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. 2009 Jan 6;67(2):161–168. [Article in Spanish] doi: 10.1016/S1695-4033(07)70578-7

Relación entre asma e infecciones virales

Association between asthma and viral infections

JA Castro-Rodríguez 1,⁎
PMCID: PMC7128541  PMID: 17692263

Abstract

Viral respiratory infections are the factor most frequently associated with asthma (independently of phenotype, age, and phase of the natural history of asthma during which the infection occurs) and there is a strong temporal association between viral respiratory infections and acute obstructive/asthmatic episodes. Nevertheless, the role of viral infections in the pathogenesis of asthma remains poorly characterized.

The factors that could explain this association are heterogeneous and sometimes contradictory. The four main causative mechanisms implicated in the association between viral respiratory infections and the subsequent development of asthma or wheezing in children are alterations in airway function and size, dysregulation (congenital and acquired) of airway tone, alterations in the immune response to infections, and the genetic variants involved in immune response. These mechanisms should be taken into account in future preventive and therapeutic strategies.

Key words: Viral respiratory infections, Asthma, Wheezing, Lung function, Children

Bibliografía

  • 1.Johnston S.L. Impact of viruses on airway diseases. Eur Respir Rev. 2005;14:57–61. [Google Scholar]
  • 2.Legg J.P., Warner J.A., Johnston S.L., Warner J.O. Frequency of detection of picornaviruses and seven other respiratory pathogens in infants. Pediatr Infect Dis J. 2005;24:611–616. doi: 10.1097/01.inf.0000168747.94999.aa. [DOI] [PubMed] [Google Scholar]
  • 3.Johnston S.L., Pattemore P.K., Sanderson G., Smith S., Lampe F., Josephs L. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ. 1995;310:1225–1229. doi: 10.1136/bmj.310.6989.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Nicholson K.G., Kent J., Ireland D.C. Respiratory viruses and exacerbations of asthma in adults. BMJ. 1993;307:982–986. doi: 10.1136/bmj.307.6910.982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Wark P.A., Johnston S.L., Moric I., Simpson J.L., Hensley M.J., Gibson P.G. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J. 2002;19:68–75. doi: 10.1183/09031936.02.00226302. [DOI] [PubMed] [Google Scholar]
  • 6.Van den Hoogen B.G., De Jong J.C., Groen J., Kuiken T., De Groot R., Fouchier R.A. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7:719–724. doi: 10.1038/89098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Williams J.V., Wang C.K., Yang C.F., Tollefson S.J., House F.S., Heck J.M. The role of human metapneumovirus in upper respiratory tract infections in children: A 20-year experience. J Infect Dis. 2006;193:387–395. doi: 10.1086/499274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Williams J.V., Harris P.A., Tollefson S.J., Halburnt-Rush L.L., Pingsterhaus J.M., Edwards K.M. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004;350:443–450. doi: 10.1056/NEJMoa025472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Heymann P.W., Platts-Mills T.A., Johnston S.L. Role of viral infections, atopy and antiviral immunity in the etiology of wheezing exacerbations among children and young adults. Pediatr Infect Dis J. 2005;24(Suppl 11):217–222. doi: 10.1097/01.inf.0000188164.33856.f9. [DOI] [PubMed] [Google Scholar]
  • 10.Tan W.C., Xiang X., Qiu D., Ng T.P., Lam S.F., Hegele R.G. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med. 2003;115:272–277. doi: 10.1016/s0002-9343(03)00353-x. [DOI] [PubMed] [Google Scholar]
  • 11.Martinez F.D. Heterogeneity of the association between lower respiratory illness in infancy and subsequent asthma. Proc Am Thorac Soc. 2005;2:157–161. doi: 10.1513/pats.200504-044AW. [DOI] [PubMed] [Google Scholar]
  • 12.Castro-Rodríguez J.A., Wright A.L., Taussig L.M., Martínez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Resp Crit Care Med. 2000;162:1403–1406. doi: 10.1164/ajrccm.162.4.9912111. [DOI] [PubMed] [Google Scholar]
  • 13.Stein R.T., Sherrill D., Morgan W.J., Holberg C.J., Halonen M., Taussig L.M. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;353:541–545. doi: 10.1016/S0140-6736(98)10321-5. [DOI] [PubMed] [Google Scholar]
  • 14.Sigurs N., Gustafsson P.M., Bjarnason R., Lundberg F., Schmidt S., Sigurbergsson F. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 2005;171:137–141. doi: 10.1164/rccm.200406-730OC. [DOI] [PubMed] [Google Scholar]
  • 15.Psarras S., Papadopoulos N.G., Johnston S.L. Pathogenesis of respiratory syncytial virus bronchiolitis-related wheezing. Paediatr Respir Rev. 2004;5(Suppl A):179–184. doi: 10.1016/s1526-0542(04)90034-6. [DOI] [PubMed] [Google Scholar]
  • 16.Martinez F.D., Morgan W.J., Wright A.L., Holberg C.J., Taussig L.M. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med. 1988;319:1112–1117. doi: 10.1056/NEJM198810273191702. [DOI] [PubMed] [Google Scholar]
  • 17.Gold D.R., Burge H.A., Carey V., Milton D.K., Platts-Mills T., Weiss S.T. Predictors of repeated wheeze in the first year of life: the relative roles of cockroach, birth weight, acute lower respiratory illness, and maternal smoking. Am J Respir Crit Care Med. 1999;160:227–236. doi: 10.1164/ajrccm.160.1.9807104. [DOI] [PubMed] [Google Scholar]
  • 18.Shay D.K., Holman R.C., Roosevelt G.E., Clarke M.J., Anderson L.J. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997. J Infect Dis. 2001;183:16–22. doi: 10.1086/317655. [DOI] [PubMed] [Google Scholar]
  • 19.Hoffjan S., Ostrovnaja I., Nicolae D., Newman D.L., Nicolae R., Gangnon R. Genetic variation in immunoregulatory pathways and atopic phenotypes in infancy. J Allergy Clin Immunol. 2003;113:511–518. doi: 10.1016/j.jaci.2003.10.044. [DOI] [PubMed] [Google Scholar]
  • 20.Choi E.H., Lee H.J., Yoo T., Chanock S.J. A common haplotype of interleukin-4 gene IL4 is associated with severe respiratory syncytial virus disease in Korean children. J Infect Dis. 2002;186:1207–1211. doi: 10.1086/344310. [DOI] [PubMed] [Google Scholar]
  • 21.Hull J., Rowlands K., Lockhart E., Moore C., Sharland M., Kwiatkowski D. Variants of the chemokine receptor CCR5 are associated with severe bronchiolitis caused by respiratory syncytial virus. J Infect Dis. 2004;188:904–907. doi: 10.1086/377587. [DOI] [PubMed] [Google Scholar]
  • 22.Hull J., Thomson A., Kwiatkowski D. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax. 2000;55:1023–1027. doi: 10.1136/thorax.55.12.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Lahti M., Lofgren J., Marttila R., Renko M., Klaavuniemi T., Haataja R. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr Res. 2002;51:696–699. doi: 10.1203/00006450-200206000-00006. [DOI] [PubMed] [Google Scholar]
  • 24.Martinez F.D., Morgan W.J., Wright A.L., Holberg C., Taussig L.M. Initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life. Am Rev Respir Dis. 1991;143:312–316. doi: 10.1164/ajrccm/143.2.312. [DOI] [PubMed] [Google Scholar]
  • 25.Tager I.B., Hanrahan J.P., Tosteson T.D., Castile R.G., Brown R.W., Weiss S.T. Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life. Am Rev Respir Dis. 1993;147:811–817. doi: 10.1164/ajrccm/147.4.811. [DOI] [PubMed] [Google Scholar]
  • 26.Dezateux C., Stocks J., Dundas I., Fletcher M.E. Impaired airway function and wheezing in infancy: the influence of maternal smoking and a genetic predisposition to asthma. Am J Respir Crit Care Med. 1999;159:403–410. doi: 10.1164/ajrccm.159.2.9712029. [DOI] [PubMed] [Google Scholar]
  • 27.Young S., Arnott J., O’Keeffe P.T., Le Souef P.N., Landau L.I. The association between early life lung function and wheezing during the first 2 years of life. Eur Respir J. 2000;15:151–157. doi: 10.1183/09031936.00.15115100. [DOI] [PubMed] [Google Scholar]
  • 28.Murray C.S., Pipis S.D., McArdle E.C., Lowe L.A., Custovic A., Woodcock A. Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population. Thorax. 2002;57:388–392. doi: 10.1136/thorax.57.5.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Stocks J., Dezateux C. The effect of parental smoking on lung function and development during infancy. Respirology. 2003;8:266–285. doi: 10.1046/j.1440-1843.2003.00478.x. [DOI] [PubMed] [Google Scholar]
  • 30.Martínez F.D., Wright A.L., Taussig L.M., Holberg C.J., Halonen M., Morgan W.J., The Group Health Medical Associates Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332:133–138. doi: 10.1056/NEJM199501193320301. [DOI] [PubMed] [Google Scholar]
  • 31.Turner S.W., Palmer L.J., Rye P.J., Gibson N.A., Judge P.K., Young S. Infants with flow limitation at 4 weeks: Outcome at 6 and 11 years. Am J Respir Crit Care Med. 2002;165:1294–1298. doi: 10.1164/rccm.200110-018OC. [DOI] [PubMed] [Google Scholar]
  • 32.Stein R.T., Holberg C.J., Sherrill D.L., Wright A.L., Morgan W.J., Taussig L.M. The influence of parental smoking on respiratory symptoms in the first decade of life: The Tucson Children's Respiratory Study. Am J Epidemiol. 1999;149:1030–1037. doi: 10.1093/oxfordjournals.aje.a009748. [DOI] [PubMed] [Google Scholar]
  • 33.Turner S.W., Palmer L.J., Rye P.J., Gibson N.A., Judge P.K., Cox M. The relationship between infant airway function, childhood airway responsiveness, and asthma. Am J Respir Crit Care Med. 2004;169:921–927. doi: 10.1164/rccm.200307-891OC. [DOI] [PubMed] [Google Scholar]
  • 34.Morgan W.J., Stern D.A., Sherrill D.L., Guerra S., Holberg C.J., Guilbert T.W. Outcome of Asthma and Wheezing in the First 6 Years of Life: Follow-up through Adolescence. Am J Respir Crit Care Med. 2005;172:1253–1258. doi: 10.1164/rccm.200504-525OC. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Palmer L.J., Rye P.J., Gibson N.A., Burton P.R., Landau L.I., Lesouef P.N. Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age. Am J Respir Crit Care Med. 2001;163:37–42. doi: 10.1164/ajrccm.163.1.2005013. [DOI] [PubMed] [Google Scholar]
  • 36.Lombardi E., Morgan W.J., Wright A.L., Stein R.T., Holberg C.J., Martinez F.D. Cold air challenge at age 6 and subsequent incidence of asthma: a longitudinal study. Am J Respir Crit Care Med. 1997;156:1863–1869. doi: 10.1164/ajrccm.156.6.9612066. [DOI] [PubMed] [Google Scholar]
  • 37.Martínez F.D., Graves P.E., Baldini M., Solomon S., Erickson R. Association between genetic polymorphisms of the beta 2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest. 1997;100:3184–3188. doi: 10.1172/JCI119874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Turner S.W., Khoo S.K., Laing I.A., Palmer L.J., Gibson N.A., Rye P. Beta-2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children. Clin Exp Allergy. 2004;34:1043–1048. doi: 10.1111/j.1365-2222.2004.02001.x. [DOI] [PubMed] [Google Scholar]
  • 39.Burrows B., Sears M.R., Flannery E.M., Herbison G.P., Holdaway M.D., Silva P.A. Relation of the course of bronchial responsiveness from age 9 to age 15 to allergy. Am J Respir Crit Care Med. 1995;152:1302–1308. doi: 10.1164/ajrccm.152.4.7551386. [DOI] [PubMed] [Google Scholar]
  • 40.Corne J.M., Marshall C., Smith S., Schreiber J., Sanderson G., Holgate S.T. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: A longitudinal cohort study. Lancet. 2002;359:831–834. doi: 10.1016/S0140-6736(02)07953-9. [DOI] [PubMed] [Google Scholar]
  • 41.Takaoka A., Hayakawa S., Yanai H., Stoiber D., Negishi H., Kikuchi H. Integration of interferon-alpha/beta signalling to 53p responses in tumour suppression and antiviral defence. Nature. 2003;424:516–523. doi: 10.1038/nature01850. [DOI] [PubMed] [Google Scholar]
  • 42.Wark P.A., Johnston S.L., Bucchieri F., Powell R., Puddicombe S., Laza-Stanca V. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201:937–947. doi: 10.1084/jem.20041901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Contoli M., Message S.D., Laza-Stanca V., Edwards M.R., Wark P.A., Bartlett N.W. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12:1023–1026. doi: 10.1038/nm1462. [DOI] [PubMed] [Google Scholar]
  • 44.Brandenburg A.H., Groen J., Van Steensel-Moll H.A., Claas E.C., Rothbarth P.H., Neijens H.J. Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection. J Med Virol. 1997;52:97–104. doi: 10.1002/(sici)1096-9071(199705)52:1<97::aid-jmv16>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  • 45.Chalmers I.M., Janossy G., Contreras M., Navarrete C. Intracellular cytokine profile of cord and adult blood lymphocytes. Blood. 1998;92:11–18. [PubMed] [Google Scholar]
  • 46.Prescott S.L., Macaubas C., Holt B.J., Smallacombe T.B., Loh R., Sly P.D. Transplacental priming of the human immune system to environmental allergens: Universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998;160:4730–4737. [PubMed] [Google Scholar]
  • 47.Guerra S., Lohman I.C., Halonen M., Martínez F.D., Wright A.L. Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age. Am J Respir Crit Care Med. 2004;169:70–76. doi: 10.1164/rccm.200304-499OC. [DOI] [PubMed] [Google Scholar]
  • 48.Bont L., Heijnen C.J., Kavelaars A., Van Aalderen W.M., Brus F., Draaisma J.M. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J Infect Dis. 2001;184:355–358. doi: 10.1086/322035. [DOI] [PubMed] [Google Scholar]
  • 49.Van Schaik S.M., Tristram D.A., Nagpal I.S., Hintz K.M., Welliver R.C., II, Welliver R.C. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol. 1999;103:630–636. doi: 10.1016/s0091-6749(99)70235-6. [DOI] [PubMed] [Google Scholar]
  • 50.Martinez F.D., Stern D.A., Wright A.L., Holberg C.J., Taussig L.M., Halonen M. Association of interleukin-2 and interferon-gamma production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy. J Allergy Clin Immunol. 1995;96:652–660. doi: 10.1016/s0091-6749(95)70264-4. [DOI] [PubMed] [Google Scholar]
  • 51.Gern J.E., Brooks D., Meyer P., Chang A., Shen K., Evans M.D. Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life. J Allergy Clin Immunol. 2006;117:72–78. doi: 10.1016/j.jaci.2005.10.002. [DOI] [PubMed] [Google Scholar]
  • 52.Juntti H., Kokkonen J., Dunder T., Renko M., Niinimaki A., Uhari M. Association of an early respiratory syncytial virus infection and atopic allergy. Allergy. 2003;58:878–884. doi: 10.1034/j.1398-9995.2003.00233.x. [DOI] [PubMed] [Google Scholar]
  • 53.Penny M.E., Murad S., Madrid S.S., Herrera T.S., Piñeiro A., Cáceres D.E. Respiratory symptoms, asthma, exercise test, spirometry, and atopy in schoolchildren from a Lima shanty town. Thorax. 2001;56:607–612. doi: 10.1136/thorax.56.8.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Juntti H., Kokkonen J., Dunder T., Renko M., Karttunen R., Uhari M. Serum concentration of interferon-γ and intercellular adhesion molecule-1 eight years after an early respiratory syncytial virus infection. Clin Exp Allergy. 2005;35:59–63. doi: 10.1111/j.1365-2222.2004.02125.x. [DOI] [PubMed] [Google Scholar]
  • 55.Aberle J.H., Aberle S.W., Rebhandl W., Pracher E., Kundi M., Popow-Kraupp T. Decreased interferon-gamma response in respiratory syncytial virus compared to other respiratory viral infections in infants. Clin Exp Immunol. 2004;137:146–150. doi: 10.1111/j.1365-2249.2004.02504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Pitrez P.M., Ponzi D., Machado D.C., Bauer M.E., Jones M.H., Stein R.T. Discrepancy between cytokine production from peripheral blood mononuclear cells and nasal secretions among infants with acute bronchiolitis. Ann Allergy Asthma Immunol. 2004;92:659–662. doi: 10.1016/S1081-1206(10)61433-0. [DOI] [PubMed] [Google Scholar]
  • 57.Bont L., Heijnen C.J., Kavelaars A., Van Aalderen W.M., Brus F., Draaisma J.T. Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study. Am J Respir Crit Care Med. 2000;161:1518–1523. doi: 10.1164/ajrccm.161.5.9904078. [DOI] [PubMed] [Google Scholar]
  • 58.Einarsson O., Geba G.P., Zhu Z., Landry M., Elias J.A. Interleukin-11: Stimulation in vivo and in vitro by respiratory viruses and induction of airway hyperresponsiveness. J Clin Invest. 1996;97:915–924. doi: 10.1172/JCI118514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Copenhaver C.C., Gern J.E., Li Z., Shult P.A., Rosenthal L.A., Mikus L.D. Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Am J Respir Crit Care Med. 2004;170:175–180. doi: 10.1164/rccm.200312-1647OC. [DOI] [PubMed] [Google Scholar]
  • 60.Korppi M., Kotaniemi-Syrjanen A., Waris M., Vainionpaa R., Reijonen T.M. Rhinovirus-associated wheezing in infancy: Comparison with respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J. 2004;23:995–999. doi: 10.1097/01.inf.0000143642.72480.53. [DOI] [PubMed] [Google Scholar]
  • 61.Halonen M., Stern D.A., Lohman I.C., Wright A.L., Brown M.A., Martinez F.D. Two subphenotypes of childhood asthma that differ in maternal and paternal influences on asthma risk. Am J Respir Crit Care Med. 1999;160:564–570. doi: 10.1164/ajrccm.160.2.9809038. [DOI] [PubMed] [Google Scholar]
  • 62.Martinez F.D., Stern D.A., Wright A.L., Taussig L.M., Halonen M. Differential immune responses to acute lower respiratory illness in early life by subsequent development of persistent wheezing and asthma. J Allergy Clin Immunol. 1998;102:915–920. doi: 10.1016/s0091-6749(98)70328-8. [DOI] [PubMed] [Google Scholar]
  • 63.Murray C.S., Poletti G., Kebadze T., Morris J., Woodcock A., Jonhston S.L. A study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospitalization in children. Thorax. 2006;61:376–382. doi: 10.1136/thx.2005.042523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Goetghebuer T., Isles K., Moore C., Thomson A., Kwiatkowski D., Hull J. Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis. Clin Exp Allergy. 2004;34:801–803. doi: 10.1111/j.1365-2222.2004.1947.x. [DOI] [PubMed] [Google Scholar]
  • 65.Heinzmann A., Ahlert I., Kurz T., Berner R., Deichmann K.A. Association study suggests opposite effects of polymorphisms within IL-8 on bronchial asthma and respiratory syncytial virus bronchiolitis. J Allergy Clin Immunol. 2004;114:671–676. doi: 10.1016/j.jaci.2004.06.038. [DOI] [PubMed] [Google Scholar]

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