Dishing the dirt on asthma: What we can learn from poor hygiene.
Allergic asthma continues to represent a huge health burden worldwide and is largely treated by non-selective immunosuppressive drugs, which often prove ineffective. The hygiene hypothesis proposes that the increased incidence of allergy and asthma in Western countries observed in the last 50 years is due to environmental changes that include improved hygiene and a lack of infections. The immunological mechanisms that must underpin such an environmental impact on immune regulation remain to be defined, making it difficult to identify specific ways of preventing development of allergy and asthma in early life. In this article we will seek to review some of the pathways that might underlie the hygiene hypothesis in an attempt to provide targets for future asthma prevention.
de Lara
Catherine
C
The Edward Jenner Institute, Compton, Newbury, Berkshire, UK.
Noble
Alistair
A
Thorax. 2006 Apr;61(4):296-9
16396947
Lancet. 2001 Jun 9;357(9271):1821-5
11410189
Immunity. 2000 Oct;13(4):453-62
11070164
Am J Respir Cell Mol Biol. 2001 May;24(5):518-26
11350820
Science. 1997 Jan 3;275(5296):77-9
8974396
Allergy. 2004 May;59(5):469-78
15080825
Eur Respir J. 1996 Dec;9(12):2541-52
8980967
BMJ. 1995 May 13;310(6989):1225-9
7767192
J Immunol. 1998 Dec 1;161(11):6375-82
9834128
Pediatr Allergy Immunol. 2005 Nov;16(7):587-92
16238584
Lancet. 2000 Dec 23-30;356(9248):2149-53
11191543
Lancet. 2000 Mar 11;355(9207):873-6
10752702
J Immunol. 2003 May 1;170(9):4601-11
12707338
Am J Respir Crit Care Med. 2002 Aug 15;166(4):451-6
12186819
Lancet. 1999 May 29;353(9167):1850
10359413
Nat Rev Immunol. 2007 Mar;7(3):231-7
17318234
J Exp Med. 2004 Jun 7;199(11):1567-75
15173208
Science. 2004 Sep 17;305(5691):1776-9
15375268
Immunology. 2003 Aug;109(4):476-86
12871213
Respirology. 2003 Dec;8(4):497-503
14629655
J Immunol. 1998 Oct 15;161(8):3813-6
9780144
Clin Exp Allergy. 2003 Aug;33(8):1083-9
12911782
J Immunol. 1997 Jun 1;158(11):5560-5
9164981
Ann Allergy. 1985 Feb;54(2):148-51
3871595
J Exp Med. 2001 Nov 19;194(10):F53-7
11714761
Clin Allergy. 1988 May;18(3):295-304
3293845
Eur J Immunol. 2004 Sep;34(9):2599-608
15307192
Am J Respir Crit Care Med. 2005 Jul 1;172(1):61-6
15805186
Nat Immunol. 2004 Nov;5(11):1149-56
15448689
J Allergy Clin Immunol. 2001 Jan;107(1):129-34
11150002
Immunity. 1998 May;8(5):591-9
9620680
J Immunol. 2000 Jun 1;164(11):5575-82
10820231
J Exp Med. 2005 Nov 7;202(9):1199-212
16275759
Immunity. 2006 Jun;24(6):677-688
16782025
Clin Exp Allergy. 1999 Jun;29(6):766-71
10336592
J Immunol. 1996 Aug 15;157(4):1432-9
8759723
J Clin Invest. 2006 Jun;116(6):1633-41
16710480
J Exp Med. 2002 Mar 4;195(5):603-16
11877483
Science. 1998 Dec 18;282(5397):2258-61
9856949
J Allergy Clin Immunol. 2003 Mar;111(3):541-9
12642835
J Biol Chem. 2000 Jan 28;275(4):2693-7
10644731
N Engl J Med. 1989 Feb 2;320(5):271-7
2911321
Infection. 1997 May-Jun;25(3):154-8
9181382
J Exp Med. 1992 Jan 1;175(1):49-56
1530961
Thorax. 2006 May;61(5):383-7
16449274
Lancet. 2006 Aug 26;368(9537):780-93
16935689
Science. 2003 Feb 14;299(5609):1033-6
12532024
BMJ. 2001 Feb 17;322(7283):390-5
11179155
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7048-53
16632602
Nat Immunol. 2001 Aug;2(8):725-31
11477409
Clin Exp Allergy. 2007 Jan;37(1):47-53
17210041
BMJ. 1997 Apr 5;314(7086):999-1003
9112843
J Allergy Clin Immunol. 2005 Jan;115(1):67-73
15637549
Nat Med. 2002 Jun;8(6):625-9
12042815
Int Arch Allergy Immunol. 2005;137 Suppl 1:51-4
15947485
J Clin Pathol. 1960 Jan;13:27-33
13818688
Am Rev Respir Dis. 1984 Nov;130(5):875-8
6594074
J Exp Med. 2002 Dec 16;196(12):1645-51
12486107
Eur J Immunol. 1997 May;27(5):1229-35
9174615
N Engl J Med. 1997 May 8;336(19):1356-63
9134876
J Exp Med. 1999 Apr 19;189(8):1355-60
10209051
Allergy. 1984 May;39(4):309-15
6731756
J Allergy Clin Immunol. 1998 Sep;102(3):368-75
9768575
J Immunol. 1997 Apr 1;158(7):3539-44
9120316
Pediatr Allergy Immunol. 1996 Aug;7(3):109-16
9116874
Eur J Immunol. 2001 Jul;31(7):2227-35
11449377
J Clin Invest. 2002 Jan;109(1):131-40
11781358
J Allergy Clin Immunol. 1997 Jul;100(1):142
9257801
Lancet. 1998 Apr 25;351(9111):1225-32
9643741
Arch Dis Child. 2006 May;91(5):405-9
16443614
Curr Opin Allergy Clin Immunol. 2005 Apr;5(2):167-72
15764908
J Clin Immunol. 2001 Jan;21(1):51-9
11321239
BMJ. 1989 Nov 18;299(6710):1259-60
2513902
Lancet. 1997 Jul 12;350(9071):85-90
9228959
Clin Exp Allergy. 2000 Feb;30(2):187-93
10651770
Clin Exp Allergy. 2004 Jul;34(7):1011-6
15248843
J Immunol. 2003 Mar 1;170(5):2399-408
12594263
Nat Immunol. 2004 Dec;5(12):1260-5
15531883
N Engl J Med. 2002 May 30;346(22):1699-705
12037149
J Immunol. 2004 Feb 1;172(3):1531-9
14734731
Clin Exp Allergy. 1995 Sep;25(9):815-9
8564719
J Immunol. 2005 May 1;174(9):5774-80
15843580
Clin Exp Allergy. 1993 Sep;23(9):785-90
10779310
Thorax. 2006 Jan;61(1):48-53
16396953
Lancet. 1999 Feb 6;353(9151):450-4
9989715
J Exp Med. 1996 Jun 1;183(6):2559-69
8676077
Nature. 1997 Oct 16;389(6652):737-42
9338786
J Immunol. 2001 Aug 15;167(4):2004-10
11489982
Neurology. 2006 Jan 24;66(2):182-6
16434650
Clin Exp Allergy. 2001 May;31(5):694-704
11422128
Thorax. 2005 Oct;60(10):814-21
16192366
Clin Exp Allergy. 1999 May;29(5):611-7
10231320
J Allergy Clin Immunol. 1995 Oct;96(4):449-56
7560654
Br Med J (Clin Res Ed). 1987 Jan 31;294(6567):279-83
3101841
J Immunol. 2007 Apr 15;178(8):4771-8
17404257
J Immunol. 1995 May 15;154(10):5071-9
7730613
BMJ. 1990 Aug 4;301(6746):266-8
2390620
Thorax. 2005 Dec;60(12):1012-8
16166100
Curr Opin Immunol. 2005 Jun;17(3):326-32
15886125
J Clin Invest. 2005 Feb;115(2):459-67
15650773
J Clin Invest. 1991 Jul;88(1):346-50
1829097
Thorax. 2005 Jul;60(7):545-8
15994260
J Allergy Clin Immunol. 2001 Sep;108(3):430-8
11544464
Arch Dis Child. 1989 Oct;64(10):1452-6
2817930
Science. 1999 Nov 12;286(5443):1377-81
10558996
J Allergy Clin Immunol. 2001 Oct;108(4):516-20
11590374
J Immunol. 2006 May 1;176(9):5374-87
16622005
J Immunol. 2006 Mar 15;176(6):3470-9
16517715
Am J Respir Crit Care Med. 2000 May;161(5):1501-7
10806145
N Engl J Med. 1990 Aug 23;323(8):502-7
2377175
Eur Respir J. 2001 Sep;18(3):598-611
11589359
Lancet. 1999 Aug 14;354(9178):541-5
10470697
Nat Rev Immunol. 2005 Apr;5(4):271-83
15775993
Eur Respir J. 1997 Aug;10(8):1795-802
9272921
J Exp Med. 2002 Jan 21;195(2):221-31
11805149
Eur J Immunol. 1996 Jun;26(6):1399-403
8647223
Am Rev Respir Dis. 1989 Mar;139(3):806-17
2923380
J Clin Invest. 2006 Feb;116(2):485-94
16424940
Clin Exp Allergy. 2003 Jun;33(6):731-6
12801305
J Immunol. 1997 Aug 15;159(4):1739-45
9257835
J Clin Invest. 2006 Jan;116(1):146-55
16341266
Blood. 2006 Jun 1;107(11):4475-83
16467201
Am J Respir Crit Care Med. 2006 Aug 15;174(4):386-92
16614348
Eur J Immunol. 2001 Nov;31(11):3281-90
11745345
Nature. 2002 Dec 5;420(6915):502-7
12466842
BMJ. 1992 Apr 4;304(6831):873-5
1392746
J Exp Med. 2003 Dec 15;198(12):1875-86
14676299
J Allergy Clin Immunol. 2000 Sep;106(3):493-9
10984369
J Allergy Clin Immunol. 1996 Jun;97(6):1402-8
8648038
J Exp Med. 1999 Sep 20;190(6):783-92
10499917
J Exp Med. 1998 Dec 7;188(11):2019-31
9841916
J Immunol. 2000 Jan 1;164(1):223-30
10605015
Allergy. 1995 Oct;50(10):806-10
8607562
Clin Exp Allergy. 2000 Sep;30(9):1230-4
10971468
Annu Rev Immunol. 2004;22:531-62
15032588
J Allergy Clin Immunol. 2007 Jan;119(1):226-34
17208606
Ann Allergy Asthma Immunol. 2005 Dec;95(6):579-85
16400899
Science. 1994 May 20;264(5162):1152-6
8178175
Lancet. 2004 Feb 21;363(9409):608-15
14987885
J Immunol. 1999 Mar 1;162(5):2997-3004
10072551
J Immunol. 2002 Jan 1;168(1):216-23
11751965
Eur Respir J. 2001 May;17(5):881-6
11488320
Am J Respir Cell Mol Biol. 2003 Jan;28(1):42-50
12495931
N Engl J Med. 1992 Jan 30;326(5):298-304
1530827
J Allergy Clin Immunol. 1996 Jun;97(6):1288-96
8648025
Eur Respir J. 2004 Mar;23(3):407-13
15065830
Science. 2006 Jun 2;312(5778):1355-9
16741115
Nat Immunol. 2005 Nov;6(11):1123-32
16200070
Nat Immunol. 2002 Jun;3(6):549-57
12006974
N Engl J Med. 2000 Aug 24;343(8):538-43
10954761