Role of infection in the development and exacerbation of asthma

Expert Review of Respiratory Medicine

Volumn 4, Issue 1, 2010, Pages 71-83

  Guilbert, Theresa W ^a   Denlinger, Loren C ^a  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Asthma; Asthma inception; Exacerbation; Respiratory infection; Virus

Indexed keywords

CORTICOSTEROID; IMMUNOGLOBULIN E; INTERLEUKIN 13; TOLL LIKE RECEPTOR 4;

ACUTE DISEASE; AGE DISTRIBUTION; ANTIBODY PRODUCTION; ASTHMA; ATOPY; BRONCHIOLITIS; CHLAMYDOPHILA INFECTION; COMORBIDITY; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE EXACERBATION; HUMAN; INCIDENCE; INFECTION COMPLICATION; INNATE IMMUNITY; LOWER RESPIRATORY TRACT INFECTION; LUNG FUNCTION; MYCOPLASMOSIS; NONHUMAN; ONSET AGE; REMISSION; RESPIRATORY TRACT INFECTION; REVIEW; RISK FACTOR; SEX DIFFERENCE; VIRAL RESPIRATORY TRACT INFECTION; VIRUS PATHOGENESIS; VIRUS SHEDDING; WHEEZING;

EID: 77951629448     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/ers.09.60     Document Type: Review

References (172)

1. Gern JE. Viral respiratory infection and the link to asthma. Pediatr. Infect. Dis. J. 27, S97-S103 (2008).
2. Gern JE, Bacharier LB, Lemanske RFJ. Infections and asthma. In: Pediatric Allergy. Leung DYM, Sampson HA, Geha RS, Szefer SJ (Eds). Mosby, St Louis, Missouri, USA, 366-378 (2003).
3. Kusel MM, de Klerk NH, Kebadze T et al. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J. Allergy Clin. Immunol. 119, 1105-1110 (2007).
4. Webley WC, Salva PS, Andrzejewski C et al. The bronchial lavage of pediatric patients with asthma contains infectious Chlamydia. Am. J. Respir. Crit. Care Med. 171, 1083-1088 (2005).
5. Sutherland ER, Brandorff JM, Martin RJ. Atypical bacterial pneumonia and asthma risk. J. Asthma 41, 863-868 (2004).
6. Hahn DL, Dodge RW, Golubjatnikov R. Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma. JAMA 266, 225-230 (1991)
7. von HL. Role of persistent infection in the control and severity of asthma: focus on Chlamydia pneumoniae. Eur. Respir. J. 19, 546-556 (2002).
8. Kraft M, Cassell GH, Henson JE et al. Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma. Am. J. Respir. Crit. Care Med. 158, 998-1001 (1998).
9. Biscardi S, Lorrot M, Marc E et al. Mycoplasma pneumoniae and asthma in children. Clin. Infect. Dis. 38, 1341-1346 (2004).
10. Esposito S, Blasi F, Arosio C et al. Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing. Eur. Respir. J. 16, 1142-1146 (2000).
11. Jackson DJ, Gangnon RE, Evans MD et al. Wheezing rhinovirus illnesses in early life predict asthma development in high risk children. Am. J. Respir. Crit. Care Med. 178(7), 667-672 (2008).
12. Stein RT, Sherrill D, Morgan WJ et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354, 541-545 (1999).
13. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the frst six years of life. The Group Health Medical Associates. N. Engl. J. Med. 332, 133-138 (1995).
14. Rakes GP, Arruda E, Ingram JM et al. Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses. Am. J. Respir. Crit. Care Med. 159, 785-790 (1999).
15. Johnston SL, Pattemore PK, Sanderson G et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am. J. Respir. Crit. Care Med. 154, 654-660 (1996).
16. Johnston SL, Pattemore PK, Sanderson G et al. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. Br. Med. J. 310, 1225-1229 (1995).
17. Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. Br. Med. J. 324, 763 (2002).
18. Copenhaver CC, Gern JE, Li Z et al. Cytokine response patterns, exposure to viruses, and respiratory infections in the frst year of life. Am. J. Respir. Crit. Care Med. 170, 175-180 (2004).
19. Ly NP, Rifas-Shiman SL, Litonjua AA et al. Cord blood cytokines and acute lower respiratory illnesses in the frst year of life. Pediatrics 119, e171-e178 (2007).
20. Gern JE, Brooks GD, Meyer P et al. Bidirectional interactions between viral respiratory illnesses and cytokine responses in the frst year of life. J. Allergy Clin. Immunol. 117, 72-78 (2006).
21. Bisgaard H, Hermansen MN, Buchvald F et al. Childhood asthma after bacterial colonization of the airway in neonates. N. Engl. J. Med. 357, 1487-1495 (2007).
22. Dodge RR, Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am. Rev. Respir. Dis. 122, 567-575 (1980).
23. Yunginger JW, Reed CE, O'Connell EJ, Melton LJ 3rd, O'Fallon WM, Silverstein MD. A community-based study of the epidemiology of asthma. Incidence rates, 1964-1983. Am. Rev. Respir. Dis. 146, 888-894 (1992).
24. De Marco R, Locatelli F, Cerveri I, Bugiani M, Marinoni A, Giammanco G. Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J. Allergy Clin. Immunol. 110, 228-235 (2002).
25. de Marco R, Locatelli F, Sunyer J, Burney P. Differences in incidence of reported asthma related to age in men and women. A retrospective ana lysis of the data of the European Respiratory Health Survey. Am. J. Respir. Crit. Care Med. 162, 68-74 (2000).
26. Lemanske RF Jr, Busse WW. 6. Asthma: factors underlying inception, exacerbation, and disease progression. J. Allergy Clin. Immunol. 117, S456-S461 (2006).
27. Bel EH. Clinical phenotypes of asthma. Curr. Opin. Pulm. Med. 10, 44-50 (2004).
28. Wenzel SE. Asthma: defning of the persistent adult phenotypes. Lancet 368, 804-813 (2006).
29. Toren K, Olin AC, Hellgren J, Hermansson BA. Rhinitis increase the risk for adult-onset asthma-a Swedish population-based case-control study (MAP-study). 96(8), 635-641 (2002).
30. Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J. Allergy Clin. Immunol. 109, 419-425 (2002).
31. Polosa R, Knoke JD, Russo C et al. Cigarette smoking is associated with a greater risk of incident asthma in allergic rhinitis. J. Allergy Clin. Immunol. 121, 1428-1434 (2008).
32. Shaaban R, Zureik M, Soussan D et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 372, 1049-1057 (2008).
33. Ronmark E, Lindberg A, Watson L, Lundback B. Outcome and severity of adult onset asthma-report from the obstructive lung disease in northern Sweden studies (OLIN). Respir. Med. 101, 2370-2377 (2007).
34. Barnes N. Most diffcult asthma originates primarily in adult life. Paediatr. Respir. Rev. 7, 141-144 (2006)
35. Gelfand EW Pediatric asthma: a different disease. Proc. Am. Thorac. Soc. 6, 278-282 (2009).
36. Sama SR, Hunt PR, Cirillo CI et al. A longitudinal study of adult-onset asthma incidence among HMO members. Environ. Health 2, 10 (2003).
37. Jartti T, Lehtinen P, Vuorinen T et al. Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children. Emerg. Infect. Dis. 10, 1095-1101 (2004).
38. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA 282, 1440-1446 (1999).
39. Openshaw PJ. Immunopathological mechanisms in respiratory syncytial virus disease. Springer Semin. Immunopathol. 17, 187-201 (1995).
40. Wu P, Dupont WD, Griffn MR et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am. J. Respir. Crit. Care Med. 178, 1123-1129 (2008).
41. Holberg CJ, Wright AL, Martinez FD, Ray CG, Taussig LM, Lebowitz MD. Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the frst year of life. Am. J. Epidemiol. 133, 1135-1151 (1991).
42. Smyth RL. Innate immunity in respiratory syncytial virus bronchiolitis. Exp. Lung Res. 33, 543-547 (2007).
43. Welliver RC Sr. The immune response to respiratory syncytial virus infection: friend or foe? Clin. Rev. Allergy Immunol. 34, 163-173 (2008).
44. Sigurs N, Gustafsson PM, Bjarnason R et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am. J. Respir. Crit. Care Med. 171, 137-141 (2005).
45. Kneyber MCJ, Steyerberg EW, de Groot R, Moll HA. Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review. Acta Paediatrica 89, 654-660 (2000).
46. Wennergren G, Kristjansson S. Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. Eur. Respir. J. 18, 1044-1058 (2001).
47. Carroll KN, Wu P, Gebretsadik T et al. The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma. J. Allergy Clin. Immunol. 123(5), 1055-1061 (2009).
48. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Allergy 64, 1359-1365 (2009).
49. Lemanske RF Jr, Jackson DJ, Gangnon RE et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J. Allergy Clin. Immunol. 116, 571-577 (2005).
50. Lehtinen P, Ruohola A, Vanto T, Vuorinen T, Ruuskanen O, Jartti T. Prednisolone reduces recurrent wheezing after a frst wheezing episode associated with rhinovirus infection or eczema. J. Allergy Clin. Immunol. 119, 570-575 (2007).
51. Kotaniemi-Syrjanen A, Vainionpaa R, Reijonen TM, Waris M, Korhonen K, Korppi M. Rhinovirus-induced wheezing in infancy-the frst sign of childhood asthma? J. Allergy Clin. Immunol. 111, 66-71 (2003).
52. Castro-Rodriguez JA, Holberg CJ, Wright AL et al. Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study. Am. J. Respir. Crit. Care Med. 159, 1891-1897 (1999).
53. Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet 370, 758-764 (2007).
54. Allander T, Jartti T, Gupta S et al. Human bocavirus and acute wheezing in children. Clin. Infect. Dis. 44, 904-910 (2007).
55. Hendley JO, Gwaltney JM Jr, Jordan WS Jr. Rhinovirus infections in an industrial population. IV. Infections within families of employees during two fall peaks of respiratory illness. Am. J. Epidemiol. 89, 184-196 (1969).
56. Dales RE, Schweitzer I, Toogood JH et al Respiratory infections and the autumn increase in asthma morbidity. Eur. Respir. J. 9, 72-77 (1996).
57. Corne JM, Marshall C, Smith S et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet 359, 831-834 (2002).
58. Heymann PW, Carper HT, Murphy DD et al. Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J. Allergy Clin. Immunol. 114, 239-247 (2004).
59. Lee WM, Kiesner C, Pappas T et al. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PLoS ONE 2, e966 (2007).
60. Lau SK, Yip CC, Tsoi HW et al. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J. Clin. Microbiol. 45, 3655-3664 (2007).
61. Miller EK, Edwards KM, Weinberg GA et al. A novel group of rhinoviruses is associated with asthma hospitalizations. J. Allergy Clin. Immunol. 123, 98-104 e1 (2009).
62. Kistler A, Avila PC, Rouskin S et al. Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J. Infect. Dis. 196, 817-825 (2007).
63. Miller EK, Griffn MR, Edwards KM et al. Infuenza burden for children with asthma. Pediatrics 121, 1-8 (2008).
64. Calvo C, Garcia-Garcia ML, Pozo F, Carvajal O, Perez-Brena P, Casas I. Clinical characteristics of human bocavirus infections compared with other respiratory viruses in Spanish children. Pediatr. Infect. Dis. J. 27, 677-680 (2008).
65. Martin RJ, Kraft M, Chu HW, Berns EA, Cassell GH. A link between chronic asthma and chronic infection. J. Allergy Clin. Immunol. 107, 595-601 (2001).
66. Hogg JC. Role of latent viral infections in chronic obstructive pulmonary disease and asthma. Am. J. Respir. Crit. Care Med. 164, S71-S75 (2001).
67. Matsuse T, Hayashi S, Kuwano K, Keunecke H, Jefferies WA, Hogg JC. Latent adenoviral infection in the pathogenesis of chronic airways obstruction. Am. Rev. Respir. Dis. 146, 177-184 (1992).
68. Macek V, Sorli J, Kopriva S, Marin J. Persistent adenoviral infection and chronic airway obstruction in children. Am. J. Respir. Crit. Care Med. 150, 7-10 (1994).
69. Cunningham AF, Johnston SL, Julious SA, Lampe FC, Ward ME. Chronic Chlamydia pneumoniae infection and asthma exacerbations in children. Eur. Respir. J. 11, 345-349 (1998).
70. Johnston SL, Martin RJ. Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis? Am. J. Respir. Crit. Care Med. 172, 1078-1089 (2005).
71. Emre U, Sokolovskaya N, Roblin PM, Schachter J, Hammerschlag MR. Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease. J. Infect. Dis. 172, 265-267 (1995).
72. Bulut Y, Faure E, Thomas L et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J. Immunol. 168, 1435-1440 (2002).
73. Henderson FW, Clyde WA Jr, Collier AM et al. The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J. Pediatr. 95, 183-190 (1979).
74. Yano T, Ichikawa Y, Komatu S, Arai S, Oizumi K. Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma. Am. J. Respir. Crit. Care Med. 149, 1348-1353 (1994).
75. Koh YY, Park Y, Lee HJ, Kim CK. Levels of interleukin-2, interferon-g, and interleukin-4 in bronchoalveolar lavage fuid from patients with Mycoplasma pneumonia: implication of tendency toward increased immunoglobulin E production. Pediatrics 107, E39 (2001).
76. Martin RJ, Chu HW, Honour JM, Harbeck RJ. Airway infammation and bronchial hyperresponsiveness after Mycoplasma pneumoniae infection in a murine model. Am. J. Respir. Cell Mol. Biol. 24, 577-582 (2001).
77. Chu HW, Kraft M, Krause JE, Rex MD, Martin RJ. Substance P and its receptor neurokinin 1 expression in asthmatic airways. J. Allergy Clin. Immunol. 106, 713-722 (2000).
78. Korppi M, Kotaniemi-Syrjanen A, Waris M, Vainionpaa R, Reijonen TM. Rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis. Pediatr. Infect. Dis. J. 23, 995-999 (2004).
79. Jartti T, Korppi M, Ruuskanen O. The clinical importance of rhinovirus-associated early wheezing. Eur. Respir. J. 33, 706-707; author reply 707-708 (2009).
80. Hartert TV. Are persons with asthma at increased risk of pneumococcal infections, and can we prevent them? J. Allergy Clin. Immunol. 122, 724-725 (2008).
81. Talbot TR, Hartert T V, Mitchel E et al. Asthma as a risk factor for invasive pneumococcal disease. N. Engl. J. Med. 352, 2082-2090 (2005).
82. Juhn YJ, Kita H, Yawn BP et al. Increased risk of serious pneumococcal disease in patients with asthma. J. Allergy Clin. Immunol. 122, 719-723 (2008).
83. Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB. The effect of telithromycin in acute exacerbations of asthma. N. Engl. J. Med. 354, 1589-1600 (2006).
84. Black PN, Blasi F, Jenkins CR et al. Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae. Am. J. Respir. Crit. Care Med. 164, 536-541 (2001).
85. Kraft M, Cassell GH, Pak J, Martin RJ. Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 121, 1782-1788 (2002).
86. Strunk RC, Bacharier LB, Phillips BR et al Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J. Allergy Clin. Immunol. 122(6), 1138-1144e4 (2008).
87. Tarlo SM, Broder I, Corey P et al. The role of symptomatic colds in asthma exacerbations: infuence of outdoor allergens and air pollutants. J. Allergy Clin. Immunol. 108, 52-58 (2001).
88. Kelly JT, Busse WW. Host immune responses to rhinovirus: mechanisms in asthma. J. Allergy Clin. Immunol 122, 671-682; quiz 83-84 (2008).
89. Laaksi I, Ruohola JP, Tuohimaa P et al An association of serum vitamin D concentrations 40 nmol/l with acute respiratory tract infection in young Finnish men. Am. J. Clin. Nutr. 86, 714-717 (2007).
90. Karatekin G, Kaya A, Salihoglu O, Balci H, Nuhoglu A. Association of subclinical vitamin D defciency in newborns with acute lower respiratory infection and their mothers. Eur. J. Clin. Nutr. 63(4), 473-477 (2007).
91. Najada AS, Habashneh MS, Khader M. The frequency of nutritional rickets among hospitalized infants and its relation to respiratory diseases. J. Trop. Pediatr. 50, 364-368 (2004).
92. Muhe L, Lulseged S, Mason KE, Simoes EA. Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 349, 1801-1804 (1997).
93. Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D defciency with severe acute lower respiratory infection in Indian children under 5 y. Eur. J. Clin. Nutr. 58, 563-567 (2004).
94. Wjst M, Altmuller J, Faus-Kessler T, Braig C, Bahnweg M, Andre E. Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway. Respir. Res. 7, 60 (2006).
95. Raby BA, Lazarus R, Silverman EK et al. Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am. J. Respir. Crit. Care Med. 170, 1057-1065 (2004).
96. Poon AH, Laprise C, Lemire M et al. Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am. J. Respir. Crit. Care Med. 170, 967-973 (2004).
97. Grant WB. Variations in vitamin D production could possibly explain the seasonality of childhood respiratory infections in Hawaii. Pediatr. Infect. Dis. J. 27, 853 (2008).
98. Binkley N, Novotny R, Krueger D et al. Low vitamin D status despite abundant sun exposure. J. Clin. Endocrinol. Metab. 92, 2130-2135 (2007).
99. Levis S, Gomez A, Jimenez C et al. Vitamin D defciency and seasonal variation in an adult South Florida population. J. Clin. Endocrinol. Metab. 90, 1557-1562 (2005).
100. Jacobs ET, Alberts DS, Foote JA et al. Vitamin D insuffciency in southern Arizona. Am. J. Clin. Nutr. 87, 608-613 (2008).
101. Wang TT, Nestel FP, Bourdeau V et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 173, 2909-2912 (2004).
102. Bastian A, Schafer H. Human a-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul. Pept. 101, 157-161 (2001).
103. Scherberich JE, Kellermeyer M, Ried C, Hartinger A. 1-a-calcidol modulates major human monocyte antigens and Toll-like receptors TLR2 and TLR4 in vitro. Eur. J. Med. Res. 10, 179-182 (2005).
104. Do JE, Kwon SY, Park S, Lee ES. Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet's disease. Rheumatology (Oxford) 47, 840-848 (2008).
105. Schauber J, Oda Y, Buchau AS et al. Histone acetylation in keratinocytes enables control of the expression of cathelicidin and CD 14 by 1,25-dihydroxyvitamin D3. J. Invest. Dermatol. 128, 816-824 (2008).
106. Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J. Cell. Biochem. 88, 227-233 (2003). (Pubitemid 36119891)
107. Sakurai R, Shin E, Fonseca S et al. 1a,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofbroblast apoptosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 297(3), L496-L505 (2009).
108. Jakiela B, Brockman-Schneider R, Amineva S, Lee WM, Gern JE. Basal cells of differentiated bronchial epithelium are more susceptible to rhinovirus infection. Am. J. Respir. Cell Mol. Biol. 38, 517-523 (2008).
109. Davies DE, Wicks J, Powell RM, Puddicombe SM, Holgate ST. Airway remodeling in asthma: new insights. J. Allergy Clin. Immunol. 111, 215-225; quiz 226 (2003).
110. Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat. Med. 15, 410-416 (2009).
111. O'Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW. Severe exacerbations and decline in lung function in asthma. Am. J. Respir. Crit. Care Med. 179, 19-24 (2009).
112. Jeffery PK, Wardlaw AJ, Nelson FC, Collins JV, Kay AB. Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am. Rev. Respir. Dis. 140, 1745-1753 (1989).
113. Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am. Rev. Respir. Dis. 131, 599-606 (1985).
114. Ordonez C, Ferrando R, Hyde DM, Wong HH, Fahy JV. Epithelial desquamation in asthma: artifact or pathology? Am. J. Respir. Crit. Care Med. 162, 2324-2329 (2000)
115. Holgate ST Epithelium dysfunction in asthma. J. Allergy Clin. Immunol. 120, 1233-1244; quiz 1245-1246 (2007).
116. Schleimer RP, Kato A, Kern R, Kuperman D, Avila PC. Epithelium: at the interface of innate and adaptive immune responses. J. Allergy Clin. Immunol. 120, 1279-1284 (2007).
117. Hackett TL, Knight DA. The role of epithelial injury and repair in the origins of asthma. Curr. Opin. Allergy Clin. Immunol. 7, 63-68 (2007).
118. Tyner JW, Kim EY, Ide K et al. Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. J. Clin. Invest. 116, 309-321 (2006).
119. Zhu Z, Homer RJ, Wang Z et al. Pulmonary expression of interleukin-13 causes infammation, mucus hypersecretion, subepithelial fbrosis, physiologic abnormalities, and eotaxin production. J. Clin. Invest. 103, 779-788 (1999).
120. DeMeo DL, Lange C, Silverman EK et al. Univariate and multivariate family-based association ana lysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program. Genet. Epidemiol. 23, 335-348 (2002).
121. Graves PE, 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. 105, 506-513 (2000).
122. Howard TD, Whittaker PA, Zaiman AL et al. Identifcation and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am. J. Respir. Cell Mol. Biol. 25, 377-384 (2001).
123. Zhen G, Park SW, Nguyenvu LT et al. IL-13 and epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production. Am. J. Respir. Cell Mol. Biol. 36, 244-253 (2007).
124. Kuperman DA, Huang X, Koth LL et al. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat. Med. 8, 885-889 (2002).
125. Matsukura S, Stellato C, Georas SN et al. Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. Am. J. Respir. Cell Mol. Biol. 24, 755-761 (2001).
126. Chu HW, Balzar S, Seedorf GJ et al. Transforming growth factor-[32 induces bronchial epithelial mucin expression in asthma. Am. J. Pathol. 165, 1097-1106 (2004).
127. Woodruff PG, Boushey HA, Dolganov GM et al. Genome-wide profling identifes epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc. Natl Acad. Sci. USA 104, 15858-15863 (2007).
128. Albanesi C, Fairchild HR, Madonna S et al. IL-4 and IL-13 negatively regulate TNF-a-and IFN-y-induced p-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3. J. Immunol. 179, 984-992 (2007).
129. Vercammen E, Staal J, Beyaert R. Sensing of viral infection and activation of innate immunity by Toll-like receptor 3. Clin. Microbiol. Rev. 21, 13-25 (2008).
130. Chen Y, Hamati E, Lee PK et al. Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. Am. J. Respir. Cell Mol. Biol. 34, 192-203 (2006).
131. Contoli M, Message SD, Laza-Stanca V et al. Role of defcient type III interferon-A. production in asthma exacerbations. Nat. Med. 12, 1023-1026 (2006).
132. Wark PA, Johnston SL, Bucchieri F et al. Asthmatic bronchial epithelial cells have a defcient innate immune response to infection with rhinovirus. J. Exp. Med. 201, 937-947 (2005).
133. Bochkov YA, Hanson KM, Keles S, Brockman-Schneider RA, Jarjour NN, Gern JE. Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma. Mucosal. Immunol. (2009) (Epub ahead of print).
134. Lopez-Souza N, Favoreto S, Wong H et al. In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects. J. Allergy Clin. Immunol. 123, 1384-1390 e2 (2009).
135. Gern JE, Vrtis R, Grindle KA, Swenson C, Busse WW. Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. Am. J. Respir. Crit. Care Med. 162, 2226-2231 (2000).
136. Avila PC, Abisheganaden JA, Wong H et al. Effects of allergic infammation of the nasal mucosa on the severity of rhinovirus 16 cold. J. Allergy Clin. Immunol. 105, 923-932 (2000).
137. Denlinger LC, Shi L, Guadarrama A et al Attenuated P2X7 pore function as a risk factor for virus-induced loss of asthma control. Am. J. Respir. Crit. Care Med. 179, 265-270 (2009).
138. Di Virgilio F. Liaisons dangereuses: P2X(7) and the infammasome. Trends Pharmacol Sci. 28, 465-472 (2007).
139. Idzko M, Hammad H, van Nimwegen M et al. Extracellular ATP triggers and maintains asthmatic airway infammation by activating dendritic cells. Nat. Med. 13, 913-919 (2007).
140. Wark PA, Johnston SL, Moric I, Simpson JL, Hensley MJ, Gibson PG. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur. Respir. J. 19, 68-75 (2002).
141. Willart MA, Lambrecht BN. The danger within: endogenous danger signals, atopy and asthma. Clin. Exp. Allergy 39, 12-19 (2009).
142. Rothberg MB, Haessler SD, Brown RB. Complications of viral infuenza. Am. J. Med. 121, 258-264 (2008).
143. Staat MA. Respiratory syncytial virus infections in children. Semin. Respir. Infect. 17, 15-20 (2002).
144. McFadden ER Jr. Improper patient techniques with metered dose inhalers: clinical consequences and solutions to misuse. J. Allergy Clin. Immunol. 96, 278-283 (1995).
145. Mosser AG, Brockman-Schneider R, Amineva S et al. Similar frequency of rhinovirus-infectible cells in upper and lower airway epithelium. J. Infect. Dis. 185, 734-743 (2002).
146. Gern JE, Galagan DM, Jarjour NN, Dick EC, Busse WW. Detection of rhinovirus RNA in lower airway cells during experimentally induced infection. Am. J. Respir. Crit. Care Med. 155, 1159-1161 (1997).
147. Papadopoulos NG, Bates PJ, Bardin PG et al. Rhinoviruses infect the lower airways. J. Infect. Dis. 181, 1875-1884 (2000).
148. Mosser AG, Vrtis R, Burchell L et al. Quantitative and qualitative ana lysis of rhinovirus infection in bronchial tissues. Am. J. Respir. Crit. Care Med. 171, 645-651 (2005).
149. Simons E, Schroth MK, Gern JE. Analysis of tracheal secretions for rhinovirus during natural colds. Pediatr. Allergy Immunol. 16, 276-278 (2005).
150. Malmstrom K, Pitkaranta A, Carpen O et al. Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. J. Allergy Clin. Immunol. 118, 591-596 (2006).
151. Harju TH, Leinonen M, Nokso-Koivisto J et al. Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma. Thorax 61, 579-584 (2006).
152. Wos M, Sanak M, Soja J, Olechnowicz H, Busse W W, Szczeklik A. The presence of rhinovirus in lower airways of patients with bronchial asthma. Am. J. Respir. Crit. Care Med. 177, 1082-1089 (2008).
153. Bardin PG, Fraenkel DJ, Sanderson G et al. Amplifed rhinovirus colds in atopic subjects. Clin. Exp. Allergy 24, 457-464 (1994).
154. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Bjorksten B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics 95, 500-505 (1995).
155. Frick OL. Effect of respiratory and other virus infections on IgE immunoregulation. J. Allergy Clin. Immunol. 78, 1013-1018 (1986).
156. Lemanske RF Jr, Dick EC, Swenson CA, Vrtis RF, Busse WW. Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions. J. Clin. Invest. 83, 1-10 (1989).
157. Calhoun WJ, Dick EC, Schwartz LB, Busse WW. A common cold virus, rhinovirus 16, potentiates airway infammation after segmental antigen bronchoprovocation in allergic subjects. J. Clin. Invest. 94, 2200-2208 (1994).
158. Sly PD, Boner AL, Bjorksten B et al. Early identifcation of atopy in the prediction of persistent asthma in children. Lancet 372, 1100-1106 (2008).
159. Laing I, Reidel F, Yap PL, Simpson H. Atopy predisposing to acute bronchiolitis during an epidemic of respiratory syncytial virus. Br. Med. J. (Clin. Res. Ed.) 284, 1070-1072 (1982).
160. Rooney JC, Williams HE. The relationship between proved viral bronchiolitis and subsequent wheezing. J. Pediatr. 79, 744-747 (1971).
161. Zweiman B, Schoenwetter WF, Pappano JE Jr, Tempest B, Hildreth EA. Patterns of allergic respiratory disease in children with a past history of bronchiolitis. J. Allergy Clin. Immunol. 48, 283-289 (1971).
162. Pullan CR, Hey EN. Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy. Br. Med. J. (Clin. Res. Ed.) 284, 1665-1669 (1982).
163. Murray M, Webb MS, O'Callaghan C, Swarbrick AS, Milner AD. Respiratory status and allergy after bronchiolitis. Arch. Dis. Child 67, 482-487 (1992).
164. Noma T, Mori A, Yoshizawa I. Induction of allergen-specifc IL-2 responsiveness of lymphocytes after respiratory syncytial virus infection and prediction of onset of recurrent wheezing and bronchial asthma. J. Allergy Clin. Immunol. 98, 816-826 (1996).
165. Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to defne risk of asthma in young children with recurrent wheezing. Am. J. Respir. Crit. Care Med. 162, 1403-1406 (2000).
166. Guilbert TW, Morgan WJ, Zeiger RS et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N. Engl. J. Med. 354, 1985-1997 (2006).
167. Murray CS, Poletti G, Kebadze T et al. Study of modifable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61, 376-382 (2006).
168. Gern JE, Calhoun W, Swenson C, Shen G, Busse W W. Rhinovirus infection preferentially increases lower airway responsiveness in allergic subjects. Am. J. Respir. Crit. Care Med. 155, 1872-1876 (1997).
169. de Kluijver J, Evertse CE, Sont JK et al. Are rhinovirus-induced airway responses in asthma aggravated by chronic allergen exposure? Am. J. Respir. Crit. Care Med. 168, 1174-1180 (2003).
170. Sakamoto M, Ida S, Takishima T. Effect of infuenza virus infection on allergic sensitization to aerosolized ovalbumin in mice. J. Immunol. 132, 2614-2617 (1984).
171. Papadopoulos NG, Xepapadaki P, Mallia P et al. Mechanisms of virus-induced asthma exacerbations: state-of-the-art. A GA2LEN and InterAirways document. Allergy 62, 457-470 (2007).
172. Brooks GD, Buchta KA, Swenson CA, Gern JE, Busse W W. Rhinovirus-induced interferon-g and airway responsiveness in asthma. Am. J. Respir. Crit. Care Med. 168, 1091-1094 (2003).