Phenotypes of childhood asthma: are they real?

Abstract

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.

Untangling asthma phenotypes and endotypes

“…A multidimensional approach combining clinical features and disease physiopathology (inflammation and remodeling), evaluated as complex parameters, has been recommended (20), which would also require to consider age and sex in such definitions.…”

Patterns of airway disease and the clinical diagnosis of asthma in the Busselton population

“…A variety of asthma phenotypes have been recognised [8][9][10] and it has been suggested that better definitions of asthma subtypes should form the basis of treatment options for patients that have, in the past, been classified mainly by clinical severity [11]. This approach is yet to be widely adopted for clinical use, since accurate characterisation of different phenotypes is difficult and not standardised.…”

Asthma: 2015 and Beyond

“…Numerous recent studies have shown that phenotypes can differ in their association with asthma risk factors, 13 and, more importantly for clinical practice, phenotypes can differ in their response to long-term treatment modalities. The pressing necessity for developing a consistent and reproducible classification system would facilitate research into etiology and pathophysiology, allow targeted treatment and preventive measures, and improve the prediction of long-term outcomes.…”

“…The term phenotype, as introduced by Johannsen and Shull, was intended to characterize different "types" of organisms distinguishable by their observable characteristics (eg, shape, structure, size, and color). 13 Today, substantial efforts are underway in the search for the variants underlying predisposition to asthma and associated phenotypes: preasthma wheezing, inflammatory markers, infections, atopy, aspirin sensitivity, exercise, severe asthma, flare-prone, lung function, elevated immunoglobulin E (IgE), highly variable time course (prognosis), and bronchial hyper-responsiveness.…”