Clinical Characteristics of Bronchopulmonary Dysplasia by Type and Severity

기관지폐이형성증의 유형 및 중증도에 따른 임상적 특징

  • Shim, Gyu-Hong (Department of Pediatrics, Inje University College of Medicine, Sanggye Paik Hospital) ;
  • Lee, Hyun-Ju (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Eun-Sun (Department of Pediatrics, Sungkyunkwan University School of Medicine Samsung Medical Center) ;
  • Lee, Jin-A (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Choi, Chang-Won (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Ee-Kyung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Han-Suk (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Beyong-Il (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Choi, Jung-Hwan (Department of Pediatrics, Seoul National University College of Medicine)
  • 심규홍 (인제대학교 의과대학 상계백병원 소아과학교실) ;
  • 이현주 (서울대학교 의과대학 소아과학교실) ;
  • 김은선 (성균관대학교 의과대학 삼성서울병원 소아과학교실) ;
  • 이진아 (서울대학교 의과대학 소아과학교실) ;
  • 최창원 (서울대학교 의과대학 소아과학교실) ;
  • 김이경 (서울대학교 의과대학 소아과학교실) ;
  • 김한석 (서울대학교 의과대학 소아과학교실) ;
  • 김병일 (서울대학교 의과대학 소아과학교실) ;
  • 최중환 (서울대학교 의과대학 소아과학교실)
  • Published : 2010.05.31

Abstract

Purpose : The increased survival of preterm infants in the neonatal intensive care unit recently has resulted in an increased frequency of bronchopulmonary dysplasia (BPD), especially with atypical forms. However, there have been few studies compairing classic and atypical BPD. The aim of this study was to investigate the differences between these two types of BPD. Methods : Infants with a gestational age less than 32 weeks born at the Seoul National University Hospital and Bundang Seoul National University Hospital from May 2004 to April 2007 were included. The data were categorized in 2 groups, classic and atypical BPD. We determined the incidence of BPD, and compared perinatal factors and postnatal managements between two groups. Results : Among 260 study subjects, 141 (54.2%) infants had BPD. Classic BPD infants were 64 and atypical BPD infants were 77. Comparison of differences between 2 groups, classic BPD infants were associated with respiratory distress syndrome, patent ductus arteriosus, intrauterine growth restriction, more high-frequency ventilator (HFV) use, low 1 and 5 minute Apgar scores. Atypical BPD infants were associated with antenatal steroid use, maternal premature rupture of membrane and chorioamnionitis (CAM). In multivariate analysis, more HFV use was associated with classic BPD. Antenatal steroid use, clinical CAM and histological CAM were associated with atypical BPD. Conclusion : The results of this study showed that antenatal factors (antenatal steroid use, clinical CAM, histological CAM) were associated with atypical BPD and postnatal factors (HFV used more) were associated with classic BPD. Further studies are needed for prevention and treatment of BPD.

목 적 : 최근 신생아중환자실에서 생존률이 향상됨에 따라서 기관지폐이형성증의 발생률이 증가하고 있고, 그 중에서도 특히 비전형적 기관지폐이형성증의 발생률이 증가하고 있다. 그러나, 전형적인 기관지폐이형성증 환아와 비전형적 기관지폐이형성증 환아의 비교 연구는 많지 않다. 이에 저자들은 두 군간의 차이점을 알아보고자 본 연구를 시행하였다. 방 법: 2004년 5월부터 2007년 4월까지 서울대학교병원과 분당 서울대학교병원에서 출생하여 신생아중 환자실에 입원한 월경 후 주령 32주 미만인 환아를 대상으로 하였고, 이를 전형적인 군과 비전형적인 군으로 나누었다. 그리고, 기관지 폐이형성증의 발생률을 조사하고, 전형적인 군과 비전형적인 군에서 주산기적 요인과 출생 후 치료를 비교하였다. 결 과:총 연구 대상은 260명이었고 이 중 141명(54.2%)이 기관지폐이형성증으로 진단되었다. 이 중 전형적 기관지폐이형성증은 64명, 비전형적 기관지폐이형성증은 77명이었다. 전형적 기관지폐이형성증 환아에서 신생아 호흡곤란 증후군, 동맥관 개존증, 자궁내 성장지연이 더 많이 동반되었고, 1분과 5분 Apgar 점수가 낮았고, 고진동 인공환기기 사용이 더 많았다. 비전형적 기관지폐이형성증 환아에서는 산전 스테로이드 사용이 더 많았고, 조기 양막파수, 임상적 융모양막염과 병리학적 융모양막염의 동반이 더 많았다. 다중 로지스틱 회귀분석을 시행하였을 때 고진동 인공환기기 사용은 전형적 기관지폐이형성증 환아에서 독립변수였고, 산전 스테로이드 사용, 임상적 융모양막염과 병리학적 융모양막염은 비전형적 기관지폐이형성증 환아에서 독립변수였다. 결 론:본 연구에서는 산전 요인(산전 스테로이드 사용, 임상적 융모양막염, 병리학적 융모양막염)은 비전형적인 기관지폐이형성증과 유의한 관계를 보였고, 산후요인(더 흔한 고진동 인공환기기 사용)은 전형적 기관지폐이형성증과 유의한 관계를 보였다. 앞으로, 위와 같은 임상 연구들을 바탕으로 기관지폐이형성증의 예방과 치료에 대한 더 많은 연구가 필요하리라 생각된다.

Keywords

References

  1. Northway WH Jr, Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline membrane disease. Bronchopulmonary dysplasia. N Engl J Med 1967;276:357-68. https://doi.org/10.1056/NEJM196702162760701
  2. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9. https://doi.org/10.1164/ajrccm.163.7.2011060
  3. Charafeddine L, D'Angio CT, Phelps DL. Atypical chronic lung disease patterns in neonates. Pediatrics 1999;103:759-65. https://doi.org/10.1542/peds.103.4.759
  4. Choi CW, Kim BI, Koh YY, Choi JH, Choi JY. Clinical characteristics of chronic lung disease without preceding respiratory distress syndrome in preterm infants. Pediatr Int 2005;47:72-9. https://doi.org/10.1111/j.1442-200x.2004.01996.x
  5. Kim BI, Choi JH, Yun C. Morphologic change of lung parenchymal tissue in neonatal rat pups under chronic hyperoxia. J Korean Pediatr Soc 1994;37:1055-64.
  6. Choi CW, Kim BI, Hong JS, Kim EK, Kim HS, Choi JH. Bronchopulmonary dysplasia in a rat model induced by intra-amniotic inflammation and postnatal hyperoxia: morphometric aspects. Pediatr Res 2009;65:323-7. https://doi.org/10.1203/PDR.0b013e318193f165
  7. Lyon A. Chronic lung disease of prematurity: The role of intra-uterine infection. Eur J Pediatr 2000;159:798-802. https://doi.org/10.1007/s004310000587
  8. Speer CP. Inflammation and bronchopulmonary dysplasia. Semin Neonatol 2003;8:29-38. https://doi.org/10.1016/S1084-2756(02)00190-2
  9. Kramer BW. Antenatal inflammation and lung injury: prenatal origin of neonatal disease. J Perinatol 2008;28 Suppl 1:21-7. https://doi.org/10.1038/jp.2008.46
  10. Bose CL, Dammann CE, Laughon MM. Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate. Arch Dis Child Fetal Neonatal Ed 2008;93:F455-61. https://doi.org/10.1136/adc.2007.121327
  11. Rojas MA, Gonzalez A, Bancalari E, Claure N, Poole C, Silva-Neto G. Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr 1995;126:605-10. https://doi.org/10.1016/S0022-3476(95)70362-4
  12. Fujimura M, Kitajima H, Nakayama M. Increased leukocyte elastase of the tracheal aspirate at birth and neonatal pulmonary emphysema. Pediatrics 1993;92:564-9.
  13. Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97:210-5.
  14. Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F, et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1997;177:825-30. https://doi.org/10.1016/S0002-9378(97)70276-X
  15. Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BI, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181:773-9. https://doi.org/10.1016/S0002-9378(99)70299-1
  16. Kim BI, Park JD, Yoon BH. Interleukin-8 and neutrophils in the tracheobronchial aspirate at birth and the risk for the development of chronic lung disease of prematurity. Prenat Neonatal Med 2000;5:375-82.
  17. Lee JA, Kim BI, Shim GH, Shin YJ, Kim EK, Park JD, et al. Immediate Postnatal Concentrations of Metalloproteinase-8 in the Tracheal Aspirates and the Development of Atypical Chronic Lung Disease of Prematurity. J Korean Soc Neonatol 2003;10:153-67.
  18. Kim BI, Lee HE, Choi CW, Jo HS, Choi EH, Koh YY, et al. Increase in cord blood soluble E-selectin and tracheal aspirate neutrophils at birth and the development of new bronchopulmonary dysplasia. J Perinat Med 2004;32:282-7. https://doi.org/10.1515/JPM.2004.053
  19. Kim DH, Kim HS, Shim SY, Lee JA, Choi CW, Kim EK, et al. Cord Blood KL-6, a Specific Lung Injury Marker, Correlates with the Subsequent Development and Severity of Atypical Bronchopulmonary Dysplasia. Neonatology 2008;93:223-9. https://doi.org/10.1159/000111100
  20. Choi CW, Kim BI, Kim HS, Park JD, Choi JH, Son DW. Increase of interleukin-6 in tracheal aspirate at birth: a predictor of subsequent bronchopulmonary dysplasia in preterm infants. Acta Paediatr 2006;95:38-43.
  21. Panickar J, Scholefield H, Kumar Y, Pilling DW, Subhedar NV. Atypical chronic lung disease in preterm infants. J Perinat Med 2004;32:162-7. https://doi.org/10.1515/JPM.2004.029
  22. Skinner J. Diagnosis of patent ductus arteriosus. Semin Neonatol 2001:6:49-61. https://doi.org/10.1053/siny.2000.0037
  23. Henry GW. Noninvasive assessment of cardiac function and pulmonary hypertension in persistent pulmonary hypertension of the newborn. Clin Perinatol 1984;11:627-40.
  24. Walsh MC, Kliegman RM, Fanaroff AA. Necrotizing enterocolitis: a practitioner's perspective. Pediatr Rev 1988;9:219-26. https://doi.org/10.1542/pir.9-7-219
  25. The Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Pediatrics 1984;74:127-33.
  26. Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982;145:1-8. https://doi.org/10.1093/infdis/145.1.1
  27. Salafia CM, Weigl C, Silberman L. The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. Obstet Gynecol 1989;73:383-9.
  28. Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006;355:343-53. https://doi.org/10.1056/NEJMoa061088
  29. Furman L, Baley J, Borawski-Clark E, Aucott S, Hack M. Hospitalization as a measure of morbidity among very low birth weight infants with chronic lung disease. J Pediatr 1996;128:447-52. https://doi.org/10.1016/S0022-3476(96)70353-0
  30. Berger TM, Bachmann II, Adams M, Schubiger G. Impact of improved survival of very lowbirth-weight infants on incidence and severity of bronchopulmonary dysplasia. Biol Neonate 2004;86:124-30. https://doi.org/10.1159/000078953
  31. Garland JS, Buck RK, Allred EN, Leviton A. Hypocarbia before surfactant therapy appears to increase bronchopulmonary dysplasia risk in infants with respiratory distress syndrome. Arch Pediatr Adolesc Med 1995;149:617-22. https://doi.org/10.1001/archpedi.1995.02170190027005
  32. Gonzalez A, Sosenko IR, Chandar J, Hummler H, Claure N, Bancalari E. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr 1996;128:470-8. https://doi.org/10.1016/S0022-3476(96)70356-6
  33. Kraybill EN, Runyan DK, Bose CL, Khan JH. Risk factors for chronic lung disease in infants with birth weights of 751 to 1000 grams. J Pediatr 1989;115:115-20. https://doi.org/10.1016/S0022-3476(89)80345-2
  34. Marshall DD, Kotelchuck M, Young TE, Bose CL, Kruyer L, O'Shea TM. Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association. Pediatrics 1999;104:1345-50. https://doi.org/10.1542/peds.104.6.1345
  35. Choi CW, Kim BI, Jo HS, Park JD, Kim CJ, Yoon BH, et al. Classification and Risk Factors for Chronic Lung Disease (CLD) of Prematurity: Classical CLD Versus Atypical CLD. J Korean Pediatr Soc 2001;44:1222-32.
  36. Kim YD, Kim HG, Kim EA, Kim KS, Pi SY. Clinical characteristics of premature infants with atypical chronic lung disease. J Korean Soc Neonatol 2002;9:45-9.
  37. Kotecha S, Wangoo A, Silverman M, Shaw RJ. Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity. J Pediatr 1996;128:464-9. https://doi.org/10.1016/S0022-3476(96)70355-4
  38. Matsuda T, Nakajima T, Hattori S, Hanatani K, Fukazawa Y, Kobayashi K, et al. Necrotizing funisitis: clinical significance and association with chronic lung disease in premature infants. Am J Obstet Gynecol 1997;177:1402-7. https://doi.org/10.1016/S0002-9378(97)70082-6
  39. Choi CW, Hwang JH, Shim JW, Ko SY, Lee EK, Kim SS et al. Decreasing incidence of chronic lung disease despite the gradual reduction of postnatal dexamethasone use in very low birth weight infants. J Korean Med Sci 2004;19:514-8. https://doi.org/10.3346/jkms.2004.19.4.514
  40. Grier DG, Halliday HL. Management of bronchopulmonary dysplasia in infants: guidelines for corticosteroid use. Drugs 2005;65:15-29. https://doi.org/10.2165/00003495-200565010-00002
  41. Bancalari E, Claure N, Sosenko IR. Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol 2003;8:63-71.o https://doi.org/10.1016/S1084-2756(02)00192-6