Recent Advances in Severe Asthma From Phenotypes to Personalized Medicine

被引:105
作者
Schoettler, Nathan [1 ]
Strek, Mary E. [1 ]
机构
[1] Univ Chicago, Sect Pulm & Crit Care, Dept Med, Chicago, IL 60637 USA
关键词
asthma; endotype; phenotype; severe asthma; DOUBLE-BLIND; ANTIBODY OMALIZUMAB; MONOCLONAL-ANTIBODY; NATURAL-HISTORY; CHILDHOOD-ONSET; RISK-FACTORS; GENOME-WIDE; CHILDREN; DISEASE; REMISSION;
D O I
10.1016/j.chest.2019.10.009
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
This review focuses on recent clinical and translational discoveries in severe and uncontrolled asthma that now enable phenotyping and personalized therapies in these patients. Although asthma is common in both children and adults and typically responds to standard therapies, a subset of individuals with asthma experience severe and/or persistent symptoms despite appropriate therapies. Airflow obstruction leading to frequent symptoms requiring higher levels of controller therapy is the cardinal feature of severe asthma, but the underlying molecular mechanisms, or endotypes, are diverse and variable between individuals. Two major risk factors that contribute to severe asthma are genetics and environmental exposures that modulate immune responses, and although these often interact in complex manners that are not fully understood, certain endotypes converge in severe asthma. A number of studies have evaluated various features of patients with severe asthma and classified patients into phenotypes with clinical relevance. This phenotyping is now incorporated into clinical practice and can be used to guide advanced biological therapies that target specific molecules and inflammatory pathways that contribute to asthma pathogenesis.
引用
收藏
页码:516 / 528
页数:13
相关论文
共 75 条
[1]   Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with acute severe asthma in a respiratory intensive care unit in North India [J].
Agarwal, Ritesh ;
Nath, Alok ;
Aggarwal, Ashutosh N. ;
Gupta, Dheeraj ;
Chakrabarti, Arunaloke .
MYCOSES, 2010, 53 (02) :138-143
[2]   Allergic Bronchopulmonary Aspergillosis [J].
Agarwal, Ritesh .
CHEST, 2009, 135 (03) :805-826
[3]  
[Anonymous], 1956, LANCET, V271, P803
[4]  
[Anonymous], EUR RESP J
[5]   A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts [J].
Bigler, Jeannette ;
Boedigheimer, Michael ;
Schofield, James P. R. ;
Skipp, Paul J. ;
Corfield, Julie ;
Rowe, Anthony ;
Sousa, Ana R. ;
Timour, Martin ;
Twehues, Lori ;
Hu, Xuguang ;
Roberts, Graham ;
Welcher, Andrew A. ;
Yu, Wen ;
Lefaudeux, Diane ;
De Meulder, Bertrand ;
Auffray, Charles ;
Chung, Kian F. ;
Adcock, Ian M. ;
Sterk, Peter J. ;
Djukanovic, Ratko .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2017, 195 (10) :1311-1320
[6]   Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Levels A Randomized Phase 3 Study [J].
Bjermer, Leif ;
Lemiere, Catherine ;
Maspero, Jorge ;
Weiss, Sivan ;
Zangrilli, James ;
Germinaro, Matthew .
CHEST, 2016, 150 (04) :789-798
[7]   Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial [J].
Bleecker, Eugene R. ;
FitzGerald, J. Mark ;
Chanez, Pascal ;
Papi, Alberto ;
Weinstein, Steven F. ;
Barker, Peter ;
Sproule, Stephanie ;
Gilmartin, Geoffrey ;
Aurivillius, Magnus ;
Werkstrom, Viktoria ;
Goldman, Mitchell .
LANCET, 2016, 388 (10056) :2115-2127
[8]   A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations [J].
Bonnelykke, Klaus ;
Sleiman, Patrick ;
Nielsen, Kasper ;
Kreiner-Moller, Eskil ;
Mercader, Josep M. ;
Belgrave, Danielle ;
den Dekker, Herman T. ;
Husby, Anders ;
Sevelsted, Astrid ;
Faura-Tellez, Grissel ;
Mortensen, Li Juel ;
Paternoster, Lavinia ;
Flaaten, Richard ;
Molgaard, Anne ;
Smart, David E. ;
Thomsen, Philip F. ;
Rasmussen, Morten A. ;
Bonas-Guarch, Silvia ;
Holst, Claus ;
Nohr, Ellen A. ;
Yadav, Rachita ;
March, Michael E. ;
Blicher, Thomas ;
Lackie, Peter M. ;
Jaddoe, Vincent W. V. ;
Simpson, Angela ;
Holloway, John W. ;
Duijts, Liesbeth ;
Custovic, Adnan ;
Davies, Donna E. ;
Torrents, David ;
Gupta, Ramneek ;
Hollegaard, Mads V. ;
Hougaard, David M. ;
Hakonarson, Hakon ;
Bisgaard, Hans .
NATURE GENETICS, 2014, 46 (01) :51-+
[9]   The oral corticosteroid-sparing effect of omalizumab in children with severe asthma [J].
Brodlie, Malcolm ;
McKean, Michael C. ;
Moss, Samantha ;
Spencer, David A. .
ARCHIVES OF DISEASE IN CHILDHOOD, 2012, 97 (07) :604-+
[10]  
Bush Andrew, 2009, Proc Am Thorac Soc, V6, P712, DOI 10.1513/pats.200906-046DP