
Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal variability of urinary concentrations observed for their metabolites, studies investigating effects of phenols and phthalates on child behaviour often relied on a limited number of spot biospecimens to assess exposure. Besides, the majority did not consider mixture effects.
To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements.
We assessed concentrations of 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites in within-subject pools of multiple urine samples (median = 21 samples per individual pool) collected at two distinct time points during pregnancy in 416 mother–child pairs from the French SEPAGES cohort. Child behaviour was evaluated at two years using the Child Behaviour Checklist 1.5–5 (CBCL). Associations between a mixture of biomarkers of exposure and externalizing and internalizing behaviour scores were studied using adjusted Weighted Quantile Sum (WQS) regressions with a repeated holdout validation (100 repetitions).
The positive WQS indexes were associated with both the externalizing and internalizing behaviour scores in the whole population, indicating greater risk of behavioural problems. Stratification for child sex suggested stronger associations in girls than boys. On average, girls externalizing and internalizing scores increased by 3.67 points (95% CI: 1.24, 6.10) and 2.47 points (95 %CI: 0.60, 4.33) respectively, for an increase of one tertile in the WQS index, compared with 1.70 points (95 %CI: −0.42, 3.81) and 1.17 points (95 %CI: −0.50, 2.84) in boys. Main contributors for the associations observed in girls were bisphenol A (weight of 18%), triclosan (17%) and monoethyl phthalate (MEP, 15%) for the externalizing score and MEP (19%), mono-benzyl phthalate (MBzP, 19%) and mono-n-butyl phthalate (MnBP, 16%) for the internalizing score.
Our results suggest adverse associations between in utero exposure to a mixture of phenols and phthalates and child behaviour, mainly in girls. Public health consequences may be substantial due to the widespread exposure of the population to these compounds.
Distribution of the phenol urinary concentrations adjusted for specific gravity in the SEPAGES cohort during pregnancy (periods second (NT2 = 477) and third trimesters ((NT3 = 456), and infancy (2 ...months (NM2 = 152) and 1 year (NY1 = 100). Compounds with less than 4% detection are not shown (bisphenols F, B, AF and triclocarban). For the bisphenol A infant samples (2 months and 1 year) the concentrations of the conjugated form instead of the total form are presented as external contamination was suspected. Abbreviations: LOD = limit of detection, LOQ = limit of quantification.
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•Phenol concentrations were assessed accurately through the collection of repeated samples.•Pregnancy and early infancy, sensitive yet rarely analyzed periods were studied.•High detection rates of bisphenol A, parabens and triclosan in mothers and infants.•Concentrations for several phenols were higher at 12 months than during pregnancy.•Cashiers had higher bisphenol S but not bisphenol A levels than unemployed women.
Parabens, bisphenol A and triclosan have been forbidden or restricted in specific types of consumer goods in Europe and France. Limited biomonitoring data are available in France since the implementation of these regulations, and exposure data on infants is scarce worldwide. Understanding the predictors of phenol urinary concentrations will help identify potential targets for prevention.
We described levels, variability and predictors of exposure to 12 phenols in pregnant women and infants recruited between 2014 and 2017 in a French couple-child cohort.
Among 479 pregnant women and 150 of their infants, we studied phenol urinary concentrations in within-subject, within-period pools of repeated urine samples collected during the second and third trimesters of pregnancy (up to 42 samples per woman), at 2 months and 12 months (up to 14 samples per infant). Time trends and associations with demographic, protocol, occupational and behavioral factors were studied using interval censored models to accommodate for undetected and unquantified urine concentrations.
Detection rates were above 90% for bisphenol A, ethylparaben, methylparaben, benzophenone-3 and triclosan and below 5% for bisphenol AF, B, F and triclocarban. Median levels of bisphenol A, bisphenol S, methylparaben, ethylparaben and propylparaben at 12 months were similar or higher than during pregnancy. For pregnant women all phenols but benzophenone-3 and bisphenol S showed a linear decrease between 2014 and 2017 (p-values < 0.02). Women with the shortest education (primary and secondary school) had higher urinary concentrations of triclosan (β = 0.58 (95% confidence interval (CI), −0.04; 1.20)), ethyl (β = 0.43 (95%CI, 0.03; 0.84)) and propyl paraben (β = 1.39 (95%CI, 0.55; 2.24)) than those with the longest education. Cashiers had higher conccentrations of bisphenol S (β = 0.99 (95%CI, −0.11; 2.09)) but not of bisphenol A (β = −0.04 (95%CI, −0.26; 0.19)) than unemployed women.
Despite recent regulations, bisphenol A, triclosan and paraben detection rates were high in women and young infants. High bisphenol and paraben median levels at 12 months require further investigation as early infancy is a sensitive period for exposure to environmental contaminants.
To what extent blood granulocyte patterns may predict asthma control remains under-studied. Our aim was to study associations between blood neutrophilia and eosinophilia and asthma control outcomes ...in adults.Analyses were conducted in 474 asthmatics from the first follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global Initiative for Asthma definition (2015), and asthma exacerbations by use of urgent care or courses of oral corticosteroids in the past year. Blood EOS
/EOS
was defined as </≥250 eosinophils·mm
, respectively, and NEU
/NEU
as </≥5000 neutrophils·mm
, respectively. Estimates were adjusted for age, sex and smoking.At EGEA2, NEU
was associated with asthma exacerbations and poor asthma control (OR >2.10). EOS
was associated with higher bronchial hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function (p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a persistent pattern between surveys. Persistent NEU
was associated with poor asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOS
at EGEA1 and persistent EOS
were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07) and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher immunoglobulin E level (p<10
) at EGEA2.Granulocyte patterns were differently associated with asthma outcomes, suggesting specific roles for each one, which could be tested as predictive signatures.
This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control as defined by the 2006 Global ...Initiative for Asthma (GINA) guidelines.
A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values.
The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost.
Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.
In vitro and toxicological studies have shown that non-persistent environmental chemicals can perturb thyroid hormone homeostasis. Epidemiological studies with improved exposure assessment (i.e., ...repeated urine samples) are needed to evaluate effects of these compounds, individually or as a mixture, in humans. We studied the associations between prenatal exposure to non-persistent environmental chemicals and neonatal thyroid hormones.
The study population consisted of 442 mother–child pairs from the French SEPAGES mother–child cohort recruited between July 2014 and July 2017. For each participant, four parabens, five bisphenols, triclosan, triclocarban, benzophenone-3 as well as metabolites of phthalates and of di(isononyl)cyclohexane-1,2-dicarboxylate were assessed in two pools of repeated urine samples (median: 21 spot urines per pool), collected in the 2nd and 3rd trimesters of pregnancy, respectively. Thyroid stimulating hormone (TSH) and total thyroxine (T4) levels were determined in newborns from a heel-prick blood spot. Maternal iodine and selenium were assessed in urine and serum, respectively. Adjusted linear regression (uni-pollutant model) and Bayesian Kernel Machine Regression (BKMR, mixture model) were applied to study overall and sex-stratified associations between chemicals and hormone concentrations.
Interaction with child sex was detected for several compounds. Triclosan, three parabens, and one phthalate metabolite (OH-MPHP) were negatively associated with T4 among girls in the uni-pollutant model. BKMR also suggested a negative association between the mixture and T4 in girls, whereas in boys the association was positive. The mixture was not linked to TSH levels, and for this hormone the uni-pollutant model revealed associations with only a few compounds.
Our study, based on repeated urine samples to assess exposure, showed that prenatal exposure to some phenols and phthalates disturb thyroid hormone homeostasis at birth. Furthermore, both uni-pollutant and mixture models, suggested effect modification by child sex, while, to date underlying mechanisms for such sex-differences are not well understood.
A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined ...a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma.
We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life.
Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure).
This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.
Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract ...illness on lung function, using both standard and intra-breath oscillometry in 3 year old children.
History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R
), frequency-dependence of resistance (R
), reactance at 7 Hz (X
), area of the reactance curve (AX), end-inspiratory and end-expiratory R (R
, R
) and X (X
, X
), and volume-dependence of resistance (ΔR = R
-R
) was estimated by linear regression adjusted on confounders.
Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher R
, R
, ΔR and R
and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R
and AX and lower X
and bronchitis with higher R
. No statistically significant association was observed for hospitalisation.
Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.
We aimed to study the associations between the household use of cleaning sprays and asthma symptoms and control of asthma, in females from the Epidemiological Study on the Genetics and Environment of ...Asthma (EGEA). Data were available for 683 females (mean age 44 yrs, 55% never smokers, 439 without asthma and 244 with current asthma). Both domestic exposures and asthma phenotypes (asthma symptom score, current asthma, poorly-controlled asthma (56%)) were evaluated as previously described in the European Community Respiratory Health Survey. Associations between the use of sprays and asthma phenotypes were evaluated using logistic and nominal regressions, adjusted for age, smoking, body mass index and occupational exposures. Significant associations were observed between the weekly use of at least two types of sprays and a high asthma symptom score (OR (95% CI) 2.50 (1.54-4.03)) compared with a null score. Consistent results were observed for current asthma (1.67 (1.08-2.56)) and poorly-controlled asthma (2.05 (1.25-3.35)) compared with females without asthma. The association for current asthma was higher in females not reporting avoidance of polluted places (2.12 (1.27-3.54)) than in those reporting such avoidance (0.99 (0.53-1.85)). The common use of household cleaning sprays is positively associated with a high asthma symptom score, current asthma and poorly-controlled asthma in females.
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