title: Which biomarkers are effective for identifying Th2-driven inflammation in asthma?
abstract: Recognition of asthma as a heterogeneous disease revealed different potential molecular targets and urged the development of targeted, customized treatment modalities. Evidence was provided for different inflammatory subsets of asthma and more recently, further refined to T helper (Th)2-high and Th2-low subphenotypes with different responsiveness to standard and targeted pharmacotherapy. Given these differences in immunology and pathophysiology, proof of concept studies of novel treatment modalities for asthma should be performed in adequate, well-defined phenotypes. In this review, we describe both existing and novel biomarkers of Th2-inflammation in asthma that can be applied to classify asthma subphenotypes in clinical studies and for treatment monitoring.
authors.affiliation: Institute for Clinical Science, Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund University, Klinikgatan 18, S-221 85, Lund, Sweden, z.diamant@gems.demon.nl.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Diamant
authors.forename: Ellen
authors.initials: E
authors.lastname: Tufvesson
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D010641:Phenotype; D018418:Th2 Cells / Q000737:chemistry / Q000276:immunology*
chemical_list: D015415:Biomarkers
references.citation: Am J Hematol. 1987 Jan;24(1):55-63
references.pmid: 3799595
references.citation: Lung. 2007 Mar-Apr;185(2):105-12
references.pmid: 17393242
references.citation: Pulm Pharmacol Ther. 2013 Jun;26(3):400-1
references.pmid: 23291284
references.citation: Eur Respir J. 2005 Jun;25(6):986-91
references.pmid: 15929952
references.citation: Clin Exp Allergy. 2004 Sep;34(9):1388-94
references.pmid: 15347371
references.citation: J Allergy Clin Immunol. 2010 Aug;126(2):404-6
references.pmid: 20621343
references.citation: Chest. 2006 Aug;130(2):371-8
references.pmid: 16899834
references.citation: Am J Respir Cell Mol Biol. 2002 Feb;26(2):202-8
references.pmid: 11804871
references.citation: Allergy. 2002 Feb;57(2):173-7
references.pmid: 11929424
references.citation: J Allergy Clin Immunol. 1999 Jul;104(1):66-71
references.pmid: 10400841
references.citation: Clin Respir J. 2008 Jul;2(3):149-57
references.pmid: 20298323
references.citation: J Allergy Clin Immunol. 2013 Sep;132(3):547-553
references.pmid: 23608729
references.citation: Clin Respir J. 2010 Apr;4(2):83-8
references.pmid: 20565481
references.citation: Thorax. 1999 May;54(5):403-8
references.pmid: 10212103
references.citation: World Allergy Organ J. 2009 Jul;2(7):144-9
references.pmid: 23283064
references.citation: Am J Respir Crit Care Med. 1998 Feb;157(2):403-9
references.pmid: 9476850
references.citation: J Investig Allergol Clin Immunol. 2012;22(7):501-7
references.pmid: 23397672
references.citation: Am J Respir Crit Care Med. 2010 Feb 15;181(4):315-23
references.pmid: 19892860
references.citation: Am J Clin Pathol. 1981 May;75(5):693-700
references.pmid: 7234755
references.citation: Clin Exp Allergy. 2008 Jun;38(6):936-46
references.pmid: 18384429
references.citation: Allergy. 2004 Jan;59(1):26-32
references.pmid: 14674929
references.citation: Clin Exp Allergy. 1995 Nov;25(11):1118-27
references.pmid: 8581845
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15858-63
references.pmid: 17898169
references.citation: Pediatr Allergy Immunol. 2001 Dec;12(6):312-7
references.pmid: 11846868
references.citation: J Allergy Clin Immunol. 1996 Jun;97(6):1179-87
references.pmid: 8648010
references.citation: Clin Exp Immunol. 1998 Jan;111(1):129-35
references.pmid: 9472672
references.citation: Clin Exp Allergy. 2001 Sep;31(9):1441-8
references.pmid: 11591195
references.citation: Respir Res. 2012 Sep 19;13:78
references.pmid: 22989372
references.citation: Thorax. 2007 Sep;62(9):750-57
references.pmid: 17389757
references.citation: J Negat Results Biomed. 2008 May 19;7:3
references.pmid: 18489783
references.citation: Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):175-82
references.pmid: 22507330
references.citation: N Engl J Med. 1989 Feb 2;320(5):271-7
references.pmid: 2911321
references.citation: Adv Med Sci. 2011;56(2):318-22
references.pmid: 21940268
references.citation: Am J Respir Crit Care Med. 2010 May 15;181(10):1033-41
references.pmid: 20133930
references.citation: Anal Chem. 2009 Mar 15;81(6):2106-14
references.pmid: 19192965
references.citation: N Engl J Med. 2013 Jun 27;368(26):2455-66
references.pmid: 23688323
references.citation: Chest. 2005 Oct;128(4):1921-7
references.pmid: 16236836
references.citation: J Allergy Clin Immunol. 2005 Nov;116(5):1007-13
references.pmid: 16275368
references.citation: Am J Respir Crit Care Med. 2008 Aug 1;178(3):218-224
references.pmid: 18480428
references.citation: J Allergy Clin Immunol. 2013 Jun;131(6):1504-12
references.pmid: 23506843
references.citation: Ann Allergy Asthma Immunol. 2001 Oct;87(4):319-26
references.pmid: 11686425
references.citation: J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):42-51
references.pmid: 7822663
references.citation: Respir Med. 2010 Feb;104(2):188-96
references.pmid: 19846286
references.citation: Respir Res. 2011 Oct 26;12:140
references.pmid: 22029856
references.citation: Lancet. 2006 Aug 26;368(9537):804-13
references.pmid: 16935691
references.citation: Ann Allergy Asthma Immunol. 2006 Sep;97(3):312-20
references.pmid: 17042136
references.citation: Eur J Immunol. 2011 Jun;41(6):1675-86
references.pmid: 21469105
references.citation: Pediatr Allergy Immunol. 2003 Apr;14(2):130-3
references.pmid: 12675759
references.citation: Am J Respir Crit Care Med. 2009 Sep 1;180(5):388-95
references.pmid: 19483109
references.citation: Respir Med. 2010 Sep;104(9):1254-62
references.pmid: 20434897
references.citation: J Allergy Clin Immunol. 2002 Sep;110(3):404-9
references.pmid: 12209086
references.citation: Respirology. 2004 Nov;9(4):507-13
references.pmid: 15612963
references.citation: Am J Respir Crit Care Med. 1995 Sep;152(3):897-905
references.pmid: 7663802
references.citation: Am J Respir Crit Care Med. 2000 Jun;161(6):2051-7
references.pmid: 10852787
references.citation: Respir Med. 2007 Mar;101(3):378-88
references.pmid: 17258900
references.citation: N Engl J Med. 2011 Sep 22;365(12):1088-98
references.pmid: 21812663
references.citation: Am J Respir Crit Care Med. 2007 Apr 15;175(8):783-90
references.pmid: 17204725
references.citation: Clin Exp Allergy. 2001 Feb;31(2):239-48
references.pmid: 11251625
references.citation: Eur Respir J. 1998 Feb;11(2):312-6
references.pmid: 9551730
references.citation: ScientificWorldJournal. 2012;2012:217518
references.pmid: 23365513
references.citation: Respir Med. 2007 Jul;101(7):1447-54
references.pmid: 17379492
references.citation: J Asthma. 2008 Oct;45(8):654-63
references.pmid: 18951256
references.citation: Clin Exp Allergy. 2010 Jan;40(1):85-93
references.pmid: 19895589
references.citation: Curr Med Chem. 2011;18(10):1415-22
references.pmid: 21428898
references.citation: Am J Respir Crit Care Med. 2013 Apr 15;187(8):804-11
references.pmid: 23471469
references.citation: Mediators Inflamm. 2000;9(3-4):175-9
references.pmid: 11132775
references.citation: J Allergy Clin Immunol. 2008 Mar;121(3):560-70; quiz 571-2
references.pmid: 18328887
references.citation: Pulm Pharmacol Ther. 2010 Dec;23(6):468-81
references.pmid: 20601050
references.citation: J Allergy Clin Immunol. 2003 Jan;111(1):79-86
references.pmid: 12532100
references.citation: N Engl J Med. 1975 May 29;292(22):1152-5
references.pmid: 1124105
references.citation: J Allergy Clin Immunol. 2004 Feb;113(2):334-40
references.pmid: 14767451
references.citation: Clin Exp Allergy. 2007 Jul;37(7):1067-73
references.pmid: 17581201
references.citation: Allergy. 1996 Aug;51(8):547-55
references.pmid: 8874658
references.citation: Thorax. 2001 May;56(5):351-7
references.pmid: 11312402
references.citation: J Clin Invest. 1998 Feb 15;101(4):834-46
references.pmid: 9466979
references.citation: Allergy. 2002 Feb;57(2):180-1
references.pmid: 11929427
references.citation: Chest. 1997 Nov 5;112(5):1241-7
references.pmid: 9367463
references.citation: J Allergy Clin Immunol. 2003 Nov;112(5):930-4
references.pmid: 14610482
references.citation: Am J Respir Cell Mol Biol. 2007 Jul;37(1):97-104
references.pmid: 17347445
references.citation: Curr Allergy Asthma Rep. 2009 Jan;9(1):18-25
references.pmid: 19063820
references.citation: N Engl J Med. 2009 Mar 5;360(10):973-84
references.pmid: 19264686
references.citation: Allergy. 2009 May;64(5):733-7
references.pmid: 19133919
references.citation: J Clin Invest. 1999 Mar;103(6):779-88
references.pmid: 10079098
references.citation: J Allergy Clin Immunol. 1996 Nov;98(5 Pt 1):859-71
references.pmid: 8939149
references.citation: Allergy. 2008 Mar;63(3):268-73
references.pmid: 18053010
references.citation: Eur Respir J. 2003 May;21(5):799-803
references.pmid: 12765424
references.citation: Mediators Inflamm. 1995;4(6):426-30
references.pmid: 18475675
references.citation: Pediatr Res. 2003 Aug;54(2):198-203
references.pmid: 12736396
references.citation: J Leukoc Biol. 2003 Oct;74(4):558-63
references.pmid: 12960268
references.citation: J Clin Immunol. 2004 Jul;24(4):426-34
references.pmid: 15163899
references.citation: J Asthma. 2010 Mar;47(2):131-4
references.pmid: 20170318
references.citation: Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):360-8
references.pmid: 7842192
references.citation: PLoS One. 2013 Apr 24;8(4):e61356
references.pmid: 23637817
references.citation: J Allergy Clin Immunol. 2012 Sep;130(3):647-654.e10
references.pmid: 22857879
references.citation: Int J Clin Pract. 2008 Apr;62(4):599-605
references.pmid: 17537187
references.citation: Thorax. 2008 Dec;63(12):1076-82
references.pmid: 18757457
references.citation: Clin Exp Allergy. 2004 Mar;34(3):437-44
references.pmid: 15005738
references.citation: J Biol Chem. 2011 Jan 21;286(3):1786-94
references.pmid: 21097505
references.citation: Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1608-14
references.pmid: 8970343
references.citation: Clin Exp Allergy. 1999 Nov;29(11):1449-53
references.pmid: 10520070
references.citation: J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):232-7
references.pmid: 9949313
references.citation: PLoS One. 2010 Dec 13;5(12):e14299
references.pmid: 21179211
references.citation: Respir Res. 2007 Sep 27;8:67
references.pmid: 17897478
references.citation: Am J Respir Crit Care Med. 1994 Oct;150(4):1038-48
references.pmid: 7921434
references.citation: Chest. 1995 Jul;108(1):10-5
references.pmid: 7606941
references.citation: J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):559-64
references.pmid: 10482828
references.citation: Respir Res. 2009 Jan 19;10:3
references.pmid: 19152703
references.citation: Int Arch Allergy Immunol. 1999 Oct;120(2):158-65
references.pmid: 10545770
references.citation: Int Arch Allergy Immunol. 2003 May;131(1):46-52
references.pmid: 12759489
references.citation: Am J Respir Crit Care Med. 1997 Nov;156(5):1384-9
references.pmid: 9372649
references.citation: J Allergy Clin Immunol. 2012 Oct;130(4):829-42; quiz 843-4
references.pmid: 22951057