Early life exposure to antibiotics and the risk of childhood allergic diseases: An update from the perspective of the hygiene hypothesis

Journal of Microbiology, Immunology and Infection

Volumn 46, Issue 5, 2013, Pages 320-329

  Kuo, Chang Hung ^a,b,c   Kuo, Hsuan Fu ^a   Huang, Ching Hua ^a   Yang, San Nan ^a,b,c   Lee, Min Sheng ^a   Hung, Chih Hsing ^a,b,c  

^a KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^b KAOHSIUNG MUNICIPAL TA TUNG HOSPITAL   (Taiwan)

^c KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

Author keywords

Allergic disease; Antibiotics; Asthma; Dendritic cells; Hygiene hypothesis

Indexed keywords

ANTIBIOTIC AGENT; CYTOKINE;

ALLERGIC DISEASE; ALLERGY; ASTHMA; ATOPY; CHILDHOOD DISEASE; ECZEMA; HAY FEVER; HUMAN; HYGIENE HYPOTHESIS; REVIEW; RHINOCONJUNCTIVITIS; TH2 CELL; WHEEZING;

ALLERGIC DISEASE; ANTIBIOTICS; ASTHMA; DENDRITIC CELLS; HYGIENE HYPOTHESIS;

ADOLESCENT; ANTI-BACTERIAL AGENTS; ASTHMA; CHILD; CHILD, PRESCHOOL; HUMANS; HYGIENE HYPOTHESIS; HYPERSENSITIVITY; INFANT; INFANT, NEWBORN; PREVALENCE; RISK ASSESSMENT;

EID: 84885176014     PISSN: 16841182     EISSN: 19959133     Source Type: Journal    
DOI: 10.1016/j.jmii.2013.04.005     Document Type: Review

References (99)

1. Wu W.F., Wan K.S., Wang S.J., Yang W., Liu W.L. Prevalence, severity, and time trends of allergic conditions in 6-to-7-year-old school children in Taipei. J Investig Allergol Clin Immunol 2011, 21:556-562.
2. Tsao S.M., Ko Y.K., Chen M.Z., Chiu M.H., Lin C.S., Lin M.S., et al. A survey of allergic rhinitis in Taiwanese asthma patients. JMicrobiol Immunol Infect 2011, 44:139-143.
3. Shyu C.S., Lin H.K., Lin C.H., Fu L.S. Prevalence of attention-deficit/hyperactivity disorder in patients with pediatric allergic disorders: a nationwide, population-based study. JMicrobiol Immunol Infect 2012, 45:237-242.
4. Droste J.H., Wieringa M.H., Weyler J.J., Nelen V.J., Vermeire P.A., Van Bever H.P. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?. Clin Exp Allergy 2000, 30:1547-1553.
5. Wickens K., Pearce N., Crane J., Beasley R. Antibiotic use in early childhood and the development of asthma. Clin Exp Allergy 1999, 29:766-771.
6. Cohet C., Cheng S., MacDonald C., Baker M., Foliaki S., Huntington N., et al. Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. J Epidemiol Community Health 2004, 58:852-857.
7. Celedon J.C., Litonjua A.A., Ryan L., Weiss S.T., Gold D.R. Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years. Am J Respir Crit Care Med 2002, 166:72-75.
8. Marra F., Lynd L., Coombes M., Richardson K., Legal M., Fitzgerald J.M., et al. Does antibiotic exposure during infancy lead to development of asthma?: a systematic review and metaanalysis. Chest 2006, 129:610-618.
9. Celedon J.C., Fuhlbrigge A., Rifas-Shiman S., Weiss S.T., Finkelstein J.A. Antibiotic use in the first year of life and asthma in early childhood. Clin Exp Allergy 2004, 34:1011-1016.
10. McKeever T.M., Lewis S.A., Smith C., Collins J., Heatlie H., Frischer M., et al. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol 2002, 109:43-50.
11. Asher M.I., Montefort S., Bjorksten B., Lai C.K., Strachan D.P., Weiland S.K., et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006, 368:733-743.
12. Bach J.F. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002, 347:911-920.
13. Strachan D.P. Hay fever, hygiene, and household size. BMJ 1989, 299:1259-1260.
14. Strachan D.P. Allergy and family size: a riddle worth solving. Clin Exp Allergy 1997, 27:235-236.
15. Lemanske R.F. The childhood origins of asthma (COAST) study. Pediatr Allergy Immunol 2002, 13:38-43.
16. Celedon J.C., Wright R.J., Litonjua A.A., Sredl D., Ryan L., Weiss S.T., et al. Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years. Am J Respir Crit Care Med 2003, 167:1239-1243.
17. Ege M.J., Mayer M., Normand A.C., Genuneit J., Cookson W.O., Braun-Fahrlander C., et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 2011, 364:701-709.
18. Braun-Fahrlander C., Gassner M., Grize L., Neu U., Sennhauser F.H., Varonier H.S., et al. Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clin Exp Allergy 1999, 29:28-34.
19. Von Ehrenstein O.S., Von Mutius E., Illi S., Baumann L., Bohm O., von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 2000, 30:187-193.
20. Ege M.J., Strachan D.P., Cookson W.O., Moffatt M.F., Gut I., Lathrop M., et al. Gene-environment interaction for childhood asthma and exposure to farming in Central Europe. J Allergy Clin Immunol 2011, 127:138-144.
21. von Mutius E., Martinez F.D., Fritzsch C., Nicolai T., Roell G., Thiemann H.H. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med 1994, 149:358-364.
22. Bjorksten B., Dumitrascu D., Foucard T., Khetsuriani N., Khaitov R., Leja M., et al. Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe. Eur Respir J 1998, 12:432-437.
23. Kramer M.S., Matush L., Bogdanovich N., Dahhou M., Platt R.W., Mazer B. The low prevalence of allergic disease in Eastern Europe: are risk factors consistent with the hygiene hypothesis?. Clin Exp Allergy 2009, 39:708-716.
24. Heinrich J., Hoelscher B., Frye C., Meyer I., Wjst M., Wichmann H.E. Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany. Eur Respir J 2002, 19:1040-1046.
25. Wegmann T.G., Lin H., Guilbert L., Mosmann T.R. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?. Immunol Today 1993, 14:353-356.
26. Holt P.G., O'Keeffe P., Holt B.J., Upham J.W., Baron-Hay M.J., Suphioglu C., et al. T-cell "priming" against environmental allergens in human neonates: sequential deletion of food antigen reactivity during infancy with concomitant expansion of responses to ubiquitous inhalant allergens. Pediatr Allergy Immunol 1995, 6:85-90.
27. Chu Y.T., Chiang W., Wang T.N., Hung C.H., Jong Y.J., Wu J.R. Changes in serum eotaxin and eosinophil cationic protein levels, and eosinophil count during treatment of childhood asthma. J Microbiol Immunol Infect 2007, 40:162-167.
28. Tsai J.J., Liu Y.H., Shen H.D., Huang S.H., Han S.H. Prevention of Der p2-induced allergic airway inflammation by Mycobacterium-bacillus Calmette Guerin. J Microbiol Immunol Infect 2002, 35:152-158.
29. Hansen G., Yeung V.P., Berry G., Umetsu D.T., DeKruyff R.H. Vaccination with heat-killed Listeria as adjuvant reverses established allergen-induced airway hyperreactivity and inflammation: role of CD8+ T cells and IL-18. J Immunol 2000, 164:223-230.
30. Kline J.N., Waldschmidt T.J., Businga T.R., Lemish J.E., Weinstock J.V., Thorne P.S., et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol 1998, 160:2555-2559.
31. Bilenki L., Wang S., Fan Y., Yang J., Han X., Yang X. Chlamydia trachomatis infection inhibits airway eosinophilic inflammation induced by ragweed. Clin Immunol 2002, 102:28-36.
32. Stampfli M.R., Ritz S.A., Neigh G.S., Sime P.J., Lei X.F., Xing Z., et al. Adenoviral infection inhibits allergic airways inflammation in mice. Clin Exp Allergy 1998, 28:1581-1590.
33. Dittrich A.M., Erbacher A., Specht S., Diesner F., Krokowski M., Avagyan A., et al. Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol 2008, 180:1792-1799.
34. Kao S.L., Yu H.R., Kuo H.C., Tsui K.Y., Wu C.C., Chang L.S., et al. Higher levels of soluble Fas ligand and transforming growth factor-beta after omalizumab treatment: a case report. J Microbiol Immunol Infect 2012, 45:69-71.
35. Klimenko O.V. Regulation of immune responses, apoptosis, and tumorigenesis by separate FOXP-3-dependent genes: connection with clinical manifestations. J Microbiol Immunol Infect 2011, 44:412-417.
36. Lu L.Y., Chu J.J., Lu P.J., Sung P.K., Hsu C.M., Tseng J.C. Expression of intracellular transforming growth factor-beta1 in CD4+CD25+ cells in patients with systemic lupus erythematosus. JMicrobiol Immunol Infect 2008, 41:165-173.
37. Wei C.M., Lee J.H., Wang L.C., Yang Y.H., Chang L.Y., Chiang B.L. Frequency and phenotypic analysis of CD4+CD25+ regulatory T cells in children with juvenile idiopathic arthritis. J Microbiol Immunol Infect 2008, 41:78-87.
38. Akbari O., Freeman G.J., Meyer E.H., Greenfield E.A., Chang T.T., Sharpe A.H., et al. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Med 2002, 8:1024-1032.
39. McGuirk P., McCann C., Mills K.H. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med 2002, 195:221-231.
40. Zuany-Amorim C., Sawicka E., Manlius C., Le Moine A., Brunet L.R., Kemeny D.M., et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 2002, 8:625-629.
41. Wilson M.S., Taylor M.D., Balic A., Finney C.A., Lamb J.R., Maizels R.M. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 2005, 202:1199-1212.
42. Lambrecht B.N., Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat Rev Immunol 2003, 3:994-1003.
43. Hsu S.C., Chen C.H., Tsai S.H., Kawasaki H., Hung C.H., Chu Y.T., et al. Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. J Biol Chem 2010, 285:7903-7910.
44. Charbonnier A.S., Hammad H., Gosset P., Stewart G.A., Alkan S., Tonnel A.B., et al. Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response. J Leukoc Biol 2003, 73:91-99.
45. Kuo C.H., Wang W.L., Chu Y.T., Lee M.S., Hung C.H. Sublingual immunotherapy in children: an updated review. Pediatr Neonatol 2009, 50:44-49.
46. Kuo C.H., Jan R.L., Chu Y.T., Wang W.L., Huang M.Y., Huang C.H., et al. Prostaglandin I(2) analogues enhance growth-related oncogene-alpha expression in human monocyte-derived dendritic cells. Inflammation 2010, 33:334-343.
47. Jiao L., Han X., Wang S., Fan Y., Yang M., Qiu H., et al. Imprinted DC mediate the immune-educating effect of early-life microbial exposure. Eur J Immunol 2009, 39:469-480.
48. Bilenki L., Gao X., Wang S., Yang J., Fan Y., Han X., et al. Dendritic cells from mycobacteria-infected mice inhibits established allergic airway inflammatory responses to ragweed via IL-10- and IL-12-secreting mechanisms. J Immunol 2010, 184:7288-7296.
49. Kuo C.H., Lin C.H., Yang S.N., Huang M.Y., Chen H.L., Kuo P.L., et al. Effect of prostaglandin I2 analogs on cytokine expression in human myeloid dendritic cells via epigenetic regulation. Mol Med 2012, 18:433-444.
50. Rutella S., Danese S., Leone G. Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 2006, 108:1435-1440.
51. Suss G., Shortman K. A subclass of dendritic cells kills CD4 T cells via Fas/Fas-ligand-induced apoptosis. J Exp Med 1996, 183:1789-1796.
52. Levings M.K., Sangregorio R., Galbiati F., Squadrone S. de Waal Malefyt R, Roncarolo MG. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 2001, 166:5530-5539.
53. Baban B., Chandler P.R., Sharma M.D., Pihkala J., Koni P.A., Munn D.H., et al. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol 2009, 183:2475-2483.
54. Steinman R.M., Hawiger D., Nussenzweig M.C. Tolerogenic dendritic cells. Annu Rev Immunol 2003, 21:685-711.
55. Vandenbulcke L., Bachert C., Van Cauwenberge P., Claeys S. The innate immune system and its role in allergic disorders. Int Arch Allergy Immunol 2006, 139:159-165.
56. Sutmuller R.P., Morgan M.E., Netea M.G., Grauer O., Adema G.J. Toll-like receptors on regulatory T cells: expanding immune regulation. Trends Immunol 2006, 27:387-393.
57. Sharland M. The use of antibacterials in children: a report of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) Paediatric Subgroup. J Antimicrob Chemother 2007, 60:i15-i26.
58. Wjst M., Hoelscher B., Frye C., Wichmann H.E., Dold S., Heinrich J. Early antibiotic treatment and later asthma. Eur J Med Res 2001, 6:263-271.
59. Illi S., von Mutius E., Lau S., Bergmann R., Niggemann B., Sommerfeld C., et al. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ 2001, 322:390-395.
60. Thomas M., Custovic A., Woodcock A., Morris J., Simpson A., Murray C.S. Atopic wheezing and early life antibiotic exposure: a nested case-control study. Pediatr Allergy Immunol 2006, 17:184-188.
61. Mullooly J.P., Schuler R., Barrett M., Maher J.E. Vaccines, antibiotics, and atopy. Pharmacoepidemiol Drug Saf 2007, 16:275-288.
62. Foliaki S., Pearce N., Bjorksten B., Mallol J., Montefort S., von Mutius E. Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III. J Allergy Clin Immunol 2009, 124:982-989.
63. Marra F., Marra C.A., Richardson K., Lynd L.D., Kozyrskyj A., Patrick D.M., et al. Antibiotic use in children is associated with increased risk of asthma. Pediatrics 2009, 123:1003-1010.
64. Mai X.M., Kull I., Wickman M., Bergstrom A. Antibiotic use in early life and development of allergic diseases: respiratory infection as the explanation. Clin Exp Allergy 2010, 40:1230-1237.
65. Wickens K., Ingham T., Epton M., Pattemore P., Town I., Fishwick D., et al. The association of early life exposure to antibiotics and the development of asthma, eczema and atopy in a birth cohort: confounding or causality?. Clin Exp Allergy 2008, 38:1318-1324.
66. Su Y., Rothers J., Stern D.A., Halonen M., Wright A.L. Relation of early antibiotic use to childhood asthma: confounding by indication?. Clin Exp Allergy 2010, 40:1222-1229.
67. Risnes K.R., Belanger K., Murk W., Bracken M.B. Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children. Am J Epidemiol 2011, 173:310-318.
68. Kozyrskyj A.L., Ernst P., Becker A.B. Increased risk of childhood asthma from antibiotic use in early life. Chest 2007, 131:1753-1759.
69. Kusel M.M., de Klerk N., Holt P.G., Sly P.D. Antibiotic use in the first year of life and risk of atopic disease in early childhood. Clin Exp Allergy 2008, 38:1921-1928.
70. Buret A.G. Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin. Can J Vet Res 2010, 74:1-10.
71. Takizawa H., Desaki M., Ohtoshi T., Kawasaki S., Kohyama T., Sato M., et al. Erythromycin modulates IL-8 expression in normal and inflamed human bronchial epithelial cells. Am J Respir Crit Care Med 1997, 156:266-271.
72. Tsai W.C., Rodriguez M.L., Young K.S., Deng J.C., Thannickal V.J., Tateda K., et al. Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection. Am J Respir Crit Care Med 2004, 170:1331-1339.
73. Shalit I., Halperin D., Haite D., Levitov A., Romano J., Osherov N., et al. Anti-inflammatory effects of moxifloxacin on IL-8, IL-1beta and TNF-alpha secretion and NFkappaB and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus. J Antimicrob Chemother 2006, 57:230-235.
74. von Mutius E., Illi S., Hirsch T., Leupold W., Keil U., Weiland S.K. Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Eur Respir J 1999, 14:4-11.
75. Downing J.F., Martinez-Valdez H., Elizondo R.S., Walker E.B., Taylor M.W. Hyperthermia in humans enhances interferon-gamma synthesis and alters the peripheral lymphocyte population. J Interferon Res 1988, 8:143-150.
76. Calvani M., Alessandri C., Bonci E. Fever episodes in early life and the development of atopy in children with asthma. Eur Respir J 2002, 20:391-396.
77. Garcia-Marcos L., Gonzalez-Diaz C., Garvajal-Uruena I., Pac-Sa M.R., Busquets-Monge R.M., Suarez-Varela M.M., et al. Early exposure to paracetamol or to antibiotics and eczema at school age: modification by asthma and rhinoconjunctivitis. Pediatr Allergy Immunol 2010, 21:1036-1042.
78. Hsu W.T., Lin T.H., Chang E.E., Hung C.H., Huang A.L., Wu T.C., et al. The effect of nonylphenol on the growth of Lactobacillus acidophilus and Bifidobacterium bifidum. J Microbiol Immunol Infect 2009, 42:451-456.
79. Oyama N., Sudo N., Sogawa H., Kubo C. Antibiotic use during infancy promotes a shift in the T(H)1/T(H)2 balance toward T(H)2-dominant immunity in mice. J Allergy Clin Immunol 2001, 107:153-159.
80. Alm J.S., Swartz J., Bjorksten B., Engstrand L., Engstrom J., Kuhn I., et al. An anthroposophic lifestyle and intestinal microflora in infancy. Pediatr Allergy Immunol 2002, 13:402-411.
81. Noverr M.C., Phare S.M., Toews G.B., Coffey M.J., Huffnagle G.B. Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect Immun 2001, 69:2957-2963.
82. Noverr M.C., Toews G.B., Huffnagle G.B. Production of prostaglandins and leukotrienes by pathogenic fungi. Infect Immun 2002, 70:400-402.
83. Matsuoka T., Hirata M., Tanaka H., Takahashi Y., Murata T., Kabashima K., et al. Prostaglandin D2 as a mediator of allergic asthma. Science 2000, 287:2013-2017.
84. Kuo C.H., Ko Y.C., Yang S.N., Chu Y.T., Wang W.L., Huang S.K., et al. Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation. J Mol Med (Berl) 2011, 89:29-41.
85. Noverr M.C., Noggle R.M., Toews G.B., Huffnagle G.B. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun 2004, 72:4996-5003.
86. Madsen C. Where are we in risk assessment of food allergens? The regulatory view. Allergy 2001, 56:91-93.
87. Russo M., Nahori M.A., Lefort J., Gomes E., de Castro Keller A., Rodriguez D., et al. Suppression of asthma-like responses in different mouse strains by oral tolerance. Am J Respir Cell Mol Biol 2001, 24:518-526.
88. Zhang X., Izikson L., Liu L., Weiner H.L. Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration. JImmunol 2001, 167:4245-4253.
89. Wold A.E. The hygiene hypothesis revised: is the rising frequency of allergy due to changes in the intestinal flora?. Allergy 1998, 53:20-25.
90. Webber M.P., Carpiniello K.E., Oruwariye T., Appel D.K. Prevalence of asthma and asthma-like symptoms in inner-city elementary schoolchildren. Pediatr Pulmonol 2002, 34:105-111.
91. Chalubinski M., Kowalski M.L. Endocrine disrupters-potential modulators of the immune system and allergic response. Allergy 2006, 61:1326-1335.
92. Kuo C.H., Yang S.N., Kuo P.L., Hung C.H. Immunomodulatory effects of environmental endocrine disrupting chemicals. Kaohsiung J Med Sci 2012, 28:S37-S42.
93. Hung C.H., Yang S.N., Kuo P.L., Chu Y.T., Chang H.W., Wei W.J., et al. Modulation of cytokine expression in human myeloid dendritic cells by environmental endocrine-disrupting chemicals involves epigenetic regulation. Environ Health Perspect 2010, 118:67-72.
94. Kalliomaki M., Salminen S., Arvilommi H., Kero P., Koskinen P., Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001, 357:1076-1079.
95. Pan S.J., Kuo C.H., Lam K.P., Chu Y.T., Wang W.L., Hung C.H. Probiotics and allergy in children-an update review. Pediatr Allergy Immunol 2010, 21:e659-e666.
96. Verhulst S.L., Vael C., Beunckens C., Nelen V., Goossens H., Desager K. A longitudinal analysis on the association between antibiotic use, intestinal microflora, and wheezing during the first year of life. J Asthma 2008, 45:828-832.
97. Alm B., Erdes L., Mollborg P., Pettersson R., Norvenius S.G., Aberg N., et al. Neonatal antibiotic treatment is a risk factor for early wheezing. Pediatrics 2008, 121:697-702.
98. Ahn K.M., Lee M.S., Hong S.J., Lim D.H., Ahn Y.M., Lee H.R., et al. Fever, use of antibiotics, and acute gastroenteritis during infancy as risk factors for the development of asthma inKorean school-age children. J Asthma 2005, 42:745-750.
99. Johnson C.C., Ownby D.R., Alford S.H., Havstad S.L., Williams L.K., Zoratti E.M., et al. Antibiotic exposure in early infancy and riskfor childhood atopy. J Allergy Clin Immunol 2005, 115:1218-1224.