R. Nadif - Academia.edu (original) (raw)

Papers by R. Nadif

Value in Health, Dec 1, 2022

07.06 - Paediatric respiratory epidemiology

06.02 - Occupational and environmental health

Allergy

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly ove... more Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always...

Background: Electronic cigarettes (e-cigarettes) have becom... more Background: Electronic cigarettes (e-cigarettes) have become increasingly popular, yet beyond social or technical features, the specific health-related reasons adults use e-cigarettes remain poorly understood. Objective: To explore the cross-sectional associations between perceived health and current e-cigarette use in a large population-based cohort. Methods: From the participants included in the French CONSTANCES cohort (a large general-purpose national population-based cohort) from 2015 to 2017, we included 18,300 ever tobacco smokers with data on their e-cigarette use. We used logistic regressions to estimate the associations between e-cigarette use and perceived health (global and respiratory), stratifying on participants' smoking status and adjusting for sociodemographic characteristics. To examine the role of objective health features (reported diagnoses and measured parameters during a health examination), we adjusted for prior history of respiratory and cardiovascular diseases, diabetes, cancer, spirometry, and blood pressure. Finally, we examined the effect of additionally adjusting for several health-related behaviors. Results: Participants with poor perceived health (global and respiratory) were at greater risk of e-cigarette use. These associations remained unchanged after adjustment for objective health features and health-related behaviors (e.g., in current smokers, for global perceived health, an odds ratio of 1.10 [95% CI 1.03–1.16] per increase on an 8-point scale from very good to very poor). Conclusions: Our findings suggest that the more current and former smokers felt unhealthy, the more they tended to currently use e-cigarettes. People who regularly use e-cigarettes should obtain medical supervision that takes into account not only objective diagnoses and measurements but also perceived health. Counseling practices could include assessing perceived health status to reinforce motivation to quit smoking.

3 Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-on... more 3 Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify associations between early respiratory infections and asthma. Association analysis was conducted in 499 children (268 with asthma, median age 11y) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The 12-year follow-up data were used to assess persistent or remittent asthma in young adulthood. Respiratory infection before 2y of age was assessed retrospectively. For the twelve 17q21 SNPs studied, the odds ratios (ORs) for association between infection and early-onset asthma (age at onset ≤4y) were higher in carriers of risk genotypes

Revue des Maladies Respiratoires Actualités, 2022

Revue des Maladies Respiratoires Actualités, 2021

Introduction L’asthme est une maladie heterogene caracterisee par plusieurs phenotypes dont les p... more Introduction L’asthme est une maladie heterogene caracterisee par plusieurs phenotypes dont les phenotypes inflammatoires. Une seule etude (etude cas-temoin EGEA) a identifie et caracterise les phenotypes inflammatoires sanguins de l’asthme non severe chez l’adulte. Notre objectif etait d’identifier et de caracteriser les phenotypes inflammatoires dans la cohorte francaise en population generale Constances. Methodes Les donnees sont issues de 133 545 participants parmi les 168 354 adultes (18–69 ans) inclus entre 2012–2019. L’asthme actuel a ete defini par la reponse positive a la question « Avez-vous deja eu de l’asthme? » et par la declaration de symptomes, de crise d’asthme ou de traitement pour asthme au cours des 12 derniers mois. Les phenotypes paucigranulocytique, neutrophilique, eosinophilique et mixte ont ete construits a partir de valeurs seuils du nombre d’eosinophiles (EOS) et de neutrophiles sanguins (NEU) (1) EGEA: 250 EOS/mm 3 et 5 000 NEU/mm3 ou (2) a l’aide de courbes ROC. Les associations entre les phenotypes et les caracteristiques cliniques ont ete etudiees a l’aide de modeles logistiques polytomiques avec ajustement sur âge, sexe, statut tabagique, indice de masse corporelle (IMC), diplome et traitement pour asthme. Resultats 12 387 participants declaraient un asthme actuel (9,3 %). A partir des valeurs seuils d’EGEA, les phenotypes paucigranulocytique, neutrophilique, eosinophilique et mixte representaient respectivement 56,6 %, 6,6 %, 32,8 % et 4 %. Compare au phenotype paucigranulocytique, le phenotype neutrophilique etait significativement associe aux symptomes nocturnes (ORs entre 1,06 et 1,27) et a la dyspnee severe (OR = 1,21 [1,07–1,36]); le phenotype eosinophilique etait significativement associe a la crise d’asthme (OR = 1,35 [1,19–1,52]), au score de symptomes (p 1,48). Des associations similaires etaient obtenues avec les valeurs seuils de 250 EOS/mm 3 et 3 420 NEU/mm 3 issues des courbes ROC. Conclusion Les phenotypes inflammatoires etaient differemment associes aux caracteristiques de l’asthme, suggerant des roles distincts pour chacun d’eux. L’etude de leur association avec l’evolution de l’asthme est en cours. Mieux caracteriser les differents phenotypes est une premiere etape vers l’amelioration de sa prise en charge, et permet une meilleure comprehension des mecanismes par lesquels l’environnement affecte l’asthme.

Revue des Maladies Respiratoires Actualités, 2021

Introduction Bien que la severite de la rhinite ait des impacts non-negligeables sur la qualite d... more Introduction Bien que la severite de la rhinite ait des impacts non-negligeables sur la qualite de vie des patients, aucune etude n’a decrit la rhinite suivant l’intensite de sa severite en population generale francaise. Notre objectif etait de decrire les caracteristiques de la rhinite selon le score de severite construit sur la base de quatre de ses principaux symptomes parmi les adultes de l’etude epidemiologique en population generale Constances. Methodes L’analyse est basee sur les reponses aux questions validees et standardisees sur la rhinite incluses dans le questionnaire de suivi annuel de 2014, adresse a 26 737 participants et complete par 21 507 (80 %). Le score de severite de la rhinite a ete construit comme decrit precedemment (Burte et al. JACI 2020) parmi les participants ayant declare des symptomes de rhinite dans les 12 derniers mois (n = 8069). Ce score se base sur les reponses concernant la severite des symptomes de rhinorrhee, congestion, eternuements et prurit n...

Content Positional cloning of a quantitative trait locus in KCNQ5 gene influencing lung function.... more Content Positional cloning of a quantitative trait locus in KCNQ5 gene influencing lung function. E. Bouzigon1, H. Aschard1, H. Tharrault1, M.-H. Dizier1, R. Matran2, M. Lathrop3, F. Kauffmann4, F. Demenais1, EGEA cooperative group 1) U946, INSERM, Paris, France; 2) Univ Lille Nord de France, CHU, Lille, France; 3) Commissariat à l’Energie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France; 4) U780, INSERM, Villejuif, France. A previous genome-wide linkage scan conducted in French EGEA families (Epidemiological study on the Genetics and Environment of Asthma) identified linkage of 6q14 to FEV1 (forced expiratory volume in one second expressed as a percentage of predicted values based on age, height and gender), with a higher signal detected in adult offspring (16 years of age or older). We investigated further this region by genotyping a panel of 399 SNPs (spanning 30Mb) in 203 EGEA families (337 adult offspring). To reduce the problem of multiple testing, ...

Revue des Maladies Respiratoires, 2021

INTRODUCTION The objectives of our study were to estimate the prevalence of asthma in adults in F... more INTRODUCTION The objectives of our study were to estimate the prevalence of asthma in adults in France and to study the effects of gender on the associations of asthma with the corpulence and socio-economic characteristics of individuals. METHODS We estimated the prevalence of current asthma (asthma attack in the past 12 months or current treatment for asthma) from data collected at inclusion in the Constances cohort study in 2013-2014. Analyses were performed separately in men and women, using robust Poisson regression for multivariate analysis. RESULTS Using data from 34,100 participants in the cohort (men: 47.7 %; mean age: 44.6 years), the prevalence of current asthma was estimated to be 5.8 % (5.1 % in men, 6.4 % in women). The risk of asthma was increased in women with high body mass index (BMI) or waist circumference. In men, only a high waist circumference was associated with an increased risk of asthma. An association with low socioeconomic status was observed only among women. CONCLUSION The associations of asthma with corpulence and socioeconomic status differed between men and women. Additional analyses should provide a better understanding of the mechanisms responsible for these differences.

Clinical and Translational Allergy, 2020

There are large between- and within-country variations in COVID-19 death rates. Some very low dea... more There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or AC...

Frontiers in Public Health, 2020

Allergy, 2020

Large differences in COVID-19 death rates exist between countries and between regions of the same... more Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT 1 R) axis associated with oxidative stress. This leads to insulin resistanceas well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT 1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are given: Kimchi in Korea, westernized foods and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2associated antioxidant effects helpful in mitigating COVID-19 severity.

Allergy, 2020

Go to publication entry in University of Southern Denmark's Research Portal Terms of use This wor... more Go to publication entry in University of Southern Denmark's Research Portal Terms of use This work is brought to you by the University of Southern Denmark. Unless otherwise specified it has been shared according to the terms for self-archiving. If no other license is stated, these terms apply: • You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access version This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Revue des Maladies Respiratoires Actualités, 2020

Introduction La prevalence de l’asthme a ete evaluee a environ 7 % chez l’adulte en France. C’est... more Introduction La prevalence de l’asthme a ete evaluee a environ 7 % chez l’adulte en France. C’est une maladie resultant de facteurs genetiques, sociaux, comportementaux et environnementaux tels que la pollution atmospherique, et des interactions entre ces facteurs. Peu d’etudes se sont interessees au lien entre exposition a long terme a la pollution atmospherique et l’asthme chez l’adulte. L’objectif de cette analyse etait d’etudier l’association entre l’exposition a long terme au dioxyde d’azote (NO 2), particules de diametre aerodynamique median ≤ 2,5 μm (PM 2.5) et carbone suie (BC) et l’asthme actuel chez l’adulte dans la cohorte francaise Constances. Methodes A leur inclusion dans la cohorte entre 2012 et 2018, les participants ont repondu a un questionnaire standardise et valide sur la sante respiratoire. L’asthme actuel a ete defini chez les participants ayant declare un asthme au cours de leur vie et par au moins une reponse positive a : un des cinq symptomes caracteristiques de l’asthme, crise d’asthme au cours des 12 derniers mois, prise actuelle de traitements pour l’asthme. L’exposition a la pollution atmospherique a ete estimee a l’adresse residentielle des participants a partir de modeles Land-Use Regression developpes en 2010 sur une maille de 100 × 100 m. Les associations entre l’exposition a long terme a la pollution atmospherique et l’asthme ont ete estimees a l’aide de modeles logistiques. Une interaction avec l’âge ayant ete mise en evidence, le modele l’a prise en compte et a ete ajuste sur le sexe, le tabagisme et le niveau de diplome. Une analyse stratifiee sur l’âge (moins de 45 ans et plus de 45 ans) et une analyse de sensibilite chez les participants non-fumeurs ont ete realisees. Resultats L’analyse a ete conduite chez 130 694 participants (âge moyen 47 ans, 54 % de femmes, 19 % fumeurs). La prevalence brute de l’asthme actuel a ete estimee a 9,6 % (n = 12 513). Les associations entre l’exposition aux differents polluants et l’asthme actuel sont presentees dans le Tableau 1. Une association significative et positive a ete mise en evidence pour une augmentation de 1 10 5.m -1 de BC : odds ratio ajuste (ORa) 1,07 [1,03–1,10]. Les resultats des analyses chez les non-fumeurs ou stratifiees sur l’âge etaient inchanges. Conclusion Ces resultats apportent des arguments supplementaires sur le role de la pollution atmospherique dans l’expression de l’asthme. Ils aident a la comprehension des effets sanitaires de la pollution atmospherique et attestent de l’enjeu de sante publique.

Revue des Maladies Respiratoires Actualités, 2020

Introduction La rhinite est l’une des affections medicales les plus courantes, caracterisee par u... more Introduction La rhinite est l’une des affections medicales les plus courantes, caracterisee par une morbidite importante et un lourd fardeau financier. Si de nombreuses etudes en population generale ont ete conduites pour estimer la prevalence de la rhinite allergique (RA), tres peu ont porte sur la rhinite non-allergique (RNA). L’objectif de cette analyse etait d’estimer la prevalence et de decrire les caracteristiques des RA et RNA chez l’adulte dans la cohorte Constances. Methodes Parmi les 26 737 participants inclus jusqu’en decembre 2013, 21 507 (80 %) ont complete le module rhinite du questionnaire de suivi annuel de 2014. La rhinite actuelle a ete definie par les questions « Au cours de votre vie, avez-vous deja eu des problemes d’eternuement, nez qui coule ou nez bouche quand vous n’etiez pas enrhume(e) et n’aviez pas la grippe ? » et « Avez-vous eu ces problemes dans les 12 derniers mois ? ». La RA et la RNA ont ete definies parmi les participants ayant declare une rhinite et par une reponse positive (RA) ou negative (RNA) a « Au cours de votre vie, avez-vous eu des allergies nasales, y compris le rhume des foins ? ». Resultats Au total, 18 735 participants ont ete inclus dans les analyses (âge moyen = 53 ans, 55,7 % de femmes, 12,8 % asthmatiques vie). Les prevalences brutes de la rhinite actuelle, de la RA et de la RNA actuelles etaient de 43,6 %, 32,9 % et 10,7 % respectivement. Les caracteristiques des groupes RA et RNA actuelles sont presentees dans le tableau ci-joint. Les participants RA declaraient en moyenne plus d’asthme, de conjonctivite et d’eczema que les participants RNA. Les participants du groupe RA declaraient egalement un âge de debut plus precoce des symptomes. La majorite des participants RA declarait les pollens comme declencheurs de leurs symptomes contre moins de 10 % pour les participants RNA ( Tableau 1 ). Conclusion Nous observons des caracteristiques differentes entre la RA et la RNA, qui sont coherentes avec celles decrites dans la litterature et connues des cliniciens. En l’absence de donnees biologiques ou de tests cutanes, un questionnaire valide et standardise semble adapte pour estimer et decrire les phenotypes allergiques et non-allergiques de la rhinite.

Allergy, 2018

Background: Children with multimorbid asthma and rhinitis show IgE polysensitization to several a... more Background: Children with multimorbid asthma and rhinitis show IgE polysensitization to several allergen sources. This association remain poorly studied in adolescents and adults using defined allergen molecules. We investigated IgE sensitization patterns towards a broad panel of aeroallergen components in adults and adolescents with a focus on individuals with asthma and rhinitis multimorbidity. Methods: IgE reactivity to 64 microarrayed aeroallergen molecules was determined with the MeDALL-chip in samples from the French EGEA study (n=840, age=40.7±17.1) and the Swedish population-based birth cohort BAMSE (n=786, age=16±0.26). The age-and sex-adjusted associations between the number of IgE-reactive allergen molecules (≥0.3 ISU) and the asthma-rhinitis phenotypes were assessed using a negative binomial model. Results: Groups representing four phenotypes were identified: no asthma-no rhinitis (A-R-; 30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A-R+; 15% and 24%), and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE-reactive aeroallergen molecules significantly differed between phenotypes

Value in Health, Dec 1, 2022

07.06 - Paediatric respiratory epidemiology

06.02 - Occupational and environmental health

Allergy

Revue des Maladies Respiratoires Actualités, 2022

Revue des Maladies Respiratoires Actualités, 2021

Revue des Maladies Respiratoires, 2021

Clinical and Translational Allergy, 2020

Frontiers in Public Health, 2020

Allergy, 2020

Revue des Maladies Respiratoires Actualités, 2020

Allergy, 2018