The contributions of allergic sensitization and respiratory pathogens to asthma inception
2016; Elsevier BV; Volume: 137; Issue: 3 Linguagem: Inglês
10.1016/j.jaci.2016.01.002
ISSN1097-6825
AutoresDaniel J. Jackson, James E. Gern, Robert F. Lemanske,
Tópico(s)Noise Effects and Management
ResumoOf the chronic diseases affecting grade-school children, asthma is the most common and accounts for the greatest number of school days missed. Moreover, it can influence family dynamics and function in other ways, and unfortunately, it can also be associated with mortality, particularly in the inner-city environments of the United States. Thus understanding factors that lead to its development in early life is essential in developing strategies aimed at primary prevention. Two risk factors that have been identified by a number of investigators include the development of allergic sensitization and wheezing respiratory tract illnesses caused by viruses and bacteria, either alone or in combination. Both of these factors appear to exert their influences within the first few years of life, such that asthma becomes established before the child enters grade school at age 5 to 6 years. Therefore, because both allergic sensitization and viral and bacterial illnesses can occur in children who do not have asthma, it is paramount to identify genetic and environmental factors that activate, interact with, and/or direct the immune system and components of the respiratory tract along pathways that allow asthma to become established and expressed clinically. Of the chronic diseases affecting grade-school children, asthma is the most common and accounts for the greatest number of school days missed. Moreover, it can influence family dynamics and function in other ways, and unfortunately, it can also be associated with mortality, particularly in the inner-city environments of the United States. Thus understanding factors that lead to its development in early life is essential in developing strategies aimed at primary prevention. Two risk factors that have been identified by a number of investigators include the development of allergic sensitization and wheezing respiratory tract illnesses caused by viruses and bacteria, either alone or in combination. Both of these factors appear to exert their influences within the first few years of life, such that asthma becomes established before the child enters grade school at age 5 to 6 years. Therefore, because both allergic sensitization and viral and bacterial illnesses can occur in children who do not have asthma, it is paramount to identify genetic and environmental factors that activate, interact with, and/or direct the immune system and components of the respiratory tract along pathways that allow asthma to become established and expressed clinically. Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: March 2016. Credit may be obtained for these courses until February 28, 2017.Copyright Statement: Copyright © 2016-2017. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Daniel J. Jackson, MD, James E. Gern, MD, and Robert F. Lemanske, Jr, MDDisclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: D. J. Jackson has received research support from the National Institutes of Health (NIH) and has received consultancy fees from Vectura. J. E. Gern has received research support from the NIH, GlaxoSmithKline, and Merck and has received consultancy fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Genentech, Amgen, and Novartis. R. F. Lemanske has received travel support to attend board meetings; is employed by the University of Wisconsin; has received research support from the National Heart, Lung, and Blood Institute (Program Project Grant [COAST], AsthmaNet, Lung Development Grant [RO-1]) and Pharmaxis; has received consultancy fees from Merck, Sepracor, SA Boney and Associates, GlaxoSmithKline, the American Institute of Research, Genentech, Double Helix Development, and Boehringer Ingelheim; has received speakers' honoraria from Michigan Public Health, Allegheny General Hospital, AAP, West Allegheny Health, California Chapter 4, the Colorado Allergy Society, the Pennsylvania Allergy Society, Howard Pilgrim Health, the California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, APAPARI, the Kuwait Allergy Society, Lurie Children's Hospital, Boston Children's Hospital, LA Children's Hospital, Northwestern University, the Western Society of Allergy, Asthma, and Immunology, and the Asthma and Allergy Foundation of America, Alaska Chapter; has received payment for manuscript preparation from the American Academy of Allergy, Asthma & Immunology; receives royalties from Elsevier and UpToDate; and has receives consultancy fees from Health Star Communications.Activity Objectives:1.To understand that exposure to viral and bacterial pathogens is associated with recurrent wheezing and increased asthma risk in preschool-aged children.2.To determine the population at risk of developing asthma during childhood.3.To assess the effect of respiratory syncytial virus (RSV) infections on the future risk for asthma, and identify which patients would benefit from RSV prophylaxis.4.To understand the mechanisms of allergy-virus interactions and the association with allergic inflammation and asthma.Recognition of Commercial Support: This CME activity has not received external commercial support.List of CME Exam Authors: Jennifer Fergeson, DO, Adeeb Bulkhi, MD, Andrew Cooke, MD, Chen Hsing Lin, MD, Sultan Alandijani, MD, Peter Ricketti, DO, and Richard F. Lockey, MD.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: The exam authors disclosed no relevant financial relationships.Discuss this article on the JACI Journal Club blog: www.jaci-online.blogspot.com. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: March 2016. Credit may be obtained for these courses until February 28, 2017. Copyright Statement: Copyright © 2016-2017. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Daniel J. Jackson, MD, James E. Gern, MD, and Robert F. Lemanske, Jr, MD Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: D. J. Jackson has received research support from the National Institutes of Health (NIH) and has received consultancy fees from Vectura. J. E. Gern has received research support from the NIH, GlaxoSmithKline, and Merck and has received consultancy fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Genentech, Amgen, and Novartis. R. F. Lemanske has received travel support to attend board meetings; is employed by the University of Wisconsin; has received research support from the National Heart, Lung, and Blood Institute (Program Project Grant [COAST], AsthmaNet, Lung Development Grant [RO-1]) and Pharmaxis; has received consultancy fees from Merck, Sepracor, SA Boney and Associates, GlaxoSmithKline, the American Institute of Research, Genentech, Double Helix Development, and Boehringer Ingelheim; has received speakers' honoraria from Michigan Public Health, Allegheny General Hospital, AAP, West Allegheny Health, California Chapter 4, the Colorado Allergy Society, the Pennsylvania Allergy Society, Howard Pilgrim Health, the California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, APAPARI, the Kuwait Allergy Society, Lurie Children's Hospital, Boston Children's Hospital, LA Children's Hospital, Northwestern University, the Western Society of Allergy, Asthma, and Immunology, and the Asthma and Allergy Foundation of America, Alaska Chapter; has received payment for manuscript preparation from the American Academy of Allergy, Asthma & Immunology; receives royalties from Elsevier and UpToDate; and has receives consultancy fees from Health Star Communications. Activity Objectives:1.To understand that exposure to viral and bacterial pathogens is associated with recurrent wheezing and increased asthma risk in preschool-aged children.2.To determine the population at risk of developing asthma during childhood.3.To assess the effect of respiratory syncytial virus (RSV) infections on the future risk for asthma, and identify which patients would benefit from RSV prophylaxis.4.To understand the mechanisms of allergy-virus interactions and the association with allergic inflammation and asthma. Recognition of Commercial Support: This CME activity has not received external commercial support. List of CME Exam Authors: Jennifer Fergeson, DO, Adeeb Bulkhi, MD, Andrew Cooke, MD, Chen Hsing Lin, MD, Sultan Alandijani, MD, Peter Ricketti, DO, and Richard F. Lockey, MD. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The exam authors disclosed no relevant financial relationships. Of the various environmental risk factors demonstrated to be influential in the inception of childhood asthma, the development of allergic sensitization in early life,1Sly P.D. Boner A.L. Bjorksten B. Bush A. Custovic A. Eigenmann P.A. et al.Early identification of atopy in the prediction of persistent asthma in children.Lancet. 2008; 372: 1100-1106Abstract Full Text Full Text PDF PubMed Scopus (302) Google Scholar followed by wheezing respiratory tract illnesses2Jackson D.J. Evans M.D. Gangnon R.E. Tisler C.J. Pappas T.E. Lee W.M. et al.Evidence for a causal relationship between allergic sensitization and rhinovirus wheezing in early life.Am J Respir Crit Care Med. 2012; 185: 281-285Crossref PubMed Scopus (274) Google Scholar caused by infection with various respiratory pathogens, appear to be the most consistent and reproducible.3Holt P.G. Strickland D.H. Sly P.D. Virus infection and allergy in the development of asthma: what is the connection?.Curr Opin Allergy Clin Immunol. 2012; 12: 151-157Crossref PubMed Scopus (63) Google Scholar It has been shown that allergic sensitization has its greatest effect on recurrent wheezing and asthma when the process occurs in the first few years of life4Kusel M.M. de Klerk N.H. Kebadze T. Vohma V. Holt P.G. Johnston S.L. et al.Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma.J Allergy Clin Immunol. 2007; 119: 1105-1110Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar, 5Simpson A. Tan V.Y. Winn J. Svensen M. Bishop C.M. Heckerman D.E. et al.Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study.Am J Respir Crit Care Med. 2010; 181: 1200-1206Crossref PubMed Scopus (355) Google Scholar, 6Stoltz D.J. Jackson D.J. Evans M.D. Gangnon R.E. Tisler C.J. Gern J.E. et al.Specific patterns of allergic sensitization in early childhood and asthma & rhinitis risk.Clin Exp Allergy. 2013; 43: 233-241Crossref PubMed Scopus (104) Google Scholar and when it involves development of sensitization to multiple aeroallergens.5Simpson A. Tan V.Y. Winn J. Svensen M. Bishop C.M. Heckerman D.E. et al.Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study.Am J Respir Crit Care Med. 2010; 181: 1200-1206Crossref PubMed Scopus (355) Google Scholar, 6Stoltz D.J. Jackson D.J. Evans M.D. Gangnon R.E. Tisler C.J. Gern J.E. et al.Specific patterns of allergic sensitization in early childhood and asthma & rhinitis risk.Clin Exp Allergy. 2013; 43: 233-241Crossref PubMed Scopus (104) Google Scholar Thus the strength of its influence appears not to be binary but more quantitative and developmental in nature. Preschool wheezing illnesses with both viral7Jackson D.J. Gangnon R.E. Evans M.D. Roberg K.A. Anderson E.L. Pappas T.E. et al.Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.Am J Respir Crit Care Med. 2008; 178: 667-672Crossref PubMed Scopus (1059) Google Scholar, 8Lemanske Jr., R.F. Jackson D.J. Gangnon R.E. Evans M.D. Li Z. Shult P.A. et al.Rhinovirus illnesses during infancy predict subsequent childhood wheezing.J Allergy Clin Immunol. 2005; 116: 571-577Abstract Full Text Full Text PDF PubMed Scopus (611) Google Scholar, 9Jackson D.J. Early-life viral infections and the development of asthma: a target for asthma prevention?.Curr Opin Allergy Clin Immunol. 2014; 14: 131-136Crossref PubMed Scopus (34) Google Scholar and bacterial10Bisgaard H. Hermansen M.N. Bonnelykke K. Stokholm J. Baty F. Skytt N.L. et al.Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study.BMJ. 2010; 341: c4978Crossref PubMed Scopus (261) Google Scholar, 11Kloepfer K.M. Lee W.M. Pappas T.E. Kang T.J. Vrtis R.F. 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Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7.Am J Respir Crit Care Med. 2000; 161: 1501-1507Crossref PubMed Scopus (952) Google Scholar and more recent data provide additional support for this relationship.14James K.M. Gebretsadik T. Escobar G.J. Wu P. Carroll K.N. Li S.X. et al.Risk of childhood asthma following infant bronchiolitis during the respiratory syncytial virus season.J Allergy Clin Immunol. 2013; 132: 227-229Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 15Wu P. Dupont W.D. Griffin M.R. Carroll K.N. Mitchel E.F. Gebretsadik T. et al.Evidence of a causal role of winter virus infection during infancy in early childhood asthma.Am J Respir Crit Care Med. 2008; 178: 1123-1129Crossref PubMed Scopus (278) Google Scholar Furthermore, animal studies provide mechanistic evidence by which RSV can cause asthma.16Krishnamoorthy N. Khare A. Oriss T.B. Raundhal M. Morse C. Yarlagadda M. et al.Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma.Nat Med. 2012; 18: 1525-1530Crossref PubMed Scopus (201) Google Scholar Treatment trials in preterm infants with palivizumab, an anti-RSV mAb, have demonstrated significant reductions in the development of recurrent wheezing.17Blanken M.O. Rovers M.M. Molenaar J.M. Winkler-Seinstra P.L. Meijer A. Kimpen J.L. et al.Respiratory syncytial virus and recurrent wheeze in healthy preterm infants.N Engl J Med. 2013; 368: 1791-1799Crossref PubMed Scopus (522) Google Scholar With the advent of molecular virology technology during the past few decades, human rhinovirus has been increasingly recognized as a major etiologic factor in preschool wheezing illnesses and a highly significant link with the risk of childhood asthma. Indeed, rhinovirus-induced wheezing illnesses are associated with an approximately 10-fold increase in asthma risk by 6 years of age,7Jackson D.J. Gangnon R.E. Evans M.D. Roberg K.A. Anderson E.L. Pappas T.E. et al.Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.Am J Respir Crit Care Med. 2008; 178: 667-672Crossref PubMed Scopus (1059) Google Scholar and potential mechanisms underlying these developments have been described.18Jackson D.J. The role of rhinovirus infections in the development of early childhood asthma.Curr Opin Allergy Clin Immunol. 2010; 10: 133-138Crossref PubMed Scopus (50) Google Scholar Certain rhinovirus species (eg, A and C > B) might be more virulent, thereby causing more lower respiratory tract illnesses19Annamalay A.A. Khoo S.K. Jacoby P. Bizzintino J. Zhang G. 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Colonization with common respiratory pathogens, such as Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae, in early life signals an increased risk for recurrent wheeze and early childhood asthma, and these same pathogens are associated with acute wheezing illnesses in young children. New tools to assess the airway microbiome are shedding additional light on relationships between beneficial versus pathogenic microbes and the risk for acute wheezing and asthma. This article will expand on the contributions of allergic sensitization and viral and bacterial respiratory tract wheezing illnesses on increased risk for both recurrent preschool wheezing and childhood asthma. When possible, we will emphasize data generated in long-term longitudinal studies that have facilitated etiologic and epidemiologic characterizations. Our understanding of the role of viral infections in wheezing has expanded with the development and evolution of molecular viral diagnostics. Results from studies using PCR and sequenced-based tests indicate that there is a long list of viruses that can cause upper and lower respiratory tract illnesses (Table I),8Lemanske Jr., R.F. Jackson D.J. Gangnon R.E. Evans M.D. Li Z. Shult P.A. et al.Rhinovirus illnesses during infancy predict subsequent childhood wheezing.J Allergy Clin Immunol. 2005; 116: 571-577Abstract Full Text Full Text PDF PubMed Scopus (611) Google Scholar, 25Heymann P.W. Carper H.T. Murphy D.D. Platts-Mills T.A. Patrie J. McLaughlin A.P. et al.Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing.J Allergy Clin Immunol. 2004; 114: 239-247Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 26Kusel M.M. de Klerk N.H. Holt P.G. Kebadze T. Johnston S.L. Sly P.D. Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study.Pediatr Infect Dis J. 2006; 25: 680-686Crossref PubMed Scopus (352) Google Scholar, 27Allander T. Jartti T. Gupta S. Niesters H.G. Lehtinen P. Osterback R. et al.Human bocavirus and acute wheezing in children.Clin Infect Dis. 2007; 44: 904-910Crossref PubMed Scopus (505) Google Scholar, 28Jartti T. Lehtinen P. Vuorinen T. Osterback R. van den H.B. Osterhaus A.D. et al.Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children.Emerg Infect Dis. 2004; 10: 1095-1101Crossref PubMed Scopus (286) Google Scholar, 29Rockett R.J. Bialasiewicz S. Mhango L. Gaydon J. Holding R. Whiley D.M. et al.Acquisition of human polyomaviruses in the first 18 months of life.Emerg Infect Dis. 2015; 21: 365-367Crossref PubMed Scopus (23) Google Scholar and the clinical manifestations of infections with these different viruses are quite similar. Infections can lead to no symptoms at all, cold symptoms, or lower respiratory syndromes, such as pneumonitis, bronchiolitis, and acute wheezing illnesses. The risk of asthma seems to be most closely associated with the occurrence and frequency of virus-induced wheezing illnesses.7Jackson D.J. Gangnon R.E. Evans M.D. Roberg K.A. Anderson E.L. Pappas T.E. et al.Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.Am J Respir Crit Care Med. 2008; 178: 667-672Crossref PubMed Scopus (1059) Google Scholar Other clinical manifestations of acute viral illnesses that are associated with increased risk of asthma include fever and pneumonitis.4Kusel M.M. de Klerk N.H. Kebadze T. Vohma V. Holt P.G. Johnston S.L. et al.Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma.J Allergy Clin Immunol. 2007; 119: 1105-1110Abstract Full Text Full Text PDF PubMed Scopus (618) Google ScholarTable IViruses that can cause wheezing illnessesVirusMajor antigenic groupsRhinovirusA, B, CRSVA, BCoronavirusesNL63, HKU1, OC43, 229EMetapneumovirusA, BParainfluenza virusesI, II, III, IVEnterovirusD68, othersInfluenza virusesA, B, CBocavirusAdenovirusSerotypes 1, 2, 3, 5, 6, 7PolyomavirusWU, KI, Malawi Open table in a new tab Nearly all wheezing illnesses in the first few years occur during viral respiratory tract infections, and the viruses most frequently associated with wheezing illnesses are RSV and rhinoviruses.28Jartti T. Lehtinen P. Vuorinen T. Osterback R. van den H.B. Osterhaus A.D. et al.Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children.Emerg Infect Dis. 2004; 10: 1095-1101Crossref PubMed Scopus (286) Google Scholar Other viruses that are commonly detected during wheezing illnesses include metapneumovirus, coronaviruses, parainfluenza viruses, and bocaviruses. Coinfections with more than 1 virus are most commonly confirmed in infants and can be associated with more severe symptoms.8Lemanske Jr., R.F. Jackson D.J. Gangnon R.E. Evans M.D. Li Z. Shult P.A. et al.Rhinovirus illnesses during infancy predict subsequent childhood wheezing.J Allergy Clin Immunol. 2005; 116: 571-577Abstract Full Text Full Text PDF PubMed Scopus (611) Google Scholar, 30Papadopoulos N.G. Moustaki M. Tsolia M. Bossios A. Astra E. Prezerakou A. et al.Association of rhinovirus infection with increased disease severity in acute bronchiolitis.Am J Respir Crit Care Med. 2002; 165: 1285-1289Crossref PubMed Scopus (280) Google Scholar Prolonged illnesses can be caused by sequential infections with more than 1 virus, infections with a virus followed by a bacterial pathogen, or, less commonly, prolonged infection with a single virus.31Jartti T. Lee W.M. Pappas T. Evans M. Lemanske Jr., R.F. Gern J.E. Serial viral infections in infants with recurrent respiratory illnesses.Eur Respir J. 2008; 32: 314-320Crossref PubMed Scopus (156) Google Scholar Adenoviruses are more likely than other respiratory viruses to cause prolonged viral shedding.32Kalu S.U. Loeffelholz M. Beck E. Patel J.A. Revai K. Fan J. et al.Persistence of adenovirus nucleic acids in nasopharyngeal secretions: a diagnostic conundrum.Pediatr Infect Dis J. 2010; 29: 746-750Crossref PubMed Scopus (66) Google Scholar RSV is an enveloped, nonsegmented, negative-strand RNA virus of the family Paramyxoviridae, and RSV infections are ubiquitous in infancy.33Ruuskanen O. Ogra P.L. Respiratory syncytial virus.Curr Probl Pediatr. 1993; 23: 50-79Abstract Full Text PDF PubMed Scopus (151) Google Scholar RSV has 2 main antigenic groups (A and B). In general, RSV-B infections tend to cause less severe illnesses, but virulence varies considerably with individual strains of RSV, even within the antigenic groups. Most RSV infections cause mild or asymptomatic illnesses; it is estimated that only 9% of infections lead to outpatient clinic visits, and 5% or less of infections lead to hospitalization.34Carroll K.N. Wu P. Gebretsadik T. Griffin M.R. Dupont W.D. Mitchel E.F. et al.The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma.J Allergy Clin Immunol. 2009; 123: 1055-1061Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar Even so, RSV infections are the most common cause of bronchiolitis in the first year of life. Risk factors for RSV-induced bronchiolitis include prematurity; comorbid conditions affecting the heart, lungs, or immune system; and age and season of birth.35Geevarghese B. Simoes E.A. Antibodies for prevention and treatment of respiratory syncytial virus infections in children.Antivir Ther. 2012; 17: 201-211Crossref PubMed Scopus (27) Google Scholar The peak age for susceptibility to RSV lower respiratory tract infection is at 2 to 3 months of age after neutralizing antibody acquired transplacentally from the mother has waned. RSV replicates in epithelial cells lining the upper airways and bronchioles and in type I pneumocytes. RSV infections that extend into the lower airways can cause airway narrowing and closure by causing epithelial cell necrosis and inducing cellular inflammation and mucus hypersecretion.36Habibi M.S. Openshaw P.J. Benefit and harm from immunity to respiratory syncytial virus: implications for treatment.Curr Opin Infect Dis. 2012; 25: 687-694Crossref PubMed Scopus (19) Google Scholar There are several lines of evidence to suggest that more severe RSV infections in early life can contribute to the risk for childhood asthma. First, approximately one third of children with RSV-induced bronchiolitis have recurrent wheezing episodes. In turn, children with recurrent wheezing are at increased risk for subsequent asthma, especially if they have atopic parents or other atopic features.37Castro-Rodriguez J.A. Holberg C.J. Wright A.L. Martinez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing.Am J Respir Crit Care Med. 2000; 162: 1403-1406Crossref PubMed Scopus (993) Google Scholar Furthermore, in a large Tennessee Medicaid database children who were born approximately 120 days before the peak RSV season were at increased risk for bronchiolitis and had a corresponding increase in the risk for asthma by age 3.5 to 5.5 years.15Wu P. Dupont W.D. Griffin M.R. Carroll K.N. Mitchel E.F. Gebretsadik T. et al.Evidence of a causal role of winter virus infection during infancy in early childhood asthma.Am J Respir Crit Care Med. 2008; 178: 1123-1129Crossref PubMed Scopus (278) Google Scholar Similarly, analysis of RSV-induced bronchiolitis in birth cohort studies indicates a positive association with the risk for asthma but not allergic sensitization.38Stein R.T. Sherrill D. Morgan W.J. Holberg C.J. Halonen M. Taussig L.M. et al.Respiratory syncytial virus in early life and risk of wheeze and all
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