Background: Allergy, an important immune disorder affecting 30% of the world9s population, is the consequence of IgE-mediated sensitization. The HLA class II genomic region may modulate the immune response to individual allergens. Aim: To assess the association between HLA-II alleles and specific IgE (sIgE) sensitization to many respiratory allergen molecules in a large cohort with varying allergen exposures. Methods: The analysis relied on 1006 participants to EGEA cohort, among which 463 asthmatics. The study focuses on the 26 aeroallergens recognized by sIgE in ≥5% of the study population (determined with MEDALL chip with sIgE ≥ 0.3 IU/ml) and the 23 imputed classical HLA-II alleles with frequency ≥5%. For each allergen-sIgE sensitization and each HLA-II allele, we fitted a logistic model adjusted on gender, age, the first four principal components to correct for population stratification and accounting for familial dependence. Results: Nineteen significant results were observed after correction for multiple comparisons. The strongest associations were found for sIgE response to pollen allergens, particularly to mugwort Art v 1 (associated with dqb1*05:01, dqa1*01:01 and drb1*01:01 with OR=5.42 (95% CI, 3.30;8.88), 4.14 (2.65 ;6.47), 3.16 (1.88;5.31), respectively) and olive Ole e 1 (associated with dqb1*02:01, drb1*03:01 and dqa1*02:01 with OR=2.64 (2.01;3.46), 2.69 (1.8;3.83) and 2.03 (1.5;2.76), respectively). No HLA-II allele was significantly associated with sIgE to indoor or animal allergens. Conclusion: Our results support the important role of classical HLA-II alleles in the predisposition to allergen-specific sensitization to pollens. Funding: ANR-19-CE36-0005-01_NIRVANA

Mugwort

10.1183/13993003.congress-2020.1118

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

Thorax (2022)

Bakari Ibrahim Djamal Achour Farid Zerimech Patricia de Nadaı̈Valérie Siroux

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.

Thymic stromal lymphopoietin

10.1136/thorax-2022-219192

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Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

PLoS ONE (2012)

Emmanuelle Bouzigon Florent Monier Mekki Boussaha Nicole Le Moual Hélène Huyvaert

Background The nitric oxide (NO) pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms (SNPs) of NO synthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma) and blood eosinophil counts. Methodology SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO (FeNO), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2–NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. Principal Findings In non-asthmatics, after correction for multiple comparisons, we found significant associations of FeNO levels with three SNPs in NOS3 and NOS2 (P≤0.002), and of EBC NO2–NO3 level with NOS2 (P = 0.002). In asthmatics, a single significant association was detected between FeNO levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on FeNO between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No significant association was found between any SNP and NO2–NO3 plasma levels or blood eosinophil counts. Conclusions Variants in NO synthase genes influence FeNO and EBC NO2–NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid.

SNP

Exhaled breath condensate

NOS1

10.1371/journal.pone.0036672

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Small airways obstruction is associated with long-term persistence of asthma (EGEA study)

Epidemiology (2015)

Valérie Siroux Anne Boudier Maïa Dolgopoloff Sébastien Chanoine Jean Bousquet

Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. The aim was to assess the association between FEF_25-75% and the persistence of current asthma over 20 yrs and the subsequent risk for uncontrolled asthma. 337 subjects, 142 children and 225 adults, with current asthma (asthma attacks or treatment in the past 12 months) recruited in the Epidemiological study on the Genetics and Environment of Asthma (EGEA1) and followed-up to the 12 yr and 20 yr surveys (EGEA2 and 3) were analyzed. Persistent current asthma was defined by current asthma reported at each survey. Lung function was measured at EGEA1 and 2. A FEF_25-75 reduced by 10% predicted at EGEA1 was significantly associated with a higher risk for long-term asthma persistence in children and adults. In subjects with FEV1>80%pred, the association remained significant in children but not in adults (OR [95%CI]=1.20[1.01-1.43] and 1.03[0.88-1.20]). A FEF_25-75 reduced by 10% at EGEA1 was significantly associated with current asthma a decade apart, and the association was more evidenced in those with asthma exacerbation as compared to those without (OR [95%CI]: 1.38 [1.12-1.69] and 1.17 [1.04-1.32]). Our analysis is the first to suggest that small-airway obstruction is associated with the long-term evolution of childhood asthma. Fundings: PHRC-2012, AGIR pour les maladies chroniques, Inserm-Itmo santé publique.

Airway obstruction

Persistence (discontinuity)

10.1183/13993003.congress-2015.oa1999

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Indoor mould exposure, asthma and rhinitis: findings from systematic reviews and recent longitudinal studies

European Respiratory Review (2018)

D. Caillaud Bénédicte Leynaert Marion Keirsbulck Rachel Nadif

Starting from the Institute of Medicine (IOM) and World Health Organization (WHO) reports, this review provides an overview of the literature published from 2006 to 2017 on the associations between indoor mould exposure and asthma and rhinitis separately in children and adults with a focus on longitudinal epidemiological studies. A systematic search of peer-reviewed literature was performed, including systematic reviews and meta-analyses, longitudinal, incident case–control and panel studies. 61 publications were identified reporting visible mould or mould odour or quantitative assessment of culturable fungi or mould species. In children, visible mould and mould odour were associated with the development and exacerbations of asthma, providing sufficient evidence of a causal relationship. Results from population-based studies in adults were too few and divergent to conclude at more than a limited level of evidence. Exposure to mould in a work building was associated with the incidence and exacerbations of occupational asthma, and we concluded at a sufficient evidence for an association. Systematic reviews, meta-analyses and longitudinal studies on the relationships between mould exposure and allergic rhinitis provide sufficient evidence of an association. This review extended the conclusions of the IOM and WHO reports, and highlighted the need for further longitudinal studies on asthma in adults, and on rhinitis.

10.1183/16000617.0137-2017

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Moisissures dans le bâti. Avis de l’Anses. Rapport d’expertise collective.

Christina Aschan-Leygonie Thomas Bayeux Valérie Bex Gabrielle Boulanger Stéphane Bretagne

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Erythrocyte antioxidant enzyme activities in coal miners from three French regions

International Archives of Occupational and Environmental Health (1998)

Rachel Nadif Jean‐Marc Porcher Martine Dusch Jean‐Marie Mur Guy Auburtin

Pneumoconiosis

10.1007/s004200050278

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SP-D as a biomarker for COPD in the Lebanese population

European Respiratory Journal (2014)

Zeina Akiki Dalia Fakih Rania Jounblat Souleima Chamat Mirna Waked

Background : Surfactant protein D (SP-D), a promising systemic biomarker of chronic obstructive pulmonary disease (COPD) was never evaluated in the Lebanese population. Objective : The validity of serum SP-D as a biomarker for COPD, in comparison with C-reactive protein (CRP) and fibrinogen was investigated. Associations between SP-D levels and lung function tests and the value of combining SP-D and the Diagnosis Score of COPD (DS-COPD) for COPD diagnosis were also evaluated. Methods: 90 COPD patients and 452 controls were recruited. Standardized questionnaires, lung function tests, COPD diagnosis (GOLD 2013), and blood collection were performed. Serum SP-D and CRP, and plasma fibrinogen levels were measured by ELISA. Associations between biological markers with lung function parameters and COPD were estimated by spearman correlation and logistic regression models respectively. Results: Median serum SP-D levels for COPD patients were 1510 ng/mL (from 986 to 2174 ng/mL). SP-D levels were positively associated with age and pack-years in controls (all p<0.01). SP-D levels above the median value were positively associated with COPD (adjusted OR (aOR)=2.86, 95%CI: 1.37-5.98). Higher DS-COPD values (aOR=1.8, 1.49-2.16) and SP-D levels above the median value (aOR=3.51, 1.21-10.1) were significantly and independently associated with COPD in patients and healthy controls aged 40 years or above. No associations were found between CRP, fibrinogen levels and COPD, or between SP-D levels and lung function tests. Conclusion : SP-D seems to be a more reliable biomarker than CRP or fibrinogen for COPD diagnosis in the Lebanese population. Used with the DSCOPD, the SP-D measure could provide a simple and inexpensive tool for COPD diagnosis.

Obstructive lung disease

Surfactant protein D

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