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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Table 1.
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 |
Table 2.
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) |
Table 3.
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 |
Table 4.
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 |
Table 5.
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 |
Table 6.
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) |
Table 7.
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 |