Bronchoscopic assessment and management of children presenting with clinically significant airway obstruction due to tuberculosis

[摘要] ENGLISH ABSTRACT: Tuberculosis (TB) in children is a common infectious disease in the world affectingapproximately 550 000 children annually and contributing to approximately 10-15% of theTB caseload. The estimate is that 75% of the children who have TB live in the 22 countriesthat have the highest burden of TB disease. In these 22 countries, the technology requiredto make the diagnosis and manage complicated cases is limited. The epidemiological datarequired to estimate the proportion of children with severe disease requiring intervention ata global level are lacking.Airway involvement is commonly seen in children with primary TB, but only in a smallgroup of children the compression is severe, needing intervention. The incidence ofchildren with airway obstruction requiring intervention due to primary TB in thechemotherapeutic era is not known. The incidence of complicated lymph node disease intwo recent reports varied from 8-38% in children younger than 15 years of age.Flexible bronchoscopy (FB) is an invasive procedure performed under general anestheticis used to assess the airways of children. Few studies have been published on the use ofFB in the diagnosis of paediatric TB and most have concentrated on the use ofbronchoscopy 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 fromdeveloped countries with a very low incidence of PTB in children. It has been postulatedthat HIV positive children with TB are more likely to have airway obstruction, but thishypothesis has not been studied. The same is true for children infected with drug-resistantstrains of tuberculosis. Similarly, there have been few reports on the correlation betweenthe findings at bronchoscopy and those found on chest computer tomography (CT).The aim of this research project was to systematically determine airways involvement inchildhood pulmonary TB and assess the role paediatric bronchoscopy plays in thediagnosis, sample collection and the management of severe airway obstruction.The first part of the thesis describes the bronchoscopic assessment of airway obstructiondue to pulmonary TB in children, specifically concentrating on the areas of the airwayinvolved and the severity of the obstruction. We investigated which factors determine theseverity 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 theyounger child.The second question that was analysed is the value of flexible bronchoscopy in collectingsamples for TB culture and drug sensitivity testing. It has previously been reported thatBAL culture was inferior to gastric lavage in isolating the bacilli. We set out to evaluatewhich factors determine if a child will be culture-positive on BAL. Most childhoodpulmonary TB is postulated to have a low yield of ZN positive cases. We found a higheryield from BAL as was previously reported, and the yield was increased if segmental orlobar pneumonia was present on the chest radiography. We developed novel interventionsof finding the organism and increasing the yield from BAL. About 80% of children with PTBhave enlarged subcarinal lymph nodes. We performed a trans-bronchial needle aspiration(TBNA) biopsy of these lymph nodes for culture. This technique enables us to differentiatethe cause of enlarged mediastinal lymph nodes. This is especially important in childrenwho 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 adiagnostic yield of 55%. The use of Xpert has been described on other tissue, but not onBAL. We wanted to test if the use of Xpert on BAL is feasible in children, and determine ifit will increase the diagnostic yield by using BAL samples.The third aspect of this research was to compare flexible bronchoscopy findings with thoseof chest CT scan finding. Firstly, the aim was to describe the CT scan findings ofmediastinal glands and lungs in children with significant airway obstruction due to PTB.The second aim was to investigate how these two investigations of airway obstructioncompared, with particular emphasis on their advantages and disadvantages. The areas ofairway obstruction as well as the severity of the obstruction as determined by CT scanwere very similar to the findings with bronchoscopy. The final part under this aspect of thestudy was to analyze airway shape using a computer model to asses if this could predictTB. This was done by extracting components of the airway surface mesh and branchradius and orientation features. This method showed the potential of computer-assisteddetection of TB and other airway pathology by using airway shape deformation analysis.The fourth aspect investigated was to determine which children with severe airwayobstruction would benefit from a surgical intervention. Surgical enucleation is done via alateral thoracotomy in children with severe airway obstruction. We investigated whichfactors determine the need for surgical enucleation, the optimal timing of this intervention, and – if surgical enucleation was done as an emergency intervention – which factorswould predict for this. The combination of trachea, left main bronchus and bronchusintermedius involvement was the best predictor for children requiring surgical enucleation.Involvement of the smaller airway divisions did not play a significant role. Children needingenucleation 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 andbronchoscopy. The response in children treated surgically were compared to those treatedmedically by estimating airway size with flexible bronchoscopy. Both groups showedsignificant improvement with the magnitude of improvement greater in those surgicallytreated.We have demonstrated in this thesis that the site and severity of severe airway obstructioncan be assessed by either bronchoscopy or chest CT scan. Approximately one third ofchildren with severe airway compression due to TB lymph nodes can be successfullytreated surgically with a low morbidity and mortality.

[发布机构] Stellenbosch University