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Association between occupational exposure to irritant agents and a distinct asthma endotype in adults
  1. Miora Valérie Andrianjafimasy1,
  2. Mickaël Febrissy2,
  3. Farid Zerimech3,4,
  4. Brigitte Dananché5,
  5. Hans Kromhout6,
  6. Régis Matran3,4,
  7. Mohamed Nadif2,
  8. Dominique Oberson-Geneste7,
  9. Catherine Quinot1,
  10. Vivi Schlünssen8,9,
  11. Valérie Siroux10,
  12. Jan-Paul Zock11,
  13. Nicole Le Moual1,
  14. Rachel Nadif1,
  15. Orianne Dumas1
  1. 1Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Équipe d'Épidémiologie respiratoire intégrative, CESP, 94807, Villejuif, Île-de-France, France
  2. 2LIPADE, Université Paris 5 Descartes, Paris, Île-de-France, France
  3. 3Univ. Lille, ULR 4483 - IMPECS, CHU Lille, F-59000 Lille, Lille, France
  4. 4Institut Pasteur de Lille, F-59000, Lille, France
  5. 5Industrial hygiene consulting, Courlaoux, France
  6. 6Utrecht University, Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht, Netherlands
  7. 7Toxibio-consultant, Lescar, France
  8. 8Aarhus University, Department of Public Health, Environment, Occupation and Health, Danish Ramazzini Centre, Aarhus, Denmark
  9. 9National Research Centre for the Working Environment, Kobenhavn, Denmark
  10. 10Universite Grenoble Alpes, Inserm, CNRS, Team of environmental epidemiology applied to Reproduction and Respiratory health, IAB, Grenoble, France
  11. 11Institute for Global Health (ISGlobal) and Universitat Pompeu Fabra (UPF), Barcelona, Spain
  1. Correspondence to Dr Orianne Dumas, Inserm, CESP, Équipe d'Épidémiologie respiratoire intégrative, 16 avenue Paul Vaillant Couturier, 94807 Villejuif, France; orianne.dumas{at}inserm.fr

Abstract

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.

  • Occupational asthma
  • epidemiology

Data availability statement

No data are available. Due to third party restrictions, EGEA data are not publicly available. Please see the following URL for more information: https://egeanet.vjf.inserm.fr/index.php/en/contacts-enInterested researchers should contact egea.cohorte@inserm.fr with further questions regarding data access.

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Data availability statement

No data are available. Due to third party restrictions, EGEA data are not publicly available. Please see the following URL for more information: https://egeanet.vjf.inserm.fr/index.php/en/contacts-enInterested researchers should contact egea.cohorte@inserm.fr with further questions regarding data access.

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Footnotes

  • Contributors MVA, RN and OD were involved in the conception, hypotheses delineation and design of the analysis strategy of the study; RM, VS, NLM and RN participated in the acquisition of the data; HK, J-PZ, NLM and OD were involved in the update of the occupational asthma-specific job exposure matrix (OAsJEM); BD and DO-G (experts), CQ and NLM were involved in the occupational exposure assessment in the EGEA survey; MVA, MF, MN and RN were involved in the identification of respiratory endotypes; MVA and RN analysed the data; MVA, RN and OD wrote the paper; MF, FZ, BD, HK, RM, MN, DO-G, CQ, VS, VS, J-PZ and NLM reviewed the paper and revised it critically. All authors approved the final version of the manuscript.

  • Funding This work was funded by the Fonds AGIR pour les maladies chroniques, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES/AFSSET, EST- 09–15, PNR-EST 2017), Merck Sharp & Dohme (MSD), the National hospital program of clinical research (PHRC-National 2012, EvAdA), the National Research Agency – Health Environment, Health-Work Program (ANR CES-2009), and the Région Hauts de France.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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