Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

OBJECTIVES: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. METHODS: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. RESULTS: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). CONCLUSION: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Predictive factors for tuberculous peripheral pulmonary lesions during radial endobronchial ultrasound.

BACKGROUND: Tuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety. METHODS: A six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed. RESULTS: 387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55-70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26-4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673-0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68-79.88). CONCLUSIONS: Despite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. OBJECTIVES: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. METHODS: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. RESULTS: Of 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0-2), medium (3-5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). CONCLUSION: The predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Performance of radial endobronchial ultrasound for peripheral pulmonary lesions without automation technology in tuberculous endemic region: real-world experience in a single institution over 6 years.

Background: Peripheral pulmonary lesions (PPLs) in tuberculous endemic regions present a unique diagnostic challenge, as tuberculous PPL can mimic malignancy and potentially delay diagnosis for both conditions without a confirmatory investigation. While bronchoscopic biopsy using radial endobronchial ultrasound (rEBUS) guidance is becoming more common among pulmonologists, it is often performed with additional automation technology such as virtual bronchoscopic and electromagnetic navigation. This study aimed to evaluate the performance of rEBUS without such automation technology over a 6-year period in our institution. Methods: Retrospective chart review of all adult patients undergoing rEBUS-guided transbronchial biopsy for PPL in our institution over 6 years duration (October 2016 to December 2022). Results: A total of 551 PPLs were included with median target lesion size of 2.70 (interquartile range, 2.10-3.70) cm. In total, 84.2% of lesion demonstrated direct bronchus sign with 46.3% demonstrating concentric rEBUS orientation. The overall diagnostic yield was 78.8% [95% confidence interval (CI): 75.1-82.1%], with 1.1% rate of pneumothorax. Among the conclusive cases, 62.7% were malignant while 37.3% were tuberculous. Bronchus sign [adjusted odds ratio (adj. OR): 2.268] and concentric rEBUS orientation (adj. OR: 3.426) are independent predictors for conclusive procedure. The sensitivity of rEBUS for malignant and tuberculous disease was 85.27% (95% CI: 80.89-88.97%) and 71.77% (95% CI: 62.99-79.49%) respectively. A significant improving trend of diagnostic yield over time with reduction of median PPL size was observed with introduction of cryobiopsy and thin bronchoscopy into rEBUS service. Conclusions: rEBUS without automation technology remains relevant and useful in this era. rEBUS provides a rapid and safe diagnosis of PPL which may translate into better patient care.

Short-acting ß2-agonist prescription patterns and clinical outcomes in Malaysia: A nationwide cohort of the SABINA III study.

Introduction: SABINA III assessed short-acting ß2-agonist (SABA) prescription patterns and their association with asthma-related outcomes globally. Herein, we examined SABA prescription and clinical outcomes in the Malaysian cohort of SABINA III. Method: In this observational, cross-sectional study, patients (≥12 years) were recruited between July and December 2019 from 15 primary and specialty care centres in Malaysia. Prescribed asthma treatments and severe exacerbation history within 12 months prior and asthma symptom control during the study visit were evaluated. Associations of SABA prescription with asthma control and severe exacerbation were analysed using multivariable regression models. Results: Seven hundred thirty-one patients (primary care, n=265 [36.3%]; specialty care, n=466 [63.7%]) were evaluated. The prevalence of SABA over-prescription (≥3 SABA prescriptions/year) was 47.4% (primary care, 47.1%; specialty care, 47.6%), 51.8% and 44.5% among all patients and patients with mild and moderate-to-severe asthma, respectively. Altogether 9.0% (n=66) purchased SABA without a prescription; among them, 43.9% (n=29) purchased ≥3 inhalers. The mean (standard deviation) number of severe asthma exacerbations was 1.38 (2.76), and 19.7% (n=144) and 25.7% (n=188) had uncontrolled and partly controlled symptoms, respectively. Prescriptions of ≥3 SABA inhalers (vs 1-2) were associated with lower odds of at least partly controlled asthma (odds ratio=0.42; 95% confidence interval [CI]=0.27-0.67) and higher odds of having severe exacerbation(s) (odds ratio=2.04; 95% CI=1.44-2.89). Conclusion: The prevalence of SABA over-prescription in Malaysia is high, regardless of the prescriber type, emphasising the need for healthcare providers and policymakers to adopt latest evidence-based recommendations to address this public health concern.

Echographic septation: A potentially useful indicator discriminating tuberculous from malignant pleural effusion.

BACKGROUND: Tuberculous (TBE) and malignant (MPE) pleural effusions present with similar lymphocytic exudates. As TBE is an inflammatory and hypersensitivity process, we hypothesized that echographic septation may be more prevalent in TBE than in MPE, potentially serving as a good clinical predictor for TBE. METHODS: A total of 183 TBE and 266 MPE patients were recruited retrospectively. Multivariate logistic regression was performed to determine significant predictors for TBE. RESULTS: TBE diagnosis was confirmed histologically (caseating granuloma) in 84.7% of the cases, while MPE was biopsy-proven in 63.9% of the cases. Echographic septation was more evident in TBE than in MPE (46.5% vs. 8.2%, p < 0.001). Multivariate logistic regression analysis showed that male sex, serum leucocyte count ≤9 × 109/L or pleural fluid protein ≥50 g/L, and echographic septation (aOR: 9.28, p < 0.001) were independent predictors for TBE. These parameters collectively provided a diagnostic accuracy of 79.61% (95% CI 74.13-84.38). CONCLUSIONS: Echographic septation may potentially facilitate discrimination between TBE and MPE as part of a clinical prediction model. Prospective validation of this prediction model in an external cohort is anticipated.

A young lady with prolonged menstruation and a large lung mass.

Clinicians should maintain a high level of clinical suspicion for invasive aspergillosis in patients receiving immunosuppression, as early diagnosis and treatment are essential to prevent significant morbidity and mortality https://bit.ly/3qLG9Yx.

Feasibility of manual bronchial branch reading technique in navigating conventional rEBUS bronchoscopy in the evaluation of peripheral pulmonary lesion.

BACKGROUND: Although radial endobronchial ultrasound (rEBUS) is an important verification tool in guided bronchoscopy, a navigational route was not provided. Manual airway mapping allows the bronchoscopist to translate the bronchial branching in computed tomography (CT) into a comparable bronchoscopic road map. We aimed to explore the feasibility of this technique in navigating conventional rEBUS bronchoscopy in the localisation of peripheral pulmonary lesion by determining navigation success and diagnostic yield. METHODS: Retrospective review of consecutive rEBUS bronchoscopy performed with a 6.2 mm conventional bronchoscope navigated via manual bronchial branch reading technique over 18 months. RESULTS: Ninety-eight target lesions were included. Median lesion size was 2.67 cm (IQR 2.22-3.38) with 96.9% demonstrating positive CT bronchus sign. Majority (86.7%) of lesions were situated in between the third and fifth airway generations. Procedure was performed with endotracheal intubation in 43.9% and fluoroscopy in 72.4%. 98.9% of lesions were successfully navigated and verified by rEBUS following the pre-planned airway road map. Bidirectional guiding device was employed in 29.6% of cases. Clinical diagnosis was secured in 88.8% of cases, majority of which were malignant disease. The discrepancy between navigation success and diagnostic yield was 10.1%. Target PPL located within five airway generations was associated with better diagnostic yield (95.1% vs. 58.8%, P < 0.001). There was 1 (1.0%) pneumothorax in our cohort. CONCLUSIONS: Manual bronchial branch reading technique in combination with conventional rEBUS is feasible in localisation of PPL, especially for lesions located within the first five airway generations.

Images of the month: Pulmonary cement embolism.

Percutaneous vertebroplasty (PV) involves injection of polymethylmethacrylate bone cement into vertebral body for relief of pain and strengthening of bone in symptomatic vertebral compression fractures.Passage of bone cement into vertebral venous plexus and then into the lungs is a rare and serious complication of PV. The reported incidence up to 26%.We present an incidental finding of pulmonary cement embolism (PCE) after PV. A 68-year-old woman with history of PV 3 years previously for T11 osteoporotic fracture presented to us with cough for 3 weeks following choking on a fish bone.Chest X-ray showed left lower zone consolidation and a high-density opacity in a tubular branching pattern, corresponding to pulmonary arterial distribution. Contrasted computed tomography of the thorax showed segmental pulmonary cement embolism of both lungs and left lower lobe consolidation.She underwent bronchoscopy with findings of a purulent secretion from the left lower lobe. Her symptoms resolved after 2 weeks of antibiotics. She was managed conservatively for the PCE as she remained asymptomatic.This case highlights the need for a standard post-PV chest X-ray, as patients with cement embolisms can be completely asymptomatic. Measures to minimise the risk of pulmonary cement embolisms during PV need to be taken.

Pleural fluid lactate as a point-of-care adjunct diagnostic aid to distinguish tuberculous and complicated parapneumonic pleural effusions during initial thoracentesis: Potential use in a tuberculosis endemic setting.

BACKGROUND: Tuberculous pleural effusions (TBEs) and parapneumonic pleural effusion (PPEs) have similar clinical presentations and fluid biochemistry. A pleural biopsy is usually required to diagnose TBE but complete fluid evacuation may not be necessary, contrasting with complicated PPE (CPPE). A point-of-care test that distinguishes between TBE and CPPE enables the appropriate procedures to be performed during the initial diagnostic thoracentesis. Lactate is a metabolic product measurable by a blood-gas analyzer. This study measured pleural fluid (Pf) lactate levels in TBE and compared them with those in PPE/CPPE. We hypothesized that Pf lactate would be significantly higher in PPE because of active metabolic activities than in TBE which is driven by delayed hypersensitivity. METHODS: All patients undergoing an initial diagnostic thoracentesis over 18 months with Pf lactate measured using a calibrated point-of-care blood gas analyzer were assessed. RESULTS: The diagnoses of the enrolled patients (n = 170) included TBE (n = 49), PPE (n = 47), malignancy (n = 63), and transudate (n = 11). Pf lactate level in TBE, median 3.70 (inter-quartile range 2.65-4.90) mmol/l, was significantly lower than in PPE and CPPE. In the subgroup of TBE and CPPE patients whose initial Pf pH and glucose could suggest either condition, Pf lactate was significantly higher in those with CPPE. Pf lactate (cutoff ≥7.25 mmol/l) had a sensitivity of 79.3%, specificity 100%, positive predictive value 100%, and negative predictive value 89.1% for discriminating CPPE from TBE (area under the curve 0.947, p < 0.001, 95% confidence interval 0.89-0.99). CONCLUSIONS: Point-of-care Pf lactate measurements may have practical value in early separation of TBE or CPPE during initial thoracentesis, and warrants further investigation.

Successful treatment of pyopneumothorax with bronchopleural fistula using endobronchial Watanabe spigots.

Bronchopleural fistula (BPF) can complicate necrotizing pneumonia. Surgery would be indicated in patients who fail conservative management, yet this group is often of poor pulmonary function and general condition. Bronchial occlusion with endobronchial Watanabe spigots (EWS) can be a potential alternative treatment when the culprit bronchi can be isolated. In this case report, we describe a middle-aged gentleman who presented with necrotizing pneumonia complicated with pyopneumothorax with right upper lobe BPF, and who had failed to respond to chest drainage and antibiotics. EWS bronchial occlusion finally led to cessation of air leak, allowing removal of chest tube. EWS were removed uneventfully six months later. This case highlights the role of EWS in the management of BPF in patients with high surgical risk.

Performance of transbronchial cryobiopsy in eccentrically and adjacently orientated radial endobronchial ultrasound lesions.

BACKGROUND: Radial endobronchial ultrasound (R-EBUS) is an effective technique in the diagnosis of peripheral pulmonary lesions (PPL). However, lesion orientation with regards to the radial probe remains an important factor for effective biopsy. "Within" orientation was associated with significantly higher diagnostic yield. Cryobiopsy is a novel technique in obtaining larger tissue samples with the frozen tip allowing biopsy in a 360° direction, thus potentially achieving more effective biopsy in eccentrically and adjacently orientated lesions. We aimed to evaluate the performance and safety of transbronchial cryobiopsy versus forceps biopsy in eccentrically and adjacently orientated R-EBUS lesions. METHODS: Retrospective review of R-EBUS transbronchial biopsy for PPL over 17 months. RESULTS: 114 R-EBUS scans were included for analysis during the study period. Forceps biopsy was performed in 76 (66.7%) cases and cryobiopsy in 38 (33.3%) cases. Baseline demographics and lesion characteristics did not differ between the two groups. Median (interquartile range) lesion size was 3.48 (2.63-4.51) cm. Overall, 41.2% of lesions were of eccentric orientation and 15.8% adjacent orientation; only 43% were concentric in orientation. Overall diagnostic yield was 67.5% (77 out of 114). Orientation remained an important factor affecting diagnostic yield. Transbronchial cryobiopsy significantly increased the diagnostic yield in eccentrically and adjacently orientated lesions to 75.0% (18 out of 24), compared to 48.8% (20 out of 41) obtained via forceps biopsy (p<0.05); but not in concentric lesions. Cryobiopsy was associated with more mild and moderate bleeding complications compared to the forceps biopsy group. CONCLUSIONS: Transbronchial cryobiopsy under R-EBUS guidance is a safe procedure which potentially increases diagnostic yield in eccentrically and adjacently orientated PPLs.

Acute chest pain and breathlessness in a haemodialysis patient.

Acute chest pain and breathlessness in a haemodialysis patient is a common but challenging clinical scenario, can you diagnose and manage it? http://bit.ly/2Qf1mXr.

Endobronchial embolization for life-threatening hemoptysis with Endobronchial Watanabe Spigot.

BACKGROUND: Massive hemoptysis is a common encounter in respiratory medicine. Bronchoscopy plays an important role in localizing the origin of bleeding, as well as endoscopic treatment of centrally located lesions. Endobronchial embolization is a novel technique enabling the management of hemoptysis arising even from peripheral lesions, via occlusion of the culprit bronchus, thereby securing the airway. Endobronchial Watanabe Spigot had been advocate in the treatment of bronchopleural fistula and the use of this novel technique had since then been expanded into the management of massive hemoptysis. To the best of our knowledge, this is the first reported case in Malaysia. CASE PRESENTATION: 78-year-old lady who presented with life-threatening hemoptysis leading rapidly to cardiac arrest upon arrival. Spontaneous circulation was restored after resuscitation with an urgent thoracic computed tomography angiogram revealed bleeding likely from the posterior basal segment of left lower lobe, with bronchiectatic changes. Urgent flexible bronchoscopy revealed airway flooding, with bleeding originating from the lingular and posterior-basal segment of the left lower lobe. Airway toileting was performed and two 7 mm Endobronchial Watanabe Spigots were plugged into the culprit bronchi. Urgent bronchial artery embolization was then attempted, but was unsuccessful. She was managed conservatively, as surgical resection was deemed high risk. The spigots were removed 4 days later uneventfully. There was no recurrence of hemoptysis, and patient remained well during 1-month follow up. CONCLUSIONS: The utmost priority in managing life-threatening hemoptysis is to prevent airway flooding. Endobronchial embolization with Endobronchial Watanabe Spigot is useful as a temporary measure before definitive therapy, or can itself be the main therapeutic player in the hemoptysis armament for high-risk patients.