Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies

被引:126
作者
Chung, Kian Fan [1 ,2 ,3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Sect, London SW3 6LY, England
[2] Royal Brompton & Harefield NHS Trust, Resp Biomed Res Unit, NIHR, London, England
[3] Univ London Imperial Coll Sci Technol & Med, London SW3 6LY, England
基金
英国医学研究理事会;
关键词
asthma clusters; asthma phenotyping; asthma treatments; eosinophils; neutrophils; T helper type 2 (Th2); EOSINOPHILIC AIRWAY INFLAMMATION; SEVERE PERSISTENT ASTHMA; EXHALED NITRIC-OXIDE; DOUBLE-BLIND; BRONCHIAL THERMOPLASTY; MONOCLONAL-ANTIBODY; CXCR2; ANTAGONIST; CLUSTER-ANALYSIS; PLACEBO; SPUTUM;
D O I
10.1111/joim.12382
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Asthma is a common heterogeneous disease with a complex pathophysiology that carries a significant mortality rate and high morbidity. Current therapies based on inhaled corticosteroids and long-acting b-agonists remain effective in a large proportion of patients with asthma, but similar to 10% (considered to have 'severe asthma') do not respond to these treatments even at high doses or with the use of oral corticosteroids. Analytical clustering methods have revealed phenotypes that include dependence on high-dose corticosteroid treatment, severe airflow obstruction and recurrent exacerbations associated with an allergic background and late onset of disease. One severe phenotype is eosinophilic inflammation-predominant asthma, with late-onset disease, rhinosinusitis, aspirin sensitivity and exacerbations. Blood and sputum eosinophilia have been used to distinguish patients with high Th2 inflammation and to predict therapeutic response to treatments targeted towards Th2-associated cytokines. New therapies in the form of humanized antibodies against Th2 targets, such as anti-IgE, anti-IL4Ra, anti-IL-5 and anti-IL-13 antibodies, have shown encouraging results in terms of reduction in exacerbations and improvement in airflow in patients with a 'Th2-high' expression profile and blood eosinophilia. Research efforts are now focusing on elucidating the phenotypes underlying the non-Th2-high (or Th2-low) group, which constitutes similar to 50% of severe asthma cases. There is an increasing need to use biomarkers to indicate the group of patients who will respond to a specifically targeted treatment. The use of improved tools to measure activity of disease, a better definition of severe asthma and the delineation of inflammatory pathways with omics analyses using computational tools, will lead to better-defined phenotypes for specific therapies.
引用
收藏
页码:192 / 204
页数:13
相关论文
共 105 条
[1]   The Cost of Persistent Asthma in Europe: An International Population-Based Study in Adults [J].
Accordini, Simone ;
Corsico, Angelo G. ;
Braggion, Marco ;
Gerbase, Margaret W. ;
Gislason, David ;
Gulsvik, Amund ;
Heinrich, Joachim ;
Janson, Christer ;
Jarvis, Deborah ;
Jogi, Rain ;
Pin, Isabelle ;
Schoefer, Yvonne ;
Bugiani, Massimiliano ;
Cazzoletti, Lucia ;
Cerveri, Isa ;
Marcon, Alessandro ;
de Marco, Roberto .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2013, 160 (01) :93-101
[2]   TH17-associated cytokines (IL-17A and IL-17F) in severe asthma [J].
Al-Ramli, Wisam ;
Prefontaine, David ;
Chouiali, Fazila ;
Martin, James G. ;
Olivenstein, Ron ;
Lamiere, Catherine ;
Hamid, Qutayba .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (05) :1185-1187
[3]   Three phenotypes of adult-onset asthma [J].
Amelink, M. ;
de Nijs, S. B. ;
de Groot, J. C. ;
van Tilburg, P. M. B. ;
van Spiegel, P. I. ;
Krouwels, F. H. ;
Lutter, R. ;
Zwinderman, A. H. ;
Weersink, E. J. M. ;
ten Brinke, A. ;
Sterk, P. J. ;
Bel, E. H. .
ALLERGY, 2013, 68 (05) :674-680
[4]   Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects [J].
Arm, J. P. ;
Bottoli, I. ;
Skerjanec, A. ;
Floch, D. ;
Groenewegen, A. ;
Maahs, S. ;
Owen, C. E. ;
Jones, I. ;
Lowe, P. J. .
CLINICAL AND EXPERIMENTAL ALLERGY, 2014, 44 (11) :1371-1385
[5]   An Integrative Systems Biology Approach to Understanding Pulmonary Diseases [J].
Auffray, Charles ;
Adcock, Ian M. ;
Chung, Kian Fan ;
Djukanovic, Ratko ;
Pison, Christophe ;
Sterk, Peter J. .
CHEST, 2010, 137 (06) :1410-1416
[6]   Increased TGF-β2 in severe asthma with eosinophilia [J].
Balzar, S ;
Chu, HW ;
Silkoff, P ;
Cundall, M ;
Trudeau, JB ;
Strand, M ;
Wenzel, S .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (01) :110-117
[7]   A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma [J].
Barnes, N. ;
Pavord, I. ;
Chuchalin, A. ;
Bell, J. ;
Hunter, M. ;
Lewis, T. ;
Parker, D. ;
Payton, M. ;
Collins, L. Pearce ;
Pettipher, R. ;
Steiner, J. ;
Perkins, C. M. .
CLINICAL AND EXPERIMENTAL ALLERGY, 2012, 42 (01) :38-48
[8]   Can guideline-defined asthma control be achieved? The gaining optimal asthma control study [J].
Bateman, ED ;
Boushey, HA ;
Bousquet, J ;
Busse, WW ;
Clark, TJH ;
Pauwels, RA ;
Pedersen, SE .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 170 (08) :836-844
[9]   Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone [J].
Baumgartner, RA ;
Martinez, G ;
Edelman, JM ;
Gomez, GGR ;
Bernstein, M ;
Bird, S ;
Angner, R ;
Polis, A ;
Dass, SB ;
Lu, S ;
Reiss, TF .
EUROPEAN RESPIRATORY JOURNAL, 2003, 21 (01) :123-128
[10]   Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma [J].
Bel, Elisabeth H. ;
Wenzel, Sally E. ;
Thompson, Philip J. ;
Prazma, Charlene M. ;
Keene, Oliver N. ;
Yancey, Steven W. ;
Ortega, Hector G. ;
Pavord, Ian D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (13) :1189-1197