Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Changes in household use of disinfectant and cleaning products during the first lockdown period in France.

BACKGROUND: Few studies evaluated the use of Household Disinfectant and Cleaning Products (HDCPs) during the COVID-19 pandemic, but no population-based cohorts used longitudinal data. We studied changes in HDCPs during the first lockdown, based on longitudinal data from the French population-based NutriNet-Santé and CONSTANCES cohorts. METHODS: Based on standardized questionnaires on household cleaning tasks in 2018-2019 and around the first lockdown in France (March17-May3 2020), we compared the duration of weekly use of HDCPs (< 1 day/week, < 10 min/week; 10-30 min/week; > 30 min/week) and the household cleaning help (yes/no) before and during the lockdown period by Bhapkar and McNemar's tests. Moreover, we assessed self-reported changes in the frequency of HDCPs during the lockdown from before (unchanged/increased). RESULTS: Analyses were carried on 31,105 participants of NutriNet-Santé (48 years, 75% women, 81% ≥ high school diploma) and 49,491 of CONSTANCES (47 years, 51% women, 87% ≥ high school diploma). During the lockdown, compared with 2018-2019, duration of HDCPs use increased (> 30 min; NutriNet-Santé: 44% versus 18%; CONSTANCES: 63% versus 16%) and household help decreased (NutriNet-Santé: 5% versus 40%; CONSTANCES: 3% versus 56%). Regarding the frequency of HDCPs use, 55% of participants of NutriNet-Santé (57% women/49% men) and 83% of CONSTANCES (86% women/81% men) reported an increased use since the beginning of the lockdown, significantly higher among women (p < 0.0001). CONCLUSIONS: The frequency and duration of weekly use of HDCPs has significantly increased since the pandemic. As the use of HDCPs is associated with health issues, further studies are now needed to evaluate the potential health impacts of these changes.

Plasma thymic stromal lymphopoietin (TSLP) in adults with non-severe asthma: the EGEA study.

Thymic stromal lymphopoietin (TSLP), a cytokine involved in severe asthma treatment, was never studied in non-severe asthma.Among 969 adults from a large epidemiological study, cross-sectional analyses showed that plasma TSLP levels were associated with increased age and BMI, male sex, smoking and high TSLP levels (one IQR increase) with current asthma and poor lung function. High TSLP levels were also associated with persistence of asthma attacks (aOR=2.14 (95% CI 1.23 to 3.72)) and dyspnoea (aOR=2.71 (95% CI 1.39 to 5.28)) 10 years later.Our results suggest that TSLP could be a cytokine of interest in non-severe asthma, and its determinants of circulating levels could be considered in asthma management.

Long-term exposure to ambient air pollution and asthma symptom score in the CONSTANCES cohort.

BACKGROUND: The asthma symptom score allows to consider asthma as a continuum and to investigate its risk factors. One previous study has investigated the association between asthma score and air pollution and only for nitrogen dioxide (NO2). We aimed to study the associations between particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC) and NO2 and the asthma symptom score in adults from CONSTANCES, a French population-based cohort. METHODS: Asthma symptom score (range: 0-5) was based on the number of five self-reported symptoms of asthma in the last 12 months. Annual individual exposure to PM2.5, BC and NO2 was estimated at participants' residential address using hybrid land-use regression models. Cross-sectional associations of each pollutant with asthma symptom score were estimated using negative binomial regressions adjusted for age, sex, smoking status and socioeconomic position. Associations with each symptom were estimated using logistic regression. The effect of BC independent of total PM2.5 was investigated with a residual model. RESULTS: Analyses were conducted on 135 165 participants (mean age: 47.2 years, 53.3% women, 19.0% smokers, 13.5% ever asthma). The ratio of mean score was 1.12 (95% CI 1.10 to 1.14), 1.14 (95% CI 1.12 to 1.16) and 1.12 (95% CI 1.10 to 1.14) per one IQR increase of PM2.5 (4.86 µg/m3), BC (0.88 10-5 m-1) and NO2 (17.3 µg/m3). Positive and significant associations were also found for each asthma symptom separately. BC effect persisted independently of total PM2.5. CONCLUSION: Exposure to each pollutant was associated with increased asthma symptom score in adults. This study highlights that BC could be one of the most harmful particulate matter components.

Rhinitis phenotypes and multimorbidities in the general population: the CONSTANCES cohort.

BACKGROUND: Scarce epidemiological studies have characterised allergic rhinitis (AR) and non-allergic rhinitis (NAR) in adults. In a population-based cohort, our aims were to 1) describe rhinitis, AR and NAR, and 2) explore how asthma and conjunctivitis may lead to the identification of novel rhinitis phenotypes. METHODS: In this cross-sectional analysis, current rhinitis was defined as present in the last 12 months using a questionnaire from the French CONSTANCES cohort. Participants with current rhinitis reporting nasal allergies were considered as AR, otherwise as NAR. We described AR and NAR phenotypes, and their phenotypes including co-occurrence with ever-asthma and ever-conjunctivitis. RESULTS: Among the 20 772 participants included in this analysis (mean±sd age 52.6±12.6 years; 55.2% female), crude prevalences of AR and NAR were 28.0% and 10.9%. AR participants more frequently reported persistent rhinitis (31.6% versus 25.1%) and moderate-to-severe rhinitis (40.1% versus 24.2%) than NAR participants. Among AR or NAR participants, those with ever-asthma reported more moderate-to-severe rhinitis. Participants with AR, ever-asthma and ever-conjunctivitis had an earlier age of rhinitis onset, more severe rhinitis and higher eosinophil counts than participants in other groups. Results were replicated in another cohort. CONCLUSIONS: In this large population-based cohort, 40% reported current rhinitis, with a lower prevalence of moderate-to-severe rhinitis than in clinical practice. For the first time in a general adult population, we showed that AR and NAR alone or in combination with asthma or in combination with asthma and conjunctivitis are different phenotypes. These results provide new insights on how best to manage rhinitis and its multimorbidities.

Occupation and occurrence of respiratory infections among adults with newly diagnosed asthma.

BACKGROUND: Work environments are potential areas for spreading respiratory infections. We hypothesized that certain occupations increase susceptibility to respiratory infections among adults with asthma. Our objective was to compare the occurrence of respiratory infections among different occupations in adults with newly diagnosed asthma. METHODS: We analysed a study population of 492 working-age adults with newly diagnosed asthma who were living in the geographically defined Pirkanmaa Area in Southern Finland during a population-based Finnish Environment and Asthma Study (FEAS). The determinant of interest was occupation at the time of diagnosis of asthma. We assessed potential relations between occupation and occurrence of both upper and lower respiratory tract infections during the past 12 months. The measures of effect were incidence rate ratio (IRR) and risk ratio (RR) adjusted for age, gender, and smoking habits. Professionals, clerks, and administrative personnel formed the reference group. RESULTS: The mean number of common colds in the study population was 1.85 (95% CI 1.70, 2.00) infections in the last 12 months. The following occupational groups showed increased risk of common colds: forestry and related workers (aIRR 2.20, 95% CI 1.15-4.23) and construction and mining (aIRR 1.67, 95% CI 1.14-2.44). The risk of lower respiratory tract infections was increased in the following groups: glass, ceramic, and mineral workers (aRR 3.82, 95% CI 2.54-5.74), fur and leather workers (aRR 2.06, 95% CI 1.01-4.20) and metal workers (aRR 1.80, 95% CI 1.04-3.10). CONCLUSIONS: We provide evidence that the occurrence of respiratory infections is related to certain occupations.

Identification of novel genes influencing eosinophil-specific protein levels in asthma families.

BACKGROUND: Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. OBJECTIVE: We sought to identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. METHODS: We performed univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1018 subjects from the EGEA study with follow-up in 153 subjects from the Saguenay-Lac-Saint-Jean study and combined the results of these 2 studies through meta-analysis. We then conducted Bayesian statistical fine mapping together with quantitative trait locus and functional annotation analyses to identify the most likely functional genetic variants and candidate genes. RESULTS: We identified 5 genome-wide significant loci (P &lt; 5 × 10^-8) including 7 distinct signals associated with ECP and/or EDN levels. The genes targeted by our fine mapping and functional search include RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively, and 4 other genes that regulate ECP and EDN levels. These 4 genes were JAK1 (1p31), a transcription factor that plays a key role in the immune response and acts as a potential therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in cellular response to stress; and CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation. CONCLUSION: Analysis of specific phenotypes produced by eosinophils allows the identification of genes that play a major role in allergic response and inflammation, and offers potential therapeutic targets for asthma.

Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults.

BACKGROUND: Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are proteins released by activated eosinophils whose role in adult asthma remains unclear. OBJECTIVE: To study associations between ECP, EDN and various asthma characteristics in adults from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). METHODS: Plasma ECP and EDN levels were measured by ELISA. Cross-sectional analyses were performed in 941 adults (43±16 years old, 39% with asthma) at EGEA2 (2003-2007). Longitudinal analyses investigated the associations between EDN level at EGEA2 and changes in asthma characteristics between EGEA2 and EGEA3 (2011-2013, n=817). We used generalised estimated equations adjusted for age, sex, smoking status and body mass index to take into account familial dependence. RESULTS: At EGEA2, both high ECP and EDN levels were associated with current asthma (adjusted OR (aOR) (95% CI): 1.69 (1.35-2.12) and 2.12 (1.76-2.57)). Among asthmatics, high EDN level was associated with asthma attacks (aOR: 1.50 (1.13-1.99)), wheezing and breathlessness (aOR: 1.38 (1.05-1.80)), use of asthma treatments (aOR: 1.91 (1.37-2.68)) and bronchial hyper-responsiveness (aOR: 2.03 (1.38-2.97)), even after further adjustment on ECP. High ECP level was associated with high neutrophil count and tended to be associated with chronic bronchitis. High EDN level at EGEA2 was associated with persistent asthma (aOR: 1.62 (1.04-2.52)), nocturnal symptoms (aOR from 2.19 to 3.57), worsening wheezing and breathlessness (aOR: 1.97 (1.36-2.85)) and nocturnal shortness of breath (aOR: 1.44 (1.04-1.98)) between EGEA2 and EGEA3. CONCLUSIONS: EDN and ECP were associated with different asthma expression in adults. EDN could be a potential biomarker to monitor asthma evolution in adults.

Trajectories of IgE sensitization to allergen molecules from childhood to adulthood and respiratory health in the EGEA cohort.

BACKGROUND: Longitudinal studies assessing the association of profiles of allergen-specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health. METHODS: IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12 years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE-reactivity to the 38 most prevalent respiratory allergens. The LCA-defined profiles were then studied in association with respiratory health. RESULTS: At baseline, the mean (min-max) age of the population was 11 (4.5-16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A: "no/few allergen(s)" (48%, 39%), B: "pollen/animal allergens" (18%, 21%), C: "most prevalent house dust mite allergens" (22%, 27%) and D: "many allergens" (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV1 % and FEF25-75 % as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function. CONCLUSION: Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.

Association between occupational exposure to irritant agents and a distinct asthma endotype in adults.

AIM: The biological mechanisms of work-related asthma induced by irritants remain unclear. We investigated the associations between occupational exposure to irritants and respiratory endotypes previously identified among never asthmatics (NA) and current asthmatics (CA) integrating clinical characteristics and biomarkers related to oxidative stress and inflammation. METHODS: We used cross-sectional data from 999 adults (mean 45 years old, 46% men) from the case-control and familial Epidemiological study on the Genetics and Environments of Asthma (EGEA) study. Five respiratory endotypes have been identified using a cluster-based approach: NA1 (n=463) asymptomatic, NA2 (n=169) with respiratory symptoms, CA1 (n=50) with active treated adult-onset asthma, poor lung function, high blood neutrophil counts and high fluorescent oxidation products level, CA2 (n=203) with mild middle-age asthma, rhinitis and low immunoglobulin E level, and CA3 (n=114) with inactive/mild untreated allergic childhood-onset asthma. Occupational exposure to irritants during the current or last held job was assessed by the updated occupational asthma-specific job-exposure matrix (levels of exposure: no/medium/high). Associations between irritants and each respiratory endotype (NA1 asymptomatic as reference) were studied using logistic regressions adjusted for age, sex and smoking status. RESULTS: Prevalence of high occupational exposure to irritants was 7% in NA1, 6% in NA2, 16% in CA1, 7% in CA2 and 10% in CA3. High exposure to irritants was associated with CA1 (adjusted OR aOR, (95% CI) 2.7 (1.0 to 7.3)). Exposure to irritants was not significantly associated with other endotypes (aOR range: 0.8 to 1.5). CONCLUSION: Occupational exposure to irritants was associated with a distinct respiratory endotype suggesting oxidative stress and neutrophilic inflammation as potential associated biological mechanisms.

Household use of green and homemade cleaning products, wipe application mode, and asthma among French adults from the CONSTANCES cohort.

While exposure to irritant and sprayed cleaning products at home is known to have a harmful role in asthma, the potential health effect of other categories or forms has not been investigated. We studied the associations of household use of cleaning products, including green, homemade products, and disinfecting wipes, with asthma based on data from the large French population-based CONSTANCES cohort. Participants completed standardized questionnaires on respiratory health and household use of cleaning products. Cross-sectional associations of cleaning products with current asthma, adjusted for gender, age, smoking status, BMI, and educational level, were evaluated by logistic regressions. Analyses were conducted in 41 570 participants (mean age: 47 years, 56% women, weekly use of the six specific products/forms studied varied from 11% to 37%). Weekly use of irritants (OR = 1.23 [1.13-1.35]), scented (OR = 1.15 [1.06-1.26]), green (OR = 1.09 [1.00-1.20]), and homemade products (OR = 1.19 [1.06-1.34]), as well as sprays (OR = 1.18 [1.08-1.29]), disinfecting wipes (OR = 1.21 [1.09-1.34]) were significantly associated with asthma, with significant trends according to the frequency of use. When they were not co-used with irritants/sprays, associations were reduced and persisted only for disinfecting wipes. Weekly use of disinfecting wipes at home was associated with current asthma, but fewer risks were observed for the use of green and homemade products.

Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort.

BACKGROUND: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate. OBJECTIVE: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. METHODS: The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate). RESULTS: Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). CONCLUSION: Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.

Underdiagnosis of obstructive lung disease: findings from the French CONSTANCES cohort.

BACKGROUND: The burden of undiagnosed obstructive lung disease (OLD) (mainly asthma and chronic obstructive pulmonary disease) is not fully established, and targets for corrective action are yet to be identified. We assessed the underdiagnosis of OLD and its determinants in France. METHODS: CONSTANCES is a French population-based cohort of adults aged 18-69 years at inception. We analysed data collected at inclusion in 2013-2014. Undiagnosed OLD was defined as spirometry-confirmed airflow limitation (FEV1/FVC < lower limit of normal) without prior diagnosis of asthma, chronic obstructive pulmonary disease, or bronchiectasis. Multivariate analysis was performed with weighted robust Poisson regression models to estimate the adjusted prevalence ratios (aPR) of undiagnosed OLD. RESULTS: Spirometry results were available for 19,398 participants. The prevalence of airflow limitation was 4.6%. Overall, 64.4% of adults with airflow limitation did not report a previous diagnosis of OLD. Individuals with high cumulative tobacco consumption (≥ 10 pack-years) (aPR: 1.72 [1.28-2.32]), without respiratory symptoms (aPR: 1.51 [1.28-1.78]), and with preserved lung function (aPR: 1.21 [1.04-1.41] for a 10-point increase in FEV1% predicted) had a higher risk of being undiagnosed. Half of symptomatic individuals with airflow limitation (45% of those with moderate to severe airflow limitation) were undiagnosed with OLD. CONCLUSION: Underdiagnosis of OLD is very common among French adults, even in patients with respiratory symptoms. Efforts should be made in France to raise awareness about OLD in the general population, improve the detection of respiratory symptoms, and increase the use of spirometry among primary care professionals.

Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts.

BACKGROUND: Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults. OBJECTIVE: We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis. METHODS: 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 NO2, PM10, PM2.5, and PMcoarse (calculated by subtracting PM2.5 from PM10) 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. RESULTS: 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 PM10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 µg/m3 increase in PM10: 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 PM2.5. Higher exposure to NO2 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 NO2. CONCLUSIONS: 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.

Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families.

BACKGROUND: A positional cloning study of bronchial hyper-responsiveness (BHR) at the 17p11 locus in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families showed significant interaction between early-life environmental tobacco smoke (ETS) exposure and genetic variants located in DNAH9. This gene encodes the heavy chain subunit of axonemal dynein, which is involved with ATP in the motile cilia function.Our goal was to identify genetic variants at other genes interacting with ETS in BHR by investigating all genes belonging to the 'ATP-binding' and 'ATPase activity' pathways which include DNAH9, are targets of cigarette smoke and play a crucial role in the airway inflammation. METHODS: Family-based interaction tests between ETS-exposed and unexposed BHR siblings were conducted in 388 EGEA families. Twenty single-nucleotide polymorphisms (SNP) showing interaction signals (p≤5.10-3) were tested in the 253 Saguenay-Lac-Saint-Jean (SLSJ) families. RESULTS: One of these SNPs was significantly replicated for interaction with ETS in SLSJ families (p=0.003). Another SNP reached the significance threshold after correction for multiple testing in the combined analysis of the two samples (p=10-5). Results were confirmed using both a robust log-linear test and a gene-based interaction test. CONCLUSION: The SNPs showing interaction with ETS belong to the ATP8A1 and ABCA1 genes, which play a role in the maintenance of asymmetry and homeostasis of lung membrane lipids.

Sensitisation to staphylococcal enterotoxins and asthma severity: a longitudinal study in the EGEA cohort.

INTRODUCTION: Evidence is accumulating that Staphylococcus aureus plays an important role as disease modifier in upper and lower airway diseases. Sensitisation to S. aureus enterotoxins (SEs) was associated with an increased risk of severe asthma in previous cross-sectional studies, but evidence from longitudinal studies is lacking. We aimed to assess associations between SE-sensitisation and the subsequent risk for asthma severity and exacerbations. METHODS: This is a nested case-control study from the 20-year Epidemiological Study of the Genetics and Environment of Asthma (EGEA) cohort, including 225 adults (75 without asthma, 76 with mild asthma and 74 with severe asthma) in EGEA2 (2003-2007). For 173 of these individuals, SE-sensitisation was measured on samples collected 11 years earlier (EGEA1). Cross-sectional associations were conducted for EGEA1 and EGEA2. Longitudinal analyses estimated the association between SE-sensitisation in EGEA1 and the risk of severe asthma and asthma exacerbations assessed in the follow-up. Models were adjusted for sex, age, smoking, parental asthma/allergy and skin-prick test to house dust mite. RESULTS: SE-sensitisation varied between 39% in controls to 58% and 76% in mild and severe asthma, respectively, in EGEA1. An adjusted cross-sectional association showed that SE-sensitisation was associated with an increased risk of severe, but not for mild asthma. SE-sensitisation in EGEA1 was associated with severe asthma (adjusted OR 2.69, 95% CI 1.18-6.15) and asthma exacerbations (adjusted OR 4.59, 95% CI 1.40-15.07) assessed 10-20 years later. CONCLUSION: For the first time, this study shows that being sensitised to SEs is associated with an increased subsequent risk of severe asthma and asthma exacerbations.

High level of fluorescent oxidation products and worsening of asthma control over time.

High Fluorescent oxidation products level (FlOPs), a global oxidative stress biomarker, was associated cross-sectionally with poor asthma outcomes but its longitudinal association with asthma evolution has never been examined. We aimed to study the associations between FlOPs level at baseline and changes in current asthma, asthma attacks and asthma control status over 8 years. We used data from the second survey of the French EGEA cohort study as baseline and the third survey as follow-up. At baseline, the mean age of the 489 participants with ever asthma was 39 (± 16) years, 49% were women. Among participants with controlled asthma at baseline, high FlOPs level was significantly associated with worsening of asthma control at follow-up (odds-ratio adjusted for age, sex and smoking status (95% CI): 2.27 (1.32-3.90). No other significant associations were observed. In conclusion, results suggest FlOPs as a predictor of asthma evolution in adults and a good candidate marker in asthma management.