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Thorax 2009;64:374-380 doi:10.1136/thx.2008.103069
  • Asthma

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
  • Received 17 June 2008
  • Accepted 30 November 2008
  • Published Online First 8 January 2009

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.

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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