Distinguishing severe asthma phenotypes: Role of age at onset and eosinophilic inflammation

• Published in: Journal of allergy and clinical immunology Vol. 113; no. 1; pp. 101 - 108
• Main Authors: Miranda, Christina, Busacker, Ashley, Balzar, Silvana, Trudeau, John, Wenzel, Sally E.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 2004; Elsevier; Elsevier Limited
• Subjects: Age of Onset; Airway management; Allergic diseases; Allergies; allergy; Asthma; Asthma - diagnosis; Biological and medical sciences; Cell Count; Chronic obstructive pulmonary disease, asthma; Cross-Sectional Studies; Disease; Eosinophils - immunology; Female; Humans; Immunopathology; Immunophenotyping; inflammation; Male; Medical sciences; phenotypes; Pneumology; Questionnaires; remodeling; Respiratory and ent allergic diseases; Respiratory Function Tests; Severity of Illness Index; Steroids; Studies; remodeling; phenotypes; PPU; inflammation; LT; allergy; BAL; Asthma; SBM; Human; Lung disease; Respiratory disease; Granulocyte; Clinical form; Inflammation; Remodeling; Eosinophil; Phenotype; Age of onset; Bronchus disease; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2003.10.041

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