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Original research
Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults
  1. Vanessa Granger1,2,
  2. Farid Zerimech3,4,5,
  3. Jinan Arab6,
  4. Valerie Siroux7,8,
  5. Patricia de Nadai9,
  6. Anne Tsicopoulos9,
  7. Régis Matran3,4,5,
  8. Zeina Akiki10,
  9. Rachel Nadif11
  1. 1 Université Paris-Saclay, inserm, Inflammation microbiome immunosurveillance, Châtenay-Malabry, France
  2. 2 APHP, HUPNVS, hôpital Bichat, UF autoimmunité Hypersensibilités et Biothérapies, Paris, France
  3. 3 CHU de Lille, F-59000, Lille, France
  4. 4 Université de Lille, ULR 4483, IMPECS, F-59000, Lille, France
  5. 5 Institut Pasteur de Lille, F59000, Lille, France
  6. 6 Lebanese University, Faculty of Public Health, Section 2, Mont Liban, Lebanon
  7. 7 Université Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology Applied to Development and Respiratory Health, IAB, Grenoble, France
  8. 8 CHU Grenoble Alpes, Pédiatrie, Grenoble, France
  9. 9 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre d'Infection et d'Immunité de Lille, Lille, France
  10. 10 INSPECT-LB, Institut National de Sante Publique, Epidemiologie Clinique et Toxicologie, Faculty of Public Health, Lebanese University, Beirut, Lebanon
  11. 11 Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Equipe d’Epidémiologie Respiratoire Intégrative, CESP, Villejuif, France
  1. Correspondence to Dr Vanessa Granger, Université Paris-Saclay, Inserm, Inflammation microbiome immunosurveillance, Châtenay-Malabry, Île-de-France, France; vanessa.granger{at}universite-paris-saclay.fr

Abstract

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.

  • asthma
  • eosinophil biology

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-en. Interested 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-en. Interested researchers should contact egea.cohorte@inserm.fr with further questions regarding data access.

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Footnotes

  • Contributors The authors’ contributions to the study were as follows: VG and RN were involved in the conception, hypotheses delineation and design of the analysis strategy of the study. FZ, PdN, AT and RM were involved in ECP and EDN measurement and interpretation. RM, RN and VS were involved in the acquisition of EGEA data and identification of asthma phenotypes. VG, JNA and RN analysed the data and performed statistical analyses. VG and RN wrote the paper. FZ, JA, VS, PdN, AT, RM and ZA reviewed the paper and revised it critically. All authors approved the final version of the manuscript.

  • Funding This work was funded by the French National Research Program for Environmental and Occupational Health of ANSES (EST/2017/1/158), the Région Hauts de France, National Hospital program of clinical research (PHRC-National 2012, EvAdA), ANR-CES-2009, and AGIR grants for chronical diseases.

  • Competing interests AT reports grant from Santelys, personal fees from ALK-Abello and non-financial support from AstraZeneca outside the submitted work.

  • 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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