儿童闭塞性细支气管炎临床特征分析
摘要
通过探讨14例闭塞性细支气管炎(Bronchiolitis Obliterans,BO)患儿的临床特征、治疗和预后,讨论BO患儿早期诊断方法、进行有效的治疗,改善BO患儿的预后。收集2006年3月至2008年12月在我院明确临床诊断为BO的14例患儿的临床症状、体征、实验室检查、影象学检查、治疗、转归,随访上述患儿并行肺功能检查,将临床资料与同期存在喘息的肺炎患儿的临床资料进行配对对比分析。达到BO诊断标准的14例BO患儿,分别存在病毒、细菌、肺炎支原体及衣原体感染,与同期喘息性肺炎患儿的病原体大致相同。14例BO患儿肺CT早期以实变为主,后期出现“马赛克”改变,而喘息性肺炎患儿肺CT示炎症。随访BO患儿肺功能示阻塞性或混合性通气功能障碍。上述患儿分别于住院时静脉、雾化吸入激素,使用支气管扩张剂、抗感染及对症支持治疗,喘息性肺炎患儿无症状及体征好转出院,而BO患儿因症状及体征持续存在,出院后需继续行相应治疗。14例BO患儿中,3例失随访,10例好转(90.9%),仅有1例症状及体征无明显改善(9.1%),目前无死亡病例。儿童BO以感染所致者多见,好发于2岁以内儿童,冬春季发病率高,诊断需结合慢性咳嗽、反复或持续性喘息以及运动后加重的症状,高分辨率肺CT表现及肺功能。若于急性下呼吸道感染4周后持续存在咳嗽及喘息,需注意本病。肺动脉高压及辅助通气治疗可能提示患儿病情严重、预后不佳,病情严重程度及预后的判定可依赖于肺功能检查,治疗以激素、大环内酯类β_2受体激动剂等药物为主,大多BO患儿预后不佳。
Objective:Postinfectious bronchiolitis obliterans(BO) designates a clinical syndrome of chronic airflow obstruction associated with inflammatory and fibrotic changes in the small airways.BO is usually observed after infection in children,with the clinical presentation of recurrent or persistent wheezing and coughing,worsening by activity.The quality of patients' life are seriously affected.The definite diagnosis depends on lung biopsy,however,the use of lung biopsy is limited since it is an invasive method for the infants.The initial clinical and radiological presentation does not differ from acute bronchiolitis or viral pneumonia,which makes it is difficult for clinicians to diagnose BO at its early stage.Fortunately,high-resolution computed tomography contributes to the elavated diagnostic rates of of BO in last few years.The aim of this study was to determine the etiology,clinical and radiological features and of postinfectious BO in children,try to identify the prognostic factors and proper treatment.
Method:We undertook a retrospective review of the medical records of 14 patients with a clinical and radiological diagnosis of postinfectious BO who were diagnosed and treated in our department and then followed up between March,2006 to the December,2008,and the patients diagnosised as pneumoniae with wheezing.BO are diagnosed by follwing clinical features and HRCT findings:(1) a previously documented acute lung infection with persistence of respirarory symptoms;(2) wheezing and(or) crackles;(3) a relatively mild impairment image of lung in chest x-ray that not parrallel with their serious clinical features.(4) HRCT features indicate mosaic perfusion pattern,uneven of ventilation,air trapping on expiration,bronchiectasia, and bronchial wall thickening.(5) Chest radiograph persents hyperlucency of single lung.(6) pulmonary funtion tests confirm airway obstruction.(7) exclusion of other causes of chronic obstructive pulmonary diseses.Furthermore,the wheezing patients who was diagnosed as pneumoniae would be excepted for BO.All documents of patients were analysed retrospectively.The medical records cover the sex, age,history,temperature,clinical symptom,physical sign,blood routine, CRP,hepatic function,ases of cardiac muscle,immunity,serum antibodies of mycoplasma pneumoniae,respiratory syncytial virus, cytomegalovirus DNA,serum hepatitis virus,the results of hemoculture and sputum culture,the history of treatment and the prognosis.All of the 14 patients were Followed-up,mornitering the respiratory tract infection, clinical features,treatment and lung function changes.Meanwhile,14 patients who have been diagnosed as wheezing pneumoniae in our department were selected as control.The parameters above of two groups were matched and compared.
Results:Our study found all of 14 patients had been infected. Bacterium,viruses,mycoplasma pneumonia and chlamydia are common etilogical pathogen.Parts of them were even infected by more than one agents.Following are pathogens involved in the infection,according to patients' data:Bacillus coli(7.1%),baumanii and pseudo-yeast fungus (7.1%),cytomegalovirus(14.2%),hepatitis B(14.2%),mycoplasma pneumoniae(21.4%),chlamydia(14.2%).The agents of dieases are as the same as the conditon in pneumoniae.All patients' chest CT presented mosaic perfusion pattern(100%),accompanying with bronchiectasis and membrana pleuralis thickening(35.7%),consolidation and minification of lung(7.1%) while all presentations of CT in wheezing pneumoniae revealed fine.Three out of 14 patients quit the rearch.Symptoms and physical signs released in 10 of 11 patients without sports(90.9%).As for the pulmonary function changes at the end of the study,only one of 7 was mixed obstruction(14.3%),one out of 7 showed severe obstruction (14.3%),2 out of 147 presented median obstruction(28.5%) and 3 out of 7 showed slight obstruction(42.9%).The values of Ti/Te,TPTEF/TE and VPTEF/VE were much less than the normal value.All of these patients were treated with methylprednisolone,budesonide and salbutamol,while being treated with antibiotics if there were identifed infection evidences in hospital.9 of 11 patients were administrated with oral hormone and 7 of 11 patients inhaling budesonide and salbutamol after leaving the hospital.All of them took up macrolide.3 out of 14 BO patients quit the follow-up.Excepting for sports,10 out of 11 BO patients showed recovery(09.9%),only 1 out of 11 BO patients showed no improvement at the end of the study(9.1%).All of them are alive.
Conclusion:The results of our study indicated that in children,BO are mostly postinfectious and the common pathogens are bactirum, viruses,mycoplasma and chlamydia.BO are diagnosised under the 2 years old infants during winter and spring.The CT of lung at the early stage of the disease shows consolidation while uneven of ventilation and mosaic perfusion pattern could only be observed later.The values of Ti/Te, TPTEF/TE,VPTEF/VE were less than the common and the pulmonary function shows the obstructive ventilation.The occurrences of pulmonary artery protrusion and mechanical ventilation may predict the bad prognosis.If the cough and wheezing stays more than 4 weeks after severe low respiratory,the CT detection should be taken in order to clearify the diagnose.The further study is necessary for revealing the value of pulmonary function test in predicting BO in patients with pneumonia with wheezing.No significant diference in clinical features was identified in patients who took 12 months or more than 12 months of oral hormone,respectively.The prognosis is not usually fine if the care of patients(especially lung care) are performed closely.Base on this study, the research suggests that the length of oral hormone is less than 1 year, and the different effects of oral hormone,inhalation of drugs and the combination treatments will be investigated in near future to evaluate the effect of inhalation of drugs,such as budesonide and salbutamol at recovery stage,and try to reduce the side effect of cortisteroid.
Objective:Postinfectious bronchiolitis obliterans(BO) designates a clinical syndrome of chronic airflow obstruction associated with inflammatory and fibrotic changes in the small airways.BO is usually observed after infection in children,with the clinical presentation of recurrent or persistent wheezing and coughing,worsening by activity.The quality of patients' life are seriously affected.The definite diagnosis depends on lung biopsy,however,the use of lung biopsy is limited since it is an invasive method for the infants.The initial clinical and radiological presentation does not differ from acute bronchiolitis or viral pneumonia,which makes it is difficult for clinicians to diagnose BO at its early stage.Fortunately,high-resolution computed tomography contributes to the elavated diagnostic rates of of BO in last few years.The aim of this study was to determine the etiology,clinical and radiological features and of postinfectious BO in children,try to identify the prognostic factors and proper treatment.
Method:We undertook a retrospective review of the medical records of 14 patients with a clinical and radiological diagnosis of postinfectious BO who were diagnosed and treated in our department and then followed up between March,2006 to the December,2008,and the patients diagnosised as pneumoniae with wheezing.BO are diagnosed by follwing clinical features and HRCT findings:(1) a previously documented acute lung infection with persistence of respirarory symptoms;(2) wheezing and(or) crackles;(3) a relatively mild impairment image of lung in chest x-ray that not parrallel with their serious clinical features.(4) HRCT features indicate mosaic perfusion pattern,uneven of ventilation,air trapping on expiration,bronchiectasia, and bronchial wall thickening.(5) Chest radiograph persents hyperlucency of single lung.(6) pulmonary funtion tests confirm airway obstruction.(7) exclusion of other causes of chronic obstructive pulmonary diseses.Furthermore,the wheezing patients who was diagnosed as pneumoniae would be excepted for BO.All documents of patients were analysed retrospectively.The medical records cover the sex, age,history,temperature,clinical symptom,physical sign,blood routine, CRP,hepatic function,ases of cardiac muscle,immunity,serum antibodies of mycoplasma pneumoniae,respiratory syncytial virus, cytomegalovirus DNA,serum hepatitis virus,the results of hemoculture and sputum culture,the history of treatment and the prognosis.All of the 14 patients were Followed-up,mornitering the respiratory tract infection, clinical features,treatment and lung function changes.Meanwhile,14 patients who have been diagnosed as wheezing pneumoniae in our department were selected as control.The parameters above of two groups were matched and compared.
Results:Our study found all of 14 patients had been infected. Bacterium,viruses,mycoplasma pneumonia and chlamydia are common etilogical pathogen.Parts of them were even infected by more than one agents.Following are pathogens involved in the infection,according to patients' data:Bacillus coli(7.1%),baumanii and pseudo-yeast fungus (7.1%),cytomegalovirus(14.2%),hepatitis B(14.2%),mycoplasma pneumoniae(21.4%),chlamydia(14.2%).The agents of dieases are as the same as the conditon in pneumoniae.All patients' chest CT presented mosaic perfusion pattern(100%),accompanying with bronchiectasis and membrana pleuralis thickening(35.7%),consolidation and minification of lung(7.1%) while all presentations of CT in wheezing pneumoniae revealed fine.Three out of 14 patients quit the rearch.Symptoms and physical signs released in 10 of 11 patients without sports(90.9%).As for the pulmonary function changes at the end of the study,only one of 7 was mixed obstruction(14.3%),one out of 7 showed severe obstruction (14.3%),2 out of 147 presented median obstruction(28.5%) and 3 out of 7 showed slight obstruction(42.9%).The values of Ti/Te,TPTEF/TE and VPTEF/VE were much less than the normal value.All of these patients were treated with methylprednisolone,budesonide and salbutamol,while being treated with antibiotics if there were identifed infection evidences in hospital.9 of 11 patients were administrated with oral hormone and 7 of 11 patients inhaling budesonide and salbutamol after leaving the hospital.All of them took up macrolide.3 out of 14 BO patients quit the follow-up.Excepting for sports,10 out of 11 BO patients showed recovery(09.9%),only 1 out of 11 BO patients showed no improvement at the end of the study(9.1%).All of them are alive.
Conclusion:The results of our study indicated that in children,BO are mostly postinfectious and the common pathogens are bactirum, viruses,mycoplasma and chlamydia.BO are diagnosised under the 2 years old infants during winter and spring.The CT of lung at the early stage of the disease shows consolidation while uneven of ventilation and mosaic perfusion pattern could only be observed later.The values of Ti/Te, TPTEF/TE,VPTEF/VE were less than the common and the pulmonary function shows the obstructive ventilation.The occurrences of pulmonary artery protrusion and mechanical ventilation may predict the bad prognosis.If the cough and wheezing stays more than 4 weeks after severe low respiratory,the CT detection should be taken in order to clearify the diagnose.The further study is necessary for revealing the value of pulmonary function test in predicting BO in patients with pneumonia with wheezing.No significant diference in clinical features was identified in patients who took 12 months or more than 12 months of oral hormone,respectively.The prognosis is not usually fine if the care of patients(especially lung care) are performed closely.Base on this study, the research suggests that the length of oral hormone is less than 1 year, and the different effects of oral hormone,inhalation of drugs and the combination treatments will be investigated in near future to evaluate the effect of inhalation of drugs,such as budesonide and salbutamol at recovery stage,and try to reduce the side effect of cortisteroid.
引文
[1]侯杰,主编.现代肺弥漫性疾病学[M].北京:人民中医出版社,2003.266-273.
[2]Kurland G,Michelson P.Bronchiolitis obliterans in children[J].Pediatr Pulmonol 2005,39:193-208.
[3]Markopoulo KD,Cool CD,Elliot TL,et al.Obliterative bronchiolitis:varying presentations and clinicopathological correlation[J].Eur Respir J 2002,19:20-30.
[4]Colom AJ,Teper AM,Vollmer WM,Diette GB.Risk factors for the development of bronchiolitis obliterans in children with bronchiolitis[J].Thorax 2006,61:503-506.
[5]Chiu CY,Wong KS,Huang YC,Lin TY.Bronchiolitis obliterans in children:clinical presentation,therapy and long-term follow-up[J].J Paediatr Child Health 2008,44:129-133.
[6]Kim CK,Kim SW,JS,et al.Bronchiolitis obiterans in the 1990s in Korea and the United States[J].Chest 2001,120:1101-1106.
[7]Hardy KA.Obliterative bronchiolitis[J].Chest 1988,93(3):460-466.
[8]Chan PW,Muridan R,Debuyne JA.Bronchiolitis obliterans in children:clinical profile and diagnosis[J].Respirology 2000,5(4):369-75.
[9]Sly PD,Soto-Quiros ME,Landau LI,Hudson I,Newton-John H.Factors predisposing to abnormal pulmonary function after adenovirus type 7 pneumonia[J].Arch Dis Child 1984,59(10):935-9.
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[13]Colby TV.Bronchiolitis.Pathologic considerations [J].Am J Clin Pathol 1998,109(1):101-9.
[14]Koh YY,Jung da E,Koh JY,et al.Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis boliterans[J].Chest 2007,131:1454-1460.
[14]Costa CL,Spilborghs GM,Martins MA,et al.Nitric acid-induced bronchiolitis in rats micics childhood Bronchiolitis obliterans[J].Respiration 2005,72:642-649.
[15]Yalcin E,Dogru D,Haliloglu M,et al.Pstinfectious bronchiolitis obliterans in children:clinical and radiological profile and prognostic factors[J].Respiration,2003,70:371-375.
[16]刘秀云,江载芳,申昆玲,等.四例闭塞性毛细支气管炎临床分析[J].中华儿科杂志,2003,41:839-841.
[17]王雷,陈贤楠.闭塞性细支气管炎的诊断与治疗[J].小儿急救医学,2004,11:61.
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[21]Ferkol TW,Davis PB.Bronchiectasis and Bronchiolitis Obliterans[J].Pediatric Respiratory Medicine,1999,784-92.
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[1]侯杰,主编.现代肺弥漫性疾病学[M].北京:人民中医出版社,2003:266-273.
[2]Kurland G,Michelson P.Bronchiolitis obliterans in children[J].Pediatr Pulmonol 2005,39:193-208.
[3]Markopoulo KD,Cool CD,Elliot TL,et al.Obliterative bronchiolitis:varying presentations and clinicopathological correlation[J].Eur Respir 2002,19:20-30.
[4]Colom A J,Teper AM,Vollmer WM,Diette GB.Risk factors for the development of bronchiolitis obliterans in children with bronchiolitis[J].Thorax 2006,61:503-506.
[5]Chiu CY,Wong KS,Huang YC,Lin TY.Bronchiolitis obliterans in children:clinical presentation,therapy and long-term follow-up[J].Paediatr Child Health 2008,44:129-133.
[6]Kim CK,Kim SW,JS,et al.Bronchiolitis obiterans in the 1990s in Korea and the United States[J].Chest 2001,120:1101-1106.
[7]Hardy KA.Obliterative bronchiolitis[J].CHEST 1988,93(3):460-466.
[8]Teper AM,Kofman CD,Maffey AF,et al.Lung function in infants with chronic pulmonary disease after severe adenoviral illness[J].Pediatr 1999,134:730-3.
[9]Chang A,Masel J,Masters B.Post-infectious bronchiolitis obliterans:clinical,radiological and pulmonary function sequelae[J].Pediatr Radiol 1998,28:23-9.
[10]Zhang L,Irion K,Kozakewich H,et al.Clinical course of postinfectious bronchiolitis obliterans[J].Pediatr Pulmonol 2000,29:341-50.
[11]Castro-Rodriguea JA,Daszenies C,Garcia M,et al.Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans:a 5-ear follow-up[J].Pediartr Pulmonol 2006,41:947-953.
[12]Yalcin E,Dogru D,Haliloglu M,et al.Pstinfectious bronchiolitis obliterans in children:clinical and radiological profile and prognostic factors[J].Respiratation,2003,70:371-375.
[13]Myers JL,Colby TV.Pathologic manifestations of bronchiolitis,constrictive bronchiolitis,cryptogenic organizing pneumonia,and diffuse panbronchiolitis(Review)[J].Clin Chest Med,1993,14:611-622.
[14]刘秀云,江载芳,申昆玲,等.四例闭塞性毛细支气管炎临床分析[J].中华儿科杂志,2003,41:839-841.
[15]Thais Mauad,Marisa Dolhnikiff and the sao Paulo Bronchiolitis Obliterans Study Group.Histology of Childhood Bronchiolitis Obliterans[J].Pediatric Pulmonology,2002,33:466-474.
[16]Epler GR,Colby TV,McLoud TC,Carrington CB,Gaensler EA.Bronchiolitis obliterans organizing pneumonia [J].N Engl J Med 1985;312(3):152-8.
[17]Thais Mauad,Annemarie van Schadewijk,Jasmijn Schrumpf,C.Erik Hack,Sandra Fernezlian,Ana L.Garippo,Bernardo Ejzenberg,Pieter S.Hiemstra,Klaus F.Rabe,Marisa Dolhnikoff and Sa~o Paulo BO Study Group5.Lymphocytic Inflammation in Childhood Bronchiolitis Obliterans [J].Pediatric Pulmonology,2004,38:233-239.
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[20]VerledenGM,Vanaudenaerde BM,Dupont LJ,Van Raemdonck DE.Azithromcin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome[J].Am J Respir Crit Care Med 2006,174:566-570.
[21]Siby P.Moonnumakal,Leland L.Fan.Bronchiolitis obliterans in children[J].Current Opinion in Pediatrics 2008,20:272-278.
[22]Fullmer JJ,Fan JJ,Dishop MK,et al.Successfue treatment of bronchiolitis obliterans in a bone marrow transplant patient with tumor necrosis factor-alpha blockade[J].Pediatrics 2005,116:767-770.
[23]ISHLT.Registry of the International Society for Heart and Lung Transplantation:Tenth Official Pediatric Lung and Heart/Lung Transplantation Report—2007[C].Texas:Journal of heart and lung transplantation,2007.
[2]Kurland G,Michelson P.Bronchiolitis obliterans in children[J].Pediatr Pulmonol 2005,39:193-208.
[3]Markopoulo KD,Cool CD,Elliot TL,et al.Obliterative bronchiolitis:varying presentations and clinicopathological correlation[J].Eur Respir J 2002,19:20-30.
[4]Colom AJ,Teper AM,Vollmer WM,Diette GB.Risk factors for the development of bronchiolitis obliterans in children with bronchiolitis[J].Thorax 2006,61:503-506.
[5]Chiu CY,Wong KS,Huang YC,Lin TY.Bronchiolitis obliterans in children:clinical presentation,therapy and long-term follow-up[J].J Paediatr Child Health 2008,44:129-133.
[6]Kim CK,Kim SW,JS,et al.Bronchiolitis obiterans in the 1990s in Korea and the United States[J].Chest 2001,120:1101-1106.
[7]Hardy KA.Obliterative bronchiolitis[J].Chest 1988,93(3):460-466.
[8]Chan PW,Muridan R,Debuyne JA.Bronchiolitis obliterans in children:clinical profile and diagnosis[J].Respirology 2000,5(4):369-75.
[9]Sly PD,Soto-Quiros ME,Landau LI,Hudson I,Newton-John H.Factors predisposing to abnormal pulmonary function after adenovirus type 7 pneumonia[J].Arch Dis Child 1984,59(10):935-9.
[10]Castro-Rodriguea JA,Daszenies C,Garcia M,et al.Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans:a 5-ear follow-up[J].Pediartr Pulmonol 2006,41:947-953.
[11]Kajon AE,Larranaga C,Suarez M,Wadell G,Avendano LF.Genome type analysis of Chilean adenovirus strains isolated in a children's hospital between 1988 and 1900[J].J Med Virol 1994,42(1):16-21.
[12]Larranaga C,Kajon A,Villagra E,Avendano LF.Adenovirus surveillance on children hospitalized for acute lower respiratory infections in Chile (1988-1996) [J].J Med Virol 2000,60(3):342-6.
[13]Colby TV.Bronchiolitis.Pathologic considerations [J].Am J Clin Pathol 1998,109(1):101-9.
[14]Koh YY,Jung da E,Koh JY,et al.Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis boliterans[J].Chest 2007,131:1454-1460.
[14]Costa CL,Spilborghs GM,Martins MA,et al.Nitric acid-induced bronchiolitis in rats micics childhood Bronchiolitis obliterans[J].Respiration 2005,72:642-649.
[15]Yalcin E,Dogru D,Haliloglu M,et al.Pstinfectious bronchiolitis obliterans in children:clinical and radiological profile and prognostic factors[J].Respiration,2003,70:371-375.
[16]刘秀云,江载芳,申昆玲,等.四例闭塞性毛细支气管炎临床分析[J].中华儿科杂志,2003,41:839-841.
[17]王雷,陈贤楠.闭塞性细支气管炎的诊断与治疗[J].小儿急救医学,2004,11:61.
[18]Zhang L,Irion K,Kozakewich H,Reid L,Camargo JJ,da Silva Porto N,et al.Clinical course of postinfectious bronchiolitis obliterans[J].Pediatr Pulmonol 2000,29(5):341-50.
[19]Chang AB,Masel JP,Masters B.Post-infectious bronchiolitis obliterans:clinical,radiological and pulmonary function sequelae[J].Pediatr Radiol 1998,28(1);23-9.
[20]Hardy KA,Schidlow DV,Zaeri N.Obliterative bronchiolitis in children[J].Chest 1988,93(3):160-6.
[21]Ferkol TW,Davis PB.Bronchiectasis and Bronchiolitis Obliterans[J].Pediatric Respiratory Medicine,1999,784-92.
[22]Zhang L,Silva FA.Bronchiolitis obliterans in children[J].J Pediatr (Rio J),2000,76:185-192.
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