Allergy, Asthma & Respiratory Disease

The Korean Academy of Asthma, Allergy and Clinical Immunology (대한천식알레르기학회)
권호 표지
DOI QR코드

DOI QR Code

Literature review and future strategies of childhood respiratory diseases in Korea

한국 소아 호흡기질환의 연구 현황과 과제

  • Han, Man Yong (Department of Pediatrics, CHA University School of Medicine) ;
  • Chung, Hai Lee (Department of Pediatrics, Catholic University of Daegu School of Medicine) ;
  • Ahn, Young Min (Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine) ;
  • Shim, Jung Yeon (Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine)
  • 한만용 (차의과대학 분당차병원) ;
  • 정혜리 (대구가톨릭대학병원) ;
  • 안영민 (을지대학교 의과대학 을지대학병원) ;
  • 심정연 (성균관대학교 의과대학 강북삼성병원)
  • Received : 2017.10.23
  • Accepted : 2018.02.15
  • Published : 2018.09.30
⟨ Previous Next ⟩

Abstract

Thirty years have passed since the Korean Association of Pediatric Allergy and Respiratory Disease was founded. There have been great changes in the pattern of respiratory diseases in Korean children during the last 30 years with economic development in the country. Pneumonia remains the leading cause of childhood morbidity, despite advances in the prevention and management. The incidence and mortality of pneumonia caused by typical bacterial pathogens have been reduced. However, the predominance of Mycoplasma pneumoniae or virus-associated diseases is emerging, which suggests that novel diagnostic and therapeutic strategies are needed. Viral bronchiolitis is one of the most substantial health burdens for infants and young children worldwide. Although respiratory syncytial virus is the most common pathogen, molecular diagnostic techniques have identified many other viruses including human rhinovirus causing bronchiolitis. Bronchiectasis is a chronic respiratory condition characterized by chronic infection, airway inflammation, and progressive lung function decline. Research into the interactions between early life respiratory infections and development of bronchiectasis is imperative to halt the disease in its origin and improve adult outcomes. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening lung disease with diffuse inflammatory lung injury leading to pulmonary edema and hypoxia. Although many modalities to treat ARDS have been studied, supportive therapies and lung protective ventilator support remains the mainstay. This review focuses on the current trends in research on these childhood respiratory diseases through literature review and aims to investigate the impact of Korean study results in this field.

Keywords

References

  1. The World Bank. GNI per capita, Atlas method (current US$), 2017 [Internet]. Washington, DC: The World Bank; c2018 [cited 2018 Jan 18] Available from: http://databank.worldbank.org/data/reports.aspx?source =2& series=NY.GNP.PCAP.CD&country=#.
  2. Yang HJ, Song DJ, Shim JY. Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. Korean J Pediatr 2017;60:167-74. https://doi.org/10.3345/kjp.2017.60.6.167
  3. Jhang WK, Park SJ, Lee E, Yang SI, Hong SJ, Seo JH, et al. The first successful heart-lung transplant in a Korean child with humidifier disinfectant-associated interstitial lung disease. J Korean Med Sci 2016;31:817-21. https://doi.org/10.3346/jkms.2016.31.5.817
  4. Lee CH, Won YK, Roh EJ, Suh DI, Chung EH. A nationwide study of children and adolescents with pneumonia who visited Emergency Department in South Korea in 2012. Korean J Pediatr 2016;59:132-8. https://doi.org/10.3345/kjp.2016.59.3.132
  5. Korea Centers for Disease Control & Prevention. Guidelines for the antibiotic use in children with lower respiratory tract infections [Internet]. Osong (Korea): Korea Centers for Disease Control & Prevention, 2017 [cited 2017 Sep 1]. Available from: http://cdc.go.kr/CDC/notice/CdcKr Together0302.jsp?menuIds=HOME001-MNU1154-MNU0005-MNU 0088&cid=74134.
  6. Jeon YH, Kim JH. Treatment of community-acquired pneumonia in Korean children. Allergy Asthma Respir Dis 2017;5:177-84. https://doi.org/10.4168/aard.2017.5.4.177
  7. Revised WHO Classification and Treatment of Pneumonia in Children at Health Facilities: Evidence Summaries. Geneva: World Health Organization; 2014.
  8. Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax 2011;66 Suppl 2:ii1-23.
  9. Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011;53:e25-76. https://doi.org/10.1093/cid/cir531
  10. Uehara S, Sunakawa K, Eguchi H, Ouchi K, Okada K, Kurosaki T, et al. Japanese guidelines for the management of respiratory infectious diseases in children 2007 with focus on pneumonia. Pediatr Int 2011;53:264-76. https://doi.org/10.1111/j.1442-200X.2010.03316.x
  11. Kim KW, Kim KE. Mycoplasma and chlamydia infection in Korea. Korean J Pediatr 2009;52:277-82. https://doi.org/10.3345/kjp.2009.52.3.277
  12. Wy HH, Min DH, Kim DS, Park MS, Shim JW, Jung HL, et al. Clinical characteristics of Mycoplasma pneumoniae pneumonia in Korean children during the recent 3 epidemics. Allergy Asthma Respir Dis 2017;5:8-14. https://doi.org/10.4168/aard.2017.5.1.8
  13. Kim JW, Seo HK, Yoo EG, Park SJ, Yoon SH, Jung HY, et al. Mycoplasma pneumoniae pneumonia in Korean children, from 1979 to 2006-a meta-analysis. Korean J Pediatr 2009;52:315-23. https://doi.org/10.3345/kjp.2009.52.3.315
  14. Shim MJ. Mycoplasma pneumonia in children. Med J Red Cross Hospital 1980;7:53-7.
  15. Lee JK, Hong CH, Sohn YM, Kim KE, Kim DH, Kim PK, et al. Mycoplasmal pneumoniain children. Yonsei Med J 1986;27:300-6. https://doi.org/10.3349/ymj.1986.27.4.300
  16. Waites KB, Xiao L, Liu Y, Balish MF, Atkinson TP. Mycoplasma pneumoniae from the Respiratory Tract and Beyond. Clin Microbiol Rev 2017;30: 747-809. https://doi.org/10.1128/CMR.00114-16
  17. Youn YS, Lee KY, Hwang JY, Yim JW, Kang JH, Lee JS. Comparison of diagnostic methods and the changes of IgG subclasses in children with mycoplasma pneumoniae pneumonia. Pediatr Allergy Respir Dis. 2009; 19:137-45.
  18. Eun BL, Park SH, Tockgo YC, Seong SC. Detection of Mycoplasma pneumoriae in clinical samples from pediatric patients by polymerase chain reaction. J Korean Pediatr Soc 1995;38:1077-86.
  19. Kang HW, Ahn BM, Song MY, Kim ER, Choi SH, Kim IS. The diagnostic value of polymerase chain reaction in Mycoplasma pneumoniae pneumonia. J Korean Pediatr Soc 1998;41:1351-8.
  20. Shin YH, Lee BC, Song TW, Kim KW, Lee KE, Kim ES, et al. Diagnostic availability of PCR and ELISA in Mycoplasma pneumoniae pneumonia. pediatr Allergy Respir Dis 2006;16:47-56.
  21. Spuesens EB, Fraaij PL, Visser EG, Hoogenboezem T, Hop WC, van Adrichem LN, et al. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS Med 2013;10:e1001444. https://doi.org/10.1371/journal.pmed.1001444
  22. Nilsson AC, Bjorkman P, Persson K. Polymerase chain reaction is superior to serology for the diagnosis of acute Mycoplasma pneumoniae infection and reveals a high rate of persistent infection. BMC Microbiol 2008; 8:93. https://doi.org/10.1186/1471-2180-8-93
  23. Canadian Agency for Drugs and Technologies in Health. Serum IgM and molecular tests for mycoplasma pneumoniae detection: a review of diagnostic test accuracy, clinical effectiveness, cost-effectiveness, and guidelines. In: Canadian Agency for Drugs and Technologies in Health, editor. CADTH rapid response reports. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2015.
  24. Choi J, Koh JY, Kim HB, Kim CG. The association of eosinophilic airway inflammation in Mycoplasma pneumonia and asthma. Pediatr Allergy Respir Dis 2009;19:63-70.
  25. Kim KW, Lee BC, Lee KE, Kim ES, Song TW, Park MY, et al. Mycoplasma pneumoniae-induced production of proasthmatic mediators in airway epithelium. Korean J Pediatr 2006;49:977-82. https://doi.org/10.3345/kjp.2006.49.9.977
  26. Yoo Y, Suh DI, Kim DK, Yu J, Koh YY, Kim CK. Association of HRCT findings suggestive of bronchiolitis obliterans with bronchial hyperresponsiveness after Mycoplasma pneumoniae pneumonia. Pediatr Allergy Respir Dis 2004;14:350-7.
  27. Park KM, Son SK, Kim HY, Kim YW, Hwang JY, Park HJ. Clinical features of necrotizing pneumonia in children. Allergy Asthma Respir Dis 2014;2014:208-12.
  28. Oh CE, Choi EH, Lee HJ. Detection of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae. Korean J Pediatr 2010; 53:178-83. https://doi.org/10.3345/kjp.2010.53.2.178
  29. Hong KB, Choi EH, Lee HJ, Lee SY, Cho EY, Choi JH, et al. Macrolide resistance of Mycoplasma pneumoniae, South Korea, 2000-2011. Emerg Infect Dis 2013;19:1281-4. https://doi.org/10.3201/eid1908.121455
  30. Seo YH, Kim JS, Seo SC, Seo WH, Yoo Y, Song DJ, et al. Predictive value of C-reactive protein in response to macrolides in children with macrolide-resistant Mycoplasma pneumoniae pneumonia. Korean J Pediatr 2014;57:186-92. https://doi.org/10.3345/kjp.2014.57.4.186
  31. Lee E, Cho HJ, Hong SJ, Lee J, Sung H, Yu J. Prevalence and clinical manifestations of macrolide resistant Mycoplasma pneumoniae pneumonia in Korean children. Korean J Pediatr 2017;60:151-7. https://doi.org/10.3345/kjp.2017.60.5.151
  32. Kim JH, Kim JY, Yoo CH, Seo WH, Yoo Y, Song DJ, et al. Macrolide resistance and its impacts on M. pneumoniae pneumonia in children: comparison of two recent epidemics in Korea. Allergy Asthma Immunol Res 2017;9:340-6. https://doi.org/10.4168/aair.2017.9.4.340
  33. Yu J. Clinical issues regarding increased macrolide-resistant Mycoplasma pneumoniae in children. Allergy Asthma Respir Dis 2017;5:1-2. https://doi.org/10.4168/aard.2017.5.1.1
  34. Youn YS, Lee KY. Mycoplasma pneumoniae pneumonia in children. Korean J Pediatr 2012;55:42-7. https://doi.org/10.3345/kjp.2012.55.2.42
  35. Lee SY, Oh JW, Lee HB, Lee HR, Ahn KM, Lee SI. Epidemiology of childhood viral respiratory tract infections in Seoul. Pediatr Allergy Respir Dis 1999;9:100-8.
  36. Park HY, Lee NY, Lee JS, Jung EH, Lee SJ, Ahn KM, et al. An epidemiological study of acute viral lower respiratory tract infections in hospitalized children from 1996 to 2002 in Seoul, Korea. Pediatr Allergy Respir Dis 2003;13:216-26.
  37. Park JS. Viral etiology and epidemiology of acute lower respiratory tract infections in hospitalized children (Choongchung Province in May 2001 through April 2004). Pediatr Allergy Respir Dis 2004;14:366-76.
  38. 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 2007;17:344-53.
  39. Kim JE, Bauer S, La KS, Lee KH, Choung JT, Roh KH, et al. CD4+/CD8+ T lymphocytes imbalance in children with severe 2009 pandemic influenza A (H1N1) pneumonia. Korean J Pediatr 2011;54:207-11. https://doi.org/10.3345/kjp.2011.54.5.207
  40. Shin HW, Cho HL, You JH, You EJ, Kim EY, Kim KS, et al. Comparison of clinical manifestations of RSV, rhinovirus and bocavirus infections in children with acute wheezing. Pediatr Allergy Respir Dis 2011;21:334-43. https://doi.org/10.7581/pard.2011.21.4.334
  41. Schroeder AR, Ralston SL. Viral testing for pediatric respiratory infections: why precise diagnoses do not always translate to patient benefit. JAMA 2017;318:472-3. https://doi.org/10.1001/jama.2017.3985
  42. Brendish NJ, Malachira AK, Armstrong L, Houghton R, Aitken S, Nyimbili E, et al. Routine molecular point-of-care testing for respiratory viruses in adults presenting to hospital with acute respiratory illness (ResPOC): a pragmatic, open-label, randomised controlled trial. Lancet Respir Med 2017;5:401-11. https://doi.org/10.1016/S2213-2600(17)30120-0
  43. Yum HY, Kim WK, Kim JT, Kim HH, Rha YH, Park YM, et al. The causative organisms of pediatric empyema in Korea. Korean J Pediatr 2007; 50:33-9. https://doi.org/10.3345/kjp.2007.50.1.33
  44. Yoon YK, Park GC, An H, Chun BC, Sohn JW, Kim MJ. Trends of antibiotic consumption in Korea according to national reimbursement data (2008-2012): a population-based epidemiologic study. Medicine (Baltimore) 2015;94:e2100. https://doi.org/10.1097/MD.0000000000002100
  45. Kang JH, Kim SM, Kim JH, Kyun HJ, Lee KY, Shin YK, et al. Penicillin resistant distribution and in-vitro susceptibility of oral antibiotics against streptococcus pneumoniae, isolated from pediatric patients with community- acquired respiratory infections in Korea. Korean J Pediatr 2005; 48:40-7.
  46. Kim SH, Song JH, Chung DR, Thamlikitkul V, Yang Y, Wang H, et al. Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian network for surveillance of resistant pathogens (ANSORP) study. Antimicrob Agents Chemother 2012;56:1418-26. https://doi.org/10.1128/AAC.05658-11
  47. Choi MS, Kim YW, Kim DS, Lee KW. Treatment outcome of penicillin-resistant S. pneumoniae infection. J Korean Pediatr Soc 2001;44:149-53.
  48. Sung JJ, Kim EJ, Sun YH, Jeon IS, Tchah H, Ryoo E, et al. Clinical presentations of Chlamydia pneumoniae in children hospitalized for acute respiratory infections: a comparison to Mycoplasma pneumonia. Allergy Asthma Respir Dis 2015;3:346-51. https://doi.org/10.4168/aard.2015.3.5.346
  49. Yum HY, Choi JY, Rheu JW, Lee KE, Kim CH, Shon MH, et al. Correlation between Chlamydia pneumonia Infection and Childhood Asthma. Pediatr Allergy Respir Dis 2000;10:218-24.
  50. Meissner HC. Viral bronchiolitis in children. N Engl J Med 2016;374: 62-72. https://doi.org/10.1056/NEJMra1413456
  51. 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. https://doi.org/10.1086/506350
  52. Kim CK, Choi J, Callaway Z, Kim HB, Chung JY, Koh YY, et al. Clinical and epidemiological comparison of human metapneumovirus and respiratory syncytial virus in Seoul, Korea, 2003-2008. J Korean Med Sci 2010;25:342-7. https://doi.org/10.3346/jkms.2010.25.3.342
  53. Chung JY, Han TH, Kim BE, Kim CK, Kim SW, Hwang ES. Human metapneumovirus infection in hospitalized children with acute respiratory disease in Korea. J Korean Med Sci 2006;21:838-42. https://doi.org/10.3346/jkms.2006.21.5.838
  54. Kim YK, Lee HJ. Human metapneumovirus-associated lower respiratory tract infections in korean infants and young children. Pediatr Infect Dis J 2005;24:1111-2. https://doi.org/10.1097/01.inf.0000190042.65120.23
  55. 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. https://doi.org/10.1001/archpediatrics.2011.1669
  56. Florin TA, Plint AC, Zorc JJ. Viral bronchiolitis. Lancet 2017;389:211-24. https://doi.org/10.1016/S0140-6736(16)30951-5
  57. Kim CK, Callaway Z, Koh YY, Kim SH, Fujisawa T. Airway IFN-gamma production during RSV bronchiolitis is associated with eosinophilic inflammation. Lung 2012;190:183-8. https://doi.org/10.1007/s00408-011-9349-5
  58. Chung HL, Park HJ, Kim SY, Kim SG. Age-related difference in immune responses to respiratory syncytial virus infection in young children. Pediatr Allergy Immunol 2007;18:94-9. https://doi.org/10.1111/j.1399-3038.2006.00501.x
  59. Yoon JS, Kim HH, Lee Y, Lee JS. Cytokine induction by respiratory syncytial virus and adenovirus in bronchial epithelial cells. Pediatr Pulmonol 2007;42:277-82. https://doi.org/10.1002/ppul.20574
  60. Chung HL, Kim WT, Kim JK, Choi EJ, Lee JH, Lee GH, et al. Relationship between atopic status and nasal interleukin 10 and 11 levels in infants with respiratory syncytial virus bronchiolitis. Ann Allergy Asthma Immunol 2005;94:267-72. https://doi.org/10.1016/S1081-1206(10)61307-5
  61. Chung JY, Han TH, Kim JS, Kim SW, Park CG, Hwang ES. Th1 and Th2 cytokine levels in nasopharyngeal aspirates from children with human bocavirus bronchiolitis. J Clin Virol 2008;43:223-5. https://doi.org/10.1016/j.jcv.2008.06.008
  62. Choi EH, Lee HJ, Chanock SJ. Human genetics and respiratory syncytial virus disease: current findings and future approaches. Curr Top Microbiol Immunol 2013;372:121-37.
  63. Choi EH, Lee HJ, Yoo T, Chanock SJ. A common haplotype of interleukin-4 gene IL4 is associated with severe respiratory syncytial virus disease in Korean children. J Infect Dis 2002;186:1207-11. https://doi.org/10.1086/344310
  64. Baek YH, Choi EH, Song MS, Pascua PN, Kwon HI, Park SJ, et al. Prevalence and genetic characterization of respiratory syncytial virus (RSV) in hospitalized children in Korea. Arch Virol 2012;157:1039-50. https://doi.org/10.1007/s00705-012-1267-1
  65. Sigurs N, Aljassim F, Kjellman B, Robinson PD, Sigurbergsson F, Bjarnason R, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010;65:1045-52. https://doi.org/10.1136/thx.2009.121582
  66. Caliskan M, Bochkov YA, Kreiner-Moller E, Bonnelykke K, Stein MM, Du G, et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N Engl J Med 2013;368:1398-407. https://doi.org/10.1056/NEJMoa1211592
  67. Jung YH, Seo JH, Kim HY, Kwon JW, Kim BJ, Kim HB, et al. The relationship between asthma and bronchiolitis is modified by TLR4, CD14, and IL-13 polymorphisms. Pediatr Pulmonol 2015;50:8-16. https://doi.org/10.1002/ppul.22978
  68. Chung HL, Lee EJ, Park HJ, Lee KH. Increased epidermal growth factor in nasopharyngeal aspirates from infants with recurrent wheeze. Pediatr Pulmonol 2015;50:841-7. https://doi.org/10.1002/ppul.23083
  69. Kim BJ, Seo JH, Jung YH, Kim HY, Kwon JW, Kim HB, et al. Air pollution interacts with past episodes of bronchiolitis in the development of asthma. Allergy 2013;68:517-23. https://doi.org/10.1111/all.12104
  70. Lee Chung H, Kim SY, Kim SG. Vascular endothelial growth factor and plasminogen activator inhibitor-1 in children with recurrent early wheeze. J Allergy Clin Immunol 2007;119:1541-2. https://doi.org/10.1016/j.jaci.2007.02.040
  71. Chung HL, Kim SG. RANTES may be predictive of later recurrent wheezing after respiratory syncytial virus bronchiolitis in infants. Ann Allergy Asthma Immunol 2002;88:463-7. https://doi.org/10.1016/S1081-1206(10)62383-6
  72. Thomsen SF, van der Sluis S, Stensballe LG, Posthuma D, Skytthe A, Kyvik KO, et al. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study. Am J Respir Crit Care Med 2009;179:1091-7. https://doi.org/10.1164/rccm.200809-1471OC
  73. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014;134:e1474-502. https://doi.org/10.1542/peds.2014-2742
  74. Yoon JS, Chun YH, Lee JW, Chung NG, Cho B. Value of screening spirometry for early diagnosis of bronchiolitis obliterans syndrome in children after allogeneic hematopoietic stem cell transplantation. J Pediatr Hematol Oncol 2015;37:e462-7. https://doi.org/10.1097/MPH.0000000000000421
  75. Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr 2008;20:272-8. https://doi.org/10.1097/MOP.0b013e3282ff62e9
  76. Jang YY, Park HJ, Chung HL. Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children. Eur J Pediatr 2017;176:971-8. https://doi.org/10.1007/s00431-017-2940-x
  77. Lee E, Yoon J, Cho HJ, Hong SJ, Yu J. Respiratory reactance in children aged three to five years with postinfectious bronchiolitis obliterans is higher than in those with asthma. Acta Paediatr 2017;106:81-6. https://doi.org/10.1111/apa.13632
  78. Yoon HM, Lee JS, Hwang JY, Cho YA, Yoon HK, Yu J, et al. Post-infectious bronchiolitis obliterans in children: CT features that predict responsiveness to pulse methylprednisolone. Br J Radiol 2015;88:20140478. https://doi.org/10.1259/bjr.20140478
  79. Koh YY, Jung DE, Koh JY, Kim JY, Yoo Y, Kim CK. Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis obliterans. Chest 2007;131:1454-60. https://doi.org/10.1378/chest.06-0188
  80. Yoo Y, Yu J, Kim DK, Choi SH, Kim CK, Koh YY. Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans. Eur Respir J 2006;27:36-41. https://doi.org/10.1183/09031936.06.00019605
  81. Brower KS, Del Vecchio MT, Aronoff SC. The etiologies of non-CF bronchiectasis in childhood: a systematic review of 989 subjects. BMC Pediatr 2014;14:4. https://doi.org/10.1186/1471-2431-14-4
  82. Koh YY, Lee MH, Sun YH, Sung KW, Chae JH. Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Eur Respir J 1997;10:994-9. https://doi.org/10.1183/09031936.97.10050994
  83. Kim HY, Kwon JW, Seo J, Song YH, Kim BJ, Yu J, et al. Bronchiectasis in children: 10-year experience at a single institution. Allergy Asthma Immunol Res 2011;3:39-45. https://doi.org/10.4168/aair.2011.3.1.39
  84. Hwang EH, Kim HY, Ryu M, Kim SH, Son SK, Kim YM, et al. Clinical characteristics and cause of bronchiectasis in children: review in a center. Allergy Asthma Respir Dis 2013;1:383-7. https://doi.org/10.4168/aard.2013.1.4.383
  85. Pizzutto SJ, Hare KM, Upham JW. Bronchiectasis in children: current concepts in immunology and microbiology. Front Pediatr 2017;5:123. https://doi.org/10.3389/fped.2017.00123
  86. Shin SA, Yang S, Oh JW, Lee HB, Park CE, Kwan JK. Ultrastructure of nasal cilia in children with recurrent or persistent respiratory diseases. Korean J Pediatr 2006;49:410-6. https://doi.org/10.3345/kjp.2006.49.4.410
  87. Chi JG, Yoon CJ. Primary Ciliary Dyskinesia(Immotile Cilia Syndrome): Clinical and electron microscopic analysis of 17 cases. Korean J Pathol 1993;27:99-107.
  88. Moon HR, Ko TS, Ko YY, Choi JH, Kim YC. Cystic fibrosis: a case presented with recurrent bronchiolitis in infancy in a Korean male infant. J Korean Med Sci 1988;3:157-62. https://doi.org/10.3346/jkms.1988.3.4.157
  89. Ahn KM, Park HY, Lee JH, Lee MG, Kim JH, Kang IJ, et al. Cystic fibrosis in Korean children: a case report identified by a quantitative pilocarpine iontophoresis sweat test and genetic analysis. J Korean Med Sci 2005; 20:153-7. https://doi.org/10.3346/jkms.2005.20.1.153
  90. Ahn YM, Choi HR, Lee HJ, Dong ES. A case of congenital central hypoventilation syndrome (ondine's curse) with hirschsprung's disease. Pediatr Allergy Respir Dis 1993;3:113-20.
  91. Baek C, Jung JM, Lim YJ, Kim KH, Yu HW, Kim GH, et al. Haddad syndrome with a germ-line mutation in the PHOX2B gene in a Korean Neonate. Neonatal Med 2015;22:162-7. https://doi.org/10.5385/nm.2015.22.3.162
  92. Ahn YM, Shin HB, Kim EJ. Differences of EEG and sleep structure in pediatric sleep apnea and controls. Sleep Med Psychophysiol 2008;15: 71-6.
  93. Seo HJ, Lee JS, Shin HB, Kim EJ, Shim HJ, Ahn YM. Discrimination between obstructive sleep apnea syndrome and primary snoring in children: comparison of clinical parameters and behavioral disturbance. Korean J Pediatr 2008;51:267-75. https://doi.org/10.3345/kjp.2008.51.3.267
  94. Jang SJ, Seo HK, Yi SJ, Kim KM, Jee HM, Han MY. Analysis of reports on orphan lung diseases in Korean children. Korean J Pediatr 2010;53: 711-7. https://doi.org/10.3345/kjp.2010.53.6.711
  95. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307:2526-33.
  96. Kim SY, Kim YH, Sol IS, Kim MJ, Yoon SH, Kim KW, et al. Application of the Berlin definition in children with acute respiratory distress syndrome. Allergy Asthma Respir Dis 2016;4:257-63. https://doi.org/10.4168/aard.2016.4.4.257
  97. Choi SJ, Jeong DS, Oh JW, Lee HB, Kang IJ, Kim KW, et al. A nationwide clinical study of acute respiratory distress syndrome in children. J Korean Pediatr Soc 1999;42:23-31.
  98. Lee TJ, Kim DS, Shin DH. A Clinical study of the acute respiratory distress syndrome in children. J Korean Pediatr Soc 2003;46:42-50.
  99. Ko JM, Ha EJ, Lee EH, Lee SY, Kim HB, Hong SJ, et al. Clinical outcome and prognostic factors of acute respiratory distress syndrome in children. Korean J Pediatr 2005;48:599-605.
  100. Kang SS, Pae RM, Lee EK, Bang KW, Kim HS, Chun YH, et al. Outcome of acute respiratory distress syndrome in children: a single center study. Allergy Asthma Respir Dis 2014;2:266-71. https://doi.org/10.4168/aard.2014.2.4.266