Severe asthma phenotypes
- Sally Wenzel, MD
Sally Wenzel, MD
- Professor of Medicine
- University of Pittsburgh
Asthma is defined and diagnosed through a combination of clinical symptoms and physiologic abnormalities, generally without reliance upon pathologic or biologic markers. However, the physiologic definition of asthma is relatively nonspecific, consisting of airway hyperreactivity and airflow limitation during expiration, which is variable and/or reversible with bronchodilators. In most asthma patients, the presence of bronchial hyperreactivity is never objectively confirmed.
The data suggesting that multiple phenotypes exist within the classification of "severe asthma" are reviewed here. Details regarding the classification, evaluation, diagnosis, and treatment of severe asthma are provided separately. (See "An overview of asthma management" and "Evaluation of severe asthma in adolescents and adults" and "Diagnosis of asthma in adolescents and adults" and "Treatment of severe asthma in adolescents and adults" and "Mechanisms and clinical implications of glucocorticoid resistance in asthma".)
DEFINITION OF SEVERE ASTHMA
The diagnosis of asthma is based upon the presence or history of symptoms consistent with asthma (most commonly episodic cough, wheezing, or dyspnea) provoked by typical triggers, combined with the demonstration of variable expiratory airflow obstruction. After confirming a diagnosis of asthma and addressing comorbidities, severe asthma is that which requires treatment with high dose inhaled glucocorticoids plus a second controller and/or systemic glucocorticoids to prevent asthma from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy .
RATIONALE FOR CHARACTERIZING ASTHMA PHENOTYPES
Patients with severe asthma present with a variety of clinical histories, physiologic changes (beyond changes in forced expiratory volume in one second [FEV1]), and airway inflammation, suggesting that severe asthma is not a single disease or is a single process that produces widely varying host responses. Patients with severe asthma may have manifested severe disease all their life, developed progressively more severe disease over time, or may never have had asthma (to the best of their recollection) until some point in their adult life, after which the disease progressed at a rapid pace . Some patients with severe asthma have a clearly defined atopic history, while others give little indication of an allergic component.
In addition to the variability in clinical features, patients with asthma do not respond in a uniform fashion to asthma medications, particularly glucocorticoids and other nonspecific anti-inflammatory/cytotoxic medications. It is hoped that exploration of asthma phenotypes will translate into improved understanding of asthma pathophysiology and optimized medication selection [1,3].
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- DEFINITION OF SEVERE ASTHMA
- RATIONALE FOR CHARACTERIZING ASTHMA PHENOTYPES
- SEVERE ASTHMA PHENOTYPES
- Childhood onset allergic asthma
- Adult onset atopic asthma
- Adult onset nonatopic asthma
- Hypereosinophilic adult onset asthma and aspirin exacerbated respiratory disease
- Asthmatic granulomatosis
- CLINICAL CHARACTERISTICS ASSOCIATED WITH SEVERE ASTHMA
- Glucocorticoid resistance
- Exacerbation frequency
- Asthma associated with obesity
- Perimenopausal onset asthma
- PHENOTYPING BASED ON BIOMARKERS OF INFLAMMATION
- Th2-like/Eosinophilic asthma
- Fraction of exhaled nitric oxide
- Neutrophilic asthma