Asthma, Rhinitis, Other Respiratory Diseases
Distinguishing severe asthma phenotypes: Role of age at onset and eosinophilic inflammation☆

https://doi.org/10.1016/j.jaci.2003.10.041Get rights and content

Abstract

Background

Asthma is a heterogeneous process, yet little is understood regarding phenotypes.

Objective

To determine whether phenotypic differences exist between early-onset, severe asthma as compared with late-onset disease and whether the presence or absence of eosinophilia influences the phenotypes.

Methods

Cross-sectional analysis of integrated clinical, physiologic, and pathologic data collected from 80 subjects with severe asthma. Subjects were divided into those with asthma onset before age 12 years (n = 50) versus after age 12 (n = 30) and by the presence or absence of lung eosinophils.

Results

Subjects with early-onset, severe asthma had significantly more allergen sensitivity (skin test positivity, 98% vs 76%, P < .007) and more allergic symptoms (P values all ≤ .02) than subjects with late-onset asthma. In contrast, subjects with late-onset asthma had lower lung function (P values = .05 to .07) than early-onset, despite a shorter (P < .0001) duration of illness. Both groups had a high degree of general asthma symptoms, but those with persistent eosinophils from either age at onset group had significantly more (multiple P values < .05). Similarly, the presence of eosinophils in either age at onset group was associated with the lowest lung function (P ≤ .02). Although late-onset asthma was associated with the highest numbers of lung eosinophils (P < .007), only early-onset severe asthma was associated with a lymphocytic/mast cell inflammatory process. Finally, subjects with late-onset asthma without eosinophils had no subepithelial basement membrane thickening, suggesting a different pathologic process.

Conclusions

Differentiating severe asthma by age at onset and presence or absence of eosinophils identifies phenotypes of asthma, which could benefit subsequent genetic and therapeutic studies.

Section snippets

Methods

Subjects with severe asthma were defined as previously described.11 These were patients referred to National Jewish for evaluation of refractory asthma, who were still symptomatic, requiring daily short-acting β-agonists, despite therapy with high-dose inhaled or oral steroids (at least 50% of previous year), and the addition of long-acting β-agonists and/or leukotriene-modulating drugs. For full details please see the Journal's Online Repository at www.mosby.com/jaci. In the interest of

Subject characteristics

Eighty subjects with severe asthma were entered into the data base. Fifty reported disease onset before age 12 years, whereas 30 reported onset after age 12. The mean age at onset in early-onset disease was 2.6 ± 1.0 years, whereas the late-onset group had a mean age at onset at 27 ± 1.3 years. As expected, subjects with early-onset disease had a significantly longer disease duration than those reporting late onset (26 ± 2 vs 14 ± 2 years, P < .0001). There was no difference in sex (56% and 59%

Discussion

This is the first study to integrate data from a detailed clinical questionnaire with extensive physiologic and pathologic data in a large number (n = 80) of asthmatic subjects with similar level of severity to evaluate phenotypes. This integrated approach suggests substantial differences between severe asthma that develops early in childhood as compared with disease that develops in adolescence or beyond. These data support the original distinctions between extrinsic/atopic and

References (35)

  • FM Rackeman

    A working classification of asthma

    Am J Med

    (1947)
  • S Romanet-Manent et al.

    Allergic vs nonallergic asthma: what makes the difference?

    Allergy

    (2002)
  • CS Ulrik et al.

    Mortality and decline in lung function in 213 adults with bronchial asthma: a ten-year follow up

    J Asthma

    (1992)
  • CS Ulrik et al.

    A 10-year follow-up of 180 adults with bronchial asthma: factors important for the decline in lung function

    Thorax

    (1992)
  • M Humbert et al.

    IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against “intrinsic” asthma being a distinct immunopathologic entity

    Am J Respir Crit Care Med

    (1996)
  • M Humbert et al.

    High affinity IgE receptor (Fc∗RI)-bearing cells in bronchial biopsies from atopic and non-atopic asthma

    Am J Respir Crit Care Med

    (1996)
  • KH Carlsen et al.

    Inflammation markers and symptom activity in children with bronchial asthma: influence of atopy and eczema

    Pediatr Allergy Immunol

    (1997)

    • Cited by (0)

    ☆

    Supported by funding from HL-64087, AI-40600, RR-00051, ALAs of Colorado, Oklahoma, and Alaska.

    View full text
    Copyright © 2004 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.