A new understanding of clinical patterns in post-TB lung disease.

Post-TB lung disease (PTLD) can be categorised based on physiological, radiological, and clinical abnormalities, delineating distinct clinical patterns; however, thus far the importance of this is unknown. People with PTLD have a high morbidity and increased mortality, but predictors of long-term outcomes are poorly understood.We conducted an observational study of PTLD patients attending a tertiary hospital in South Africa between 1 October 2021 and 30 September 2022. Patient demographics, risk factors, symptoms, lung function tests and outcomes were captured.A total of 185 patients were included (mean age: 45.2 years, SD ±14.3). Half of patients reported only one previous episode of Mycobacterium tuberculosis infection (n = 94, 50.8%). There was a statistically significant association between TB-associated obstructive lung disease (OLD) and dyspnoea (P = 0.002), chest pain (P = 0.014) and smoking (P = 0.005). There were significant associations between haemoptysis and both cavitation (P = 0.015) and fungal-associated disease (P < 0.001). Six patients (3.2%) died by study end.PTLD can affect young people even with only one previous episode of TB, and carries a high mortality rate. For the first time, clinical patterns have been shown to have meaningful differences; TB-related OLD is associated with dyspnoea, chest pain and smoking; while haemoptysis is associated with cavitary and fungal-associated disease..

Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes.

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions.

En 2020, il est estimé qu'il y a 155 millions de survivants de la TB dans le monde, tous exposés à un risque d'invalidité post-TB. Le deuxième Symposium International Post-Tuberculose (Stellenbosch, Afrique du Sud) a été organisé dans le but de sensibiliser davantage à l'échelle mondiale et de permettre aux communautés touchées par la TB de contribuer activement à la mise en œuvre de l'agenda. De plus, nous avons entrepris de mettre à jour les connaissances sur la vie et les maladies post-TB, de déterminer les domaines de recherche prioritaires, d'établir des partenariats de recherche et de souligner l'importance d'intégrer les résultats sur la santé pulmonaire dans les essais cliniques et les services de soins de la TB. Le symposium était une réunion de travail pluridisciplinaire rassemblant des praticiens, des chercheurs, des personnes ayant survécu à la TB, des donateurs, des décideurs politiques et d'autres acteurs clés. Dix groupes de travail académiques ont établi leurs propres objectifs et ont abordé les sujets thématiques suivants : 1) engagement et perspectives des patients ; 2) épidémiologie et modélisation ; 3) pathogénie des séquelles post-TB ; 4) maladie pulmonaire post-TB (PTLD, pour l'anglais «post-TB lung disease ¼) ; 5) complications cardiovasculaires et vasculaires pulmonaires ; 6) complications neuromusculaires et squelettiques ; 7) complications pédiatriques ; 8) conséquences économiques, sociales et psychologiques (ESP, pour l'anglais «economic-social and psychological¼) ; 9) prévention, traitement et gestion ; 10) plaidoyer, politique et engagement des parties prenantes. Les groupes de travail académiques ont apporté des mises à jour significatives dans leurs domaines respectifs, ont mis en évidence les priorités de recherche et ont avancé vers la normalisation et l'harmonisation des résultats et des définitions de la post-TB.

The effect of inhaled nitric oxide on shunt fraction in mechanically ventilated patients with COVID-19 pneumonia.

Background: Studies in patients with severe acute respiratory distress syndrome (ARDS) with refractory hypoxaemia suggest that inhaled nitric oxide (iNO) can be added to ventilatory strategies as a potential bridge to clinical improvement. However, the potential role of iNO as a management strategy in severe COVID-19 pneumonia remains unclear. The authors describe their clinical findings of using iNO for severe COVID-19 pneumonia in 10 patients with refractory hypoxaemia in a tertiary respiratory intensive care unit. The results showed an improvement in shunt fraction, P/F ratio, PaO2 and arterial oxygen saturation but the improvements did not translate into a mortality benefit. This report adds to the current body of literature indicating that the correct indications, timing, dose and duration of iNO therapy and how to harness its pleiotropic effects still remain to be elucidated. What the study adds: This brief report adds to the body of literature exploring the potential use of inhaled nitric oxide as a management strategy in patients with severe COVID-19 pneumonia with refractory hypoxaemia. What are the implications of the findings: The findings of the report shows that there is a beneficial role of using inhaled nitric oxide to improve respiratory parameters, but that it does not translate to a mortality benefit. It adds to the investigation of establishing which patients, the duration and at what dose, inhaled nitric oxide should be used to gain maximum benefit for this subgroup of patients.

Issues in Medicine.

Rasmussen aneurysms are abnormalities of the pulmonary arterial system caused by tuberculosis (TB). They are associated with a highmortality rate when they cause life-threatening haemoptysis. High TB-prevalence regions have a large burden of TB-related haemoptysisbut often limited resources. This series of 25 patients who presented with life-threatening haemoptysis from current and/or previous TBwere found to have abnormal pulmonary arteries on computed tomography pulmonary angiogram (CTPA), which were judged to belikely contributors to their bleeding, either in isolation or with concomitant abnormal bronchial or systemic vasculature. These patientsunderwent transcatheter placement of Amplatzer vascular plugs in the feeder pulmonary artery. Bronchial and systemic lesions wereaddressed separately as needed. Immediate technical success was achieved in all patients, but four of them experienced intraoperativehaemoptysis related to dislodgement of the occluding platelet plug by the high-pressure automatic injector and wire. At 48 hours after theprocedure, 18 (72%) remained haemoptysis-free. Six of these experienced recurrence within 1 year of their procedure. Pulmonary arteryplacement of an Amplatzer vascular plug is a feasible option for treating bleeding Rasmussen aneurysms, but should be part of a combinedapproach to addressing suspected culprit vascular lesions in all intrathoracic vascular systems.

South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023.

Background: Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published. Objectives: To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA. Methods: The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA. Results: A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA. Conclusion: Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required. Abstract: The South African Thoracic Society mandated a multidisciplinary team of healthcare providers to compile a position statement on the management of non-cystic fibrosis bronchiectasis in South Africa (SA). International guidelines on the management of bronchiectasis were reviewed and used as a basis from which the current position statement was compiled. This is the first position statement on the management of adult non-cystic fibrosis bronchiectasis in SA. A description of the epidemiology and aetiology of bronchiectasis is provided, as well as guidance on its diagnosis and management. The position statement provides guidance on the management of bronchiectasis to healthcare providers, policymakers and regulatory authorities.

Pulmonary hypertension in adults completing tuberculosis treatment.

Background: Pulmonary hypertension (PH) after tuberculosis (TB) is typically not included among the chronic lung diseases causing PH (group 3 PH), with few data available to support the inclusion. Objectives: To determine the prevalence of PH in an adult population completing TB treatment. Methods: This single-centre, cross-sectional study only included patients with their first documented episode of TB, and who were in the second half of treatment or had recently completed treatment. PH was assessed using transthoracic echocardiography. Questionnaires were completed, and spirometry and a 6-minute walk test were performed. Results: One hundred patients were enrolled, with a mean age of 37.1 years, of whom 58% were male and 46% HIV positive. The median time since initiation of TB treatment was 22 weeks. The mean (standard deviation) measured right ventricular systolic pressure (RVSP) was 23.6 (6.24) mmHg. One participant had PH (defined as RVSP ≥40 mmHg; 95% confidence interval (CI) 0.0 - 3.0) and a further 3 had possible PH (RVSP ≥35 and <40 mmHg), with a combined PH prevalence of 4% (95% CI 0.2 - 7.8). Airflow obstruction on spirometry was found in 13.3% of 98 patients, while 25.5% had a reduced forced vital capacity. There was no association between RVSP or PH/possible PH and sex, age, HIV status, systemic hypertension, spirometry measurements or 6-minute walking distance. Smoking status was associated with RVSP, but not with the presence of PH/possible PH. Conclusion: There was a significant prevalence of PH in this preliminary study of predominantly young patients completing treatment for a first episode of TB. Larger and more detailed studies are warranted. Study synopsis: What the study adds. Of 100 adult patients with their first episode of tuberculosis (TB) who underwent echocardiograms near the end of treatment completion to determine the prevalence of pulmonary hypertension (PH), 1 (1%) had PH and a further 3 (3%) had possible PH. There was no association between sex, age, HIV status, lung function or 6-minute walking distance and the presence of PH. The study adds to the growing awareness of the association of TB with pulmonary vascular disease. It shows that even in a young population with a first episode of TB treated in an ambulatory setting, there is a significant prevalence of PH on treatment completion.Implications of the findings. Given that 10.6 million people acquire TB annually, the absolute global burden of cases with PH is likely to be high, but is underappreciated to date. Further work is urgently needed in this field.

An outbreak within an outbreak: The impact of Infection Prevention and Control strategies on hospital-acquired infections and the occurrence of multi-drug resistant organisms during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic placed an unprecedented strain on intensive care units (ICUs) in South Africa. Infection prevention and control (IPC) strategies were highlighted to minimise the risk to healthcare workers and for the protection of patients from contracting hospital-acquired infections (HAIs). During the third wave, our institution adopted a shift system to address severe burnout among ICU personnel. We noted an upstroke in the occurrence of HAIs, specifically carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant (MDR) Acinetobacter baumannii. OBJECTIVES: To report these outbreaks, compare the rate of CRE and A. baumannii infections with the first COVID-19 wave and to analyse its impact on patient outcomes. METHOD: We retrospectively analysed data from a prospectively collected registry involving all adult patients with severe COVID-19 admitted to the dedicated COVID-19 ICU from May 2021 to September 2021. Information from the admission database, including the patients' demographics, comorbidities, laboratory results and length of ICU stay were extracted. RESULTS: Ninety patients were admitted with severe COVID-19 during the third wave. There was an outbreak of both CRE (the majority Klebsiella pneumoniae) and A. baumannii. Furthermore, 18 patients cultured the same CRE organism, and 25 patients cultured the environmental organism A. baumannii. The HAI rate was significantly higher compared with the first wave published data: 59/90 (65.6%) v. 73/363 (20.1%, p<0.01). Patients with any HAI had a longer mean stay in ICU (10.1 days v. 6.7 days (p<0.01) and a higher mortality of 48/59 (81%) v. 19/31 (61%) (p=0.05). CONCLUSION: We observed a very significant rise in HAIs in the COVID-19 ICU during the third wave compared with the first, with almost three times as many patients developing HAIs. Unsurprisingly, it was associated with a longer mean stay in ICU and a higher mortality. The outbreak of both CRE and A. baumannii, and the fact that many patients cultured the same CRE organism and A. baumannii, strongly suggests that a critical breakdown in IPC measures had occurred.

Performance of spirometry assessment at TB diagnosis.

BACKGROUND: Spirometry is considered relevant for the diagnosis and monitoring of post-TB lung disease. However, spirometry is rarely done in newly diagnosed TB patients.METHODS: Newly diagnosed, microbiologically confirmed TB patients were recruited for the study. Spirometry was performed within 21 days of TB treatment initiation according to American Thoracic Society/European Respiratory Society guidelines. Spirometry analysis was done using Global Lung Initiative equations for standardisation.RESULTS: Of 1,430 eligible study participants, 24.7% (353/1,430) had no spirometry performed mainly due to contraindications and 23.0% (329/1,430) had invalid results; 52.3% (748/1,430) of participants had a valid result, 82.8% (619/748) of whom had abnormal spirometry. Of participants with abnormal spirometry, 70% (436/619) had low forced vital capacity (FVC), 6.1% (38/619) had a low ratio of forced expiratory volume in 1 sec (FEV1) to FVC, and 19.1% (118/619) had low FVC, as well as low FEV1/FVC ratio. Among those with abnormal spirometry, 26.3% (163/619) had severe lung impairment.CONCLUSIONS: In this population, a high proportion of not performed and invalid spirometry assessments was observed; this was addressed by removing tachycardia as a (relative) contraindication from the study guidance and retraining. The high proportion of patients with severe pulmonary impairment at the time of TB diagnosis suggests a huge morbidity burden and calls for further longitudinal studies on the relevance of spirometry in predicting chronic lung impairment after TB.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

The utility of chest ultrasound-guided fine-needle biopsy in the diagnosis of plasmacytoma.

Background: Plasmacytoma is a plasma cell dyscrasia originating from a single clone of plasma cells of B-lymphocyte lineage and produces a monoclonal immunoglobulin. Transthoracic fine-needle aspiration (TTNA) under ultrasound (US) guidance is a well-validated technique for the diagnosis of many neoplasms and has been shown to be safe and cost effective, with diagnostic yields comparable to more invasive techniques. However, the role of TTNA in the diagnosis of thoracic plasmacytoma is not well established. Objectives: The aim of this study was to assess the utility of TTNA and cytology in confirming a diagnosis of plasmacytoma. Methods: All cases of plasmacytoma diagnosed from January 2006 to December 2017 by the Division of Pulmonology, Tygerberg Hospital, were retrospectively identified. All patients who underwent an US-guided TTNA and of whose clinical records could be retrieved were included in this cohort. The International Myeloma Working Group's definition of a plasmacytoma was used as the gold standard. Results: A total of 12 cases of plasmacytoma were identified and 11 patients included (one patient was excluded owing to missing medical records). Six of the 11 patients (mean age 59.5 ± 8.5 years) were male. Radiologically, most had multiple lesions (n=7), most commonly bony (n=6) with vertebral body involvement (n=5) and pleural-based lesions (n=2). Rapid onsite evaluation (ROSE) was performed and documented in 6 of the 11 cases, and a provisional diagnosis of plasmacytoma was suggested in 5 of the 6 patients (83.3%). The final laboratory cytological diagnoses of all 11 cases were compatible with plasmacytoma which was further confirmed via a bone marrow biopsy (n=4) and by serum electrophoresis (n=7). Conclusion: US-guided fine-needle aspiration is feasible and is useful to confirm a diagnosis of plasmacytoma. Its minimally invasive nature may be the ideal investigation of choice in suspected cases.

Correlation between lung function tests and peak oxygen consumption in post-TB lung disease.

BACKGROUND: After TB treatment, many patients have post-TB lung disease (PTLD), associated with increased mortality and morbidity. Nevertheless, relationships between lung function testing and exercise capacity in people with PTLD are poorly understood.METHODS: This single-centre study investigated the association between lung function testing and peak oxygen consumption (VO2peak) and percentage-predicted VO2peak (VO2peak (%pred)) in adults with PTLD investigated for surgery.RESULTS: Eighty-two patients (52 males, 30 females) with a mean age of 43.2 years (SD 11.3) were included. Spirometric values of forced vital capacity (FVC) percentage predicted (%pred) and forced expiratory volume in 1 sec (FEV1) %pred suggested significant correlations with VO2peak (%pred) (P < 0.001 and P < 0.001), whereas FEV1/FVC did not. Diffusing capacity for carbon monoxide (DLCO) %pred also correlated significantly with VO2peak (%pred) (P = 0.002). However, the magnitude of all significant correlation coefficients were weak. No significant correlations for any plethysmographic values with VO2peak (%pred) could be robustly concluded. Correlations with VO2peak (ml/kg/min) for most physiological variables were less robust than for VO2peak (%pred).CONCLUSIONS: Although statistically significant, the correlations between any measure of lung function and VO2peak or VO2peak (%pred) were weak, with only FVC correlation coefficient surpassing 0.50.

Immunologic and imaging signatures in post tuberculosis lung disease.

Post Tuberculosis Lung Disease (PTLD) affects millions of tuberculosis survivors and is a global health burden. The immune mechanisms that drive PTLD are complex and have historically been under investigated. Here, we discuss two immune-mediated paradigms that could drive human PTLD. We review the characteristics of a fibrotic granuloma that favors the development of PTLD via an abundance of T-helper-2 and T-regulatory cells and an upregulation of TGF-ß mediated collagen deposition. Next, we discuss the post-primary tuberculosis paradigm and the complex mixture of caseous pneumonia, cavity formation and fibrosis that can also lead to PTLD. We review the delicate balance between cellular subsets and cytokines of the innate and adaptive immune system in conjunction with host-derived proteases that can perpetuate the parenchymal lung damage seen in PTLD. Next, we discuss the role of novel host directed therapies (HDT) to limit the development of PTLD and in particular, the recent repurposing of established medications such as statins, metformin and doxycycline. Finally, we review the emerging role of novel imaging techniques as a non-invasive modality for the early recognition of PTLD. While access to computed tomography imaging is unlikely to be available widely in countries with a high TB burden, its use in research settings can help phenotype PTLD. Due to a lack of disease-specific biomarkers and controlled clinical trials, there are currently no evidence-based recommendations for the management of PTLD. It is likely that an integrated antifibrotic strategy that could simultaneously target inflammatory and pro-fibrotic pathways will probably emerge as a successful way to treat this complex condition. In a disease spectrum as wide as PTLD, a single immunologic or radiographic marker may not be sufficient and a combination is more likely to be a successful surrogate that could aid in the development of successful HDTs.

Position statement for adult and paediatric spirometry in South Africa: 2022 update.

Spirometry is required as part of the comprehensive evaluation of both adult and paediatric individuals with suspected or confirmed respiratory diseases and occupational assessments. It is used in the categorisation of impairment, grading of severity, assessment of potential progression and response to interventions. Guidelines for spirometry in South Africa are required to improve the quality, standardisation and usefulness in local respiratory practice. The broad principles of spirometry have remained largely unchanged from previous versions of the South African Spirometry Guidelines; however, minor adjustments have been incorporated from more comprehensive international guidelines, including adoption of the Global Lung Function Initiative 2012 (GLI 2012) spirometry reference equations for the South African population. All equipment should have proof of validation regarding resolution and consistency of the system. Daily calibration must be performed, and equipment quality control processes adhered to. It is important to have standard operating procedures to ensure consistency and quality and, additionally, strict infection control as highlighted during the COVID-19 pandemic. Adequate spirometry relies on a competent, trained operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. All manoeuvres must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Results must be categorised and graded according to current guidelines, taking into consideration the indication for the test.

Position statement on endoscopic lung volume reduction in South Africa: 2022 update.

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV1) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country.

The optimal management of the patient with COVID-19 pneumonia: HFNC, NIV/CPAP or mechanical ventilation?

The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID-19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient. This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes. On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet-CPAP (continuous positive airway pressure) (although not widely available) may be superior to high-flow nasal cannula (HFNC) therapy or facemask non-invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces. In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.

Are interferon-γ release assays useful for diagnosing active tuberculosis in a high-burden setting?

Although interferon-γ release assays (IGRAs) are intended for diagnosing latent tuberculosis (TB), we hypothesised that in a high-burden setting: 1) the magnitude of the response when using IGRAs can distinguish active TB from other diagnoses; 2) IGRAs may aid in the diagnosis of smear-negative TB; and 3) IGRAs could be useful as rule-out tests for active TB. We evaluated the accuracy of two IGRAs (QuantiFERON®-TB Gold In-tube (QFT-GIT) and T-SPOT®.TB) in 395 patients (27% HIV-infected) with suspected TB in Cape Town, South Africa. IGRA sensitivity and specificity (95% CI) were 76% (68-83%) and 42% (36-49%) for QFT-GIT and 84% (77-90%) and 47% (40-53%) for T-SPOT®.TB, respectively. Although interferon-γ responses were significantly higher in the TB versus non-TB groups (p<0.0001), varying the cut-offs did not improve discriminatory ability. In culture-negative patients, depending on whether those with clinically diagnosed TB were included or excluded from the analysis, the negative predictive value (NPV) of QFT-GIT, T-SPOT®.TB and chest radiograph in smear-negative patients varied between 85 and 89, 87 and 92, and 98% (for chest radiograph), respectively. Overall accuracy was independent of HIV status and CD4 count. In a high-burden setting, IGRAs alone do not have value as rule-in or -out tests for active TB. In smear-negative patients, chest radiography had better NPV even in HIV-infected patients.

High prevalence of smoking among patients with suspected tuberculosis in South Africa.

There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). There are no data validating the accuracy of self-reported smoking in TB patients and limited data about the prevalence of smoking in TB patients from high-burden settings. We performed a cross-sectional analysis of 500 patients with suspected TB in Cape Town, South Africa. All underwent comprehensive diagnostic testing. The accuracy of their self-reported smoking status was determined against serum cotinine levels. Of the 424 patients included in the study, 56 and 60% of those with active and latent TB infection (LTBI), respectively, were current smokers. Using plasma cotinine as a reference standard, the sensitivity of self-reported smoking was 89%. No statistically significant association could be found between smoking and active TB or LTBI. In Cape Town, the prevalence of smoking among patients with suspected and confirmed TB was much higher than in the general South African population. Self-reporting is an accurate measure of smoking status. These results suggest the need to actively incorporate tobacco cessation programmes into TB services in South Africa.

A severity-of-illness score in patients with tuberculosis requiring intensive care.

BACKGROUND: We previously retrospectively validated a 6-point severity-of-illness score aimed at identifying patients at risk of dying of tuberculosis (TB) in the intensive care unit (ICU). Parameters included septic shock, HIV infection with a CD4 count <200 cells/µL, renal dysfunction, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F) <200 mmHg, a chest radiograph demonstrating diffuse parenchymal infiltrates, and no TB treatment on admission. OBJECTIVES: To prospectively validate the severity-of-illness scoring system in patients with TB requiring intensive care, and to refine and simplify the score in order to expand its clinical utility. METHODS: We performed a prospective observational study with a planned post hoc retrospective analysis, enrolling all adult patients with confirmed TB admitted to the medical ICU of a tertiary hospital in Cape Town, South Africa, from 1 February 2015 to 31 July 2018. The admission data of all adult patients with TB requiring admission to the ICU were used to calculate the 6-point severity-of-illness score and a refined 4-point score (based on the planned post hoc analysis). Descriptive statistics and χ2 or Fisher's exact tests (where indicated) were performed on dichotomous categorical variables, and t-tests on continuous data. Patients were categorised as hospital survivors or non-survivors. RESULTS: Forty-one of 78 patients (52.6%) died. The 6-point scores of non-survivors were higher than those of survivors (mean (standard deviation (SD)) 3.5 (1.3) v. 2.7 (1.2); p=0.01). A score ≥3 v. <3 was associated with increased mortality (64.0% v. 32.1%; odds ratio (OR) 3.75; 95% confidence interval (CI) 1.25 - 10.01; p=0.01). Post hoc, a P/F ratio <200 mmHg and no TB treatment on admission failed to predict mortality, whereas any immunosuppression did. A revised 4-point score (septic shock, any immunosuppression, acute kidney injury and lack of lobar consolidation) demonstrated higher scores in non-survivors than survivors (mean (SD) 2.8 (1.1) v. 1.6 (1.1); p<0.001). A score ≥3 v. ≤2 was associated with increased mortality (78.4% v. 29.3%; OR 8.76; 95% CI 3.12 - 24.59; p<0.001). CONCLUSIONS: The 6-point severity-of-illness score identified patients at increased risk of death. We were able to derive and retrospectively validate a simplified 4-point score with superior predictive power.

Pulmonary manifestations of IgG4­related disease in a South African patient.

Immunoglobin 4-related disease (IgG4-RD) is an auto-immune, multisystem inflammatory disorder characterised by storiform fibrosis, lymphoplasmacytic infiltration and obliterative phlebitis on histology. Its pathophysiology is not well understood, but is thought to occur due to complex interactions between T helper 2 cells, their cytokines, chemokines, and B lymphocytes that become dysregulated and produce dysfunctional immunoglobulins. Here, we present a case report of a 54-year-old man who was initially suspected of having lung cancer on imaging, but was ultimately diagnosed with IgG4-RD on histological analysis of a pneumonectomy specimen. Treatment with glucocorticoids can establish disease remission, with a small proportion of patients relapsing, if the diagnosis is made before significant fibrosis occurs.

Respiratory presentations to acute services at a tertiary hospital in South Africa.

BACKGROUND: Respiratory diseases account for >10% of the global burden of disease when measured in disability-adjusted life-years. The burden of chronic respiratory diseases (CRDs) increases as the world's population ages, with a much greater increase in low- to middle-income countries. OBJECTIVES: To characterise and quantify the reasons for acute respiratory presentations to the acute care services at a tertiary hospital in Cape Town, South Africa. METHODS: A cross-sectional descriptive study was conducted. Casualty registers and electronic record databases were reviewed to determine the diagnoses of consecutive patients attending the casualty unit from May 2019 to January 2020. RESULTS: A total of 1 053 individual patients presented with a primary respiratory diagnosis. Fewer than 10% of admissions were from outside the Cape Town metropole, while >60% were from the subdistrict immediately adjacent to the hospital. Of all patients, 8.3% were readmitted at least once within the 9-month study period. Six hundred and forty-three (61.1%) of the patients presented with non-CRDs. The main reasons for presentation in these patients were pulmonary tuberculosis (PTB) (n=224; 21.3%), other infections including lower respiratory tract infections, pneumonia and bronchitis (n=272; 25.8%), and cancer (n=140; 13.3%). Haemoptysis was seen in 9.8% of all patients, mainly explained by post-tuberculosis lung disease (PTLD) (37.9%) and PTB (36.9%). Of the patients, 410 (38.9%) had an underlying CRD, with chronic pulmonary obstructive disease (COPD) being the most common (n=192; 18.2%), followed by PTLD (n=88; 8.5%) and asthma (n=52; 5.1%). CONCLUSIONS: Over a 9-month period, acute respiratory presentations to a tertiary hospital were mainly for primary/secondary level of care indications, highlighting disparity in accessing tertiary services. COPD and PTLD predominated among CRDs, while infections and cancers were common. A high readmission rate was found for several diseases, suggesting the potential for targeted interventions to prevent both admissions and readmissions and reduce acute hospital utilisation costs.