Search

No pleural intervention in a patient with confirmed malignant pleural effusion (MPE) prolongs life, but even the recommended interventions for diagnosis and palliation can be costly and therefore unavailable in large parts of the world. However, there is good evidence to guide clinicians working in low- and middle-income countries on the most cost-effective and clinically effective strategies for the diagnosis and management of MPE. Transthoracic ultrasound-guided closed pleural biopsy is a safe method of pleural biopsy with a diagnostic yield approaching that of thoracoscopy. With the use of pleural fluid cytology and ultrasound-guided biopsy, ≥90% of cases can be diagnosed. Cases with an associated mass lesion are best suited to an ultrasound-guided fine needle aspiration with/without core needle biopsy. Those with diffuse pleural thickening and/or nodularity should have an Abrams needle (<1 cm thickening) or core needle (≥1 cm thickening) biopsy of the area of interest. Those with insignificant pleural thickening should have an ultrasound-guided Abrams needle biopsy close to the diaphragm. The goals of management are to alleviate dyspnoea, prevent re-accumulation of the pleural effusion and minimise re-admissions to hospital. As the most cost-effective strategy, we suggest early use of indwelling pleural catheters with daily drainage for 14 days, followed by talc pleurodesis if the lung expands. The insertion of an intercostal drain with talc slurry is an alternative strategy which is noninferior to thoracoscopy with talc poudrage., Educational Aims: To provide clinicians practising in resource-constrained settings with a practical evidence-based approach to the diagnosis and management of malignant pleural effusions.To explain how to perform an ultrasound-guided closed pleural biopsy.To explain the cost-effective use of indwelling pleural catheters., Competing Interests: Conflict of interest: J.A. Shaw reports receiving an honorarium from AstraZeneca, outside the submitted work. E.H. Louw has nothing to disclose. C.F.N. Koegelenberg reports receiving an honorarium from GSK and AstraZeneca, outside the submitted work., (Copyright ©ERS 2023.)

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features., Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed., Results: 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL -1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL -1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L -1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL -1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival., Conclusion: Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed., Competing Interests: Conflict of interest: J.M. Porcel has received consultancy fees from Becton Dickinson and Suministros Hospitalarios SA (SH Medical Group), and is an associate editor of this journal. Conflict of interest: The remaining authors declare that they have no relevant conflicts of interest., (Copyright ©The authors 2023.)

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse., Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes., Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died., Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shaw, Meiring, Snyders, Everson, Sigwadhi, Ngah, Tromp, Allwood, Koegelenberg, Irusen, Lalla, Baines, Zemlin, Erasmus, Chapanduka, Matsha, Walzl, Strijdom, du Plessis, Zumla, Chegou, Malherbe and Nyasulu.)

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis., Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis., Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09)., Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP., Competing Interests: Conflict of interest: J.M. Porcel is an associate editor of this journal. C.F.N. Koegelenberg declares honoraria for lectures from AstraZeneca and GlaxoSmithKline, in the 36 months prior to manuscript submission. All other authors declare no competing interests., (Copyright ©The authors 2023.)

Background: There is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB)., Methods: We conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed., Results: PWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02-1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12-1.72, p = 0.003) and being "overweight or obese" (AHR 1.30 95%CI 1.03-1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95-1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84-2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm 3 , higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels., Conclusion: In a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population., (© 2022. The Author(s).)

Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, via hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotze, van der Spuy, Leonard, Penn-Nicholson, Musvosvi, McAnda, Malherbe, Erasmus, Scriba, Koegelenberg, Allwood, Walzl and du Plessis.)

After the results of two large, randomized trials, the global implementation of lung cancer screening is of utmost importance. However, coronavirus disease 2019 infections occurring at heightened levels during the current global pandemic and also other respiratory infections can influence scan interpretation and screening safety and uptake. Several respiratory infections can lead to lesions that mimic malignant nodules and other imaging changes suggesting malignancy, leading to an increased level of follow-up procedures or even invasive diagnostic procedures. In periods of increased rates of respiratory infections from severe acute respiratory syndrome coronavirus 2 and others, there is also a risk of transmission of these infections to the health care providers, the screenees, and patients. This became evident with the severe acute respiratory syndrome coronavirus 2 pandemic that led to a temporary global stoppage of lung cancer and other cancer screening programs. Data on the optimal management of these situations are not available. The pandemic is still ongoing and further periods of increased respiratory infections will come, in which practical guidance would be helpful. The aims of this report were: (1) to summarize the data available for possible false-positive results owing to respiratory infections; (2) to evaluate the safety concerns for screening during times of increased respiratory infections, especially during a regional outbreak or an epidemic or pandemic event; (3) to provide guidance on these situations; and (4) to stimulate research and discussions about these scenarios., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those - already available tests that remain suboptimally utilized., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Pleural tuberculosis (TB) is common and often follows a benign course but may result in serious long-term morbidity. Diagnosis is challenging because of the paucibacillary nature of the condition. Advances in Mycobacterium culture media and PCR-based techniques have increased the yield from mycobacteriologic tests. Surrogate biomarkers perform well in diagnostic accuracy studies but must be interpreted in the context of the pretest probability in the individual patient. Confirming the diagnosis often requires biopsy, which may be acquired through thoracoscopy or image-guided closed pleural biopsy. Treatment is standard anti-TB therapy, with optional drainage and intrapleural fibrinolytics or surgery in complicated cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Colistin use is increasing with the rise in MDR Gram-negative infections globally. Effective antibiotic stewardship is essential to preserve this antibiotic of last resort., Objectives: This study investigated stewardship and safety errors related to colistin use to identify opportunities for improvement., Patients and Methods: A prospective descriptive study involving all patients 13 years and older treated with colistin at a tertiary hospital in Cape Town, South Africa, between August 2018 and June 2019. We collected clinical, laboratory and outcome data and assessed provided treatment for stewardship and safety errors., Results: We included 44 patients. Treatment errors were identified for 34 (77%) patients (median = 1), most commonly inadequate monitoring of renal function ( N  =   16, 32%). We also identified no rational indication for colistin ( N  =   9, 20%), loading dose error ( N  =   12, 27%); maintenance dose error ( N  =   10, 23%); no prior culture ( N  =   11, 25%); and failure to de-escalate (2 of 9) or adjust dose to changes in renal function (6 of 15). All cause in-hospital mortality was 47%. Amongst survivors, median ICU stay was 6 days and hospital stay more than 30 days. Eight (18%) patients developed renal injury or failure during treatment. Three (7%) patients in this study were found to have colistin-resistant organisms including two prior to colistin exposure., Conclusions: This study has identified opportunities to enhance colistin stewardship and improve efficacy and safety of prescription. The appearance of colistin-resistant organisms reinforces the urgent need to ensure effective and appropriate use of colistin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Tuberculous granulomas that develop in response to Mycobacterium tuberculosis (M. tuberculosis) infection are highly dynamic entities shaped by the host immune response and disease kinetics. Within this microenvironment, immune cell recruitment, polarization, and activation are driven not only by coexisting cell types and multicellular interactions but also by M. tuberculosis-mediated changes involving metabolic heterogeneity, epigenetic reprogramming, and rewiring of the transcriptional landscape of host cells. There is an increased appreciation of the in vivo complexity, versatility, and heterogeneity of the cellular compartment that constitutes the tuberculosis (TB) granuloma and the difficulty in translating findings from animal models to human disease. Here, we describe a novel biomimetic in vitro three-dimensional (3D) human lung spheroid granuloma model, resembling early "innate" and "adaptive" stages of the TB granuloma spectrum, and present results of histological architecture, host transcriptional characterization, mycobacteriological features, cytokine profiles, and spatial distribution of key immune cells. A range of manipulations of immune cell populations in these spheroid granulomas will allow the study of host/pathogen pathways involved in the outcome of infection, as well as pharmacological interventions. IMPORTANCE TB is a highly infectious disease, with granulomas as its hallmark. Granulomas play an important role in the control of M. tuberculosis infection and as such are crucial indicators for our understanding of host resistance to TB. Correlates of risk and protection to M. tuberculosis are still elusive, and the granuloma provides the perfect environment in which to study the immune response to infection and broaden our understanding thereof; however, human granulomas are difficult to obtain, and animal models are costly and do not always faithfully mimic human immunity. In fact, most TB research is conducted in vitro on immortalized or primary immune cells and cultured in two dimensions on flat, rigid plastic, which does not reflect in vivo characteristics. We have therefore conceived a 3D, human in vitro spheroid granuloma model which allows researchers to study features of granuloma-forming diseases in a 3D structural environment resembling in vivo granuloma architecture and cellular orientation.

Background: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied., Methods: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO., Findings: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P a O2/FiO 2 ) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P a O2/FiO 2 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed ( p <0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%)., Interpretation: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation., Competing Interests: BA has received speakers fees from Novartis, and CK has served on an advisory board from AstraZeneca, both outside the submitted work., (© 2020 The Author(s).)

Background: The potentially curative and/or palliative therapy for non-resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub-typing of non-small cell lung carcinoma (NCSLC) has become paramount., Objectives: As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas., Methods: All cases of NSCLC diagnosed during a 3-year period were retrospectively identified. All FNA biopsy and formalin-fixed paraffin-embedded cases that were stained with TTF-1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data., Results: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF-1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma., Conclusion: All four immunostaining methods had high sensitivities. TTF-1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF-1. The specificity of CK5 for squamous cell carcinoma was higher than p63., (© 2019 John Wiley & Sons Ltd.)

Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered., (© 2019 Asian Pacific Society of Respirology.)

Lung cancer remains the leading cause of cancer-related deaths in southern Africa. Early trials of chest radiograph-based screening in males at high risk for lung cancer found no mortality benefit of a radiograph alone, or a radiograph plus sputum cytology screening strategy. Large prospective studies, including the National Lung Screening Trial, have shown an all-cause mortality benefit when low-dose computed tomography (LDCT) was used as a screening modality in patients that are at high risk of developing lung cancer. The South African Thoracic Society, based on these findings, and those from several international guidelines, recommend that annual LDCT should be offered to patients between 55-74 years of age who are current or former smokers (having quit within the preceding 15 years), with at least a 30-pack year smoking history and with no history of lung cancer. Patients should be in general good health, fit for surgery, and willing to undergo further investigations if deemed necessary. Given the high local prevalence of tuberculosis (TB) infection and post-TB lung disease, which can radiographically mimic lung cancer, a conservative threshold (nodule size ≥6 mm) should be used to determine whether the baseline LDCT screen is positive (thus nodules <6 mm require no action until the next annual screen). If a non-calcified, solid or partly solid nodule is ≥6 mm, but <10 mm with no malignant features (e.g., distinct spiculated margins), the LDCT should be repeated in 6 months. If a solid nodule or the largest component of a non-solid nodule is ≥10 or ≥6 mm and enlarging or with additional malignant features present, definitive action to exclude lung cancer is warranted. Patients should be screened annually until 15 years have elapsed from date of smoking cessation, they turn 80, become unfit for a curative operation or significant changes are observed., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

The estimation of predicted postoperative (PPO) lung function is important in lung resection candidates. We utilized simple anatomical calculations and single-photon emission computed tomography combined with computed tomography (SPECT-CT) to calculate PPO in 24 consecutive patients with impaired pulmonary function who underwent lung resection. PPO values calculated by anatomical calculations and three-dimensional lobar SPECT-CT quantification both correlated well with the postoperative forced expiratory volume in 1 s, with r = 0.825, p < 0.001 and r = 0.796, p < 0.001, respectively. Both techniques fared well at predicting postoperative lung function, but our observations unexpectedly suggested that simple anatomical calculations might be equivalent to three-dimensional SPECT-CT lobar quantification., (© 2019 S. Karger AG, Basel.)

We describe an exceptionally rare case of a male patient with newly diagnosed advanced human immunodeficiency virus (HIV) infection, who presented with a plasmablastic lymphoma involving the right maxillary alveolar ridge with associated cervical lymphadenopathy. On a staging positron emission tomography computed tomography (PET-CT) scan, he was incidentally found to have an endotracheal tumour involving the anterolateral aspect of the mid-trachea. The tumour appeared to be well-vascularised at bronchoscopy and was confirmed as well-differentiated plasmablastic lymphoma. Plasmablastic lymphoma is a rare form of non-Hodgkin lymphoma and is associated with HIV. Tracheal involvement to the extent seen in our patient is exceptionally rare, and, to the best of our knowledge, has never been described., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Optimal management of malignant pleural effusion (MPE) is important in the care of patients with advanced cancer. Surgical (especially video-assisted thoracoscopic surgery (VATS)) and non-surgical strategies are available. Clinicians should be aware of the evidence supporting the use of different modalities to guide treatment choice. Areas covered: This review covers published evidence of the advantages and disadvantages of VATS and non-surgical alternatives for MPE management. Expert commentary: Randomized clinical trials (RCTs) are needed to define the roles and benefits of VATS as existing literature is often flawed by selection bias. Three RCTs have failed to show benefits of VATS talc poudrage over bedside talc pleurodesis. VATS-pleurectomy offered no survival advantage in a RCT of mesothelioma patients. Modification of VATS techniques has reduced the invasiveness and associated risks. Future trials should compare VATS with contemporary, non-surgical approaches (especially combined Indwelling Pleural Catheter (IPC) and chemical pleurodesis therapy). Individualized management for different subgroups of MPE patients should be a long-term research goal. Studies are needed on better patient selection, and adjunct non-invasive, supportive (e.g. nutrition and exercise) therapies.

Malignant pleural effusion (MPE) affects more than 1 million people globally. There is a dearth of evidence on the therapeutic approach to MPE, and not surprisingly a high degree of variability in the management thereof. We aimed to provide practicing clinicians with an overview of the current evidence on the management of MPE, preferentially focusing on studies that report patient-related outcomes rather than pleurodesis alone, and to provide guidance on how to approach individual cases. A pleural intervention for MPE will perforce be palliative in nature. A therapeutic thoracentesis provides immediate relief for most. It can be repeated, especially in patients with a slow rate of recurrence and a short anticipated survival. Definitive interventions, individualized according the patient's wishes, performance status, prognosis and other considerations (including the ability of the lung to expand) should be offered to the remainder of patients. Chemical pleurodesis (achieved via intercostal drain or pleuroscopy) and indwelling pleural catheter (IPC) have equal impact on patient-based outcomes, although patients treated with IPC spend less time in hospital and have less need for repeat pleural drainage interventions. Talc slurry via IPC is an attractive recently validated option for patients who do not have a nonexpandable lung.

In this report, we describe a male patient who presented with recurrent life-threatening hemoptysis due to the sequential formation of multiple pulmonary aneurysms. Both pulmonary artery coil embolization and right lower lobectomy were performed, with limited success. The patient experienced extensive bilateral femoral DVT extending into the inferior vena cava, with massive hemoptysis, fulfilling the diagnosis of Hughes-Stovin syndrome. A final diagnosis of Behçet disease was made following extensive investigation, and the patient responded well to prednisone 20 mg orally and azathioprine 100 mg orally., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The use of thoracic ultrasound outside the radiology department and in everyday clinical practice is becoming increasingly common, having been incorporated into standards of care for many specialties. For the majority of practitioners, their experience of, and exposure to, thoracic ultrasound will be in its use as an adjunct to pleural and thoracic interventions, owing to the widely recognised benefits for patient safety and risk reduction. However, as clinicians become increasingly familiar with the capabilities of thoracic ultrasound, new directions for its use are being sought which might enhance practice and patient care. This article reviews the ways in which the advent of thoracic ultrasound is changing the approach to the investigation and treatment of respiratory disease from an interventional perspective. This will include the impact of thoracic ultrasound on areas including patient safety, diagnostic and therapeutic procedures, and outcome prediction; and will also consider potential future research and clinical directions., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Significant iatrogenic bleeding during flexible bronchoscopy is fortunately rare and usually self-limiting. Life-threatening bleeding, however, can occur, especially after conventional or cryoprobe-assisted transbronchial biopsy. The aim of this review is to provide the practising pulmonologist with a concise overview of the incidence, severity and risk factors for bleeding, to provide sensible advice on prophylactic measures and to suggest a plan of action in the case of significant bleeding. Bronchoscopy units should have a standardised approach and plan of action in the case of life-threatening haemorrhage. Wedging the bronchoscope in the bleeding segment, turning the patient in an anti-Trendelenburg position and onto the side in order for the bleeding lung to be in the dependent position, installing vasoconstrictors and using a tamponade balloon early are the recommended first-line strategies. Involving a resuscitation team should be considered early in the case of massive bleeding, desaturation and haemodynamic instability., Competing Interests: Conflict of interest: None declared.

Treatment options for intractable life-threatening haemoptysis in mechanically ventilated patients with structural lung disease who do not respond to bronchial artery embolisation (BAE) and who are deemed unfit for surgery are limited. A 26-year-old HIV-positive male with a poorly preserved CD4 count and active pulmonary tuberculosis was intubated and mechanically ventilated for persistent life-threatening haemoptysis. Two attempts at BAE failed, and life-threatening haemoptysis recurred daily for 14 days despite antituberculous therapy. He was deemed unfit for surgery during that period. We proceeded to identify the source of bleeding endoscopically and implanted an endobronchial valve in the left upper lobe bronchus. Following the collapse of the affected lobe, haemoptysis ceased and the patient was promptly liberated from mechanical ventilation. He remained haemoptysis free for the duration of his hospitalisation. Endobronchial valves, therefore, may be a viable option in patients mechanically ventilated with persistent life-threatening haemoptysis in whom all other conventional measures fail and who are considered unfit for surgery., (© 2017 S. Karger AG, Basel.)

Idiopathic pulmonary fibrosis (IPF) is a very specific form of a chronic, progressive fibroproliferative interstitial pneumonia of unknown aetiology. The disease is generally associated with a poor prognosis. Several international evidence-based guidelines on the diagnosis and management of IPF and other interstitial lung diseases (ILDs) have been published and updated in the last decade, and while the body of evidence for the use of some treatment modalities has grown, others have been shown to be futile and even harmful to patients. In a patient who presents with the classic clinical features, restrictive ventilatory impairment with impaired diffusion and a high resolution computed tomography (HRCT) scan of the lungs showing a usual interstitial pneumonia (UIP) pattern, a definitive diagnosis of IPF can be made, provided all other causes of a radiological UIP pattern are excluded. Patients who present with atypical clinical features or an HRCT pattern classified as "possible" UIP, should be referred for a surgical lung biopsy. Once the diagnosis of IPF is confirmed, a patient-centred approached should be followed, as the stage of the disease, degree of impairment, rate of disease progression, comorbid illnesses and patient preferences all impact on long-term management. The South African Thoracic Society (SATS) suggests that anti-fibrotic treatment should be offered to appropriate candidates [confirmed IPF with a forced vital capacity (FVC) of 50-80%], but discontinued should there be evidence of disease progression (a decline in FVC of ≥10% within any 12-month period). The routine use of high dose oral steroids, immunosuppressive drugs and anticoagulants is not recommended whilst anti-acid therapy may be considered in patients without advanced disease., Competing Interests: GM Ainslie and EM Irusen report an honorarium for having attended the Boehringer Ingelheim National Respiratory Advisory Board Meeting for Nintedanib. The other authors have no conflicts of interest to declare.

A 66-year-old female from a rural area in South Africa presented with non-life-threatening haemoptysis. Radiologic and serological investigations attributed her symptoms to bilateral, large echinococcal cysts. She declined surgery despite her lung physiologic parameters, which deemed her eligible. Medical therapy with oral albendazole was initiated with excellent clinical and radiologic response during a follow-up period of 18 months. To our knowledge, this is one of the first reported cases in the literature that shows complete resolution of bilateral large echinococcal cysts with medical treatment alone in an adult patient., (© 2016 S. Karger AG, Basel.)

Emphysema is a very common cause of morbidity and mortality in South Africa (SA). Therapeutic options in severe emphysema are limited. Endoscopic lung volume reduction (ELVR) is increasingly being used internationally for the treatment of advanced emphysema in a subset of patients with advanced disease, aiming to obtain the same functional advantages as surgical lung volume reduction while reducing risks and costs. In addition to endobronchial valves, ELVR using endobronchial coils is now available in SA. The high cost of these interventions underscores the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The Assembly on Interventional Pulmonology of the South African Thoracic Society appointed a committee comprising both local and international experts to extensively review all relevant evidence and provide advice on the use of ELVR in SA based on published evidence, expert opinion and local access to the various devices.

Approximately 5% of the ~3 million asthmatics in South Africa have severe asthma that is associated with substantial morbidity, cost, absenteeism, preventable mortality, and the requirement for costly chronic medication that may be associated with significant adverse events. There is an unmet need for alternative safer and more effective interventions for severe asthma. A recently introduced option, bronchial thermoplasty (BT), imparts radiofrequency-generated heat energy to the airways to cause regression of airway smooth muscle. The effectiveness of this technique has been confirmed in randomised control trials and is now endorsed by several international guidelines, including the Global Initiative for Asthma (GINA) guideline, the British Asthma Guideline, and the UK National Institute of Clinical Excellence (NICE) guideline. We recommend BT as a potential therapeutic intervention for severe uncontrolled asthma, provided that it is performed by an experienced pulmonologist at an accredited centre and done within the broader context of appropriate management of the disease by doctors experienced in treating difficult-to-control asthma.

Background: Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB., Methods: All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis., Results: Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings., Conclusion: Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis.