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Heterogeneity of asthma according to blood inflammatory patterns
  1. R Nadif1,
  2. V Siroux2,
  3. M-P Oryszczyn1,
  4. C Ravault1,
  5. C Pison1,
  6. I Pin3,
  7. F Kauffmann1,
  8. on behalf of the Epidemiological study on the Genetics and Environment of Asthma (EGEA)
  1. 1
    INSERM, U780, Epidemiology and Biostatistics, and Université Paris-Sud, IFR69, Villejuif, France
  2. 2
    INSERM, U823, Epidemiologie des cancers et des affections graves, Centre de Recherche Albert Bonniot, and Université Joseph Fourier, Grenoble, France
  3. 3
    CHU Grenoble, Pédiatrie, and INSERM, U823, Grenoble, France
  1. Mrs R Nadif, Institut National de la Santé et de la Recherche Médicale, Recherche en Epidémiologie et Biostatistique U780-IFR69, 16 avenue Paul Vaillant Couturier, 94807 Villejuif cedex, France; rachel.nadif{at}inserm.fr

Abstract

Rationale: There is increasing interest regarding asthma heterogeneity in relation to inflammatory patterns.

Objectives: To assess phenotypic characteristics, in particular clinical presentation of the disease, in 381 well-characterised adults with asthma from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) according to their blood inflammatory pattern.

Methods: Four blood inflammatory patterns were defined according to eosinophil (EOS) and neutrophil (NEU) count cut-off points. Samples with ⩾250 EOS/mm3 were classified as EOShi and those with ⩾5000 NEU/mm3 as NEUhi. Clinical characteristics include typical asthma and chronic obstructive pulmonary disease (COPD)-like symptoms, as well as composite quantitative scores addressing the activity of the disease.

Results: A substantial number of those with asthma (56.2%) had the EOSlo pattern (<250 EOS/mm3). Patients with asthma who had the EOShi pattern had higher immunoglobulin E (IgE), a lower forced expiratory volume in 1 s (FEV1) and presented a more active asthma than those with the EOSlo pattern. Among those with the EOSlo pattern, neutrophil inflammation (NEUhi) was related to a less frequent positive skin prick test response (OR 0.44, 95% CI 0.20 to 0.96). Among those with the EOShi pattern, neutrophil inflammation did not explain current asthma or asthma activity, and was significantly related to nocturnal symptoms (OR 5.21, 95% CI 1.44 to 18.8) independently of age, sex, smoking and inhaled corticosteroid treatment. In non-smokers with asthma, COPD-like symptoms, in particular chronic phlegm, were more frequent in those with neutrophil inflammation, independent of eosinophil inflammation (OR 2.35, 95% CI 1.08 to 5.10).

Conclusions: Besides eosinophilia, neutrophil inflammation assessed in the blood is related to specific characteristics of asthma. Considering simultaneously neutrophilic and eosinophilic inflammation may contribute to help to disentangle this complex disease.

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Footnotes

  • Funding: This research was funded in part by the INSERM/Ministry of Research, ANR 05-SEST-020-02/05-9-97, ANR-06-CEBS and the GA2LEN project, Global Allergy and Asthma European Network.

  • Competing interests: CP has not received any research grants from companies but received reimbursement from Novartis France, GlaxoSmithKline France, Boehringer Ingelheim France, AstraZeneca France and Actélion France for attending several conferences: ISHLT, ERS, CPLF.

  • Ethics approval: The study was approved by the relevant institutional review boards, and written informed consent was obtained from each subject.

  • The EGEA cooperative group. Coordination: F Kauffmann; F Demenais (genetics); I Pin (clinical aspects). Respiratory epidemiology: INSERM U 700, Paris, M Korobaeff (EGEA1), F Neukirch (EGEA1); INSERM U 707, Paris, I Annesi-Maesano; INSERM U 780, Villejuif, F Kauffmann, N Le Moual, R Nadif, MP Oryszczyn; INSERM U 823, Grenoble, V Siroux. Genetics: INSERM U 393, Paris, J Feingold; INSERM U 535, Villejuif: MH Dizier; Inserm U 794, Evry: E Bouzigon, F Demenais; CNG, Evry: I Gut, M Lathrop. Clinical centres: Grenoble, I Pin, C Pison; Lyon, D Ecochard (EGEA1), F Gormand, Y Pacheco; Marseille, D Charpin (EGEA1), D Vervloet; Montpellier, J Bousquet; Paris Cochin, A Lockhart (EGEA1), R Matran (now in Lille); Paris Necker, E Paty, P Scheinmann; Paris-Trousseau, A Grimfeld, J Just. Data and quality management: INSERM ex-U155 (EGEA1), J Hochez; INSERM U 780, Villejuif, N Le Moual, C Ravault; INSERM U 794, Paris, N Chateigner; Grenoble, J Ferran.

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