Pharmacotherapy of severe asthma.
Severe asthma is a complex and heterogeneous phenotype where management can be challenging. While many patients with severe asthma respond to high-dose inhaled corticosteroids in combination with a long-acting beta-agonist, there remains a significant subset of patients that require oral corticosteroids to control symptoms. Alternative therapies are needed to help reduce the need for continuous oral corticosteroids; however, there are currently very few effective options. Several new alternatives to oral corticosteroids have been evaluated in severe asthma as add-on to conventional therapy. These include macrolide antibiotics, omalizumab, tumor necrosis factor-alpha inhibitors, cytokine receptor antagonists, and bronchial thermoplasty. The challenge with these entities is determining the appropriate phenotype of severe asthma where effectiveness is demonstrated, given the significant heterogeneity of the disease. Therefore, there is a crucial need to better understand the mechanisms and pathophysiology of severe asthma so more effective immunomodulators and biologic therapies can emerge.
Firszt
Rafael
R
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
Kraft
Monica
M
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D010641:Phenotype; D012720:Severity of Illness Index
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D007155:Immunologic Factors
Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003559
16625585
N Engl J Med. 2009 Mar 5;360(10):985-93
19264687
J Allergy Clin Immunol. 2001 Aug;108(2):184-90
11496232
N Engl J Med. 1999 Dec 23;341(26):1966-73
10607813
Thorax. 2008 Jul;63(7):584-91
18245148
Chest. 2004 Apr;125(4):1378-86
15078749
Chest. 2005 Sep;128(3):1128-35
16162697
Respiration. 1996;63(1):42-8
8833992
Am J Respir Crit Care Med. 2008 Nov 15;178(10):1002-8
18787222
Chest. 1994 Oct;106(4):1116-23
7924482
Am J Respir Crit Care Med. 2006 Jul 15;174(2):112-9
16627866
Am J Respir Crit Care Med. 2005 Nov 1;172(9):1078-89
15961690
J Allergy Clin Immunol. 2001 Apr;107(4):595-601
11295645
Eur Respir J. 2006 Mar;27(3):495-503
16507848
J Allergy Clin Immunol. 2007 Feb;119(2):405-13
17291857
N Engl J Med. 2007 Mar 29;356(13):1327-37
17392302
Clin Exp Allergy. 2004 Apr;34(4):632-8
15080818
N Engl J Med. 2006 Feb 16;354(7):697-708
16481637
Clin Exp Allergy. 2009 Jun;39(6):788-97
19302249
Lancet. 2007 Oct 20;370(9596):1422-31
17950857
Chest. 2000 Dec;118(6):1826-7
11115481
N Engl J Med. 2009 Apr 9;360(15):1487-99
19357404
Chest. 2002 Jun;121(6):1782-8
12065339
Antimicrob Agents Chemother. 2003 Jan;47(1):48-53
12499168
Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91
17901415
Am J Respir Crit Care Med. 2007 Dec 1;176(11):1062-71
17872493
Paediatr Respir Rev. 2004 Mar;5(1):40-4
15222953
Lancet. 2000 Dec 23-30;356(9248):2144-8
11191542
Eur Respir J. 2003 Sep;22(3):470-7
14516137
Am J Respir Crit Care Med. 2006 Mar 1;173(5):519-26
16322642
Am J Respir Crit Care Med. 2010 Apr 1;181(7):676-87
19910613
Am J Respir Crit Care Med. 2009 Apr 1;179(7):549-58
19136369
Am J Respir Crit Care Med. 2008 Jan 15;177(2):148-55
17947611
Curr Opin Allergy Clin Immunol. 2006 Feb;6(1):43-50
16505611
Lancet. 2009 Nov 21;374(9703):1754-64
19932356
Am J Respir Crit Care Med. 2008 Oct 1;178(7):682-7
18635892
Thorax. 2005 Dec;60(12):1012-8
16166100
Am J Respir Crit Care Med. 2000 Dec;162(6):2341-51
11112161
J Allergy Clin Immunol. 2007 Dec;120(6):1373-7
17996286
Am J Respir Crit Care Med. 2006 May 15;173(10):1091-7
16357331
N Engl J Med. 2009 Mar 5;360(10):973-84
19264686
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002997
16034882
Am J Respir Crit Care Med. 2003 Jun 15;167(12):1655-9
12649124
Am J Respir Crit Care Med. 2001 Aug 15;164(4):536-41
11520711
Chest. 2002 Dec;122(6):2137-45
12475858
Am J Respir Crit Care Med. 2010 Jan 15;181(2):116-24
19815809
Cochrane Database Syst Rev. 2005 Oct 19;(4):CD005076
16235393
Epidemiol Infect. 1996 Dec;117(3):513-7
8972677