Genetics of Environmental Asthma

David Zaas; David A. Schwartz

doi:10.1055/s-2003-39017

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2003; 24(2): 185-196
DOI: 10.1055/s-2003-39017

Genetics of Environmental Asthma

David Zaas, David A. Schwartz

Pulmonary and Critical Care Division, Department of Medicine; Department of Veterans Affairs Medical Center; and Duke University Medical Center, Durham, North Carolina

Abstract

ABSTRACT

The prevalence of asthma continues to increase throughout Western societies and now is estimated to affect nearly 10% of Americans. Asthma is a syndrome that results when a genetically susceptible individual is exposed to specific allergens, which triggers airway inflammation, bronchial hyperresponsiveness, and airway remodeling. Family and twin studies have shown that there is a major genetic component to the development of asthma and have attempted to determine the heritable risk. Linkage analysis has identified several areas of interest on multiple different chromosomes that have been associated with different asthma phenotypes. Candidate gene studies have looked at specific gene polymorphisms that are associated with the development of asthma. Finally, several genes are associated with the development of asthma in response to specific environmental allergen exposures. Asthma is a heterogeneous collection of diseases that can result from multiple different pathological processes. The inheritance of asthma is complex and not due to a single gene mutation. Rather, asthma appears to be the result of multiple genetic mutations that influence an individual's susceptibility to develop asthma in response to specific allergens.

KEYWORDS

Asthma - genetics - allergens - environmental medicine

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Referenzen

REFERENCES

1 Busse W, Kiecolt-Glaser J, Coe C, Martin R, Weiss S, Parker S. Stress and asthma. Am J Respir Crit Care Med . 1995; 151 249-252
2 Wiener A, Zieve I, Fries J. The inheritance of allergic disease. Ann Hum Genet . 1936; 7 141-162
3 Schwartz M. Heredity in bronchial asthma. Acta Allergol . 1952; 5 1-19
4 Sibbald B, Horn M, Brain E, Gregg I. Genetic factors in childhood asthma. Thorax . 1980; 35 671-674
5 Holberg C J, Halonen M, Wright A L, Martinez F D. Familial aggregation and segregation analysis of eosinophil levels. Am J Respir Crit Care Med . 1999; 160 1604-1610
6 Niu T, Rogus J J, Chen C. et al . Familial aggregation of bronchodilator response: a community-based study. Am J Respir Crit Care Med . 2000; 162 1833-1837
7 Palmer L J, Burton P R. Familial aggregation and segregation analysis of eosinophil levels. Am J Respir Crit Care Med . 2000; 162 759-760
8 Palmer L J, Burton P R, Faux J A, James A L, Musk A W, Cookson W O. Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness. Am J Respir Crit Care Med . 2000; 161 1836-1843
9 von Mutius E, Nicolai T. Familial aggregation of asthma in a South Bavarian population. Am J Respir Crit Care Med . 1996; 153 1266-1272
10 Edfors-Lubs M-L. Allergy in 7000 twin pairs. Acta Allergologica . 1971; 26 249-285
11 Harris J R, Magnus P, Samuelsen S O, Tambs K. No evidence for effects of family environment on asthma: a retrospective study of Norwegian twins. Am J Respir Crit Care Med . 1997; 156 43-49
12 Duffy D L, Martin N G, Battistutta D, Hopper J L, Mathews J D. Genetics of asthma and hay fever in Australian twins. Am Rev Respir Dis . 1990; 142 1351-1358
13 Koppelman G, Los H, Postma D. Genetic and environment in asthma: the answer of twin studies. Eur Respir J . 1999; 13 2-4
14 Laitinen T, Rasanen M, Kaprio J, Koskenvuo M, Laitinen L A. Importance of genetic factors in adolescent asthma: a population-based twin-family study. Am J Respir Crit Care Med . 1998; 157 1073-1078
15 Nieminen M M, Kaprio J, Koskenvuo M. A population-based study of bronchial ashthma in adult twin pairs. Chest . 1991; 100 70-75
16 Holberg C J, Elston R C, Halonen M. et al . Segregation analysis of physician-diagnosed asthma in Hispanic and non-Hispanic white families. Am J Respir Crit Care Med . 1996; 154 144-150
17 Jenkins M A, Hopper J L, Giles G G. Regressive logistic modeling of familial aggregation for asthma in 7394 population-based nuclear families. Genet Epidemiol . 1997; 14 317-332
18 Ober C, Cox N, Abney M. et al . Genome-wide search for asthma susceptibility loci in a founder population. Hum Mol Genet . 1998; 7 1393-1398
19 Ober C, Tsalenko A, Parry R, Cox N J. A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet . 2000; 67 1154-1162
20 Daniels S E, Bhattacharrya S, James A. et al . A genome-wide search for quantitative trait loci underlying asthma. Nature . 1996; 383 247-250
21 Hizawa N, Freidhoff L, Ehrlich E. et al . Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families. J Allergy Clin Immunol . 1998; 102 449-453
22 Holloway J W, Lonjou C, Beghe B. et al . Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families. Genes Immun . 2001; 2 20-24
23 Yokouchi Y, Nukaga Y, Shibasaki M. et al . Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin-12 B locus by a genome-wide search in Japanese families. Genomics . 2000; 66 152-160
24 Holberg C J, Halonen M, Solomon S. et al . Factor analysis of asthma and atopy traits shows two major components, one of which is linked to markers on chromosome 5q. J Allergy Clin Immunol . 2001; 108 772-780
25 Palmer L, Daniels S, Rye P. et al . Linkage of chromosome 5q and 11q gene markers to asthma-associated quantitative traits in Australiam children. Am J Respir Crit Care Med . 1998; 158 1825-1830
26 Shek L P, Tay A H, Chew F T, Goh D L, Lee B W. Genetic susceptibility to asthma and atopy among Chinese in Singapore: linkage to markers on chromosome 5q31-33. Allergy . 2001; 56 749-753
27 Postma D S, Bleecker E R, Amelung P J. et al . Genetic susceptibility to asthma-bronchial hyperresponsiveness coinherited with a major gene for atopy. N Engl J Med . 1995; 333 894-900
28 Lympany P, Welsh K, MacCochrane G, Kemeny D M, Lee T H. Genetic analysis using DNA polymorphism of the linkage between chromosome 11q13 and atopy and bronchial hyperresponsiveness to methacholine. J Allergy Clin Immunol . 1992; 89 619-628
29 Shirakawa T, Hashimoto T, Furuyama J, Takeshita T, Morimoto K. Linkage between severe atopy and chromosome 11q13 in Japanese families. Clin Genet . 1994; 46 228-232
30 Simon Thomas N, Wilkinson J, Lonjou C, Morton N E, Holgate S T. Linkage analysis of markers on chromosome 11q13 with asthma and atopy in a United Kingdom population. Am J Respir Crit Care Med . 2000; 162 1268-1272
31 Wong Z, Tsonis D, van Herwerden L. et al . Linkage analysis of bronchial hyuprreactivity and atopy with chromosome 11q13. Electrophoresis . 1997; 18 1641-1645
32 Wjst M, Fischer G, Immervoll T. et al . A genome-wide search for linkage to asthma. Genomics . 1999; 58 1-8
33 Xu J, Meyers D A, Ober C. et al . Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three United States populations: collaborative study on the genetics of asthma. Am J Hum Genet . 2001; 68 1437-1446
34 Barnes K C, Neely J D, Duffy D L. et al . Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics . 1996; 37 41-50
35 Barnes K C, Freidhoff L R, Nickel R. et al . Dense mapping of chromosome 12q13.12-q23.3 and linkage to asthma and atopy. J Allergy Clin Immunol . 1999; 104 485-491
36 Heinzmann A, Grotherr P, Jerkic S P. et al . Studies on linkage and association of atopy with the chromosomal region 12q13-24. Clin Exp Allergy . 2000; 30 1555-1561
37 Malerba G, Lauciello M C, Scherpbier T. et al . Linkage analysis of chromosome 12 markers in Italian families with atopic asthmatic children. Am J Respir Crit Care Med . 2000; 162 1587-1590
38 Wilkinson J, Grimley S, Collins A, Thomas N S, Holgate S T, Morton N. Linkage of asthma to markers on chromosome 12 in a sample of 240 families using quantitative phenotype scores. Genomics . 1998; 53 251-259
39 Moffatt M F, Hill M R, Cornelis F. et al . Genetic linkage of T-cell receptor a/b complex to specific IgE responses. Lancet . 1994; 343 1597-1600
40 Hakonarson H, Bjornsdottir U S, Ostermann E. et al . Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland. Am J Respir Crit Care Med . 2001; 164 2036-2044
41 Liggett S. Polymorphisms of the beta2-adrenergic receptor and asthma. Am J Respir Crit Care Med . 1997; 156(suppl 4, pt 2) S156-S162
42 Szefler S J, Ando R, Cicutto L C, Surs W, Hill M R, Martin R J. Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma. Clin Pharmacol Ther . 1991; 49 59-68
43 Weir T, Mallek N, Sandford A. et al . b₂-adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma. Am J Respir Crit Care Med . 1998; 158 787-791
44 Turki J, Pak J, Green S A, Martin R J, Liggett S B. Genetic polymorphisms of the b₂-adrenergic receptor in nocturnal and nonnocturnal asthma. J Clin Invest . 1995; 95 1635-1641
45 Hall I P, Wheatley A, Wilding P, Liggett S B. Association of Glu 27 b₂-adrenoceptor polymorphism with lower airway reactivity in asthmatic subjects. Lancet . 1995; 345 1213-1214
46 Israel E, Drazen J, Liffett S. et al . The effect of polymorphisms of the beta2-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med . 2000; 162 75-80
47 Marsh D G, Neely J D, Breazeale D R. et al . Linkage analysis of IL-4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science . 1994; 264 1152-1156
48 Meyers D A, Beaty T H, Colyer C R, Marsh D G. Genetics of total serum IgE levels: a regressive model approach to segregation analysis. Genet Epidemiol . 1991; 8 351-359
49 Thomas N, Wilkinson J, Holgate S. The candidate region approach to the genetics of asthma and allergy. Am J Respir Crit Care Med . 1997; 156 S144-S151
50 Sandford A J, Chagani T, Zhu S. et al . Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity. J Allergy Clin Immunol . 2000; 106 135-140
51 Hershey G K, Friedrich M F, Esswein L A, Thomas M L, Chatila T A. The association of atopy with a gain-of-function mutation in the a subunit of the interleukin-4 receptor. N Engl J Med . 1997; 337 1720-1725
52 Grunig G, Warnock M, Wakil A E. et al . Requirement for IL-13 independently of IL-4 in experimental asthma. Science . 1998; 282 2261-2263
53 Graves P E, Kabesch M, Halonen M. et al . A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol . 2000; 105 506-513
54 Heinzmann A, Mao X, Akaiwa M. et al . Genetic variants of IL-13 signalling and human asthma and atopy. Hum Mol Gen . 2000; 9 549-559
55 Liu X, Nickel R, Beyer K. et al . An IL-13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90). J Allergy Clin Immunol . 2000; 106 167-170
56 van der Pouw Kraan C T, van Veen A, Boeije L C. et al . An IL-13 promoter polymorphism associated with increased risk of allergic asthma. Genes Immun . 1999; 1 61-65
57 Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S. Interleukin-10 regulation in normal subjects and patients with asthma. J Allergy Clin Immunol . 1996; 97 1288-1296
58 Hobbs K, Negri J, Klinnert M, Rosenwasser L, Borish L. Interleukin-10 and transforming growth factor-b promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med . 1998; 158 1958-1962
59 Rosenwasser L J, Borish L. Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med . 1997; 156 (suppl 4, pt 2) S152-S155
60 Hill M R, James A L, Faux J A. et al . FceRI-B polymorphism and risk of atopy in a general population sample. BMJ . 1995; 311 776-779
61 Shirakawa T, Li A, Dubowitz M. et al . Association between atopy and variants of the b subunit of the high-affinity immunoglobulin E receptor. Nature Genet . 1994; 7 125-130
62 Hill M, Cookson W. A new variant of the b subunit of the high-affinity receptor for immunoglobulin E (FceRI-b Ed237G): associations with measures of atopy and bronchial hyper-responsiveness. Hum Mol Genet . 1996; 5 959-962
63 Virchow J-C, Walker C, Hafner D. et al . T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provovation in atopic asthma. Am J Respir Crit Care Med . 1995; 151 960-968
64 Moffatt M, Cookson W. Tumour necrosis factor haplotypes and asthma. Hum Mol Genet . 1997; 6 551-554
65 Winchester E C, Millwood I Y, Rand L, Penny M A, Kessling A M. Association of the TNF-alpha-308 (G->A) polymorphism with self-reported history of childhood asthma. Hum Genet . 2000; 107 591-596
66 Castro J, Telleria J J, Linares P, Blanco-Quiros A. Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients. J Investig Allergol Clin Immunol . 2000; 10 149-154
67 Louis R, Leyder E, Malaise M, Bartsch P, Louis E. Lack of association between adult asthma and the tumour necrosis factor alpha-308 polymorphism gene. Eur Respir J . 2000; 16 604-608
68 MMWR. Current trends asthma-United States 1982-1992. Morb Mortal Wkly Rep . 1995; 43 952-955
69 Weiss K B, Wagener D K. Changing patterns of asthma mortality: identifying target populations at high risk. JAMA . 1990; 264 1683-1687
70 Weiss K B, Wagener D K. Geographic variations in US asthma mortality: small-area analyses of excess mortality, 1981-1985. Am J Epidemiol . 1990; 132(suppl 1) S107-S115
71 Los H, Koppelman G, Postma D. The importance of genetic influences in asthma. Eur Respir J . 1999; 14 1210-1227
72 Executive summary: guidelines for the diagnosis and management of asthma. Washington, DC: 1991.
73 Evans R, Mulally D I, Wilson R W. et al . National trends in the morbidity and mortality of asthma in the United States. Chest . 1987; 91(suppl 6) S65-S74
74 Sporik R, Holgate S T, Platts-Mills T A, Cogswell J J. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood: a prospective study [see comments]. N Engl J Med . 1990; 323 502-507
75 Young S, Le Souef N P, Geelhoed G C, Stick S M, Turner K J, Landau L I. The influence of a family history of asthma and parental smoking on airway responsiveness in early infancy [published erratum appears in N Engl J Med 1991;325:747]. N Engl J Med . 1991; 324 1168-1173
76 Chan-Yeung M, Malo J-L. Occupational asthma. Current Concepts . 1995; 333 107-112
77 Samet J M, Lambert W E. Epidemiologic approaches for assessing health risks from complex mixtures in indoor air. Environ Health Perspect . 1991; 95 71-74
78 Speizer F E. Asthma and persistent wheeze in the Harvard six cities study. Chest . 1990; 98 S191-S195
79 Folkerts G, Busse W, Nijkamp F, Sorkness R, Gern J. State of the art: virus-induced airway hyperresponsiveness and asthma. Am J Respir Crit Care Med . 1998; 157 1708-1720
80 Michel O, Ginanni R, Duchateau J, Vertongen F, Le Bon B, Sergysels R. Domestic endotoxin exposure and clinical severity of asthma. Clin Exp Allergy . 1991; 21 441-448
81 Michel O, Kips J, Duchateua J. et al . Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med . 1996; 154 1641-1646
82 Park J H, Gold D R, Spiegelman D L, Burge H A, Milton D K. House dust endotoxin and wheeze in the first year of life. Am J Respir Crit Care Med . 2001; 163 322-328
83 Gereda J, Leung D, Thatayatikom A. et al . Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet . 2000; 355 1680-1683
84 Rylander R, Bake B, Fischer J J, Helander I M. Pulmonary function and symptoms after inhalation of endotoxin. Am Rev Respir Dis . 1989; 140 981-986
85 Schwartz D A, Thorne P S, Yagla S J. et al . The role of endotoxin in grain dust-induced lung disease. Am J Respir Crit Care Med . 1995; 152 603-608
86 Schwartz D A, Donham K J, Olenchock S A. et al . Determinants of longitudinal changes in spirometric functions among swine confinement operators and farmers. Am J Res Crit Care Med . 1995; 151 47-53
87 Kennedy S M, Christiani D C, Eisen E A. et al . Cotton dust and endotoxin exposure-response relationships in cotton textile workers. Am Rev Respir Dis . 1987; 135 194-200
88 Haglind P, Rylander R. Exposure to cotton dust in an experimental cardroom. Br J Ind Med . 1984; 41 340-345
89 Rylander R, Haglind P, Lundholm M. Endotoxin in cotton dust and respiratory function decrement among cotton workers in an experimental cardroom. Am Rev Respir Dis . 1985; 131 209-213
90 Donham K, Haglind P, Peterson Y, Rylander R, Belin L. Environmental and health studies of farm workers in Swedish swine confinement buildings. Br J Ind Med . 1989; 46 31-37
91 Thelin A, Tegler O, Rylander R. Lung reactions during poultry handling related to dust and bacterial endotoxin levels. Eur J Respir Dis . 1984; 65 266-271
92 Shirakawa T, Enomoto T, Shimazu S I, Hopkin J M. The inverse association between tuberculin responses and atopic disorder. Science . 1997; 275 77-79
93 Chan-Yeung M, Manfreda J, Dimich-Ward H, Ferguson A, Watson W, Becker A. A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Arch Pediatr Adolesc Med . 2000; 154 657-663
94 Levine B B, Stember R H, Fotino M. Ragweed hay fever: genetic control and linkage to HL-A haplotypes. Science . 1972; 178 1201-1203
95 Zwollo P, Ehrlich-Kautzky E, Scharf S J, Ansari A A, Erlich H A, Marsh D G. Sequencing of HLA-D in responders and nonresponders to short ragweed allergen, Amb a V. Immunogenetics . 1991; 33 141-151
96 Marsh D G, Freidhoff L R, Ehrlich-Kautzky E, Bias W B, Roebber M. Immune responsiveness to Ambrosia artemisiifolia (short ragweed) pollen allergen Amb a VI (Ra6) is associated with HLA-DR5 in allergic humans. Immunogenetics . 1987; 26 230-236
97 Marsh D G, Zwollo P, Huang S K. Molecular and cellular studies of human immune responsiveness to the short ragweed allergen, Amb a V. Eur Respir J Suppl . 1991; 13 S60-S67
98 Ansari A A, Freidhoff L R, Meyers D A, Bias W B, Marsh D G. Human immune responsiveness to Lolium perenne pollen allergen Lol p III (rye III) is associated with HLA-DR3 and DR5. Hum Immunol . 1989; 25 59-71
99 Freidhoff L R, Ehrlich-Kautzky E, Meyers D A, Ansari A A, Bias W B, Marsh D G. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects. Tissue Antigens . 1988; 31 211-219
100 Cardaba B, Vilches C, Martin E. et al . DR7 and DQ2 are positively associated with immunoglobulin-E response to the main antigen of olive pollen (Ole e I) in allergic patients. Hum Immunol . 1993; 38 293-299
101 Howell W M, Holgate S T. Human leukocyte antigen genes and allergic disease. Monogr Allergy . 1996; 33 53-70
102 Bignon J S, Aron Y, Ju L Y. et al . HLA class II alleles in isocyanate-induced asthma. Am J Respir Crit Care Med . 1994; 149 71-75
103 Fabbri L M, Mapp C E, Balboni A, Baricordi R. HLA class II molecules and asthma induced by toluene diisocyanate. Int Arch Allergy Immunol . 1995; 107 400-401
104 Young R P, Barker R D, Pile K D, Cookson W O, Taylor A J. The association of HLA-DR3 with specific IgE to inhaled acid anhydrides. Am J Respir Crit Care Med . 1995; 151 219-221
105 Wedderburn L R, O'Hehir R E, Hewitt C R, Lamb J R, Owen M J. In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens. Proc Natl Acad Sci U S A . 1993; 90 8214-8218
106 Breiteneder H, Scheiner O, Hajek R. et al . Diversity of TCRAV and TCRBV sequences used by human T-cell clones specific for a minimal epitope of Bet v 1, the major birch pollen allergen. Immunogenetics . 1995; 42 53-58
107 Huang S K, Zwollo P, Marsh D G. Class II major histocompatibility complex restriction of human T cell responses to short ragweed allergen, Amb a V. Eur J Immunol . 1991; 21 1469-1473
108 Mohapatra S S, Mohapatra S, Yang M. et al . Molecular basis of cross-reactivity among allergen-specific human T cells: T-cell receptor V alpha gene usage and epitope structure. Immunology . 1994; 81 15-20
109 Schiffer M, Wu T T, Kabat E A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci USA . 1986; 83 4461-4463
110 Schiffer M, Kabat E A, Wu T T. Subgroups of Tcr alpha chains and correlation with T-cell function. Immunogenetics . 1992; 35 224-234
111 Moffatt M F, Schou C, Faux J A, Cookson W O. Germline TCR-A restriction of immunoglobulin E responses to allergen. Immunogenetics . 1997; 46 226-230
112 von Mutius E, Braun-Fahrlander C, Schierl R. et al . Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy . 2000; 30 1230-1234
113 Hoshino K, Takeuchi O, Kawai T. et al . Cutting edge: toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol . 1999; 162 3749-3752
114 Arbour N C, Lorenz E, Schutte B. et al . TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet . 2000; 25 187-191
115 Baldini M, Lohman I C, Halonen M, Erickson R P, Holt P G, Martinez F D. A polymorphism in the 5' flanking region of the CD-14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol . 1999; 20 976-983
116 Koppelman G H, Reijmerink N E, Colin Stine O. et al . Association of a promoter polymorphism of the CD14 gene and atopy. Am J Respir Crit Care Med . 2001; 163 965-969
117 Alexis N E, Soukup J, Nierkens S, Becker S. Association between airway hyperreactivity and bronchial macrophage dysfunction in individuals with mild asthma. Am J Physiol Lung Cell Mol Physiol . 2001; 280 L369-375
118 Dubin W, Martin T R, Swoveland P. et al . Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment. Am J Physiol (Lung Cell Mol Physiol) . 1996; 270 L736-L744
119 Garty B Z, Monselise Y, Nitzan M. Soluble CD14 in children with status asthmaticus. Isr Med Assoc J . 2000; 2 104-107
120 Virchow Jr C J, Julius P, Matthys H, Kroegel C, Luttmann W. CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma. Eur Respir J . 1998; 11 317-323
121 Martinez F D. Context dependency of markers of disease. Am J Respir Crit Care Med . 2000; 162(suppl 2, pt 2) S56-S57