兒童閉塞性細支氣管炎Bronchiolitis

Obliterans(BO)in

children患兒，男，2歲。2009.12,曾因發(fā)熱，喘息1周入PICU。

診斷毛細支氣管炎，

EB病毒感染，呼吸衰竭，中毒性腦病。20

天后

出院。出院口服順爾寧，但一直有咳嗽，喘息癥狀。出院1個月后，因咳嗽、喘息，診斷：兒童哮喘。吸入普米克/可必特治療。咳嗽減輕，但仍喘息，每于活動

后喘息明顯，休息后緩解。既往史：患兒有濕疹史(較重),曾有2次喘息史；家族史：其小姨的孩子有哮喘。病歷摘要吉林大學

第二醫(yī)院THE

SECONDHOSPITAL

OF

JILINUNIVERSITY病例(1)輔助檢查：血常規(guī)：

WBC:4.5×10(9)/L,NE:66.2%,

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

陰性血總

Ig

E:

679U/ML,血食物+呼吸特異性Ig

E:

牛羊肉

2.0血氣：

PH7.32,Pa0?66.8mmHg,輔助檢查PaCO?54.1mmHg,BE2.4mmol/l.吉林大學第二醫(yī)院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYHb:10cm5120812402:L11R0Hm451020他2ww.12

WL-#0

12*31eMUMANHeipAAo12#0521017700V1200ma3F?4400@

20mm1

10lw121eM2msnhm40020網(wǎng)吉林太學

第二醫(yī)院THESECOND

HOSPITALOFJILIN

UNIVERSITY0

ieWu-600網(wǎng)

兩CMQE*JRGH

Fhdererti200年12月26日2210000P

W1000Ww120t

m40m

0900005128512|200mmt61002mWwE23marttt

?310301h2#M2)meh原*?物

?20CMUE

HorErNW120的

AF?vth

o200mm+12FQw9000200mint心6mm5009年12#2E

042!1049040UwM2Dmor#hi

423001202*日

G2:101i?di?S中JwW.12mF(8621%Ww12ait12000

mt網(wǎng)m10cm10mB患兒，男，2歲因發(fā)熱5天，皮疹1天住院。診斷麻疹。住院第4天咳嗽，住院后6天家長要求出院。出院5天后，再次出現(xiàn)發(fā)熱39.8

度，咳嗽加重，再次入院，診斷：重癥肺炎。MPP(1:1280),

住院20余天，癥狀好轉出院。回家后霧化

吸入普米克和可必特治療?；顒雍笕源ⅰＨ齻€月后，再次因發(fā)熱，咳嗽、喘息加重住院，診斷大葉

肺炎，肺膿腫，兒童哮喘，住院20天好轉出院，出院后仍

喘息，咳嗽。既往史：濕疹(+),既往無喘息史。不愛揉鼻、眼

家族史：無喘息家族史。IgE

14.5U/ml

血食物+呼吸特異性Ig

E:陰性。病歷摘要吉林太學第二醫(yī)院THESECONDHOSPITALOFJILINUNIVERSITY病

例(

2

)M/10

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

■

Fhiips

Brilliance

64

102009年5月23日

009

13:28:43.55000

99938-2

]37/83[入院時(2009-05-23)

發(fā)熱，喘重雙肺密集水泡音C.M

USHENGJING

Hosp;

Fhilips

Brilliance

64

2009年5月23日

13:28:42.549000;C.M.USHENGJING

HospPhilips

Erilliance642009年5月23日

13:28-42.7039991000999938-2[43f73]田

目

用

■1000999938-2[29/73]ID:1000999938WUEN

EOM/10

monthsSe:2lm:25-804.90ID:1000999938

WU

EN

BOM/10monthsSe:2lm:29-796.90D:1000999938WU

EN

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

512X51210cm66.21%

Ww:1200WL-600:F10cm66.21%

Ww:1200

WL-600512X51266.21%

Ww:1200

WL-600

512X5122009年5月23日

13:28:43.250000ID:1000999938

WU

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),輕咳、活動后喘促，

雙肺散在水泡音ID:1001092907WUEN

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調(diào)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

ENBQSe:3Im:42-464.50C.M.U.SHENGJING

HOSPITALCM.USHENGJING

HOSPITALCM.U

SHENGJING

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

EN

BQ[R]F一十g呼吸道粘膜RespiratoryMucosa肺泡橫切面CneeCactinn

of

AlveolusRghtmddle

lcharbnchor

ViewUngulardwelonbronchusLaftsuperioelotarbronchus

左下葉支氣管終末細支氣管

Terminal

bronchiode右肺副裂Horizontal

fissure通氣規(guī)體進出呼小

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吉林大學第二醫(yī)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.吉林大學

第二醫(yī)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吉林大學

第二醫(yī)院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYPathogenesis(1)Epithelial

injury

inducedby

lowerrespiratorytract

infectionsuchasvirusand

mycoplasma(3)Smooth

muscle

hyperplasia

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

第二醫(yī)院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITY(4)CD?T

cell

(5)Th17

cell

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

cell(2)Neutrophil感染性用塞性細支氣管炎，常見病喜(腺病毒、呼吸道合胞病毒、流感病喜、副流感病喜)支原體結締組織病(類風濕性關節(jié)炎和嗜酸性筋膜炎)公吸入性損傷(二氧化氮、二氧化硫、氨、氟、光氣、灼熱氣體、飛灰等)毒物服入異體移植物受者(心肺聯(lián)合移植或肺移植、骨髓移植

)藥物(青零胺、洛莫司汀、可卡因、金等)其他異發(fā)癥：夾癥性腸病、種經(jīng)內(nèi)分泌細胞增生

、

多

發(fā)性類癌樣微瘤、

副腫霜天皰瘡吉林大學

第二醫(yī)院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITYBO

相關病因和基礎疾病PIBO與腺病毒

(ADV)呼吸道合胞病毒

(RSV)支原體感染麻疹病毒流感病毒副流感病毒巨細胞病毒Etiology

inchildren吉林大學

第二醫(yī)院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYRisk

FactorP

I

B

O

發(fā)

生

的

危

險

因

素ADV毛細支氣管炎住院時間超過30天

多病灶肺炎需機械通氣治療高碳酸血癥(OR=49.9)(OR=27.2)(OR=26.6)(OR=11.9)(OR=5.6)。病因不同，但組織病理學改變相似縮窄性細支氣管炎和增殖性細支氣管炎增殖性細支氣管炎以肉芽組織在氣道內(nèi)呈息肉團塊增生為特征肺泡腔內(nèi)亦出現(xiàn)肉芽組織時，則稱為閉塞性細支氣管炎伴機化性肺炎(BOOP)PathologyChildhood

PIBO

絕大多數(shù)為縮窄性早期上皮細胞壞死，氣道炎癥細胞浸潤相鄰肺實質(zhì)正?；騼H有輕微改變細支氣管變形，膠原沉積，黏液滲出后期形成黏膜下纖維化，管腔進行性變窄，

最終形成閉塞氣道阻塞間接征象黏液潴留巨噬細胞聚集肺過度充氣細支氣管變形擴張支氣管上皮細胞肥大，上皮層變厚，管腔可出現(xiàn)阻塞甚或閉塞Constrictivebronchiolitisin

SLE吉林太學

第二醫(yī)院THESECOND

HOSPITALOFJILIN

UNIVERSITY肺泡灌洗液中以中性粒細胞增多為主

部分區(qū)域淋巴細胞增多中性粒細胞趨化因子IL-8

濃度增高

這些變化仍存在于肺損傷數(shù)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).吉林大學

第二醫(yī)院THE

SECONDHOSPITAL

OF

JILINUNIVERSITYClinicalsymptomsandsigns

Brazilianstudies(6,9,10,18)

foundthat

characteristicfindings

in

HRCTwere:amosaic

patternof

perfusionbronchiectasisbronchialwallthickeningairtrappingatelectasishigh-resolutionchesttomography(HRCT)吉林太學

第二醫(yī)院THE

SECOND

HOSPITAL

OF

JILIN

UNIVERSITY吉林太學

第二醫(yī)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改變例數(shù)(N)構成比馬賽克灌注空氣滯留支氣管壁增厚支氣管擴張肺不張支氣管黏液栓2202301952401651459278966658250例兒童及青少年CT

改變AlthoughadiagnosisofPIBO

should

beconfirmedbyhistopathology,most

pediatric

pulmonologistsdiagnose

PIBObasedonhistoryandclinicalfindingsaccordingtothefollowingcriteria:Diagnosis吉林大學

第二醫(yī)院THE

SECONDHOSPITALOF

JILINUNIVERSITY(1)acutesevererespiratory

infectionduringchildhood,especiallyearlychildhood;(2)persistentairwayobstructionafterinitialinsultandunresponsivenesstosystemicsteroidsandbronchodilators,asdemonstrated

byclinicalsymptomsandsigns,anda

lungfunctiontest,ifitcan

be

performed;(3)

mosaic

perfusion,airtrapping,and/orbronchiectasisinchestcomputedtomography;

and吉林大學

第二醫(yī)院THESECONDHOSPITALOFJILINUNIVERSITY(4)exclusionofotherchronic

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

andalpha-1-antitrypsindeficiency(Table

1).吉林大學

第二醫(yī)院THESECONDHOSPITALOFJILINUNIVERSITYRecentstudiesofclinical

predictionrulesto

diagnose

PIBO

inchildrenfoundthattypical

clinical

history,adenovirus

infection,and

high-resolutioncomputedtomographywithmosaic

perfusionwere

highly

predictable

variables32).吉林大學第二醫(yī)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

學第二醫(yī)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)吉林大學

第二醫(yī)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.吉林太學

第二醫(yī)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).吉林大學

第二醫(yī)院THESECONDHOSPITALOFJILINUNIVERSITYAlthough,theoretically,abronchodilatorresponseshouldbeabsent

inchildrenwith

fixedairwayobstructionsuchas

in

PIBO,a

positivebronchodilatorresponserangingfrom10%to42.9%was

presentinchildrenwith

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

individualbasisaccordingtothebronchodilatorresponse.吉