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DOI 10.1007/s40265-014-0213-9
CURRENT OPINION
Key Points
Unbiased approaches to classifying asthma will
continue to lead to the identification of distinct
phenotypes linked to known mechanisms. A Th2high identifies patients with high eosinophilia and
good therapeutic response to corticosteroids.
Other characteristic traits of severe asthma include
non-eosinophilic asthma, corticosteroid insensitivity,
obesity-associated and exacerbation-prone, and these
need to be linked to mechanisms.
Newer treatments for asthma will emerge from better
endotyping, and will be targeted to specific
phenotypes. This will lead to a future world of
personalized medicine in asthma.
1 Introduction
K. F. Chung (&)
Experimental Studies, National Heart and Lung Institute,
Imperial College London, Dovehouse St, London SW3 6LY, UK
e-mail: [email protected]
K. F. Chung
Royal Brompton NIHR Biomedical Research Unit, London, UK
720
K. F. Chung
721
Early-onset atopic asthma with normal lung function treated with two or fewer controller medications and minimal healthcare
utilization
Cluster 2
Early-onset atopic asthma and preserved lung function but increased medication requirements and healthcare utilization
Cluster 3
Mostly older obese women with late-onset non-atopic asthma, moderate reductions in FEV1, and frequent oral corticosteroid use
to manage exacerbations
Cluster 4 and
5
Severe airflow obstruction with bronchodilator responsiveness but differ in their ability to attain normal lung function, age of
asthma onset, atopic status, and use of oral corticosteroids
Early-onset atopic asthma, with airway dysfunction and eosinophilic inflammation; increased number of hospitalizations
Cluster 2
Cluster 3
Benign asthma with little evidence of active disease. No significant airway hyper-responsiveness in 58 % of cluster
Early-onset atopic asthma, with airway dysfunction and eosinophilic inflammation; increased number of hospitalizations
Cluster 2
Cluster 3
Cluster 4
ECRHS II [10]
Phenotype A
Active-treated allergic childhood-onset asthma. Atopic asthma, active disease, greater bronchial hyper-responsiveness
Phenotype B
Active treated adult-onset asthma. Older subjects with adult-onset asthma. Female, active disease. Asthma attack in previous
12 months
Phenotype C
Phenotype D
EGEA 2 [10]
Phenotype E
Phenotype F
Phenotype G
Phenotype H
ECRHS European Community Respiratory Health Survey, FEV1 forced expiratory volume in 1 sec
722
reduced the exacerbation rates requiring oral corticosteroids, improved lung function (forced expiratory volume in
1 sec [FEV1]) and decreased the need for rescue shortacting b-agonists [1]. With combination LABA and ICS,
asthma control can be reasonably achieved in *68 % of
patients, with the least effectiveness in the most severe
group [21], indicating that such treatment, even at the
maximal doses allowable, is not effective in all asthmatic
patients. With increasing severity and poor control of
asthma, other controller medications are added to the
combination LABA and ICS therapy, such as slow-release
theophylline and leukotriene inhibitors [22]. Finally, at the
highest step (5), the addition of oral therapy with corticosteroids is advocated, and a new class of therapy, an antiIgE humanized monoclonal antibody, is now also used as
an additive treatment for severe allergic asthma.
Even with maximization of such therapies, between 5
and 10 % of patients with asthma are refractory to these
treatments and such patients have been labelled as severe
asthma or refractory-resistant asthma [2, 3]. It is in this
group of patients that more efficacious treatments are needed. It is now becoming evident that asthma, particularly
severe asthma, cannot be considered as one disease but as a
heterogeneous collection of several different phenotypes
that could be determined by different pathway mechanisms.
The idea that all asthma treatments are beneficial to all
asthmatics is seen in most current guidelines, but this is less
applicable in the severe asthma patient. The recently published joint European Respiratory Society and American
Thoracic Society severe asthma guidelines have recognized
the heterogeneity of severe asthma and proposes targeted
therapies for defined phenotypes of asthma [23]. Recommendations regarding the determination of sputum eosinophilia to help in directing treatments for severe asthma have
been made; use of sputum eosinophilia may be useful in
pinpointing the patients who may benefit from treatment
with T-helper (Th)-2 cytokine-targeted therapies.
K. F. Chung
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724
K. F. Chung
725
8 Conclusion
Clinicians have always placed a high value on individualized treatments, and the time has come for more personalized medicine in a disease as complex as asthma. In the
field of asthma, there has been a conventional one size fits
all approach in terms of the treatment of asthma. However,
we are now getting more tools to approach personalized
medicine for asthma such as the validated measures of
activity and severity of asthma [88], and with the definition
of severe asthma using control measures of asthma [23].
The recent addition of biomarkers that characterize the
eosinophilic phenotype and that predicts response to specific therapies will add to the increasing confidence of
delivering more personalized management for asthma,
particularly for severe asthma.
Acknowledgments The author has no potential conflicts of interest
to declare in relation to the contents of this review. The author is
funded through the Innovative Medicines Initiative in terms of the
UBIOPRED project, which is looking into a systems biology
approach to severe asthma. No funding was obtained for the writing
of this manuscript.
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