Bronchiolitis severity according to the infected viruses

Su Jin Lee; Sang Kyu Park; Ji Hyun Kim; Sung Min Cho

doi:10.4168/aard.2018.6.1.47

Journal List > Allergy Asthma Respir Dis > v.6(1) > 1095715

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Lee, Park, Kim, and Cho: Bronchiolitis severity according to the infected viruses

Original Article

Allergy Asthma Respir Dis 2018;6(1):47-53.

Published online: 5 January 2018

DOI: https://doi.org/10.4168/aard.2018.6.1.47

Bronchiolitis severity according to the infected viruses

Su Jin Lee, Sang Kyu Park, Ji Hyun Kim, Sung Min Cho

Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea

Correspondence to: Ji Hyun Kim https://orcid.org/0000-0001-8493-2881 Department of Pediatrics, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang 10326, Korea Tel: +82-31-961-7190, Fax: +82-31-961-7188, E-mail: eogurdl@gmail.com

Received 10 March 201724 October 2017 Accepted 24 October 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

The aim of this study was to evaluate the severity of disease in children with acute bronchiolitis according to the type of infected virus.

Methods

From November 2007 to May 2015, 768 patients under 2 years of age who underwent real time-polymerase chain reaction of nasopharyngeal aspirates admitted to the Department of Pediatrics of Dongguk University Ilsan Hospital for acute bronchiolitis were enrolled. Severe bronchiolitis was defined as presence of one or more kinds among tachypnea, chest retraction, needs of O2 inhalation or ventilator care.

Results

The severity of bronchiolitis was increased with shorter fever duration (P <0.001) and previous wheezing episodes (P =0.005). In the case of single infection, respiratory syncytial virus (RSV) A only increased the severity of acute bronchiolitis (P =0.012). However, the severity of illness decreased when RSV A coinfected with adenovirus (P =0.034), human rhinovirus (P=0.038), or human coronavirus NL63 (P=0.042). On the other hand, when human rhinovirus was coinfected with enterovirus (P=0.013) or parainfluenza 3 (P=0.019), the severity was increased. When human metapneumovirus coinfected with human bocavirus, the severity was increased (P=0.038).

Conclusion

Acute bronchiolitis was associated with increased severity only when RSV A infected solely, but several viruses increased or decreased the severity when coinfection occurred. Therefore, it may be helpful in predicting the course of the acute bronchiolitis according to the affected virus.

Keywords: Bronchiolitis, Infant, Respiratory syncytial virus, Severity

REFERENCES

1. Roh EJ, Won YK, Lee MH, Chung EH. Clinical characteristics of patients with acute bronchiolitis who visited 146 Emergency Department in Korea in 2012. Allergy Asthma Respir Dis. 2015; 3:334–40.

2. Coastes BM. Wheezing in infants:bronchiolitis. Kliegman RM, Stanton BF, St. Geme JW Ш, Schor NF, Behrman RE, editors. Nelson textbook of pediatrics. 20th ed.Philadelphia (PA): Elsevier;2016. p. 2044–8.

3. Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, et al. Diagnosis and testing in bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2004; 158:119–26.

4. Skjerven HO, Megremis S, Papadopoulos NG, Mowinckel P, Carlsen KH, L⊘drup Carlsen KC, et al. Virus type and genomic load in acute bronchiolitis: severity and treatment response with inhaled adrenaline. J Infect Dis. 2016; 213:915–21.

5. Kang SY, Hong CR, Kang HM, Cho EY, Lee HJ, Choi EH, et al. Clinical and epidemiological characteristics of human metapneumovirus infections, in comparison with respiratory syncytial virus A and B. Pediatr Infect Vaccine. 2013; 20:168–77.

6. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadom-ski AM, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014; 134:e1474–502.

7. Park HJ, Kim JH, Chun YH, Lee SY, Kim SY, Kang JH. Clinical manifestations, management, and natural course of infants with recurrent bron-chiolitis or reactive airways disease. Pediatr Infect Vaccine. 2014; 21:37–42.

8. Colby TV. Bronchiolitis. Pathologic considerations. Am J Clin Pathol. 1998; 109:101–9.

9. Jeong Y, Hwang JH, Kwon JY, Shin J, Kwon JH, Han K, et al. Prediction of the severity and length of hospital stay in infants with acute bronchiolitis using the severity score. Allergy Asthma Respir Dis. 2016; 4:429–35.

10. Walsh EE, McConnochie KM, Long CE, Hall CB. Severity of respiratory syncytial virus infection is related to virus strain. J Infect Dis. 1997; 175:814–20.

11. Mansbach JM, Piedra PA, Teach SJ, Sullivan AF, Forgey T, Clark S, et al. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012; 166:700–6.

12. Rhedin S, Lindstrand A, Rotzén-Östlund M, Tolfvenstam T, Ohrmalm L, Rinder MR, et al. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014; 133:e538–45.

13. Lim JS, Woo SI, Kwon HI, Baek YH, Choi YK, Hahn YS. Clinical characteristics of acute lower respiratory tract infections due to 13 respiratory viruses detected by multiplex PCR in children. Korean J Pediatr. 2010; 53:373–9.

14. Kim KH, Lee JH, Sun DS, Kim YB, Choi YJ, Park JS, et al. Detection and clinical manifestations of twelve respiratory viruses in hospitalized children with acute lower respiratory tract infections: focus on human metapneumovirus, human rhinovirus and human coronavirus. Korean J Pediatr. 2008; 51:834–41.

15. Choi EH, Lee HJ, Kim SJ, Eun BW, Kim NH, Lee JA, et al. The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children, 2000-2005. Clin Infect Dis. 2006; 43:585–92.

16. Huguenin A, Moutte L, Renois F, Leveque N, Talmud D, Abely M, et al. Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT-PCR DNA microarray system. J Med Virol. 2012; 84:979–85.

17. Hasegawa K, Pate BM, Mansbach JM, Macias CG, Fisher ES, Piedra PA, et al. Risk factors for requiring intensive care among children admitted to ward with bronchiolitis. Acad Pediatr. 2015; 15:77–81.

18. Rolfsjord LB, Skjerven HO, Carlsen KH, Mowinckel P, Bains KE, Bakke-heim E, et al. The severity of acute bronchiolitis in infants was associated with quality of life nine months later. Acta Paediatr. 2016; 105:834–41.

19. Mikalsen IB, Halvorsen T, Øymar K. The outcome after severe bronchiolitis is related to gender and virus. Pediatr Allergy Immunol. 2012; 23:391–8.

20. Kim WK. Human rhinoviruses and asthma in children. Korean J Pediatr. 2010; 53:129–35.

21. Rodriguez R, Ramilo O. Respiratory syncytial virus: how, why and what to do. J Infect. 2014; 68(Suppl 1):S115–8.

22. Boivin G, Caouette G, Frenette L, Carbonneau J, Ouakki M, De Serres G. Human respiratory syncytial virus and other viral infections in infants receiving palivizumab. J Clin Virol. 2008; 42:52–7.

23. Martin ET, Kuypers J, Wald A, Englund JA. Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza Other Respir Viruses. 2012; 6:71–7.

24. Park JS. Acute viral lower respiratory tract infections in children. Korean J Pediatr. 2009; 52:269–76.

25. Harada Y, Kinoshita F, Yoshida LM, Minh le N, Suzuki M, Morimoto K, et al. Does respiratory virus coinfection increases the clinical severity of acute respiratory infection among children infected with respiratory syncytial virus? Pediatr Infect Dis J. 2013; 32:441–5.

26. Rodríguez DA, Rodríguez-Martínez CE, Cárdenas AC, Quilaguy IE, Mayorga LY, Falla LM, et al. Predictors of severity and mortality in children hospitalized with respiratory syncytial virus infection in a tropical region. Pediatr Pulmonol. 2014; 49:269–76.

27. Asner SA, Rose W, Petrich A, Richardson S, Tran DJ. Is virus coinfection a predictor of severity in children with viral respiratory infections? Clin Microbiol Infect. 2015; 21:264.e1–6.

28. Brand HK, de Groot R, Galama J, Brouwer ML, Teuwen K, Hermans PW, et al. Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis. Pediatr Pulmonol. 2012; 47:393–400.

29. Calvo C, García-García ML, Pozo F, Paula G, Molinero M, Calderón A, et al. Respiratory syncytial virus coinfections with rhinovirus and human bocavirus in hospitalized children. Medicine (Baltimore). 2015; 94:e1788.

30. Mohapatra SS, Boyapalle S. Epidemiologic, experimental, and clinical links between respiratory syncytial virus infection and asthma. Clin Microbiol Rev. 2008; 21:495–504.

31. Yun HJ. Respiratory syncytial virus infection and asthma. Pediatr Allergy Respir Dis. 1999; 9:24–31.

32. Ojosnegros S, Beerenwinkel N, Antal T, Nowak MA, Escarmís C, Do-mingo E. Competition-colonization dynamics in an RNA virus. Proc Natl Acad Sci U S A. 2010; 107:2108–12.

33. 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.

Fig. 1.

Year-round change of acute bronchiolitis with 16 respiratory viruses isolated for 768 hospitalized children.

Table 1.

Clinical characteristics of hospitalized children with acute bronchiolitis

Characteristic	Number (%)
Sex
Female	287 (37.4)
Male	481 (62.6)
Age (yr)
≤1	583 (75.9)
>1, <2	185 (24.1)
Hospitalization period (day)
<3	96 (12.5)
4	188 (24.5)
5	169 (22)
6	132 (17.2)
7	58 (7.6)
≥8	125 (16.3)
Fever (day)
None	343 (44.7)
1	94 (12.2)
2	86 (11.2)
≥3	245 (31.8)
Ventilator care, yes	62 (8.1)
Siblings, yes	440 (57.3)

Table 2.

Clinical characteristics of hospitalized children with acute bronchiolitis analyzed according to disease severity

Characteristic	Nonsevere (n=269)	Severe (n=499)	P-value
Age (mo)∗	3.39	2.62	0.054
Hospitalization period (day)∗	4.2	6.35	<0.001
Fever (day)∗	2.20	1.60	<0.001
ICU hospitalization (day)∗	0	0.05	0.001
CRP (mg/dL)∗	1.05	1.20	0.261
Lymphocyte (%)∗	55.99	52.94	0.006
Male sex^†	160 (59.5)	321 (64.3)	0.185
Siblings, yes^†	151 (56.1)	289 (57.9)	0.634
Previous wheezing episode^†	25 (9.3)	83 (16.6)	0.005
Allergic disease family history^†	2 (0.7)	8 (1.6)	0.316
Previous admission history^†	53 (19.7)	145 (29.1)	0.005

Values are presented as mean or number (%). CRP: normal range, 0–0.5 mg/dL; lymphocyte: normal range, 20%–50%.

ICU, intensive care unit; CRP, C-reactive protein.

^∗ Student t-test.

^† Chi-square test.

Table 3.

The ratio of single infection to coinfection of respiratory viruses isolated for 768 hospitalized children with acute bronchiolitis

Variable	Total (n)	Single infection, n (%)	Coinfection, n (%)
Adenovirus	139	16 (10.5)	123 (88.5)
Influenza A virus	16	6 (37.5)	10 (62.5)
Influenza B virus	9	3 (33.3)	6 (66.7)
Metapneumovirus	40	13 (32.5)	27 (67.5)
Respiratory syncytial virus A	252	95 (37.7)	157 (62.3)
Respiratory syncytial virus B	140	57 (40.7)	83 (59.3)
Parainfluenza 1	35	10 (28.6)	25 (71.4)
Parainfluenza 2	10	3 (30.4)	7 (70.0)
Parainfluenza 3	33	7 (21.2)	26 (78.8)
Parainfluenza 4	27	9 (33.3)	18 (66.7)
Human rhinovirus	257	53 (20.6)	204 (79.4)
Corona 229E virus	8	0 (0)	8 (100)
Corona NL63 virus	11	3 (27.3)	8 (72.3)
Corona OC43 virus	22	2 (9.1)	20 (90.9)
Enterovirus	60	2 (3.3)	58 (96.7)
Human bocavirus	96	12 (12.5)	84 (87.5)

Table 4.

Correlation of severity with coinfected viruses for 768 hospitalized children with acute bronchiolitis∗

Infection	Coinfected viruses
Infection	ADV (n=139)	hMPV (n=96)	RSV A (n=252)	RSV B (n=140)	hRV (n=257)	ETV (n=60)	hBoV (n=96)
ADV	-	0.239 (0.137)	–0.133 (0.034)^†	0.046 (0.589)	–0.002 (0.975)	0.092 (0.484)	0.012 (0.907)
Flu A	0.103 (0.226)	-	0.106 (0.094)	0.053 (0.532)	0.117 (0.061)	0.066 (0.614)	0.134 (0.195)
Flu B	–0.100 (0.239)	-	–0.074 (0.245)	-	–0.085 (0.175)	-	–0.106 (0.306)
hMPV	–0.004 (0.960)	-	0.005 (0.940)	-	–0.081 (0.194)	0.053 (0.688)	0.092 (0.373)
RSV A	–0.051 (0.550)	0.106 (0.516)		–0.057 (0.500)	–0.042 (0.503)	0.073 (0.577)	–0.027 (0.794)
RSV B	0.115 (0.176)	-	–0.050 (0.432)	-	0.077 (0.216)	–0.066 (0.615)	–0.069 (0.507)
hRV	0.015 (0.863)	0.189 (0.242)	–0.131 (0.038)^†	0.011 (0.897)		0.195 (0.135)	0.190 (0.064)
PIV 1	–0.098 (0.252)	-	–0.082 (0.197)	-	0.055 (0.378)	0.099 (0.452)	0.085 (0.411)
PIV 2	0.127 (0.136)	-	–0.023 (0.718)	-	0.093 (0.136)	0.172 (0.189)	0.160 (0.118)
PIV 3	–0.070 (0.415)	0.280 (0.080)	–0.023 (0.718)	-	0.146 (0.019)^‡	0.152 (0.246)	0.053 (0.609)
PIV 4	–0.057 (0.512)	-	0.015 (0.840)	0.068 (0.481)	0.016 (0.809)	–0.029 (0.826)	–0.114 (0.268)
ETV	0.132 (0.124)	0.271 (0.115)	0.121 (0.106)	–0.010 (0.920)	0.164 (0.013)^‡	-	0.170 (0.097)
hCoV 229E	-	-	–0.031 (0.627)	-	–0.031 (0.624)	–0.149 (0.257)	-
hCoV NL63	–0.144 (0.093)	–0.136 (0.437)	–0.152 (0.042)^†	-	–0.002 (0.981)	-	-
hCoV OC43	–0.047 (0.587)	-	–0.024 (0.700)	–0.039 (0.651)	0.062 (0.322)	-	–0.106 (0.306)
hBoV	–0.073 (0.397)	0.351 (0.038)^‡	–0.034 (0.651)	0.078 (0.418)	0.063 (0.344)	0.035 (0.792)	-

ADV, adenovirus; hMPV, human metapneumovirus; RSV, respiratory syncytial virus; hRV, human rhinovirus; ETV, enterovirus; hBoV, human bocavirus; Flu, influenza virus; PIV, parainfluenza virus; hCoV, human coronavirus.

^∗ Spearman correlation analysis and then chi-square test.

^† Negative correlation (reduced severity).

^‡ Positive correlation (elevated severity).

TOOLS

Similar articles