Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease

被引:764
作者
Anderson, Gary P. [1 ,2 ]
机构
[1] Univ Melbourne, Lung Dis Res Grp, Dept Med, Parkville, Vic 3010, Australia
[2] Univ Melbourne, Lung Dis Res Grp, Dept Pharmacol, Parkville, Vic 3010, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0140-6736(08)61452-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Clinical asthma is very widely assumed to be the net result of excessive inflammation driven by aberrant T-helper-2 (Th2) immunity that leads to inflamed, remodelled airways and then functional derangement that, in turn, causes symptoms. This notion of disease is actually poorly supported by data, and there are substantial discrepancies and very poor correlation between inflammation, damage, functional impairment, and degree of symptoms. Furthermore, this problem is compounded by the poor understanding of the heterogeneity of clinical disease. Failure to recognise and discover the underlying mechanisms of these major variants or endotypes of asthma is, arguably, the major intellectual limitation to progress at present. Fortunately, both clinical research and animal models are very well suited to dissecting the cellular and molecular basis of disease endotypes. This approach is already suggesting entirely novel pathways to disease-eg, alternative macrophage specification, steroid refractory innate immunity the interleukin-17-regulatory T-cell axis, epidermal growth factor receptor co-amplification, and Th2-mimicking but non-T-cell, interleukins 18 and 33 dependent processes that can offer unexpected therapeutic opportunities for specific patient endotypes.
引用
收藏
页码:1107 / 1119
页数:13
相关论文
共 150 条
[1]  
Alexander HL, 1921, ARCH INTERN MED, V27, P184, DOI 10.1001/archinte.1921.00100080047004
[2]   Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients [J].
Alvarez, MJ ;
Olaguibel, JM ;
Garcia, BE ;
Tabar, AI ;
Urbiola, E .
ALLERGY, 2000, 55 (06) :531-539
[3]   Airway inflammation in asthma and perennial allergic rhinitis.: Relationship with nonspecific bronchial responsiveness and maximal airway narrowing [J].
Alvarez, MJ ;
Olaguibel, JM ;
García, BE ;
Rodríguez, A ;
Tabar, AI ;
Urbiola, E .
ALLERGY, 2000, 55 (04) :355-362
[4]   Airway smooth muscle dynamics:: a common pathway of airway obstruction in asthma [J].
An, S. S. ;
Bai, T. R. ;
Bates, J. H. T. ;
Black, J. L. ;
Brown, R. H. ;
Brusasco, V. ;
Chitano, P. ;
Deng, L. ;
Dowell, M. ;
Eidelman, D. H. ;
Fabry, B. ;
Fairbank, N. J. ;
Ford, L. E. ;
Fredberg, J. J. ;
Gerthoffer, W. T. ;
Gilbert, S. H. ;
Gosens, R. ;
Gunst, S. J. ;
Halayko, A. J. ;
Ingram, R. H. ;
Irvin, C. G. ;
James, A. L. ;
Janssen, L. J. ;
King, G. G. ;
Knight, D. A. ;
Lauzon, A. M. ;
Lakser, O. J. ;
Ludwig, M. S. ;
Lutchen, K. R. ;
Maksym, G. N. ;
Martin, J. G. ;
Mauad, T. ;
McParland, B. E. ;
Mijailovich, S. M. ;
Mitchell, H. W. ;
Mitchell, R. W. ;
Mitzner, W. ;
Murphy, T. M. ;
Pare, P. D. ;
Pellegrino, R. ;
Sanderson, M. J. ;
Schellenberg, R. R. ;
Seow, C. Y. ;
Silveira, P. S. P. ;
Smith, P. G. ;
Solway, J. ;
Stephens, N. L. ;
Sterk, P. J. ;
Stewart, A. G. ;
Tang, D. D. .
EUROPEAN RESPIRATORY JOURNAL, 2007, 29 (05) :834-860
[5]   T(H)2 AND T(H)2-LIKE CELLS IN ALLERGY AND ASTHMA - PHARMACOLOGICAL PERSPECTIVES [J].
ANDERSON, GP ;
COYLE, AJ .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (09) :324-332
[6]   Interactions between corticosteroids and β-adrenergic agonists in asthma disease induction, progression, and exacerbation [J].
Anderson, GP .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (03) :S188-S196
[7]   50 years of asthma: UK trends from 1955 to 2004 [J].
Anderson, H. Ross ;
Gupta, Ramyani ;
Strachan, David P. ;
Limb, Elizabeth S. .
THORAX, 2007, 62 (01) :85-90
[8]   Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma [J].
Aoki, Haruka ;
Hisada, Takeshi ;
Ishizuka, Tamotsu ;
Utsugi, Mitsuyoshi ;
Kawata, Tadayoshi ;
Shimizu, Yasuo ;
Okajima, Fumikazu ;
Dobashi, Kunio ;
Mori, Masatomo .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 367 (02) :509-515
[9]   Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients [J].
Araya, Jun ;
Cambier, Stephanie ;
Markovics, Jennifer A. ;
Wolters, Paul ;
Jablons, David ;
Hill, Arthur ;
Finkbeiner, Walter ;
Jones, Kirk ;
Broaddus, V. Courtney ;
Sheppard, Dean ;
Barzcak, Andrea ;
Xiao, Yuanyuan ;
Erle, David J. ;
Nishimura, Stephen L. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (11) :3551-3562
[10]   IRAK-M is involved in the pathogenesis of early-onset persistent asthma [J].
Balaci, Lenuta ;
Spada, Maria Cristina ;
Olla, Nazario ;
Sole, Gabriella ;
Loddo, Laura ;
Anedda, Francesca ;
Naitza, Silvia ;
Zuncheddu, Maria Antonietta ;
Maschio, Andrea ;
Altea, Daniele ;
Uda, Manuela ;
Pilia, Sabrina ;
Sanna, Serena ;
Masala, Marco ;
Crisponi, Laura ;
Fattori, Matilde ;
Devoto, Marcella ;
Doratiotto, Silvia ;
Rassu, Stefania ;
Mereu, Simonetta ;
Giua, Enrico ;
Cadeddu, Natalina Graziella ;
Atzeni, Roberto ;
Pelosi, Umberto ;
Corrias, Adriano ;
Perra, Roberto ;
Torrazza, Pier Luigi ;
Pirina, Pietro ;
Ginesu, Francesco ;
Marcias, Silvano ;
Schintu, Maria Grazia ;
Del Giacco, Gennaro Sergio ;
Manconi, Paolo Emilio ;
Malerba, Giovanni ;
Bisognin, Andrea ;
Trabetti, Elisabetta ;
Boner, Attilio ;
Pescollderungg, Lydia ;
Pignatti, Pier Franco ;
Schlessinger, David ;
Cao, Antonio ;
Pilia, Giuseppe .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (06) :1103-1114