Вирусиндуцированная бронхиальная астма: возможности профилактики и лечения

1. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». IV издание. М., 2012. / Natsional'naia programma «Bronkhial'naia astma u detei. Strategiia lecheniia i profilaktika». IV izdanie. M., 2012. [in Russian]
2. Chuchalin A, Khaltaev N, Antonov N et al. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int J COPD 2014; 9: 963–74.
3. GINA 2015. ginasthma.org
4. Reddel H, Ware S, Marks G et al. Differences between asthma exacerbations and poor asthma control. Lancet 1999; 353: 364–9.
5. 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 (2): 137–41, 2005.
6. Sigurs N, Aljassim F, Kjellman B et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010; 65 (12): 1045–52.
7. Weiss ST, Tager IB, Munoz A et al. The relationship of respiratory infections in early childhood to the occurrence of increased levels of bronchial responsiveness and atopy. Am Rev Respir Dis 1985; 131 (4): 573–8.
8. 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 1999; 354 (9178): 541–5.
9. Szabo SM, Levy AR, Gooch KL et al. Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy. Paediatr Respir Rev 2013; 13 (Suppl. 2): S9–S15.
10. Stein RT. Long-term airway morbidity following viral LRTI in early infancy: recurrent wheezing or asthma? Paediatr Respir Rev 2009; 10 (Suppl 1): 29–31.
11. 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 2007; 119 (5): 1105–10.
12. Takeyama A, Hashimoto K, Sato M et al. Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years. Eur J Pediatr 2014; 173: 959–66.
13. O’Callaghan-Gordo C, Bassat Q, Diez-Padrisa N et al. Lower respiratory tract infections associated with rhinovirus during infancy and increased risk of wheezing during childhood. A cohort study. PLoS One 2013; 8 (7): e69370. doi: 10.1371/journal.pone.0069370
14. 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 2008; 178: 667–72.
15. Sly PD, Boner AL, Bjorksten B et al. Earlyidentification of atopy in the predictionof persistent asthma in children. Lancet 2008; 372: 1100–6.
16. Woodruff P, Bhakta N, Fahy J. Asthma: Pathogenesis and Phentoypes. In: Murray and Nadel’s textbook of respiratory medicine. 6-th Edition, printed of Elsevier Inc., 2016; p. 713–30.
17. Martinez FD, Wright AL, Taussig LM et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332 (3): 133–8.
18. Martinez FD, Stern DA, Wright AL et al. Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma. J Allergy Clin Immunol 1998; 102 (6 Pt 1): 915–20.
19. Soto-Quiros M, Avila L, Platts-Mills T et al. High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. 
J Allergy Clin Immunol 2012; 129: 1499–505.
20. Macaubas C, de Klerk NH, Holt BJ et al. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet 2003; 362: 1192–7.
21. Johnston NW, Johnston SL, Duncan JM et al. The September epidemic of asthma exacerbations in children: a search for etiology. J Allergy Clin Immunol 2005; 115: 132–8.
22. Longini IM, Monto AS, Koopman JS. Statistical procedures for esti- mating the community probability of illness in family studies: rhinovirus and influenza. Int J Epidemiol 1984; 13: 99–106.
23. Freymuth F, Vabret A, Brouard J et al. Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children. J Clin Virol 1999; 13: 131–9.
24. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ 1993; 307: 982–6.
25. Teichtahl H, Buckmaster N, Pertnikovs E. The incidence of respiratory tract infection in adults requiring hospitalization for asthma. Chest 1997; 112: 591–6.
26. Atmar RL, Guy E, Guntupalli KK et al. Respiratory tract viral infections in inner-city asthmatic adults. Arch Intern Med 1998; 158: 2453–9.
27. Дзюблик А.Я., Симонов С.С., Ячник В.А. Клиническая эффективность и безопасность противовирусного препарата Ингавирин в комплексном лечении больных с обострением бронхиальной астмы, ассоциированным с ОРВИ. Пульмонология. 2013; 6: 43–50. / Dziublik A.Ia., Simonov S.S., Iachnik V.A. Klinicheskaia effektivnost' i bezopasnost' protivovirusnogo preparata Ingavirin v kompleksnom lechenii bol'nykh s obostreniem bronkhial'noi astmy, assotsiirovannym s ORVI. Pul'monologiia. 2013; 6: 43–50. [in Russian]
28. Message SD, Laza-Stanca V, Mallia P et al. Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci U S A 2008; 105: 13562–7.
29. Green RM, Custovic A, Sanderson G et al. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. BMJ 2002; 324: 763.
30. Busse WW, Morgan WJ, Gergen PJ et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011; 364: 1005–15.
31. Bui RH, Molinaro GA, Kettering JD et al. Virus-specific IgE and IgG4 antibodies in serum of children infected with respiratory syncytial virus. J Pediatr 1987; 110: 87–90.
32. Rabatic S, Gagro A, Lokar-Kolbas R et al. Increase in CD23+ B cells in infants with bronchiolitis is accompanied by appearance of IgE and IgG4 antibodies specific for respiratory syncytial virus. J Infect Dis 1997; 175: 32–7.
33. Cheung DS, Ehlenbach SJ, Kitchens RT et al. Cutting edge: CD49d+ neutrophils induce FcepsilonRI expression on lung dendritic cells in a mouse model of postviral asthma. J Immunol. 2010; 185: 4983–7.
34. Stephens R, Randolph DA, Huang G et al. Antigen-nonspecific recruitment of Th2 cells to the lung as a mechanism for viral infection-induced allergic asthma. J Immunol 2002; 169: 5458–67.
35. Cheung DS, Ehlenbach SJ, Kitchens T et al. Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol 2010; 105: 437–43.
36. Cheung DS, Grayson MH. Role of Viruses in the Development of Atopic Disease in Pediatric Patients. Curr Allergy Asthma Rep 2012. DOI 10.1007/s11882-012-0295-y
37. Al-Garawi AA, Fattouh R, Walker TD et al. Acute, but not resolved, influenza A infection enhances susceptibility to house dust mite-induced allergic disease. J Immunol 2009; 182: 3095–104.
38. Durrani SR, Montville DJ, Pratt AS et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol 2012; 130: 489–95.
39. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest 2012; 122 (8): 2741–8.
40. Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allegic inflammation and asthma. Immunol Rev 2011; 242 (1): 69–90.
41. Wark PA, Johnston SL, Bucchieri F et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 2005; 201 (6): 937–47.
42. Contoli M, Message SD, Laza-Stanca V et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 2006; 12 (9): 1023–6.
43. 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 2009; 123 (6): 1384–90 e2.
44. Schwantes E, Denlinger L, Evans M et al. Severity of virus-induced asthma symptoms is inversely related to resolution IFN-l expression. J Allergy Clin Immunol 2015; 135 (6): 1656–9.
45. Shadman KA, Wald ER. A review of palivizumab and emerging therapies for respiratory syncytial virus. Expert Opin Biol Ther 2011; 11 (11): 1455–67.
46. Simoes EA, Groothuis JR, Carbonell-Estrany X et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr 2007; 151: 34–42. 42 e31.
47. Suissa S, Ernst P, Benayoun S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343: 332–6.
48. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392–7.
49. Matz J, Emmett A, Rickard K et al. Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations. J Allergy Clin Immunol 2001; 107: 783–9.
50. Prazma C, Kral K, Gul N et al. Controller medications and their effects on asthma exacerbations temporally associated with upper respiratory infections. Respir Med 2010; 104: 780–7.
51. Walter MJ, Castro M, Kunselman SJ et al. Predicting worsening asthma control following the common cold. Eur Respir J 2008; 32: 1548–54.
52. Wark PA, Grissell T, Davies B et al. Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains. Respirology 2009; 14: 180–6.
53. Calvo C, Garcia ML, Pozo F et al. Role of rhinovirus C in apparently life-threatening events in infants, Spain. Emerg Infect Dis 2009; 15: 1506–8.
54. Çalışkan M, Bochkov Y, Kreiner-Møller E et al. Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma. N Engl J Med 2013; 368: 1398–407.
55. Van Ly D, King NJ, Moir LM et al. Effects of b2 agonists, corticosteroids, and novel therapies on rhinovirus-induced cytokine release and rhinovirus replication in primary airway fibroblasts. J Allergy 2011; 2011: 457169.
56. Tacon CE, Newton R, Proud D et al. Rhinovirus-induced MMP-9 expression is dependent on Fra-1, which is modulated by formoterol and dexamethasone. J Immunol 2012; 188: 4621–30.
57. Papi A, Contoli M, Adcock I et al. Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor kB and c-Jun N-terminal kinase activation. 
J Allergy Clin Immunol 2013; 132: 1075–85.
58. Gruunberg K, Sharon RF, Sont JK et al. Rhinovirus-induced airway inflammation in asthma. Am J Respir Crit Care Med 2001; 164: 1816–22.
59. Grunberg K, Sharon RF, Hiltermann TJ et al. Experimental rhinovirus 16 infection increases intercellular adhesion molecule-1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment. Clin Exp Allergy 2000; 30: 1015–23.
60. Gustafson L, Proud D, Hendley J et al. Oral prednisone therapy in experimental rhinovirus infections. J Allergy Clin Immunol 1996; 97: 1009–14.
61. Farr BM, Gwaltney JM, Hendley JO et al. Randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection. J Infect Dis 1990; 162: 1173–7.
62. Harrison TW, Oborne J, Newton S et al. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004; 363: 271–5.
63. FitzGerald JM, Becker A, Sears MR et al. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 2004; 59: 550–6.
64. Oborne J, Mortimer K, Hubbard RB et al. Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Am J Respir Crit Care Med 2009; 180: 598–602.
65. Ducharme FM, Lemire C, Noya FJ et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med 2009; 360: 339–53.
66. Oliver B, Robinson P, Peters M, Black J. Viral infections and asthma:an inflammatory interface? Eur Respir J 2014; 44: 1666–81.
67. Van Ly D, Faiz A, Jenkins C et al. Characterising the mechanism of airway smooth muscle b2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells. PLoS One 2013; 8: e56058.
68. Wos M, Sanak M, Soja J et al. The presence of rhinovirus in lower airways of patients with bronchial asthma. Am J Respir Crit Care Med 2008; 177: 1082–9.
69. Peters-Golden M, Henderson WR. Leukotrienes. N Engl J Med 2007; 357: 1841–54.
70. Busse W, Kraft M. Cysteinyl leukotrienes in allergic inflammation: strategic target for therapy. Chest 2005; 127: 1312–26.
71. Hallstrand TS, Henderson WR Jr. An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol 2010; 10: 60–6.
72. Mehrotra AK, Henderson WR Jr. The role of leukotrienes in airway remodeling. Curr Mol Med 2009; 9: 383–91.
73. McCarthy M, Weinberg J. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets. Mediat Inflamm 2012, Article ID 236345.
74. Seymour ML, Gilby N, Bardin PG et al. Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. J Infect Dis 2002; 185: 540–4.
75. Gentile DA, Fireman P, Skoner DP. Elevations of local leukotriene C4 levels during viral upper respiratory tract infections. Ann Allergy Asthma Immunol 2003; 91: 270–4.
76. Matsuse H, Hirose H, Tsuchida T et al. Effects of respiratory syncytial virus infection on dendritic cells and cysteinyl leukotrienes in lung tissues of a murine model of asthma. Allergol Int 2007; 56: 165–9.
77. van Schaik SM, Tristram DA, Nagpal IS et al. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol 1999; 103: 630–6.
78. Wedde-Beer K, Hu C, Rodriguez MM, Piedimonte G. Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus. Am J Physiol Lung Cell Mol Physiol 2002; 282: L1143 (L1L50).
79. Amrani Y, Moore PE, Hoffman R et al. Interferon-gamma modulates cysteinyl leukotriene receptor-1 expression and function in human airway myocytes. Respir Crit Care Med 2001; 164: 2098–101.
80. Fey C, Thyroff-Friesinger U, Jones S. Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults. Clin Transl Allergy 2014; 4: 29.
81. Barnes NC, Miller CJ. Effect of leukotriene receptor antagonist therapy on therisk of asthma exacerbations in patients with mild to moderate asthma: an integratedanalysis of zafirlukast trials. Thorax 2000; 55: 478–83.
82. Johnston NW, Mandhane PJ, Dai J et al. Attenuation of the September epidemic of asthma exacerbations in children: a randomized, controlled trial of montelukast added to usual therapy. Pediatrics 2007; 120: e702–12.
83. Bisgaard H, Zielen S, Garcia-Garcia ML et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med 2005; 171: 315 22.
84. Peng WS, Chen X, Yang XY, Liu EM. Systematic review of montelukast’s efficacy for preventing post-bronchiolitis wheezing. Pediatr Allergy Immunol 2014; 25 (2): 143–50.
85. Matsuse H, Fukahori S, Tsuchida T et al. Effects of a short course of pranlukast combined with systemic corticosteroid on acute asthma exacerbation induced by upper respiratory tract infection. J Asthma 2012; 49 (6): 637–41.
86. Matsuse H, Tsuchida T, Fukahori S et al. Retrospective cohort study of leukotriene receptor antagonist therapy for preventing upper respiratory infection-induced acute asthma exacerbations. Allergy Rhinol 2013; 4: 127–31.
87. Venarske DL, Busse WW, Griffin MR et al. The relationship of rhinovirus-associated asthma hospitalizations with inhaled corticosteroidsand smoking. J Infect Dis 2006; 193: 1536–43.
88. Matsuse H, Kondo Y, Saeki S et al. Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes. Int Arch Allergy Immunol 2005; 138: 267–72.
89. Dworski R, Fitzgerald GA, Oates JA, Sheller JR. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med 1994; 149: 953–9.
90. Chaudhuri R, Livingston E, McMahon D et al. Cigarette Smoking Impairs the Therapeutic Response to Oral Corticosteroids in Chronic Asthma. Am J Respir Crit Care Med 2003; 168: 1308–11.
91. Peters-Golden M, Swern A, Bird S et al. Influence of body mass index on the response to asthma controller agents. Eur Respir J 2006; 27: 495–503.
92. Dahlén SE, Malmstróm K, Nizankowska E et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med 2002; 165: 9–14.

________________________________________________

1. Natsional'naia programma «Bronkhial'naia astma u detei. Strategiia lecheniia i profilaktika». IV izdanie. M., 2012. [in Russian]
2. Chuchalin A, Khaltaev N, Antonov N et al. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int J COPD 2014; 9: 963–74.
3. GINA 2015. ginasthma.org
4. Reddel H, Ware S, Marks G et al. Differences between asthma exacerbations and poor asthma control. Lancet 1999; 353: 364–9.
5. 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 (2): 137–41, 2005.
6. Sigurs N, Aljassim F, Kjellman B et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010; 65 (12): 1045–52.
7. Weiss ST, Tager IB, Munoz A et al. The relationship of respiratory infections in early childhood to the occurrence of increased levels of bronchial responsiveness and atopy. Am Rev Respir Dis 1985; 131 (4): 573–8.
8. 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 1999; 354 (9178): 541–5.
9. Szabo SM, Levy AR, Gooch KL et al. Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy. Paediatr Respir Rev 2013; 13 (Suppl. 2): S9–S15.
10. Stein RT. Long-term airway morbidity following viral LRTI in early infancy: recurrent wheezing or asthma? Paediatr Respir Rev 2009; 10 (Suppl 1): 29–31.
11. 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 2007; 119 (5): 1105–10.
12. Takeyama A, Hashimoto K, Sato M et al. Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years. Eur J Pediatr 2014; 173: 959–66.
13. O’Callaghan-Gordo C, Bassat Q, Diez-Padrisa N et al. Lower respiratory tract infections associated with rhinovirus during infancy and increased risk of wheezing during childhood. A cohort study. PLoS One 2013; 8 (7): e69370. doi: 10.1371/journal.pone.0069370
14. 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 2008; 178: 667–72.
15. Sly PD, Boner AL, Bjorksten B et al. Earlyidentification of atopy in the predictionof persistent asthma in children. Lancet 2008; 372: 1100–6.
16. Woodruff P, Bhakta N, Fahy J. Asthma: Pathogenesis and Phentoypes. In: Murray and Nadel’s textbook of respiratory medicine. 6-th Edition, printed of Elsevier Inc., 2016; p. 713–30.
17. Martinez FD, Wright AL, Taussig LM et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332 (3): 133–8.
18. Martinez FD, Stern DA, Wright AL et al. Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma. J Allergy Clin Immunol 1998; 102 (6 Pt 1): 915–20.
19. Soto-Quiros M, Avila L, Platts-Mills T et al. High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. 
J Allergy Clin Immunol 2012; 129: 1499–505.
20. Macaubas C, de Klerk NH, Holt BJ et al. Association between antenatal cytokine production and the development of atopy and asthma at age 6 years. Lancet 2003; 362: 1192–7.
21. Johnston NW, Johnston SL, Duncan JM et al. The September epidemic of asthma exacerbations in children: a search for etiology. J Allergy Clin Immunol 2005; 115: 132–8.
22. Longini IM, Monto AS, Koopman JS. Statistical procedures for esti- mating the community probability of illness in family studies: rhinovirus and influenza. Int J Epidemiol 1984; 13: 99–106.
23. Freymuth F, Vabret A, Brouard J et al. Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children. J Clin Virol 1999; 13: 131–9.
24. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ 1993; 307: 982–6.
25. Teichtahl H, Buckmaster N, Pertnikovs E. The incidence of respiratory tract infection in adults requiring hospitalization for asthma. Chest 1997; 112: 591–6.
26. Atmar RL, Guy E, Guntupalli KK et al. Respiratory tract viral infections in inner-city asthmatic adults. Arch Intern Med 1998; 158: 2453–9.
27. Dziublik A.Ia., Simonov S.S., Iachnik V.A. Klinicheskaia effektivnost' i bezopasnost' protivovirusnogo preparata Ingavirin v kompleksnom lechenii bol'nykh s obostreniem bronkhial'noi astmy, assotsiirovannym s ORVI. Pul'monologiia. 2013; 6: 43–50. [in Russian]
28. Message SD, Laza-Stanca V, Mallia P et al. Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci U S A 2008; 105: 13562–7.
29. Green RM, Custovic A, Sanderson G et al. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. BMJ 2002; 324: 763.
30. Busse WW, Morgan WJ, Gergen PJ et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011; 364: 1005–15.
31. Bui RH, Molinaro GA, Kettering JD et al. Virus-specific IgE and IgG4 antibodies in serum of children infected with respiratory syncytial virus. J Pediatr 1987; 110: 87–90.
32. Rabatic S, Gagro A, Lokar-Kolbas R et al. Increase in CD23+ B cells in infants with bronchiolitis is accompanied by appearance of IgE and IgG4 antibodies specific for respiratory syncytial virus. J Infect Dis 1997; 175: 32–7.
33. Cheung DS, Ehlenbach SJ, Kitchens RT et al. Cutting edge: CD49d+ neutrophils induce FcepsilonRI expression on lung dendritic cells in a mouse model of postviral asthma. J Immunol. 2010; 185: 4983–7.
34. Stephens R, Randolph DA, Huang G et al. Antigen-nonspecific recruitment of Th2 cells to the lung as a mechanism for viral infection-induced allergic asthma. J Immunol 2002; 169: 5458–67.
35. Cheung DS, Ehlenbach SJ, Kitchens T et al. Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol 2010; 105: 437–43.
36. Cheung DS, Grayson MH. Role of Viruses in the Development of Atopic Disease in Pediatric Patients. Curr Allergy Asthma Rep 2012. DOI 10.1007/s11882-012-0295-y
37. Al-Garawi AA, Fattouh R, Walker TD et al. Acute, but not resolved, influenza A infection enhances susceptibility to house dust mite-induced allergic disease. J Immunol 2009; 182: 3095–104.
38. Durrani SR, Montville DJ, Pratt AS et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol 2012; 130: 489–95.
39. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest 2012; 122 (8): 2741–8.
40. Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allegic inflammation and asthma. Immunol Rev 2011; 242 (1): 69–90.
41. Wark PA, Johnston SL, Bucchieri F et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 2005; 201 (6): 937–47.
42. Contoli M, Message SD, Laza-Stanca V et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 2006; 12 (9): 1023–6.
43. 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 2009; 123 (6): 1384–90 e2.
44. Schwantes E, Denlinger L, Evans M et al. Severity of virus-induced asthma symptoms is inversely related to resolution IFN-l expression. J Allergy Clin Immunol 2015; 135 (6): 1656–9.
45. Shadman KA, Wald ER. A review of palivizumab and emerging therapies for respiratory syncytial virus. Expert Opin Biol Ther 2011; 11 (11): 1455–67.
46. Simoes EA, Groothuis JR, Carbonell-Estrany X et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr 2007; 151: 34–42. 42 e31.
47. Suissa S, Ernst P, Benayoun S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343: 332–6.
48. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392–7.
49. Matz J, Emmett A, Rickard K et al. Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations. J Allergy Clin Immunol 2001; 107: 783–9.
50. Prazma C, Kral K, Gul N et al. Controller medications and their effects on asthma exacerbations temporally associated with upper respiratory infections. Respir Med 2010; 104: 780–7.
51. Walter MJ, Castro M, Kunselman SJ et al. Predicting worsening asthma control following the common cold. Eur Respir J 2008; 32: 1548–54.
52. Wark PA, Grissell T, Davies B et al. Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains. Respirology 2009; 14: 180–6.
53. Calvo C, Garcia ML, Pozo F et al. Role of rhinovirus C in apparently life-threatening events in infants, Spain. Emerg Infect Dis 2009; 15: 1506–8.
54. Çalışkan M, Bochkov Y, Kreiner-Møller E et al. Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma. N Engl J Med 2013; 368: 1398–407.
55. Van Ly D, King NJ, Moir LM et al. Effects of b2 agonists, corticosteroids, and novel therapies on rhinovirus-induced cytokine release and rhinovirus replication in primary airway fibroblasts. J Allergy 2011; 2011: 457169.
56. Tacon CE, Newton R, Proud D et al. Rhinovirus-induced MMP-9 expression is dependent on Fra-1, which is modulated by formoterol and dexamethasone. J Immunol 2012; 188: 4621–30.
57. Papi A, Contoli M, Adcock I et al. Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor kB and c-Jun N-terminal kinase activation. 
J Allergy Clin Immunol 2013; 132: 1075–85.
58. Gruunberg K, Sharon RF, Sont JK et al. Rhinovirus-induced airway inflammation in asthma. Am J Respir Crit Care Med 2001; 164: 1816–22.
59. Grunberg K, Sharon RF, Hiltermann TJ et al. Experimental rhinovirus 16 infection increases intercellular adhesion molecule-1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment. Clin Exp Allergy 2000; 30: 1015–23.
60. Gustafson L, Proud D, Hendley J et al. Oral prednisone therapy in experimental rhinovirus infections. J Allergy Clin Immunol 1996; 97: 1009–14.
61. Farr BM, Gwaltney JM, Hendley JO et al. Randomized controlled trial of glucocorticoid prophylaxis against experimental rhinovirus infection. J Infect Dis 1990; 162: 1173–7.
62. Harrison TW, Oborne J, Newton S et al. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004; 363: 271–5.
63. FitzGerald JM, Becker A, Sears MR et al. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 2004; 59: 550–6.
64. Oborne J, Mortimer K, Hubbard RB et al. Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Am J Respir Crit Care Med 2009; 180: 598–602.
65. Ducharme FM, Lemire C, Noya FJ et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med 2009; 360: 339–53.
66. Oliver B, Robinson P, Peters M, Black J. Viral infections and asthma:an inflammatory interface? Eur Respir J 2014; 44: 1666–81.
67. Van Ly D, Faiz A, Jenkins C et al. Characterising the mechanism of airway smooth muscle b2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells. PLoS One 2013; 8: e56058.
68. Wos M, Sanak M, Soja J et al. The presence of rhinovirus in lower airways of patients with bronchial asthma. Am J Respir Crit Care Med 2008; 177: 1082–9.
69. Peters-Golden M, Henderson WR. Leukotrienes. N Engl J Med 2007; 357: 1841–54.
70. Busse W, Kraft M. Cysteinyl leukotrienes in allergic inflammation: strategic target for therapy. Chest 2005; 127: 1312–26.
71. Hallstrand TS, Henderson WR Jr. An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol 2010; 10: 60–6.
72. Mehrotra AK, Henderson WR Jr. The role of leukotrienes in airway remodeling. Curr Mol Med 2009; 9: 383–91.
73. McCarthy M, Weinberg J. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets. Mediat Inflamm 2012, Article ID 236345.
74. Seymour ML, Gilby N, Bardin PG et al. Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. J Infect Dis 2002; 185: 540–4.
75. Gentile DA, Fireman P, Skoner DP. Elevations of local leukotriene C4 levels during viral upper respiratory tract infections. Ann Allergy Asthma Immunol 2003; 91: 270–4.
76. Matsuse H, Hirose H, Tsuchida T et al. Effects of respiratory syncytial virus infection on dendritic cells and cysteinyl leukotrienes in lung tissues of a murine model of asthma. Allergol Int 2007; 56: 165–9.
77. van Schaik SM, Tristram DA, Nagpal IS et al. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol 1999; 103: 630–6.
78. Wedde-Beer K, Hu C, Rodriguez MM, Piedimonte G. Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus. Am J Physiol Lung Cell Mol Physiol 2002; 282: L1143 (L1L50).
79. Amrani Y, Moore PE, Hoffman R et al. Interferon-gamma modulates cysteinyl leukotriene receptor-1 expression and function in human airway myocytes. Respir Crit Care Med 2001; 164: 2098–101.
80. Fey C, Thyroff-Friesinger U, Jones S. Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults. Clin Transl Allergy 2014; 4: 29.
81. Barnes NC, Miller CJ. Effect of leukotriene receptor antagonist therapy on therisk of asthma exacerbations in patients with mild to moderate asthma: an integratedanalysis of zafirlukast trials. Thorax 2000; 55: 478–83.
82. Johnston NW, Mandhane PJ, Dai J et al. Attenuation of the September epidemic of asthma exacerbations in children: a randomized, controlled trial of montelukast added to usual therapy. Pediatrics 2007; 120: e702–12.
83. Bisgaard H, Zielen S, Garcia-Garcia ML et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med 2005; 171: 315 22.
84. Peng WS, Chen X, Yang XY, Liu EM. Systematic review of montelukast’s efficacy for preventing post-bronchiolitis wheezing. Pediatr Allergy Immunol 2014; 25 (2): 143–50.
85. Matsuse H, Fukahori S, Tsuchida T et al. Effects of a short course of pranlukast combined with systemic corticosteroid on acute asthma exacerbation induced by upper respiratory tract infection. J Asthma 2012; 49 (6): 637–41.
86. Matsuse H, Tsuchida T, Fukahori S et al. Retrospective cohort study of leukotriene receptor antagonist therapy for preventing upper respiratory infection-induced acute asthma exacerbations. Allergy Rhinol 2013; 4: 127–31.
87. Venarske DL, Busse WW, Griffin MR et al. The relationship of rhinovirus-associated asthma hospitalizations with inhaled corticosteroidsand smoking. J Infect Dis 2006; 193: 1536–43.
88. Matsuse H, Kondo Y, Saeki S et al. Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes. Int Arch Allergy Immunol 2005; 138: 267–72.
89. Dworski R, Fitzgerald GA, Oates JA, Sheller JR. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med 1994; 149: 953–9.
90. Chaudhuri R, Livingston E, McMahon D et al. Cigarette Smoking Impairs the Therapeutic Response to Oral Corticosteroids in Chronic Asthma. Am J Respir Crit Care Med 2003; 168: 1308–11.
91. Peters-Golden M, Swern A, Bird S et al. Influence of body mass index on the response to asthma controller agents. Eur Respir J 2006; 27: 495–503.
92. Dahlén SE, Malmstróm K, Nizankowska E et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med 2002; 165: 9–14.

________________________________________________