Exercise-induced bronchoconstriction in asthmatic children: a comparative systematic review of the available treatment options.
The aim of this article is to critically review the efficacy and safety data from randomized controlled trials (RCTs) using inhaled corticosteroids (ICSs), long- or short-acting beta(2)-adrenoceptor agonists (LABAs, SABAs), parasympatholytics and oral leukotriene receptor antagonists in the management of exercise-induced bronchoconstriction (EIB) in children with persistent asthma (EIA). The studies with sufficient information on patient characteristics and outcomes were chosen using a MEDLINE search. Results from the individual searches were combined and repeated. Studies were also found by reviewing the reference lists of the articles not included in this review. Studies focusing solely on individuals with asthma and other allergic co-morbidities (i.e. a degree of bronchial reversibility) were considered in this review. To make the paper evidence-based, the design and the quality of different studies were assessed employing the Sign criteria (evidence level [EL] and grades of recommendation [GR]). No additional statistical analyses were performed. Most of studies included paediatric patients with underlying EIA. We need to distinguish children with recurrent asthma symptoms in whom EIB is also present (patients with EIA) from asthmatic subjects whose symptoms appear only as a result of exercise (patients with EIB). Further controller treatment is indicated in patients with EIA and further reliever treatment in patients with EIB. ICSs are the first-choice controller drugs for EIA in children with persistent asthma (Sign grade of recommendation [GR]:A). In children with EIA without complete control with ICSs, SABAs (GR:A), leukotriene receptor antagonists (LTRAs) [GR:A] or LABAs (GR:A) may be added to gain control. Treatment with relievers such as SABAs (GR:A), parasympatholytics (GR:B) or, eventually, LABAs (GR:A), administered 10-15 minutes before exercise is the most preferable method of preventing EIB symptoms in children; however, not as monotherapy in children with EIA. The disadvantages and controversy relating to inhaled beta(2)-adrenoceptor agonist use lie in the development of tolerance to their effect when they are used on a regular basis, and the possibility of a resulting underuse of ICSs in patients with EIA. Researchers and guidelines recommend that if any patient requires treatment with a beta(2)-adrenoceptor agonist more than twice weekly, a low dose of ICSs should be administered. Inhaled parasympatholytics may be effective as preventive relievers in some children with EIB or EIA, especially among those with increased vagal activity. LTRAs have a well balanced efficacy-safety profile in preventing the occurrence of EIB symptoms in children. Compared with LABAs, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue SABA therapy in persistent asthmatic patients with EIA. A disadvantage of LTRAs is a non-response phenomenon. There are still insufficient data on the efficacy-safety profiles of ICS/LABA combination drugs in the treatment of EIA in children to recommend this treatment without caution. Safety profiles of inhaled SABAs, anticholinergics and montelukast in approved dosages seem sufficient enough to recommend use of these drugs in the prevention of EIB symptoms in children. Many researchers agree that treatment of EIA in children should always be individualized.
Grzelewski
Tomasz
T
N. Copernicus Hospital, Department of Pediatrics and Allergy, Medical University of Lodz, 65 Pabianicka Str., Lodz, Poland. tomaszgrzelew@wp.pl
Stelmach
Iwona
I
D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology*; D002648:Child; D015444:Exercise / Q000502:physiology*; D006801:Humans
D018927:Anti-Asthmatic Agents
Respir Med. 1994 May;88(5):363-8
7913549
Chest. 2006 May;129(5):1203-9
16685010
Eur Respir J. 2002 Jul;20(1):104-7
12166555
J Allergy Clin Immunol. 1992 Jun;89(6):1176-82
1351489
Ann Allergy. 1990 Oct;65(4):273-6
2145791
Allergy. 2000 Aug;55(8):740-8
10955700
Pediatr Allergy Immunol. 2004 Feb;15(1):32-9
14998380
Respiration. 2002;69(6):509-12
12457003
N Engl J Med. 1998 Jul 16;339(3):141-6
9664089
Allergy. 2001;56 Suppl 66:12-7
11421936
Ann Allergy Asthma Immunol. 2002 Oct;89(4):407-12
12392386
Chest. 2007 Sep;132(3):875-83
17573489
Allergy. 2007 Oct;62(10):1182-8
17845589
Eur Respir J. 1995 Nov;8(11):1852-5
8620951
J Allergy Clin Immunol. 2007 Jun;119(6):1349-58
17433829
Am J Med. 1998 May;104(5):431-8
9626025
Arzneimittelforschung. 2008;58(6):303-9
18677973
Pediatr Allergy Immunol. 2000 May;11(2):120-5
10893016
Respir Med. 1993 Aug;87(6):439-44
8105520
Eur Respir J. 2006 Aug;28(2):291-5
16641126
J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):547-53
10482826
Pharmacogenet Genomics. 2008 Jul;18(7):551-8
18551035
Am Rev Respir Dis. 1983 Dec;128(6):993-7
6359989
Pediatr Pulmonol. 1992 Nov;14(3):156-9
1480441
Am J Respir Cell Mol Biol. 2009 Feb;40(2):159-67
18688040
Eur Respir J. 2004 Dec;24(6):932-7
15572534
Ann Allergy Asthma Immunol. 1999 Feb;82(2):205-11
10071526
Pediatr Pulmonol. 1993 Feb;15(2):98-104
8474789
Ann Allergy Asthma Immunol. 1998 Apr;80(4):352-6
9564987
Clin Exp Allergy. 2008 Jan;38(1):51-9
18031559
Pediatrics. 1997 May;99(5):655-9
9113940
Am J Respir Crit Care Med. 1996 Jan;153(1):65-9
8542164
Am J Respir Crit Care Med. 2000 Jan;161(1):309-29
10619836
Allergy. 2008 Apr;63(4):387-403
18315727
BMJ. 1993 Apr 17;306(6884):1034-7
8098238
Respir Med. 2002 Jun;96(6):412-7
12117040
Pediatr Pulmonol. 1990;8(4):240-4
2115156
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD004106
18646100
Pulm Pharmacol Ther. 2007;20(6):691-700
17046300
Acta Paediatr. 1996 Jun;85(6):684-7
8816204
Respir Med. 2007 Dec;101(12):2437-46
17905575
Arch Dis Child. 1992 Aug;67(8):1014-7
1355645
Respir Med. 2000 Jul;94(7):661-7
10926337
Eur Respir J. 2002 Sep;20(3):624-9
12358338
Eur Respir J. 1998 Nov;12(5):1099-104
9864004
J Allergy Clin Immunol. 1999 Mar;103(3 Pt 1):427-35
10069876
J Allergy Clin Immunol. 2006 May;117(5):1008-13
16675326
Respir Med. 1993 Feb;87(2):111-4
8497679
Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1612-5
7952623
Allergy. 2008 May;63(5):492-505
18394123
Drugs. 1998 Feb;55(2):303-22
9506248
Ann Allergy Asthma Immunol. 2005 Jan;94(1):65-72
15702819
Allergol Immunopathol (Madr). 2004 Jan-Feb;32(1):18-20
14980191
Ann Intern Med. 2000 Jan 18;132(2):97-104
10644288
Cochrane Database Syst Rev. 2007 Jul 18;(3):CD002739
17636704
Pediatr Pulmonol. 2006 Mar;41(3):222-7
16429427
Eur Respir J. 1996 Oct;9(10):2099-103
8902473
Ann Allergy Asthma Immunol. 2001 Jun;86(6):655-8
11428738
Drugs. 1991 Nov;42(5):895-912
1723379
Pediatr Allergy Immunol. 1998 Nov;9(4):181-5
9920215
Eur Respir J. 2001 Dec;18(6):928-34
11829098
Respir Med. 2004 Nov;98(11):1051-62
15526805
Thorax. 1996 Feb;51(2):207-9
8711660
Med Sci Sports Exerc. 2005 Mar;37(3):354-9
15741830
J Allergy Clin Immunol. 2002 Nov;110(5 Suppl):S141-219
12542074
Eur J Med Res. 2004 Jul 30;9(7):365-70
15337638
Eur Respir J. 1998 Sep;12(3):573-9
9762782
Ann Allergy Asthma Immunol. 1998 Oct;81(4):366-72
9809502
Pediatrics. 1999 Sep;104(3 Pt 1):501-6
10469776
Pediatrics. 1999 Sep;104(3):e38
10469821
Pediatr Pulmonol. 2000 Jun;29(6):415-23
10821721
Qual Life Res. 1996 Feb;5(1):35-46
8901365
Eur Respir J. 1991 Nov;4(10):1174-7
1687130
Eur Respir J. 1994 Jan;7(1):43-9
8143831
Pediatrics. 1986 Feb;77(2):173-8
3945530
Am Rev Respir Dis. 1992 Sep;146(3):547-54
1355640
Eur Respir J. 2002 May;19(5):865-71
12030726
Chest. 2006 Jan;129(1):15-26
16424409
J Int Med Res. 1993 Mar-Apr;21(2):81-8
8243793
Pulm Pharmacol Ther. 2008;21(1):152-9
17376722
J Asthma. 1995;32(3):207-14
7759460
J Clin Invest. 1999 Mar;103(6):779-88
10079098
J Allergy Clin Immunol. 2008 Feb;121(2):383-9
17980416
Eur Respir J. 1997 Sep;10(9):2105-9
9311511
J Investig Allergol Clin Immunol. 2001;11(3):176-82
11831450
Pharmacotherapy. 2008 Mar;28(3):287-94
18294107
Pediatr Pulmonol. 2005 Feb;39(2):162-6
15633203
Lancet. 2004 Oct 23-29;364(9444):1505-12
15500895
Pediatr Allergy Immunol. 2002 Dec;13(6):434-7
12485319
J Pediatr. 1998 Sep;133(3):424-8
9738728
Eur Respir J. 1998 Feb;11(2):350-4
9551737
J Allergy Clin Immunol. 2003 Feb;111(2):301-7
12589349
Clin Exp Allergy. 2007 Oct;37(10):1487-93
17883728
Clin Ther. 2002 Dec;24(12):2077-87
12581546
Allergy. 2008 Jan;63(1):5-34
18053013
Clin Exp Allergy. 2002 Nov;32(11):1566-73
12569976
Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):935-9
7908246
Am Rev Respir Dis. 1992 Jun;145(6):1285-8
1595992
Eur Respir J. 1993 May;6(5):652-6
8519374
Curr Opin Pulm Med. 2006 Jan;12(1):12-7
16357573
Chest. 1995 Nov;108(5):1235-9
7587422
Pediatr Pulmonol. 1989;6(2):81-5
2522620
Allergy. 1991 Apr;46(3):203-5
2058816
Can Respir J. 2003 Jan-Feb;10(1):23-6
12650133
Pediatrics. 1980 Jul;66(1):109-14
6447269
Thorax. 2006 Nov;61(11):940-4
16772309