Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Tuberculosis (TB) in children is a common infectious disease in the world affecting
approximately 550 000 children annually and contributing to approximately 10-15% of the
TB caseload. The estimate is that 75% of the children who have TB live in the 22 countries
that have the highest burden of TB disease. In these 22 countries, the technology required
to make the diagnosis and manage complicated cases is limited. The epidemiological data
required to estimate the proportion of children with severe disease requiring intervention at
a global level are lacking.
Airway involvement is commonly seen in children with primary TB, but only in a small
group of children the compression is severe, needing intervention. The incidence of
children with airway obstruction requiring intervention due to primary TB in the
chemotherapeutic era is not known. The incidence of complicated lymph node disease in
two recent reports varied from 8-38% in children younger than 15 years of age.
Flexible bronchoscopy (FB) is an invasive procedure performed under general anesthetic
is used to assess the airways of children. Few studies have been published on the use of
FB in the diagnosis of paediatric TB and most have concentrated on the use of
bronchoscopy as an intervention for obtaining samples to diagnose pulmonary TB (PTB).
All previous studies only examined broncho-alveolar lavage (BAL) for Ziehl Neelsen (ZN)
positive organisms and mycobacterial culture. All the published studies are from
developed countries with a very low incidence of PTB in children. It has been postulated
that HIV positive children with TB are more likely to have airway obstruction, but this
hypothesis has not been studied. The same is true for children infected with drug-resistant
strains of tuberculosis. Similarly, there have been few reports on the correlation between
the findings at bronchoscopy and those found on chest computer tomography (CT).
The aim of this research project was to systematically determine airways involvement in
childhood pulmonary TB and assess the role paediatric bronchoscopy plays in the
diagnosis, sample collection and the management of severe airway obstruction.
The first part of the thesis describes the bronchoscopic assessment of airway obstruction
due to pulmonary TB in children, specifically concentrating on the areas of the airway
involved and the severity of the obstruction. We investigated which factors determine the
severity of airway obstruction and this included age, sex, HIV status and drug sensitivities.
We have shown that there was no difference in airway obstruction in HIV positive children and in children with drug resistance TB. More severe airway obstruction was seen in the
younger child.
The second question that was analysed is the value of flexible bronchoscopy in collecting
samples for TB culture and drug sensitivity testing. It has previously been reported that
BAL culture was inferior to gastric lavage in isolating the bacilli. We set out to evaluate
which factors determine if a child will be culture-positive on BAL. Most childhood
pulmonary TB is postulated to have a low yield of ZN positive cases. We found a higher
yield from BAL as was previously reported, and the yield was increased if segmental or
lobar pneumonia was present on the chest radiography. We developed novel interventions
of finding the organism and increasing the yield from BAL. About 80% of children with PTB
have enlarged subcarinal lymph nodes. We performed a trans-bronchial needle aspiration
(TBNA) biopsy of these lymph nodes for culture. This technique enables us to differentiate
the cause of enlarged mediastinal lymph nodes. This is especially important in children
who are HIV positive, as they are prone to have other causes of enlarged lymph nodes.
We successfully performed TBNA, even in very young infants, which resulted in a
diagnostic yield of 55%. The use of Xpert has been described on other tissue, but not on
BAL. We wanted to test if the use of Xpert on BAL is feasible in children, and determine if
it will increase the diagnostic yield by using BAL samples.
The third aspect of this research was to compare flexible bronchoscopy findings with those
of chest CT scan finding. Firstly, the aim was to describe the CT scan findings of
mediastinal glands and lungs in children with significant airway obstruction due to PTB.
The second aim was to investigate how these two investigations of airway obstruction
compared, with particular emphasis on their advantages and disadvantages. The areas of
airway obstruction as well as the severity of the obstruction as determined by CT scan
were very similar to the findings with bronchoscopy. The final part under this aspect of the
study was to analyze airway shape using a computer model to asses if this could predict
TB. This was done by extracting components of the airway surface mesh and branch
radius and orientation features. This method showed the potential of computer-assisted
detection of TB and other airway pathology by using airway shape deformation analysis.
The fourth aspect investigated was to determine which children with severe airway
obstruction would benefit from a surgical intervention. Surgical enucleation is done via a
lateral thoracotomy in children with severe airway obstruction. We investigated which
factors determine the need for surgical enucleation, the optimal timing of this intervention,
and – if surgical enucleation was done as an emergency intervention – which factors
would predict for this. The combination of trachea, left main bronchus and bronchus
intermedius involvement was the best predictor for children requiring surgical enucleation.
Involvement of the smaller airway divisions did not play a significant role. Children needing
enucleation were younger and had more severe airway obstruction.
The fifth aspect of this thesis was to measure the outcome following surgical enucleation.
Measurements used included clinical measurements, radiological measurements and
bronchoscopy. The response in children treated surgically were compared to those treated
medically by estimating airway size with flexible bronchoscopy. Both groups showed
significant improvement with the magnitude of improvement greater in those surgically
treated.
We have demonstrated in this thesis that the site and severity of severe airway obstruction
can be assessed by either bronchoscopy or chest CT scan. Approximately one third of
children with severe airway compression due to TB lymph nodes can be successfully
treated surgically with a low morbidity and mortality. / AFRIKAANSE OPSOMMING: Tuberkulose (TB) by kinders is wêreldwyd ’n algemene siekte wat jaarliks ongeveer 550
000 kinders raak en sowat 10-15% van die algehele TB-siektelas uitmaak. Na raming kom
75% van alle kinders met TB van die 22 lande met die hoogste TB-siektelas. Hierdie 22
lande beskik oor beperkte tegnologie om die siekte te diagnoseer en ingewikkelde gevalle
te bestuur. Die vereiste epidemiologiese data om te raam watter persentasie kinders
wêreldwyd ernstig siek is en intervensie vereis, ontbreek ook.
Lugwegaantasting word algemeen by kinders met primêre TB aangetref. Tog is die
kompressie by slegs ’n klein groepie kinders so erg dat dit intervensie vereis. Die
voorkoms van kinders in die chemoterapeutiese era met primêre-TB-verwante obstruksie
van die lugweë wat intervensie vereis, is onbekend. In twee onlangse verslae het die
voorkoms van gekompliseerde limfkliersiekte by kinders jonger as 15 jaar van 8% tot 38%
gewissel.
Buigbare brongoskopie is ’n indringende prosedure wat onder algemene verdowing
uitgevoer word om kinders se lugweë te ondersoek. ’n Paar studies is reeds gepubliseer
oor die gebruik van buigbare brongoskopie om pediatriese TB te diagnoseer. Die meeste
daarvan het gekonsentreer op die gebruik van brongoskopie as intervensie vir die
insameling van monsters om pulmonêre TB (PTB) te diagnoseer. Alle vorige studies het
uitsluitlik ondersoek ingestel na brongo-alveolêre spoeling (BAS) vir die opsporing van
Ziehl Neelsen- (ZN-)positiewe materiaal en vir kweking. Geen ander diagnostiese tegnieke
is tot dusver ondersoek nie, wat die waarde daarvan vir populasies met ’n hoë siektelas
beperk. Boonop is alle gepubliseerde studies in ontwikkelde lande met ’n baie lae
voorkoms van PTB by kinders onderneem. Daar word aangevoer dat MIV-positiewe
kinders met TB meer waarskynlik aan obstruksie van die lugweë sal ly, hoewel hierdie
hipotese nog nie bestudeer is nie. Dieselfde geld vir kinders wat aan middelweerstandige
vorme van TB ly. Daar is ook weinig verslae oor die verband tussen die bevindinge van
brongoskopie en dié van rekenaartomografie (RT) van die borskas.
Die doel van hierdie navorsing was om stelselmatig vas te stel hoe pulmonêre TB by
kinders die lugweë aantas, en watter rol pediatriese brongoskopie in diagnose,
monsterinsameling en die hantering van ernstige obstruksie van die lugweë speel.
Die eerste deel van die tesis beskryf die brongoskopiese voorkoms van PTB-verwante
obstruksie van die lugweë, met bepaalde klem op die aangetaste dele van die lugweg en die erns van die obstruksie. Daar is ondersoek ingestel na watter faktore die erns van die
obstruksie bepaal, onder meer ouderdom, geslag, MIV-status en middelsensitiwiteit. Die
resultate toon geen verskil in obstruksie by MIV-positiewe kinders en kinders met
middelweerstandige TB nie, hoewel ernstiger obstruksie van die lugweë by die jonger kind
opgemerk is.
Die tweede kwessie wat ontleed is, is die waarde van buigbare brongoskopie in die
verkryging van monsters vir TB-kweking en toetse vir middelsensitiwiteit. Daar is voorheen
aangemeld dat BAS-kweking minder doeltreffend is as gastriese spoeling om die basille te
isoleer. Hierdie studie was daarop toegespits om te beoordeel watter faktore bepaal of ’n
kind kwekingspositief met BAS sal wees. Die meeste PTB by kinders toon na bewering ’n
lae opbrengs van ZN-positiewe gevalle. Tog het BAS in hierdie studie ’n hoër opbrengs
gehad as wat voorheen aangemeld is, welke opbrengs hoër was met die aanwesigheid
van segmentale of lobêre pneumonie op die borskasradiogram. Innoverende intervensies
is ontwikkel om die organisme op te spoor en die opbrengs met BAS te verhoog. Sowat
80% van kinders met PTB het vergrote subkarinale limfkliere. ’n Transbrongiale
naaldaspirasie- (TBNA-)biopsie is gevolglik vir die doeleinde van kweking op hierdie kliere
uitgevoer. Hierdie tegniek het die navorser in staat gestel om tussen die verskillende
oorsake vir vergrote mediastinale limfkliere te onderskei. Dít is veral belangrik by MIVpositiewe
kinders, wat geneig is om ander oorsake vir vergrote limfkliere te toon. Die
TBNA-biopsies is selfs by baie jong babas suksesvol uitgevoer, wat tot ’n diagnostiese
opbrengs van 55% gelei het. Die gebruik van Xpert op ander weefsel as BAS is al
voorheen beskryf. Die navorser wou dus vasstel of die gebruik van Xpert by BAS haalbaar
is by kinders, en of dit die diagnostiese opbrengs deur die gebruik van BAS-monsters sal
verhoog.
Die derde aspek van hierdie navorsing was om die bevindinge van buigbare brongoskopie
met dié van RT-skanderings van die borskas te vergelyk. Die doel was eerstens om die
bevindinge van die RT-skanderings van mediastinale kliere en longe by kinders met
beduidende PTB-verwante lugweg-obstruksie te beskryf. Tweedens wou die navorser
vasstel wat die verskille tussen hierdie twee ondersoeke van lugweg-obstruksie is, met
bepaalde klem op die voordele en nadele daarvan. Die RT-skandering en die bevindinge
van brongoskopie lewer betreklik soortgelyke resultate op wat die aangetaste gedeeltes
van die lugweg sowel as die erns van sodanige obstruksie betref. Die laaste doel onder
hierdie studieaspek was om die vorm van die lugweg met behulp van ’n rekenaarmodel te
ontleed om te bepaal of dit TB kan voorspel. Dít is gedoen deur komponente van die die erns van die obstruksie. Daar is ondersoek ingestel na watter faktore die erns van die
obstruksie bepaal, onder meer ouderdom, geslag, MIV-status en middelsensitiwiteit. Die
resultate toon geen verskil in obstruksie by MIV-positiewe kinders en kinders met
middelweerstandige TB nie, hoewel ernstiger obstruksie van die lugweë by die jonger kind
opgemerk is.
Die tweede kwessie wat ontleed is, is die waarde van buigbare brongoskopie in die
verkryging van monsters vir TB-kweking en toetse vir middelsensitiwiteit. Daar is voorheen
aangemeld dat BAS-kweking minder doeltreffend is as gastriese spoeling om die basille te
isoleer. Hierdie studie was daarop toegespits om te beoordeel watter faktore bepaal of ’n
kind kwekingspositief met BAS sal wees. Die meeste PTB by kinders toon na bewering ’n
lae opbrengs van ZN-positiewe gevalle. Tog het BAS in hierdie studie ’n hoër opbrengs
gehad as wat voorheen aangemeld is, welke opbrengs hoër was met die aanwesigheid
van segmentale of lobêre pneumonie op die borskasradiogram. Innoverende intervensies
is ontwikkel om die organisme op te spoor en die opbrengs met BAS te verhoog. Sowat
80% van kinders met PTB het vergrote subkarinale limfkliere. ’n Transbrongiale
naaldaspirasie- (TBNA-)biopsie is gevolglik vir die doeleinde van kweking op hierdie kliere
uitgevoer. Hierdie tegniek het die navorser in staat gestel om tussen die verskillende
oorsake vir vergrote mediastinale limfkliere te onderskei. Dít is veral belangrik by MIVpositiewe
kinders, wat geneig is om ander oorsake vir vergrote limfkliere te toon. Die
TBNA-biopsies is selfs by baie jong babas suksesvol uitgevoer, wat tot ’n diagnostiese
opbrengs van 55% gelei het. Die gebruik van Xpert op ander weefsel as BAS is al
voorheen beskryf. Die navorser wou dus vasstel of die gebruik van Xpert by BAS haalbaar
is by kinders, en of dit die diagnostiese opbrengs deur die gebruik van BAS-monsters sal
verhoog.
Die derde aspek van hierdie navorsing was om die bevindinge van buigbare brongoskopie
met dié van RT-skanderings van die borskas te vergelyk. Die doel was eerstens om die
bevindinge van die RT-skanderings van mediastinale kliere en longe by kinders met
beduidende PTB-verwante lugweg-obstruksie te beskryf. Tweedens wou die navorser
vasstel wat die verskille tussen hierdie twee ondersoeke van lugweg-obstruksie is, met
bepaalde klem op die voordele en nadele daarvan. Die RT-skandering en die bevindinge
van brongoskopie lewer betreklik soortgelyke resultate op wat die aangetaste gedeeltes
van die lugweg sowel as die erns van sodanige obstruksie betref. Die laaste doel onder
hierdie studieaspek was om die vorm van die lugweg met behulp van ’n rekenaarmodel te
ontleed om te bepaal of dit TB kan voorspel. Dít is gedoen deur komponente van die lugwegoppervlaknetwerk en vertakkingsradius- en oriëntasiekenmerke te onttrek. Hierdie
metode het daarop gedui dat rekenaargesteunde opsporing van TB en ander
lugwegpatologie deur middel van ’n ontleding van lugwegvervorming wél potensiaal toon.
Die vierde aspek was om te bepaal watter kinders met ernstige obstruksie van die lugweë
by intervensie sal baat vind. By sulke kinders word chirurgiese enukleëring deur ’n laterale
torakotomie uitgevoer. Die studie het ondersoek ingestel na watter faktore die behoefte
aan chirurgiese enukleëring bepaal, wat die optimale tyd vir sodanige intervensie sou
wees, en – indien chirurgiese enukleëring as noodintervensie uitgevoer word – watter
faktore so ’n noodintervensie sou vereis. Die kombinasie van aantasting van die tragea,
linkerhoofbrongus en brongus intermedius was die beste voorspeller van kinders wat
chirurgiese enukleëring benodig. Aantasting van die kleiner lugwegverdelings het nie ’n
beduidende rol gespeel nie. Kinders wat enukleëring vereis, was jonger en het aan
ernstiger obstruksie van die lugweë gely.
Die vyfde aspek van hierdie tesis was om die uitkoms na afloop van chirurgiese
enukleëring te meet. Kliniese metings, radiologiese metings en brongoskopie is hiervoor
gebruik. Die reaksie by kinders wat chirurgies behandel is, is vergelyk met diegene wat
medies behandel is deur lugweggrootte met behulp van buigbare brongoskopie te raam.
Albei groepe het beduidende verbetering getoon.
In die studie het ons getoon dat die ligging en die erns van ernstige lugwegobstruksie kan
geassesseer word deur óf brongoskopie of rekenaartomografie van die borskas. Ongeveer
een derde van kinders met 'n ernstige lugweg-obstruksie weens TB limfkliersiekte kan
suksesvol chirurgies met 'n lae morbiditeit en mortaliteit behandel word.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/97039 |
| Date | 04 1900 |
| Creators | Goussard, Pierre |
| Contributors | Gie, R. P., Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | xi, 291 pages : illustrations (some colour) |
| Rights | Stellenbosch University |
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