儿童闭塞性细支气管炎课件

儿童闭塞性细支气管炎Bronchiolitis

Obliterans(BO)in

children患儿，男，2岁。2009.12,曾因发热，喘息1周入PICU。

诊断毛细支气管炎，

EB病毒感染，呼吸衰竭，中毒性脑病。20

天后

出院。出院口服顺尔宁，但一直有咳嗽，喘息症状。出院1个月后，因咳嗽、喘息，诊断：儿童哮喘。吸入普米克/可必特治疗。咳嗽减轻，但仍喘息，每于活动

后喘息明显，休息后缓解。既往史：患儿有湿疹史(较重),曾有2次喘息史；家族史：其小姨的孩子有哮喘。病历摘要吉林大学

第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITY病例(1)辅助检查：血常规：

WBC:4.5×10(9)/L,NE:66.2%,

128g/LCRP:3.29mg/L。MP-IgM:1:40;CP-IgM:

阴性血总

Ig

E:

679U/ML,血食物+呼吸特异性Ig

E:

牛羊肉

2.0血气：

PH7.32,Pa0₂66.8mmHg,辅助检查PaCO₂54.1mmHg,BE2.4mmol/l.吉林大学第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYHb:10cm5120812402:L11R0Hm451020他2ww.12

WL-#0

12*31eMUMANHeipAAo12#0521017700V1200ma3F⁰4400@

20mm1

10lw121eM²msnhm40020网吉林太学

第二医院THESECOND

HOSPITALOFJILIN

UNIVERSITY0

ieWu-600网

两CMQE*JRGH

Fhdererti200年12月26日2210000P

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042!1049040UwM²Dmor#hi

423001202*日

G2:101i⁶di⁰S中JwW.12mF(8621%Ww¹2ait12000

mt网m10cm10mB患儿，男，2岁因发热5天，皮疹1天住院。诊断麻疹。住院第4天咳嗽，住院后6天家长要求出院。出院5天后，再次出现发热39.8

度，咳嗽加重，再次入院，诊断：重症肺炎。MPP(1:1280),

住院20余天，症状好转出院。回家后雾化

吸入普米克和可必特治疗。活动后仍喘息。三个月后，再次因发热，咳嗽、喘息加重住院，诊断大叶

肺炎，肺脓肿，儿童哮喘，住院20天好转出院，出院后仍

喘息，咳嗽。既往史：湿疹(+),既往无喘息史。不爱揉鼻、眼

家族史：无喘息家族史。IgE

14.5U/ml

血食物+呼吸特异性Ig

E:阴性。病历摘要吉林太学第二医院THESECONDHOSPITALOFJILINUNIVERSITY病

例(

2

)M/10

monthsSe:2Im:43-768.90R10cmKV:120.00mA:51FOV:500.002.00mm1-768.90C.M.USHENGJINGHosp

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102009年5月23日

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BOM/1d

monthsSe:2lm:38-778.90kV:120.00mA51FOV:500.002.00mmt-778.90kV:120.00mA;5FOV500.002.00mm-796.90V:120.00mA51FOV:500.002.00mm-804.90C.MUSHENGJIING

Hosp

Philips

Erilliance6410cm66.21%

ww:1200WL-600

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WL-600512X51266.21%

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512X5122009年5月23日

13:28:43.250000ID:1000999938

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EN

BO同

田

日

田用

日

田田RIRIRISe:2Im:46-793.10[R]9cmkV:120.00mA:51FOW:500.002.00mm/-79310Se:2lm:53-778.10[R]Gcmkv:120.00mA:51FOV:500.002.00mm-779m10Se:2lm:50-785.10[R]9cmKV:120.00mA.51FOv500.002.00mm-78510出院2月后(2009-08-04),轻咳、活动后喘促，

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BOM112

monthsC.M.U

SHENGJING

HosrFhilips

Erilliance

642009年8月4日ID:1001092907WU

EN

BOM12

monthsCM.U

SHENGJING

HospFhilipsErilliance642009年8月4日ID:1001092907WU

EN

BOM/12

monthsCM.U

SHENGJINGHospFhilips

Erilliance642009年8月4日CM

U

SHENGJING

Hosp

Fhilips

Erilliance

64

2009年8月4日13:06:37.92995;ID:1001092907WU

EN

BO;M12

monthsSe:2;Im:398-807.10KV:120.00mA:51FOv:500.002.00mm1-807109cm66.21%

Ww:1201WL-6066.21%ww:1200

WL-600512×51266.21%

ww:1200WL-600

512×51266.21%Ww:1200

WL-600

512X51213:06:37.63900013:06:37.52199813:06:37.366001调RID:1001614350WU

EN

BOMi2vearsCM

USHENGJING

HOSPITALSIEMENS

Sensation64

2010年8月23日[R

FkV:120.00mA:30FOV:500.002.00mm/-488:50SIEMENS

Sensation64

2010年8月23F10:24:23.63304kV:120.00mA.90FOv500.002.00mm1-494.50kV:120.00mA:90FOv:500.002.00mm/-472:50SIEMENS

Sensation64

2010年8月23日

10:24:23.441415kv:120.00mA:90FOV:500.002.00mm-464.50WU

EN

BOMI2yearsSe:3lm:38-472.5010cm66.21%ww:1200WL-600512×512左肺散在水泡音10cm66.21%ww:1200WL-600512X51210cm66.21%ww:1200WL-600512X512Mr2years

Se:3;lm:27-494.50Ml2

yearsSe:3Im:30-488.5010cm66.21%ww:1200WL:-6002010年8月23日10:24:23.172698SIEMENS

Sensation64WU

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HOSPITALCM.U

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HOSPITAL10:24:23.587824ID:1001614350ID:1001614350ID:1001614350WU

EN

BQ[R]F一十g呼吸道粘膜RespiratoryMucosa肺泡横切面CneeCactinn

of

AlveolusRghtmddle

lcharbnchor

ViewUngulardwelonbronchusLaftsuperioelotarbronchus

左下叶支气管终末细支气管

Terminal

bronchiode右肺副裂Horizontal

fissure通气规体进出呼小

管TubueMnus

celsobigue

fissurerior

lobe:Cardiac

notch肺尖Apex

of

lungLateral

basal=}Alveolar

ductsTerminalbronchioleSmooth

muscleElastic

fibersAlveolusSubdivisionsandStructureofIntrapulmonaryAirwaysRespiratoryl

ndaarductsAlveo

gs

gmentalns)io5tieesuLaS(a

oaultl

onchio

rcd

s.ershiolonTerminalbronchiolesalveolar

sacs'generationsSegmentalbronchusAlveolaiand

alvCartilageBronchiBronchiolesAcinusAcinusLobuleBronchiolitis

obliterans

(BO)is

an

irreversibleobstructive

lung

disease

characterizedbysubepithelial

inflammation

and

fibroticnarrowing

ofthe

bronchioles1)In

the

pediatric

clinical

field,three

main

categoriesof

BOare

generally

encountered:(1)postinfectiousBO(PIBO),(2)BO

after

hematopoietic

stem

celltransplantation

(HSCT),and

(3)BO

after

lung

transplantation(LT).Introduction吉林大学第二医院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITYPostinfectious

bronchiolitis

obliterans

(PIBO)is

an

irreversibleobstructive

lung

disease

characterized

by

subepithelialinflammation

and

fibrotic

narrowing

of

the

bronchioles

afterlower

respiratory

tract

infection

during

childhood,especially

earlychildhood.Postinfectious

bronchiolitis

obliterans

in

children:lessons

from

bronchiolitisobliteransafterlungtransplantationandhematopoieticstemcelltransplantationReviewarticleKoreanJPediatr2015;58(12):459-465CurrentresearchonpediatricpatientswithbronchiolitisobliteransinBrazilIntractable

Rare

Dis

Res.2015

February;4(1):7-11.吉林大学

第二医院THESECOND

HOSPITALOFJILIN

UNIVERSITYAlthoughtheprevalence

ofPIBOhasnot

been

estimatedaccurately,0.6%of3,141

autopsies

and

lung

biopsiesperformed

at

a

single

center

were

diagnosed

as

BO,andmostof

thesecases

were

PIBO).The

prevalence

of

BO

after

HSCT

among

cases

with

allogeneic

HSCT

is

2%-6%

).The

prevalence

of

BO

after

LT

was

markedly

higher,up

to

35%within

5

years

posttransplant13),than

theprevalence

of

PIBO

andBO

afterHSCT.Epidemiology吉林大学

第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYPathogenesis(1)Epithelial

injury

inducedby

lowerrespiratorytract

infectionsuchasvirusand

mycoplasma(3)Smooth

muscle

hyperplasia

(2)1L-8,proinfammatorycytokines3MMPohermediats吉林太学

第二医院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITY(4)CD⁸T

cell

(5)Th17

cell

IL-17(3)Matixdegradation,collagendeposition(3)Fibroblasttransformation(3)NeovascularizationEpithelial

cell(2)Neutrophil感染性用塞性细支气管炎，常见病喜(腺病毒、呼吸道合胞病毒、流感病喜、副流感病喜)支原体结缔组织病(类风湿性关节炎和嗜酸性筋膜炎)公吸入性损伤(二氧化氮、二氧化硫、氨、氟、光气、灼热气体、飞灰等)毒物服入异体移植物受者(心肺联合移植或肺移植、骨髓移植

)药物(青零胺、洛莫司汀、可卡因、金等)其他异发症：夹症性肠病、种经内分泌细胞增生

、

多

发性类癌样微瘤、

副肿霜天疱疮吉林大学

第二医院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITYBO

相关病因和基础疾病PIBO与腺病毒

(ADV)呼吸道合胞病毒

(RSV)支原体感染麻疹病毒流感病毒副流感病毒巨细胞病毒Etiology

inchildren吉林大学

第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYRisk

FactorP

I

B

O

发

生

的

危

险

因

素ADV毛细支气管炎住院时间超过30天

多病灶肺炎需机械通气治疗高碳酸血症(OR=49.9)(OR=27.2)(OR=26.6)(OR=11.9)(OR=5.6)。病因不同，但组织病理学改变相似缩窄性细支气管炎和增殖性细支气管炎增殖性细支气管炎以肉芽组织在气道内呈息肉团块增生为特征肺泡腔内亦出现肉芽组织时，则称为闭塞性细支气管炎伴机化性肺炎(BOOP)PathologyChildhood

PIBO

绝大多数为缩窄性早期上皮细胞坏死，气道炎症细胞浸润相邻肺实质正常或仅有轻微改变细支气管变形，胶原沉积，黏液渗出后期形成黏膜下纤维化，管腔进行性变窄，

最终形成闭塞气道阻塞间接征象黏液潴留巨噬细胞聚集肺过度充气细支气管变形扩张支气管上皮细胞肥大，上皮层变厚，管腔可出现阻塞甚或闭塞Constrictivebronchiolitisin

SLE吉林太学

第二医院THESECOND

HOSPITALOFJILIN

UNIVERSITY肺泡灌洗液中以中性粒细胞增多为主

部分区域淋巴细胞增多中性粒细胞趋化因子IL-8

浓度增高

这些变化仍存在于肺损伤数年之后The

initialsymptomsandsignsofBOare

similartoacuteviralbronchiolitis:

fever,cough,tachypnea,andwheezing

(1,3).Butthediseasedoes

not

progressasexpectedandsymptomsandsignspersistforweeksor

months.PatientswithBOhavetachypnea,dyspnea,hypoxemia,

crackles,wheezing,an

increasedantero-posteriordiameterofthechest,digitalclubbing,andcyanosis(3,Z,12,17).Ina

previousstudy

bythecurrentauthors

(10),themostcommonsymptomsandsignsof

BO

in40patientswerewheezing,dyspnea,andcoughing(Table

1).吉林大学

第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYClinicalsymptomsandsigns

Brazilianstudies(6,9,10,18)

foundthat

characteristicfindings

in

HRCTwere:amosaic

patternof

perfusionbronchiectasisbronchialwallthickeningairtrappingatelectasishigh-resolutionchesttomography(HRCT)吉林太学

第二医院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITY吉林太学

第二医院THESECOND

HOSPITALOFJILIN

UNIVERSITYCT

inObliterative

BronchiolitisCardinal

FeaturesAreasof

decreasedattenuationReducednumber/calibreof

vesselsBronchialdilatationNoparenchymaldistortionNozonal

predilectionID:1001614350C.M.U.SHENGJING

HOSPITALID:1001614350CM.U

SHENGJING

HOSPITALWU

EN

BQSIEMENS

Sensation64WU

ENBQSIEMENS

Sensation64Ml2

years2010年8月23日Mr2years2010年8月23日Se:310:24:23.172698Se:310:24:23.63304Im:30;lm:27-488.50-494.50ID:1001614350

CM

U

SHENGJING

HOSPITAL

ID:1001614350

CM.U

SHENGJING

HOSPITAL[R

FkV:120.00mA90FOw500.002.00mm1-494.50kV:120.00mA:90FOv:500.002.00mm/-472:50SIEMENS

Sensation64

2010年8月23日

10:24:23.441415kV:120.00mA:90FOV:500.002.00mm-488.50kv:120.00mA:90FOV:500.002.00mm-464.50WU

EN

BOMI2yearsSe:3lm:38-472.5010cm66.21%ww:1200WL-600512×51210cm66.21%ww:1200WL-600512X51210cm66.21%

ww:1200WL-600512X512SIEMENS

Sensation64

2010年8月23日10cm66.21%ww:1200WL:-600Se:3Im:42-464.50WU

EN

BO

Mi2vears10:24:23.587824[R]FCT改变例数(N)构成比马赛克灌注空气滞留支气管壁增厚支气管扩张肺不张支气管黏液栓2202301952401651459278966658250例儿童及青少年CT

改变AlthoughadiagnosisofPIBO

should

beconfirmedbyhistopathology,most

pediatric

pulmonologistsdiagnose

PIBObasedonhistoryandclinicalfindingsaccordingtothefollowingcriteria:Diagnosis吉林大学

第二医院THE

SECONDHOSPITALOF

JILINUNIVERSITY(1)acutesevererespiratory

infectionduringchildhood,especiallyearlychildhood;(2)persistentairwayobstructionafterinitialinsultandunresponsivenesstosystemicsteroidsandbronchodilators,asdemonstrated

byclinicalsymptomsandsigns,anda

lungfunctiontest,ifitcan

be

performed;(3)

mosaic

perfusion,airtrapping,and/orbronchiectasisinchestcomputedtomography;

and吉林大学

第二医院THESECONDHOSPITALOFJILINUNIVERSITY(4)exclusionofotherchronic

lungdiseasessuchassevereasthma,bronchopulmonarydysplasia,chronicaspiration,primaryciliarydyskinesia,cysticfibrosis,immunodeficiency,

andalpha-1-antitrypsindeficiency(Table

1).吉林大学

第二医院THESECONDHOSPITALOFJILINUNIVERSITYRecentstudiesofclinical

predictionrulesto

diagnose

PIBO

inchildrenfoundthattypical

clinical

history,adenovirus

infection,and

high-resolutioncomputedtomographywithmosaic

perfusionwere

highly

predictable

variables32).吉林大学第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYHistory

of

lower

respiratory

infection,particularly

adenovirus,mycoplasma,ormeasles. Persistent

airway

obstruction

symptoms

and

signs,or

recurrent

airway

obstruction

symptoms

and

signs

in

a

mild

form. Sign

of

obstruction:FEV1/FVC<0.8or

FEV1percent

predicted<80%. Irreversible

airway

obstruction

demonstrated

by

lung

function

test:absent

BDR,but

positive

BDR

in

some

patients. CT(inspiration

and

expiration):mosaic

perfusion,air

trapping,and/or

bronchiectasis.Exclusion

of

other

chronic

lung

disease

(asthma,BPD,chronic

aspiration,PCD,cystic

fibrosis,and

immunodeficiency). Postinfectious

bronchiolitis

obliterans

is

clinically

diagnosed

when

all

of

the

above

criteria

are

met.FEV1,forced

expiratory

volume

in1second;FVC,forced

vital

capacity;BDR,

bronchodilator

response;BPD,bronchopulmonary

dysplasia;CT,computed

tomography;PCD,primary

ciliary

dyskinesia.吉

林

大

学第二医院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYTable

1.Diagnosisof

postinfectiousbronchiolitisobliteransAlthough

the

optimal

treatment

of

PIBO

has

notbeen

established,corticosteroids

have

been

usedto

combat

the

inflammatory

component.Systemic

steroids

can

be

used

rather

than

inhaled

steroids

in

consideration

ofthe

obliteration

ofthe

small

airways. Prolonged

oral

steroid

therapy

over

a

period

of

2months

to

2

years

was

applied

to

about

70%ofchildren

with

PIBO

in

a

relatively

long-termobservational

study13)吉林大学

第二医院THESECONDHOSPITALOFJILINUNIVERSITYTreatment Some

studies

have

used

pulse

therapy

with

methylprednisolone(30mg/kg/day)for3days

per

month

to

treat

PIBO,and

this

strategy

isexpected

to

have

fewer

side

effects

comparedto

daily

oral

steroids5,38).Systemicsteroidsshouldbegiven

intheearlyperiodofthedisease,before

fibrosisis

established.吉林太学

第二医院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITYBythetimeadiagnosisofPIBO

is

made,the

smallairwaysmightalreadybeobliteratedwithfibrosis.Furthermore,afterthestartofsystemicsteroidsto

treat

PIBO,thequestionarisesastohow

longinflammation

lastsafterthedevelopmentofPIBO.Sincetheanswertothisquestion

is

unknown,it

isdifficulttoknowwhentostartandfinishsystemicsteroidtherapy.Althoughthetimingofthedecision

to

treatthediseaseandthedurationofsmallairwayinflammationdiffersbetween

BOafterHSCT

and

PIBO,sevenofninepatientsafter

HSCT

receiving

upto

six

cyclesofmethylprednisolonepulsetherapywereclinicallystablewithoutfurtherdeclineoflungfunction39).吉林大学

第二医院THESECONDHOSPITALOFJILINUNIVERSITYAlthough,theoretically,abronchodilatorresponseshouldbeabsent

inchildrenwith

fixedairwayobstructionsuchas

in

PIBO,a

positivebronchodilatorresponserangingfrom10%to42.9%was

presentinchildrenwith

PIBO13,30,45).Theuseofabronchodilatorbeta-2-agonistshouldbeappliedonan

individualbasisaccordingtothebronchodilatorresponse.吉