Skip to main content

Advertisement

SpringerLink
Log in

Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Most wheezing episodes in infants are caused and exacerbated by virus-induced lower respiratory tract infections. However, there are few reports of epidemiologic and clinical virus-specific research with a focus on virus-induced wheezing. The purpose of the current study was to characterize the clinical presentation of virus-induced wheezing in pediatric patients <3 years of age who were hospitalized with lower respiratory tract infections. Of the 412 patients in the study, 216 were followed for 3 years. Nasopharyngeal aspirates collected from the patients at the time of admission were examined for the presence of respiratory syncytial virus (RSV), rhinovirus (RV), parainfluenza-3 virus (PIV-3), human metapneumovirus (hMPV), and influenza virus (Flu) using reverse-transcription polymerase chain reaction and rapid diagnostic tests. Clinical signs were assessed using a severity scoring system. In patients with wheezing at the time of admission, RSV, RV, RSV+RV, Flu, PIV-3, and hMPV were detected in 33, 14, 8, 8, 5, and 3 % of samples, respectively. There were no differences in age and severity scores between patients harboring more prevalent viruses (RSV and RV) and those with less common infections. Patients with wheezing and RV-positive aspirates at the time of admission were more likely to develop subsequent wheezing during the following 3 years. Conclusion: RSV and RV infections are factors in the development and exacerbation of wheezing after virus-induced lower respiratory tract infections. Moreover, RV-induced wheezing may be associated with subsequent recurrent wheezing and the development of asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bacharier LB, Cohen R, Schweiger T, Yin-Declue H, Christie C, Zheng J, Schechtman KB, Strunk RC, Castro M (2012) Determinants of asthma after severe respiratory syncytial virus bronchiolitis. J Allergy Clin Immunol 130:91–100

    Article  PubMed Central  PubMed  Google Scholar 

  2. Bendelja K, Gagro A, Bace A, Lokar-Kolbas R, Krsulovic-Hresic V, Drazenovic V, Mlinaric-Galinovic G, Rabatic S (2000) Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry. Clin Exp Immunol 121:332–338

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Bont L, Aalderen WM, Kimpen JL (2000) Long-term consequences of respiratory syncytial virus (RSV) bronchiolitis. Paediatr Respir Rev 1:221–227

    Article  CAS  PubMed  Google Scholar 

  4. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, Geelen SM, Kimpen JL (2000) 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 161:1518–1523

    Article  CAS  PubMed  Google Scholar 

  5. Bosis S, Esposito S, Niesters HG, Zuccotti GV, Marseglia G, Lanari M, Zuin G, Pelucchi C, Osterhaus AD, Principi N (2008) Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences. Clin Microbiol Infect 14:677–684

    Article  CAS  PubMed  Google Scholar 

  6. Calışkan M, Bochkov YA, Kreiner-Møller E, Bønnelykke K, Stein MM, Du G, Bisgaard H, Jackson DJ, Gern JE, Lemanske RF Jr, Nicolae DL, Ober C (2013) Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med 368:1398–1407

    Article  PubMed Central  PubMed  Google Scholar 

  7. Calvo C, García-García ML, Pozo F, Carvajal O, Pérez-Breña P, Casas I (2008) Clinical characteristics of human bocavirus infections compared with other respiratory viruses in Spanish children. Pediatr Infect Dis J 27:677–680

    Article  PubMed  Google Scholar 

  8. Chung JY, Han TH, Kim SW, Kim CK, Hwang ES (2007) Detection of viruses identified recently in children with acute wheezing. J Med Virol 79:1238–1243

    Article  CAS  PubMed  Google Scholar 

  9. Chung HL, Kim SG (2002) RANTES may be predictive of later recurrent wheezing after respiratory syncytial virus bronchiolitis in infants. Ann Allergy Asthma Immunol 88:463–467

    Article  CAS  PubMed  Google Scholar 

  10. Drosten C, Günther S, Preiser W, van der Werf S, Brodt HR, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RA, Berger A, Burguière AM, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Müller S, Rickerts V, Stürmer M, Vieth S, Klenk HD, Osterhaus AD, Schmitz H, Doerr HW (2003) Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348:1967–1976

    Article  CAS  PubMed  Google Scholar 

  11. Ebihara T, Endo R, Kikuta H, Ishiguro N, Ishiko H, Hara M, Takahashi Y, Kobayashi K (2004) Human metapneumovirus infection in Japanese children. J Clin Microbiol 42:126–132

    Article  PubMed Central  PubMed  Google Scholar 

  12. Ermers MJ, Janssen R, Onland-Moret NC, Hodemaekers HM, Rovers MM, Houben ML, Kimpen JL, Bont LJ (2011) IL10 family member genes IL19 and IL20 are associated with recurrent wheeze after respiratory syncytial virus bronchiolitis. Pediatr Res 70:518–523

    Article  CAS  PubMed  Google Scholar 

  13. Fujitsuka A, Tsukagoshi H, Arakawa M, Goto-Sugai K, Ryo A, Okayama Y, Mizuta K, Nishina A, Yoshizumi M, Kaburagi Y, Noda M, Tashiro M, Okabe N, Mori M, Yokota S, Kimura H (2011) A molecular epidemiological study of respiratory viruses detected in Japanese children with acute wheezing illness. BMC Infect Dis 11:168

    Article  PubMed Central  PubMed  Google Scholar 

  14. García-García ML, Calvo C, Casas I, Bracamonte T, Rellán A, Gozalo F, Tenorio T, Pérez-Breña P (2007) Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5. Pediatr Pulmonol 42:458–464

    Article  PubMed  Google Scholar 

  15. García-García ML, Calvo C, Falcón A, Pozo F, Pérez-Breña P, De Cea JM, Casas I (2010) Role of emerging respiratory viruses in children with severe acute wheezing. Pediatr Pulmonol 45:585–591

    PubMed  Google Scholar 

  16. Gern JE (2010) The ABCs of rhinoviruses, wheezing, and asthma. J Virol 84:7418–7426

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Gern JE, Martin MS, Anklam KA, Shen K, Roberg KA, Carlson-Dakes KT, Adler K, Gilbertson-White S, Hamilton R, Shult PA, Kirk CJ, Da Silva DF, Sund SA, Kosorok MR, Lemanske RF Jr (2002) Relationships among specific viral pathogens, virus-induced interleukin-8, and respiratory symptoms in infancy. Pediatr Allergy Immunol 13:386–393

    Article  PubMed  Google Scholar 

  18. Houben ML, Coenjaerts FE, Rossen JW, Belderbos ME, Hofland RW, Kimpen JL, Bont L (2010) Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community. J Med Virol 82:1266–1271

    Article  CAS  PubMed  Google Scholar 

  19. Hu A, Colella M, Tam JS, Rappaport R, Cheng SM (2003) Simultaneous detection, subgrouping, and quantitation of respiratory syncytial virus A and B by real-time PCR. J Clin Microbiol 41:149–154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee WM, Shult PA, Reisdorf E, Carlson-Dakes KT, Salazar LP, DaSilva DF, Tisler CJ, Gern JE, Lemanske RF Jr (2008) Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 178:667–672

    Article  PubMed Central  PubMed  Google Scholar 

  21. Jartti T, Gern JE (2011) Rhinovirus-associated wheeze during infancy and asthma development. Curr Respir Med Rev 7:160–166

    Article  PubMed Central  PubMed  Google Scholar 

  22. Jartti T, Lehtinen P, Vanto T, Hartiala J, Vuorinen T, Mäkelä MJ, Ruuskanen O (2006) Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus. Pediatr Infect Dis J 25:482–488

    Article  PubMed  Google Scholar 

  23. Jartti T, Lehtinen P, Vuorinen T, Ruuskanen O (2009) Bronchiolitis: age and previous wheezing episodes are linked to viral etiology and atopic characteristics. Pediatr Infect Dis J 28:311–317

    Article  PubMed  Google Scholar 

  24. Kotaniemi-Syrjänen A, Vainionpää R, Reijonen TM, Waris M, Korhonen K, Korppi M (2003) Rhinovirus-induced wheezing in infancy—the first sign of childhood asthma? J Allergy Clin Immunol 111:66–71

    Article  PubMed  Google Scholar 

  25. Korppi M, Kotaniemi-Syrjänen A, Waris M, Vainionpää R, Reijonen TM (2004) Rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J 23:995–999

    Article  PubMed  Google Scholar 

  26. Lehtinen P, Ruohola A, Vanto T, Vuorinen T, Ruuskanen O, Jartti T (2007) Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema. J Allergy Clin Immunol 119:570–575

    Article  CAS  PubMed  Google Scholar 

  27. Lemanske RF Jr (2002) The childhood origins of asthma (COAST) study. Pediatr Allergy Immunol 13:38–43

    Article  PubMed  Google Scholar 

  28. Lemanske RF Jr, Jackson DJ, Gangnon RE, Evans MD, Li Z, Shult PA, Kirk CJ, Reisdorf E, Roberg KA, Anderson EL, Carlson-Dakes KT, Adler KJ, Gilbertson-White S, Pappas TE, Dasilva DF, Tisler CJ, Gern JE (2005) Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol 116:571–577

    Article  PubMed  Google Scholar 

  29. Louie JK, Roy-Burman A, Guardia-Labar L, Boston EJ, Kiang D, Padilla T, Yagi S, Messenger S, Petru AM, Glaser CA, Schnurr DP (2009) Rhinovirus associated with severe lower respiratory tract infections in children. Pediatr Infect Dis J 28:337–339

    Article  PubMed  Google Scholar 

  30. Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL (2008) 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 105:13562–13567

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Midulla F, Pierangeli A, Cangiano G, Bonci E, Salvadei S, Scagnolari C, Moretti C, Antonelli G, Ferro V, Papoff P (2012) Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up. Eur Respir J 39:396–402

    Article  CAS  PubMed  Google Scholar 

  32. Pala P, Bjarnason R, Sigurbergsson F, Metcalfe C, Sigurs N, Openshaw PJ (2002) Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy. Eur Respir J 20:376–382

    Article  CAS  PubMed  Google Scholar 

  33. Price JF (1990) Acute and long-term effects of viral bronchiolitis in infancy. Lung 168:414–421

    Article  PubMed  Google Scholar 

  34. Scheltinga SA, Templeton KE, Beersma MF, Claas EC (2005) Diagnosis of human metapneumovirus and rhinovirus in patients with respiratory tract infections by an internally controlled multiplex real-time RNA PCR. J Clin Virol 33:306–311

    Article  CAS  PubMed  Google Scholar 

  35. Schuurhof A, Janssen R, de Groot H, Hodemaekers HM, de Klerk A, Kimpen JL, Bont L (2011) Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze. Respir Res 12:121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Singh AM, Moore PE, Gern JE, Lemanske RF Jr, Hartert TV (2007) Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am J Respir Crit Care Med 175:108–119

    Article  CAS  PubMed  Google Scholar 

  37. Takeyama A, Hashimoto K, Sato M, Sato T, Kanno S, Takano K, Ito M, Katayose M, Nishimura H, Kawasaki Y, Hosoya M (2012) Rhinovirus load and disease severity in children with lower respiratory tract infections. J Med Virol 84:1135–1142

    Article  PubMed  Google Scholar 

  38. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T (2009) Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Allergy 64:1359–1365

    Article  CAS  PubMed  Google Scholar 

  39. Van Piggelen RO, van Loon AM, Krediet TG, Verboon-Maciolek MA (2010) Human rhinovirus causes severe infection in preterm infants. Pediatr Infect Dis J 29:364–365

    PubMed  Google Scholar 

  40. Watts KD, Goodman DM (2007) Wheezing in infants: bronchiolitis. In: Kliegman RM, Behrman RE (eds) Nelson textbook of pediatrics, 18th edn. Saunders, Philadelphia, pp 1773–1777

    Google Scholar 

  41. Watzinger F, Suda M, Preuner S, Baumgartinger R, Ebner K, Baskova L, Niesters HG, Lawitschka A, Lion T (2004) Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients. J Clin Microbiol 42:5189–5198

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Welliver RC, Sun M, Rinaldo D, Ogra PL (1986) Predictive value of respiratory syncytial virus-specific IgE responses for recurrent wheezing following bronchiolitis. J Pediatr 109:776–780

    Article  CAS  PubMed  Google Scholar 

  43. Welliver RC, Duffy L (1993) The relationship of RSV-specific immunoglobulin E antibody responses in infancy, recurrent wheezing, and pulmonary function at age 7-8 years. Pediatr Pulmonol 15:19–27

    Article  CAS  PubMed  Google Scholar 

  44. Wright PF, Deatly AM, Karron RA, Belshe RB, Shi JR, Gruber WC, Zhu Y, Randolph VB (2007) Comparison of results of detection of rhinovirus by PCR and viral culture in human nasal wash specimens from subjects with and without clinical symptoms of respiratory illness. Clin Microbiol 45:2126–2129

    Article  Google Scholar 

  45. Wu P, Hartert TV (2011) Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Rev Anti Infect Ther 9:731–745

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Honzumi K and Tanji M for their technical support. We also thank the staff of the pediatric unit of the Soma General Hospital for their assistance with sample collection.

Conflicts of interest and source of funding

This work was supported in part by the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Soma General Hospital, 142 Tubogasaku-Niinuma, Soma City, Fukushima, 976-0011, Japan

    Aya Takeyama, Yoichi Tomita, Ryo Maeda, Masaki Ito & Masahiko Katayose

  2. Department of Pediatrics, School of Medicine, Fukushima Medical University, Fukushima, Japan

    Aya Takeyama, Koichi Hashimoto, Masatoki Sato, Toshiko Sato, Yukihiko Kawasaki & Mitsuaki Hosoya

Authors
  1. Aya Takeyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koichi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masatoki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshiko Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoichi Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryo Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masaki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masahiko Katayose
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yukihiko Kawasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mitsuaki Hosoya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aya Takeyama.

Additional information

Communicated by Willem Proesmans

Rights and permissions

Reprints and permissions

About this article

Cite this article

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 173, 959–966 (2014). https://doi.org/10.1007/s00431-014-2277-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-014-2277-7

Keywords

Search

Navigation