Journal List > Pediatr Allergy Respir Dis > v.21(4) > 1033141

Kim, Kim, and Kang: Association of Respiratory Viral Infection and Atopy with Severity of Acute Bronchiolitis in Infants

Abstract

Purpose

We investigated the influence of respiratory virus and atopic characteristics on the severity of bronchiolitis.

Methods

Four hundred and eighteen infants <2-years-old and hospitalized at Daegu Fatima Hospital with bronchiolitis from March 2007 to February 2010 were evaluated. They were detected for specific respiratory viruses in nasopharyngeal aspirates by multiplex reverse transcription-polymerase chain reaction. Clinical severity score, based on respiratory rate, wheezing, chest retraction, and oxygen saturation was assessed at admission. According to the scores, all patients were divided into a mild to moderate bronchiolitis group and a severe group. Clinical data related to host factors, including atopic characteristics and respiratory viruses, were compared among individual groups. Multivariate logistic regression analyses were performed to identify independent risk factors for severe bronchiolitis.

Results

A single virus was identified in 365 infants (87%) and multiple viruses in 53 (13%). Respiratory syncytial virus (RSV) was the most common virus detected (51%). RSV and rhinovirus were the viruses most frequently identified in mixed infections in infants hospitalized with bronchiolitis. Infants with coinfections were 3.28 times (95% confidence interval, 1.36 to 7.89) more at risk for severe bronchiolitis than those with a single infection. Host factors associated with more severe bronchiolitis included male gender, younger age, prematurity, and chronic cardiorespiratory illness. Type of viruses, personal and family history of atopy, and passive smoking were not significantly associated with bronchiolitis severity.

Conclusion

Viral coinfections and host factors, including male gender, younger age, prematurity, and chronic cardiorespiratory illness are relevant risk factors for infants with severe bronchiolitis.

References

1. Papadopoulos NG, 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; 165:1285–9.
crossref
2. Wainwright C. Acute viral bronchiolitis in children-a very common condition with few therapeutic options. Paediatr Respir Rev. 2010; 11:39–45.
3. Marguet C, Lubrano M, Gueudin M, Le Roux P, Deschildre A, Forget C, et al. In very young infants severity of acute bronchiolitis depends on carried viruses. PLoS One. 2009; 4:e4596.
crossref
4. Richard N, Komurian-Pradel F, Javouhey E, Perret M, Rajoharison A, Bagnaud A, et al. The impact of dual viral infection in infants admitted to a pediatric intensive care unit associated with severe bronchiolitis. Pediatr Infect Dis J. 2008; 27:213–7.
crossref
5. Deng Yu, Chen Jiehua, Bai Hua, Wang Lijia, Liu Wei, Yang Xiqiang, et al. The severity of bronchiolitis is not dependent on the coinfection of RSV with other respiratory viruses. J Pediatr Infect Dis. 2010; 5:255–61.
crossref
6. Bueno FU, Piva JP, Garcia PC, Lago PM, Einloft PR. Outcome and characteristics of infants with acute viral bronchiolitis submitted to mechanical ventilation in a Brazilian pediatric intensive care. Rev Bras Ter Intensiva. 2009; 21:174–82.
7. Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis. 2003; 9:372–5.
crossref
8. Aberle JH, Aberle SW, Pracher E, Hutter HP, Kundi M, Popow-Kraupp T. Single versus dual respiratory virus infections in hospitalized infants: impact on clinical course of disease and interferon-gamma response. Pediatr Infect Dis J. 2005; 24:605–10.
9. Drews AL, Atmar RL, Glezen WP, Baxter BD, Piedra PA, Greenberg SB. Dual respiratory virus infections. Clin Infect Dis. 1997; 25:1421–9.
crossref
10. Semple MG, Cowell A, Dove W, Greensill J, McNamara PS, Halfhide C, et al. Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis. 2005; 191:382–6.
crossref
11. Portnoy B, Eckert HL, Hanes B, Salvatore MA. Multiple respiratory virus infections in hospitalized children. Am J Epidemiol. 1965; 82:262–72.
12. Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O. Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol. 2004; 72:695–9.
crossref
13. AlShehri MA, Sadeq A, Quli K. Bronchiolitis in Abha, Southwest Saudi Arabia: viral etiology and predictors for hospital admission. West Afr J Med. 2005; 24:299–304.
crossref
14. Damore D, Mansbach JM, Clark S, Ramundo M, Camargo CA Jr. Prospective multicenter bronchiolitis study: predicting intensive care unit admissions. Acad Emerg Med. 2008; 15:887–94.
crossref
15. Stensballe LG, Kristensen K, Simoes EA, Jensen H, Nielsen J, Benn CS, et al. Atopic disposition, wheezing, and subsequent respiratory syncytial virus hospitalization in Danish children younger than 18 months: a nested case-control study. Pediatrics. 2006; 118:e1360–8.
crossref
16. Miller EK, Williams JV, Gebretsadik T, Carroll KN, Dupont WD, Mohamed YA, et al. Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness. J Allergy Clin Immunol. 2011; 127:883–91.
crossref
17. Simoes EA, Carbonell-Estrany X. Impact of severe disease caused by respiratory syncytial virus in children living in developed countries. Pediatr Infect Dis J. 2003; 22(2 Suppl):S13–8.
crossref
18. Bradley JP, Bacharier LB, Bonfiglio J, Schechtman KB, Strunk R, Storch G, et al. Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Pediatrics. 2005; 115:e7–14.
crossref
19. Carroll KN, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, Wu P, et al. Maternal asthma and maternal smoking are associated with increased risk of bronchiolitis during infancy. Pediatrics. 2007; 119:1104–12.
crossref
20. Miron D, Srugo I, Kra-Oz Z, Keness Y, Wolf D, Amirav I, et al. Sole pathogen in acute bronchiolitis: is there a role for other organisms apart from respiratory syncytial virus? Pediatr Infect Dis J. 2010; 29:e7–e10.
21. Broughton S, Bhat R, Roberts A, Zuckerman M, Rafferty G, Greenough A. Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. Arch Dis Child. 2006; 91:26–30.
crossref
22. Saleh Zaid Al-Muhsen. Clinical profile of Respiratory Syncytial Virus (RSV) bronchiolitis in the intensive care unit at a TertiaryCareHos-pital. Curr Pediatr Res. 2010; 14:75–80.
23. El Saleeby CM, Li R, Somes GW, Dahmer MK, Quasney MW, DeVincenzo JP. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population. J Pediatr. 2010; 156:409–14.
crossref
24. Grimwood K, Cohet C, Rich FJ, Cheng S, Wood C, Redshaw N, et al. Risk factors for respiratory syncytial virus bronchiolitis hospital admission in New Zealand. Epidemiol Infect. 2008; 136:1333–41.
crossref
25. Castro M, Schweiger T, Yin-Declue H, Ram-kumar TP, Christie C, Zheng J, et al. Cytokine response after severe respiratory syncytial virus bronchiolitis in early life. J Allergy Clin Immunol. 2008; 122:726–33.e3.
crossref
26. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980; 92:44–7.
27. Castro-Rodrí guez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000; 162(4 Pt 1):1403–6.
crossref
28. Lee HB, Park KC, Yang S, Kim YJ, Oh JW, Moon SJ, et al. A study of serum total and house dust mite-specific IgE, and ECP levels in healthy Korean children under 7 years of age. Pediatr Allergy Respir Dis(Korea). 1999; 9:157–66.
29. Heymann PW, Carper HT, Murphy DD, Platts-Mills TA, Patrie J, McLaughlin AP, et al. Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol. 2004; 114:239–47.
crossref
30. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med. 2001; 344:1917–28.
crossref
31. Cheong HY, Lee JH, Kim YB, Nam HS, Choi YJ, Kim CJ, et al. Viral etiologic agents in acute viral lower respiratory tract detected by multiplex RT-PCR. Pediatr Allergy Respir Dis (Korea). 2007; 17:344–53.
32. Stempel HE, Martin ET, Kuypers J, Englund JA, Zerr DM. Multiple viral respiratory pathogens in children with bronchiolitis. Acta Paediatr. 2009; 98:123–6.
crossref
33. García CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010; 126:e1453–60.
crossref
34. Louie JK, Roy-Burman A, Guardia-Labar L, Boston EJ, Kiang D, Padilla T, et al. Rhinovirus associated with severe lower respiratory tract infections in children. Pediatr Infect Dis J 2009. 28:337–9.
crossref
35. Nascimento MS, Souza AV, Ferreira AV, Rodrigues JC, Abramovici S, Silva Filho LV. High rate of viral identification and coinfections in infants with acute bronchiolitis. Clinics (Sao Paulo). 2010; 65:1133–7.
crossref
36. Friedrich L, Stein RT, Pitrez PM, Corso AL, Jones MH. Reduced lung function in healthy preterm infants in the first months of life. Am J Respir Crit Care Med. 2006; 173:442–7.
crossref
37. Hoo AF, Dezateux C, Henschen M, Costeloe K, Stocks J. Development of airway function in infancy after preterm delivery. J Pediatr. 2002; 141:652–8.
crossref
38. Weisman LE. Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions. Pediatr Infect Dis J. 2003; 22(2 Suppl):S33–7.
crossref
39. Semple MG, Dankert HM, Ebrahimi B, Correia JB, Booth JA, Stewart JP, et al. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P. PLoS One. 2007; 2:e1038.
crossref
40. Lanari M, Giovannini M, Giuffre L, Marini A, Rondini G, Rossi GA, et al. Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. Pediatr Pulmonol. 2002; 33:458–65.
crossref
41. La Via WV, Grant SW, Stutman HR, Marks MI. Clinical profile of pediatric patients hospitalized with respiratory syncytial virus infection. Clin Pediatr (Phila). 1993; 32:450–4.
crossref
42. Tal A, Bavilski C, Yohai D, Bearman JE, Goro-discher R, Moses SW. Dexamethasone and salbutamol in the treatment of acute wheezing in infants. Pediatrics. 1983; 71:13–8.
crossref

Table 1.
Clinical Severity Score (Modified from Tal A, Bavilski C, Yohai D, Bearman JE, Gorodischer R, Moses SW. Pediatrics 1983;71:13–8, with permission of American Academy of Pediatrics) [42].
Parameters 0 1 2 3
Respiratory rate (breaths/min) <30 31–45 46–60 >60
Wheezing None Terminal expiratory or heard only with stethoscope Entire expiration or on expiration without stethoscope Inspiration and expiration without stethoscope
Chest retraction None Intercostal only Tracheosternal Severe with nasal flaring
TcSaO2 (%) 99 ≥ 96–98 93–95 <93

If no wheezing is audible due to minimal air entry, score 3.

Tc, transcutaneous.

Table 2.
Demographic Features of Studied Subjects
  Mild to moderate (n=378) Severe (n=40) Total (n=418) P -Value
Age, mo       0.000
  3 35 (9.3) 12 (30.0) 47 (11.2)  
  3–6 109 (28.9) 19 (47.5) 128 (30.6)  
  7–12 99 (26.2) 5 (12.5) 104 (24.9)  
  13–24 135 (35.7) 4 (10.0) 139 (33.3)  
Sex       0.018
  Male 241 (63.8) 33 (82.5) 274 (65.6)  
  Female 137 (36.2) 7 (17.5) 144 (34.4)  
Season       0.184
  Spring 55 (14.6) 9 (22,5) 64 (15.3)  
  Summer 54 (14.3) 3 (7.5) 57 (13.6)  
  Autumn 115 (30.4) 13 (32.5) 128 (30.6)  
  Winter 154 (40.7) 15 (37.5) 169 (40.4)  

Values are presented as no. of cases (%).

P -value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 3.
Birth History and Preexisting Disease of Studied Subjects
Variable Mild to moderate (n=378) Severe (n=40) Total (n=418) P -Value
Gestational age, wk
  32 ˂ 9 (2.4) 7 (17.5) 16 (3.8) 0.000
  32–36 28 (7.4) 8 (20.0) 36 (8.6)  
  37 ≥ 341 (90.2) 25 (62.5) 366 (87.6)  
Birth weight, gm
  2,500 ˂ 24 (6.3) 12 (30.0) 36 (8.6) 0.000
  2,500 ≥ 354 (93.7) 28 (70.0) 382 (91.4)  
Delivery method
  C-sec 145 (38.4) 20 (50.0) 165 (39.5) 0.152
  NVD 233 (61.6) 20 (50.0) 253 (60.5)  
CLD 8 (2.1) 9 (22.5) 17 (4.1) 0.000
CHD 8 (2.1) 3 (7.5) 11 (2.6) 0.043
ND 2 (0.5) 0 (0.0) 2 (0.5) 0.645

Values are presented as no. of cases (%).

C-sec, cesarean section; NVD, normal vaginal devlivery; CLD, chronic lung disease; CHD, congenital heart disease; ND, neurologic disease.

P -value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 4.
Atopic Family History and Past History of Studied Subjects
  Mild to moderate (n=378) Severe (n=40) Total (n=418) P -Value
Family Hx. of atopy 183 (48.4) 14 (35.0) 197 (47.1) 0.594
Personal Hx. of AD 142 (37.6) 10 (25.0) 152 (36.4) 0.116
Previous wheezing episodes
  1st 234 (61.9) 29 (72.5) 263 (62.9) 0.187
  2nd 83 (22.0) 7 (17.5) 90 (21.5) 0.514
  3rd ≥ 61 (16.1) 4 (10.0) 65 (15.6) 0.308
Passive smokers 177 (46.8) 25 (62.5) 202 (48.3) 0.059

Values are presented as no. of cases (%).

Hx, history; AD, atopic dermatitis.

P -value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 5.
Viral Prevalence in Studied Subjects
Variable Mild to moderate (n=378) Severe (n=40) Total (n=418) P -value
RSV A, B 190 (50.2) 21 (52.5) 211 (50.5) 0.883
PIV 1,2,3 40 (10.6) 2 (5.0) 42 (10.0) 0.460
RV 33 (8.7) 2 (5.0) 35 (8.4) 0.338
MPV 23 (6.1) 1 (2.5) 24 (5.7) 0.453
ADV 21 (5.6) 1 (2.5) 22 (5.3) 0.315
IF A, B 16 (4.2) 0 (0.0) 16 (3.8) 0.398
CoV 15 (4.0) 0 (0.0) 15 (3.6) 0.344
Dual Pathogens 40 (10.6) 13 (32.5) 53 (12.7) 0.000

Values are presented as no. of cases (%).

RSV, respiratory syncytial virus; PIV, parainfluenza virus; RV, rhinovirus; MPV, metapneumovirus; ADV, adenovirus; IF, influenza virus; CoV, corona virus.

P-value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 6.
Viral Distribution of Detected Dual Infection Cases
Primary viral agent Associated virus Mild to moderate (n=40) Severe (n=13) Total (n=53) P -Value
RSV A, B RV 10 (25.0) 3 (23.1) 13 (24.5) 0.571
CoV 8 (20.0) 3 (23.1) 11 (20.8)  
ADV 5 (12.5) 3 (23.1) 9 (17.0)  
IF A, B 2 (5.0) 1 (7.7) 3 (5.7)  
PIV 1,2,3 1 (2.5) 0 (0.0) 1 (1.9)  
RV PIV 1,2,3 4 (10.0) 2 (15.4) 6 (11.3)  
ADV 3 (7.5) 0 (0.0) 3 (5.7)  
CoV 0 (0.0) 1 (7.7) 1 (1.9)  
PIV 1,2,3 CoV 4 (10.0) 0 (0.0) 4 (7.5)  
IF A, B 2 (5.0) 0 (0.0) 2 (3.8)  
ADV 3 (7.5) 0 (0.0) 3 (5.7)  

Values are presented as no. of cases (%).

RSV, respiratory syncytial virus; PIV, parainfluenza virus; RV, rhinovirus; ADV, adenovirus; IF, influenza virus; CoV, corona virus.

P-value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 7.
Atopic Laboratory Findings of Studied Subjects
  Mild to moderate (n=378) Severe (n=40) Total (n=418) P -Value
Eosinophilia 4% ≥ 30 (7.9) 4 (10.0) 34 (8.1) 0.650
Serum ECP, g/L (mean SD) μ ± 14.04 18.87 ± 17.86 14.53 ± 14.27 18.63 ± 0.457
Log IgE (M SD) ± 2.35 0.68 ± 1.81 0.61 ± 2.30 0.69 ± 0.000
Serum IgE 47 IU/mL ≥ 94 (24.9) 2 (5.0) 96 (23.0) 0.004
Specific IgE, IU/mL
  Food 76 (20.1) 10 (25.0) 86 (20.6) 0.467
  Inhalants 30 (7.9) 4 (10.0) 34 (8.1) 0.650
  Mixed 10 (2.4) 1 (0.2) 11 (2.6) 0.843

Values are presented as no. of cases (%) or mean SD.

ECP, eosinophilic cationic protein; IgE, immunoglobulin E.

P -value represents the comparisons between mild to moderate and severe bronchiolitis in each parameter.

Table 8.
Univariate and Multivariate Logistic Regression Analysis of Risk Factors of Severe Bronchiolitis
Variable Univariate analysis P -value Multivariate analysis P -value
OR 95% CI aOR 95% CI
Coinfection (n=53) 4.07 1.94–8.51 0.000 3.25 1.37–7.70 0.008
Personal Hx. of AD (n=152) 0.55 0.26–1.17 0.120 1.36 0.58–3.17 0.477
Family Hx. of atopy (n=197) 0.56 0.27–1.16 0.121 1.62 0.70–3.73 0.261
Serum IgE 47 IU/ml ≥ 6.29 1.49–26.57 0.012 4.48 0.93–21.57 0.062
Passive smoker (n=202) 1.89 0.97–3.70 0.062 1.85 0.86–3.97 0.118
Male (n=274) 2.68 1.15–6.22 0.022 2.87 1.13–7.27 0.027
Age<12 wk (n=47) 4.20 1.96–8.99 0.000 3.41 1.41–8.26 0.007
Prematurity<37 wk (n=52) 6.81 3.34–13.89 0.000 3.48 1.38–8.82 0.009
Chronic cardiorespiratory illness (n=28) 12.43 4.38–28.29 0.000 4.78 1.51–15.14 0.008

OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval; Hx, History; AD, atopic dermatitis.

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