Elsevier

The Lancet

Volume 368, Issue 9537, 26 August–1 September 2006, Pages 804-813
The Lancet

Review
Asthma: defining of the persistent adult phenotypes

https://doi.org/10.1016/S0140-6736(06)69290-8Get rights and content

Summary

The common disease asthma is probably not a single disease, but rather a complex of multiple, separate syndromes that overlap. Although clinicians have recognised these different phenotypes for many years, they have remained poorly characterised, with little known about the underlying pathobiology contributing to them. Development of targeted therapies for asthma, and phenotype-specific clinical trials have raised interest in these phenotypes. Improved understanding of these phenotypes in complex diseases such as asthma will also improve our ability to link specific genotypes to their associated disease, which should help development of biomarkers. However, there is no standardised method to define asthma phenotypes. This Review analyses some of the methods that have been used to define asthma phenotypes and proposes an integrated method of classification to improve our understanding of these phenotypes.

Section snippets

Phenotypic categories

Many categories have been used to define asthma phenotypes, mostly with general or clinical criteria. Although allergic and non-allergic asthma are probably the most commonly discussed phenotypes, the determination of additional phenotypes, is possible. This Review proposes to analyse the broad categories of phenotypes and classify them in three categories: phenotypes defined by clinical or physiological criteria; phenotypes related to environmental triggers; and phenotypes defined by their

Severity-defined asthma

Clinicians have identified many different asthma, phenotypes including those based on severity, liability (or not) of airflow restriction, response to therapy, and age at onset.6, 7, 8 National and international guidelines are the biggest proponents of phenotyping by severity with fairly stringent criteria to define four categories of asthma severity.6, 9 However, several publications have suggested that these definitions, which were developed on the basis of lung function, symptoms, and use of

Allergic asthma

Allergic sensitisation that triggers asthma might be the largest overall phenotype, especially in childhood asthma, but probably also in a high proportion of adults with asthma.45 As noted above, this phenotype can present at any age, but it commonly begins in early childhood. The acute pathobiology of this group has been studied extensively with allergen-challenge protocols. In some studies a relation to T helper type 2 (Th2) inflammatory reactions has been reported, although the evidence to

Inflammatory phenotypes

Perhaps the most important advance in the treatment of asthma has been the realisation that asthma pathology has an inflammatory component, which led to the widespread use of inhaled corticosteroids, and their rank as the gold-standard for asthma treatment. Early pathological studies of patients with mild asthma who were not treated with corticosteroids, recorded high numbers of eosinophils and lymphocytes in the large airway mucosa. The number of these cells decreased significantly in response

Additional pathological phenotypes

The description of pathological phenotypes of asthma is in its infancy. In the future, more specific biomarkers than we know about now will almost certainly be found that better discriminate phenotypes. However, only cysteinyl leukotrienes, and IgE, have been associated with an identifiable phenotype (aspirin-sensitive and allergic asthma, respectively) or a response to a targeted therapy such as anti-leukotriene therapy in children, and anti-IgE drugs.5, 55, 56, 112 An increased emphasis on

How does it all fit together?

Few studies have attempted to link different approaches to describing phenotypes in asthma. This is probably because of the insufficient pathological or immunological information available from large studies of asthma patients. As minimally invasive tests, such as exhaled nitric oxide and sputum analysis, become more commonplace, we will be able to link clinical, immunological and pathological characteristics of various asthma phenotypes. New approaches to statistical modeling, such as factor

Search strategy and selection criteria

We searched PubMed for articles containing the keyword, “asthma” in combination with “phenotypes”, “biomarkers”, “eosinophil”, “neutrophil”, “aspirin sensitive”, “allergic”, “corticosteroid resistance”, “exercise”, “extrinsic”, “intrinsic”, “severe exacerbation”. We made an effort to include only peer-reviewed publications. Selection for inclusion was on the basis of results that were reproducible or had support from other studies. No limit was placed on date or language of publication,

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