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..

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.

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.

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.

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.

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.

Postmortem lung biopsies from four patients with COVID-19 at a tertiary hospital in Cape Town, South Africa.

BACKGROUND: An outbreak of a novel coronavirus in China in late 2019 has resulted in a global pandemic. The virus (SARS-CoV-2) causes a severe acute respiratory syndrome and had been responsible for >14 000 deaths in South Africa (SA) at the time of writing, 30 August 2020. Autopsies in our setting have not been prioritised owing to the infective risks for staff, resulting in a lack of information on the histopathology of the disease in the SA setting. Postmortem biopsies are relatively quick and easy to perform and reduce the infective risk posed by full autopsies. OBJECTIVES: To determine whether postmortem biopsies of lung tissue could be used to determine cause of death in lieu of full autopsies in patients dying from COVID-19. METHODS: We performed postmortem biopsies of lung tissue on 4 patients with SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction who died in the Tygerberg Hospital (Cape Town, SA) intensive care unit (ICU) in June - July 2020, in order to determine their cause of death. The biopsies were performed in the ICU with the necessary personal protective equipment within 2 hours after death. Clinical information was obtained from the hospital records and the histopathology was reviewed by two consultant histopathologists. Microbiology and electron microscopy were also performed on this tissue. RESULTS: All 4 patients were aged >50 years and had multiple comorbidities. Pulmonary pathology was present in only 3 cases, and the findings were surprisingly heterogeneous. One case demonstrated several findings including diffuse alveolar damage, extensive fibrin thrombi in pulmonary arteries with pulmonary infarction, organising pneumonia and bronchopneumonia. Other findings included type 2 pneumocyte hyperplasia, intra-alveolar macrophages and squamous metaplasia. An organising pneumonia was present in 2 other cases, although these findings were not deemed to be severe enough to be the cause of death. Fibrin thrombi were present in pulmonary arteries of 3 cases. One case showed no significant acute pulmonary pathology. The cause of death could only be determined in 1 case. CONCLUSIONS: The pulmonary findings we observed are in keeping with those described in the international literature. However, the pathology was surprisingly heterogeneous between cases, and was only deemed severe enough to be the cause of death in 1 of 4 cases. While lung-targeted, standardised postmortem biopsies may be safe, easy to perform and provide useful insights into the disease, they are not suitable to replace full autopsies in determining cause of death.

Histologically confirmed tuberculosis-associated obstructive pulmonary disease.

Although chronic airflow limitation (CAL) is an important long-term consequence of tuberculosis (TB), little is known about the disease process. We present what we believe to be the first case of histologically confirmed residual TB-associated obstructive pulmonary disease (TOPD) in a 23-year-old non-smoking man who developed severe CAL after one episode of TB, with no other plausible risk factors. Lung biopsies identified residual post-TB pathology affecting the small airways and vessels throughout his lung; this has not been reported previously. These findings strengthen the argument that TOPD may be a phenotype of CAL distinct from both smoking-related chronic obstructive pulmonary disease and bronchiectasis.

Complete resolution of apparently definite radiological and histological usual interstitial pneumonia.

Idiopathic pulmonary fibrosis is considered to be the most common form of pulmonary fibrosis. It is a progressive and irreversible disease with a reported median survival of ~3 years. The pathological correlate is usual interstitial pneumonia (UIP), and although antifibrotic agents can slow down lung function decline, they do not completely reverse the disease process. To date, there have been no case reports describing reversal of UIP. We present a case where both the imaging and histology were compatible with definite UIP, yet it reversed with immunosuppressive therapy without the use of antifibrotic agents.

The current aetiology of malignant pleural effusion in the Western Cape Province, South Africa.

BACKGROUND: Malignant pleural effusion (MPE) represents a very common cause of pleural exudates, and is one of the most challenging pleural disorders to manage. This could be attributed to the paucity of high-quality experimental evidence, and inconsistent practice worldwide. South Africa (SA) currently has no data regarding the aetiology of MPE. OBJECTIVES: To identify the most common malignancies causing MPE in a population served by a large tertiary hospital in SA, and specifically the relative contribution of mesothelioma. A secondary objective was to evaluate the efficacy of chemical pleurodesis in a subset of patients. METHODS: We retrospectively included all known cases of MPE evaluated at our institution over a 3-year period with a tissue diagnosis of MPE. RESULTS: The most common causes of MPE in a total of 274 patients were lung cancer (n=174, 63.5%), breast cancer (n=32, 11.7%), unknown primary (n=22, 11.7%) and mesothelioma (n=27, 9.9%). Talc pleurodesis was performed in 81 of 194 patients (41.8%) referred to our division, and was radiologically successful in 22 of 25 (88.0%) followed up to 3 months. CONCLUSIONS: The main cause of MPE in our setting was lung cancer, followed by breast cancer, unknown primary and mesothelioma. Chemical pleurodesis was a viable palliative measure for MPE in this population.

Five-year follow-up of participants diagnosed with chronic airflow obstruction in a South African Burden of Obstructive Lung Disease (BOLD) survey.

BACKGROUND: A community-based prevalence survey performed in two suburbs in Cape Town, South Africa (SA), in 2005, using the international Burden of Obstructive Lung Disease (BOLD) method, confirmed a prevalence of chronic airflow obstruction (CAO) in 23.1% of adults aged >40 years. OBJECTIVES: To study the clinical course and prognosis over 5 years of patients with CAO identified in the 2005 survey. METHODS: Patients with CAO in 2005 were invited to participate. Standard BOLD and modified questionnaires were completed. Spirometry was performed using spirometers of the same make as in 2005. RESULTS: Of 196 eligible participants from BOLD 2005, 45 (23.0%) had died, 8 from respiratory causes, 10 from cardiovascular causes and 6 from other known causes, while in 21 cases the cause of death was not known. On multivariate analysis, only age and Global initiative for Obstructive Lung Disease (GOLD) stage 4 disease at baseline were significantly associated with death. Of the 151 survivors, 11 (5.6% of the original cohort) were unavailable and 33 (16.8%) declined or had medical exclusions. One hundred and seven survivors were enrolled in the follow-up study (54.6%, median age 63.1 years, 45.8% males). Post-bronchodilator spirometry performed in 106 participants failed to confirm CAO, defined as a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of <0.7, in 16 participants (15.1%), but CAO was present in 90. The median decline in FEV1 was 28.9 mL/year (interquartile range -54.8 - 0.0) and was similar between GOLD stages. The median total decline in FVC was 75 mL, and was significantly greater in GOLD stage 1 (-350 mL) than in stages 2 or 3 (-80  mL and +140 mL, respectively; p<0.01). Fifty-eight participants with CAO in 2005 (64.4%) remained in the same GOLD stage, while 21 (23.3%) deteriorated and 11 (12.2%) improved by ≥1 stage. Only one-third were receiving any treatment for chronic obstructive pulmonary disease (COPD). CONCLUSIONS: The prevalence, morbidity and mortality of CAO and COPD in SA are high and the level of appropriate treatment is very low, pointing to underdiagnosis and inadequate provision of and access to effective treatments and preventive strategies for this priority chronic non-communicable disease.

Assessment of previous tuberculosis status using questionnaires, chest X-rays and computed tomography scans.

SETTING: Accurate diagnosis of previous pulmonary tuberculosis disease (PPTB) status is important clinically and in research. Reliable records of bacteriologically confirmed tuberculosis (TB) are frequently unavailable. OBJECTIVES: To evaluate the use of questionnaires and chest imaging to determine PPTB status in a high TB prevalence population. DESIGN: PPTB status was assessed using two questionnaires, chest X-ray (CXR) and high-resolution chest computed tomography (CT) scans reported by experienced readers. The study population comprised adults aged >40 years diagnosed with obstructive lung disease in a community-based prevalence survey. RESULTS: The Burden of Obstructive Lung Disease (BOLD) questionnaire and a second comprehensive questionnaire (PTbQ) provided a history of PPTB in respectively 38% (n = 41) and 36.4% (n = 39) of 107 participants. On CXR, 43.3% (45/104) had evidence of PPTB, with good inter-reader agreement (κ = 0.73). Changes compatible with PPTB were identified on chest CT in 68.3% (71/104) of the subjects. Questionnaire and CXR had negative predictive values for PPTB of 48% and 47%, respectively, compared to a composite definition. CONCLUSION: Both questionnaire and CXR markedly underestimate the prevalence of previous TB in patients with chronic obstructive pulmonary disease. The combination of a structured questionnaire and CT scan is more useful when a diagnosis of PPTB needs to be ruled out.