Yong Ju Lee; Hyo-Bin Kim; Bong-Seong Kim; Chang-Keun Kim; Cheol Hong Kim; Hyung Young Kim; Sangyoung Kim; Yunsun Kim; Chorong Park; Ju-Hee Seo; In Suk Sol; Myongsoon Sung; Min Seob Song; Dae Jin Song; Young Min Ahn; Ju Suk Lee; Yoon Young Jang; Eun Hee Chung; Hai Lee Chung; Sung-Min Choi; Yun Jung Choi; Man Yong Han; Hyeon-Jong Yang; Jung Yeon Shim; Jin-Tack Kim; Hea Lin Oh; Jinho Yu; Kyung Suk Lee; Eun Lee; Gwang Cheon Jang

doi:10.4168/aard.2019.7.2.78

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Lee, Kim, Kim, Kim, Kim, Kim, Kim, Kim, Park, Seo, Sol, Sung, Song, Song, Ahn, Lee, Jang, Chung, Chung, Choi, Choi, Han, Yang, Shim, Kim, Oh, Yu, Lee, Lee, and Jang: Seasonal patterns and etiologies of croup in children during the period 2010–2015: A multicenter retrospective study

Original Article

Allergy Asthma Respir Dis 2019;7(2):78-85.

Published online: 12 April 2019

DOI: https://doi.org/10.4168/aard.2019.7.2.78

Seasonal patterns and etiologies of croup in children during the period 2010–2015: A multicenter retrospective study

Yong Ju Lee¹, Hyo-Bin Kim², Bong-Seong Kim³, Chang-Keun Kim², Cheol Hong Kim⁴, Hyung Young Kim⁵, Sangyoung Kim⁶, Yunsun Kim⁶, Chorong Park⁶, Ju-Hee Seo⁷, In Suk Sol⁸, Myongsoon Sung⁹, Min Seob Song¹⁰, Dae Jin Song¹¹, Young Min Ahn¹², Ju Suk Lee, Yoon Young Jang¹⁸, Eun Hee Chung¹⁹, Hai Lee Chung¹⁸, Sung-Min Choi²⁰, Yun Jung Choi^21,²², Man Yong Han²³, Hyeon-Jong Yang^6,²⁴, Jung Yeon Shim²⁵, Jin-Tack Kim²⁶, Hea Lin Oh¹³, Jinho Yu¹⁴, Kyung Suk Lee¹⁵, Eun Lee¹⁶, Gwang Cheon Jang¹⁷

^¹Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul Korea

^²Department of Pediatrics, Asthma and Allergy Center, Inje University Sanggye Paik Hospital, Seoul Korea

^³Department of Pediatrics, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung

^⁴Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon

^⁵Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan

^⁶SCH Biomedical Informatics Research Unit, Soonchunhyang University Seoul Hospital, Seoul Korea

^⁷Department of Pediatrics, Dankook University Hospital, Cheonan

^⁸Department of Pediatrics, Yonsei University Severance Hospital, Seoul Korea

^⁹Department of Pediatrics, Soonchunhyang University Gumi Hospital, Gumi

^¹⁰Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan

^¹¹Department of Pediatrics, Korea University Guro Hospital, Seoul Korea

^¹²Department of Pediatrics, Eulji University Eulji General Hospital, Seoul Korea

^¹³Department of Pediatrics, Korea Cancer Center Hospital, Seoul Korea

^¹⁴Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul Korea

^¹⁵Department of Pediatrics, Hanyang University Guri Hospital, Guri

^¹⁶Department of Pediatrics, Chonnam National University Hospital, Gwangju

^¹⁷Department of Pediatrics, National Health Insurance Service, Ilsan Hospital, Ilsan

^¹⁸Department of Pediatrics, Daegu Catholic University Medical Center, Daegu

^¹⁹Department of Pediatrics, Chungnam National University Hospital, Daejeon

^²⁰Department of Pediatrics, Dongguk University Gyungju Hospital, Gyungju

^²¹Department of Pediatrics, Sowha Children's Hospital, Seoul Korea

^²²Department of Pediatrics, Seoul National University Children Hospital, Seoul Korea

^²³Department of Pediatrics, CHA University CHA Bundang Medical Center, Seongnam

^²⁴Department of Pediatrics, Soonchunhyang University Seoul Hospital, Seoul Korea

^²⁵Division of Pediatric Allergy & Pulmonology, Department of Pediatrics, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul Korea

^²⁶Department of Pediatric Allergy & Pneumology, Catholic University Uijeongbu St. Mary's Hospital, Uijeongbu, Korea

Correspondence to: Hyeon-Jong Yang https://orcid.org/0000-0002-7287-4300 Department of Pediatrics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-709-9390, Fax: +82-2-709-9083, E-mail: pedyang@schmc.ac.kr Co-correspondence to: Jung Yeon Shim https://orcid.org/0000-0001-9367-2233 Division of Pediatric Allergy & Pulmonology, Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 31116, Korea Tel: +82-2-2001-2484, Fax: +82-2-2001-2199, E-mail: jy7.shim@samsung.com

*These authors contributed equally to this study as co-first authors.

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI16C2300).

Received 11 October 2018 Revised 4 January 2019 Accepted 14 January 2019

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

Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of para-influenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to examine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period.

Methods

Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medical records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical information were cross-sectionally reviewed and analyzed.

Results

Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a

Conclusion

It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most common cause of childhood croup; however, croup epidemics could be attributed to other viruses.

Keywords: Child, Croup, Hospitalization, Retrospective studies, Seasons

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Fig. 1.

Pathogens detected in hospitalized children with croup between 2010 and 2015. A total of 927 children with croup were hospitalized between 1 January 2010 through 31 December 2015. Among them, most prevalent age group was <2 years old (n=584, 63.0%). Most commonly detected pathogen was parainfluenza virus under the age of 4 years. MP, Mycoplasma pneumoniae; AdV, adenovirus; RV, human rhinovirus; Flu, influenza virus; PIV, parainfluenza virus; HMPV, human metapneumovirus; RSV, respiratory syncytial virus; BoV, bocavirus; CoV, coronavirus.

Fig. 2.

Numbers of hospitalized children with croup and pathogen-detected croup between 1 January 2010 through 31 December 2015, according to month and year. A total of 2,598 hospitalized children with croup were identified. Among them respiratory pathogens were detected in 927 children.

Fig. 3.

Distribution of pathogen-detected croup between 1 January 2010 and 31 December 2015, according to month and year. (A) Pathogens detected in hospitalized children with croup. (B) Distribution of PIV, and PIV subtypes. (C) Distribution of CoV and CoV subtypes. AdV, adenovirus; HRV, human rhinovirus; Flu, influenza virus; PIV, parainfluenza virus; HMPV, human metapneumovirus; RSV, respiratory syncytial virus; BoV, bocavirus; HCoV, human coronavirus.

Table 1.

Characteristics among 927 hospitalized childhood croup from 1 January 2010 to 31 December 2015

Variable	Value
Age (mo), median (IQR)	19 (11–31)
Age group (yr)
<2	584 (63.0)
2–4	266 (28.7)
5–9	62 (6.7)
10–17	15 (1.6)
Male sex	570 (61.5)
Season at hospitalization
Spring (March–May)	264 (28.5)
Summer (June–August)	253 (27.3)
Autumn (September–November)	247 (26.6)
Winter (December–February)	163 (17.6)
Hospitalization-related information
Length of stay (hr), mean±SD	126.7±92.1
Intensive care unit admission	1 (0.1)
Oxygen supply	84 (9.1)
Use of corticosteroids	166 (17.9)
Oral prednisolone	44 (4.8)
Methylprednisolone	42 (4.5)
Dexamethasone	121 (13.1)

Values are presented number (%) unless otherwise indicated. IQR, interquartile range; SD, standard deviation.

Table 2.

Respiratory pathogens and laboratory findings among 927 hospitalized childhood croup from 1 January 2010 to 31 December 2015

Variable	Value
Identified-pathogen	721 (77.8)
Single	521 (56.2)
Adenovirus	14 (2.7)
Human rhinovirus	65 (12.5)
Influenza virus	34 (6.5)
Parainfluenza virus	207 (39.7)
Human metapneumovirus	24 (4.61)
Respiratory syncytial virus	78 (15.0)
Bocavirus	6 (1.2)
Coronovirus	38 (7.3)
Mycoplama pneumoniae	55 (10.6)
Multiple	200 (21.6)
No identification	206 (22.2)
Laboratory findings
WBC (×10³/μL)	11.3±4.8
Neutrophil (%)	48.7±19.5
Lymphocyte (%)	38.9±17.6
Eosinophil (%)	1.4±2.1
Platelet count (×10³/μL)	294.5±104.8
AST (U/L)	40.6±33.3
ALT (U/L)	22.5±45.9
LDH (U/L)	361.8±45.9
CRP (mg/dL)	3.2±6.9
ESR (mm/hr)	18.2±16.7

Values are presented as number (%) or mean±standard deviation.

Multiple, multiple pathogens with coinfection; WBC, white blood cell; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.

Table 3.

Comparison of clinical characteristics and laboratory findings among hospitalized children with croup due to single adenovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, corona virus, and Mycoplasma pneumoniae infection

Variable	1. AdV (n=14)	2. Flu (n=34)	3. PIV (n=207)	4. RSV (n=78)	5. CoV (n=24)	6. MP (n=27)	P-value	Post hoc test
Age (mo), median (IQR)	24.5 (23.0)	26.0 (32.0)	17.0 (16.0)	16.0 (11.0)	13.0 (12.0)	66.0 (51.0)	<0.01	5≤4=3≤1=2≤6
Male sex, n (%)	8 (57.1)	22 (64.7)	126 (60.9)	52 (66.7)	24 (63.2)	27 (49.1)	0.46
LOS (hr), median (IQR)	120.0 (72.0)	120.0 (48.0)	96.0 (48.0)	120.0 (48.0)	96.0 (24.0)	144.0 (96.0)	<0.01	3=5=4≤1=2≤6
ICU admission, n (%)	0 (0)	0 (0)	1 (0.5)	0 (0)	0 (0)	0 (0)
Oxygen supply, n (%)	0 (0)	3 (8.8)	19 (9.2)	6 (7.7)	6 (15.8)	1 (1.8)	0.19
Use of steroids, no. (%)	5 (35.7)	6 (17.7)	41 (19.8)	9 (11.5)	11 (29.0)	18 (32.7)	0.03
Laboratory findings
WBC (×10³/μL), median (IQR)	10.47 (5.65)	8.77 (4.04)	9.80 (5.42)	10.97 (4.68)	12.99 (7.24)	7.89 (3.39)	<0.01	6≤2≤3≤1≤4≤5
Neutrophil	48.5 (14.0)	58.0 (36.1)	46.0 (30.2)	45.5 (25.6)	49.8 (18.1)	56.6 (21.7)	0.12	4=3≤1=5≤6=2
Lymphocyte	32.7 (17.9)	32.0 (31.2)	40.7 (28.1)	40.3 (23.8)	36.3 (17.5)	30.4 (18.3)	0.03	6≤2=1=5=4≤3
Eosinophil	0.5 (1.4)	0.4 (0.8)	0.3 (0.8)	0.5 (1.4)	0.35 (1.3)	1.8 (3.0)	<0.01	3=5=1=2=4<6
Platelet (×10³/μL), median (IQR)	297.0 (81.0)	228.5 (60.0)	249.0 (104.0)	300.0 (108.5)	298.0 (90.0)	273.0 (118.0)	<0.01	2=3≤6=1≤5=4
CRP (mg/dL), median (IQR)	2.05 (3.0)	0.83 (2.27)	0.96 (2.47)	1.08 (2.56)	1.06 (1.45)	1.50 (4.20)	0.37
ESR (mm/hr), median (IQR)	33.0 (31.0)	7.0 (13.0)	10.0 (15.0)	11.0 (15.5)	7.0 (8.0)	26.0 (30.0)	<0.01	2=5=3=4<6=1
AST (U/L), median (IQR)	30.0 (10.0)	39.5 (17.0)	37.0 (12.0)	39.0 (13.0)	37.0 (10.0)	31.0 (8.0)	<0.01	1=6≤5=3=4=2
ALT (U/L), median (IQR)	15.5 (8.0)	15.0 (9.0)	16.0 (8.0)	17.0 (9.0)	19.5 (8.0)	12.0 (6.0)	<0.01	6≤2=1=3=4=5
LDH (U/L), median (IQR)	270.0 (81.0)	286.0 (170.0)	327.0 (88.0)	324.0 (151.0)	516.0 (246.0)	436.0 (218.5)	0.24

IQR, interquartile range; LOS, length of stay; AdV, adenovirus; Flu, influenza virus; PIV, parainfluenza virus; RSV, respiratory syncytial virus; CoV coronavirus; MP, Mycoplasma pneumoniae; ICU, intensive care unit; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase.

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