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Background The study aimed to analyze frequency and severity of adverse events (AEs) and other reasons for interruption of treatment and loss to follow up (LTFU) during first six months of treatment among tuberculosis patients on bedaquiline containing regimens. Methods This pilot exploratory observational study included 275 patients enrolled consecutively over two years who received bedaquiline containing regimen under programmatic conditions in India. Results Among 275 patients with median age of 25 years, 86 (31.3%) patients had at least one interruption with 122 total episodes of interruption. Among these 70 were temporary, 35 were permanent interruptions and 17 were LTFU. The AEs due to drugs were the commonest reason for interruption observed in 81.4% of temporary interruption group and 97.1% of permanent interruption group. Among a total 192 adverse event episodes, (49.5%) were minor (grade 1–2) and (50.5%) were serious (grade 3–5). Personal factors were the commonest reason for interruption observed in LTFU (94.1%) group. The most common temporarily interrupted drug was bedaquiline in 8.7% and permanently stopped drug was linezolid in 5% of patients. Conclusions Our study observed that drug related AEs are important risk factors associated with treatment interruptions in bedaquiline containing regimens. Bedaquiline is the most common temporarily interrupted drug due to AEs.

Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is a significant burden on global tuberculosis (TB) prevention and eradication efforts. MDR-TB can be treated, but it is expensive, takes a long time (typically two years), and contains potentially toxic drugs. Under certain conditions, the WHO recommends standard regimens lasting 9 to 11 months rather than individual regimens lasting at least 18-20 months. The current study sought to identify factors associated with treatment outcome in RR/MDR-TB patients receiving an injection-based regimen for 9-11 months. This ambispective (prospective and retrospective) observational study was conducted at a tertiary tuberculosis institute in New Delhi, India. Between February 2021 and March 2022, patients with RR/MDR-pulmonary TB who received an injection-based shorter regimen were enrolled. Factors related to treatment outcome were investigated and compared in patients who had a successful outcome versus those who did not. A total of 55 patients were enrolled, with 50.91% being successful (cured/treatment completed) and 49.09% failing (including failure, lost to follow up, death, and regimen changed). The following factors were significantly associated with the unsuccessful outcome, according to univariate analysis: BMI (18.5 kg/m2), anaemia, previous anti-TB treatment, bilateral chest X-ray involvement, and far advanced disease on chest X-ray BMI (18.5 kg/m2), anaemia, and far advanced disease on chest X-ray were all significantly associated with mortality. Anaemia was associated with an unsuccessful outcome (p=0.049) and mortality (p=0.048) in the multiple logistic regression analysis. Early treatment initiation, improved nutrition and anaemia, and regular monitoring can all improve RR/MDR-TB patients' outcomes and prognoses.

Background and objectives Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. Methods This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). Results Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. Conclusions The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

We regret that this article is behind a paywall., BACKGROUND: Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens. METHODS: We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug. FINDINGS: 58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed. INTERPRETATION: Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.

Although a simple and useful pulmonary function test, spirometry remains underutilized in India. The Indian Chest Society and National College of Chest Physicians (India) jointly supported an expert group to provide recommendations for spirometry in India. Based on a scientific grading of available published evidence, as well as other international recommendations, we propose a consensus statement for planning, performing and interpreting spirometry in a systematic manner across all levels of healthcare in India. We stress the use of standard equipment, and the need for quality control, to optimize testing. Important technical requirements for patient selection, and proper conduct of the vital capacity maneuver, are outlined. A brief algorithm to interpret and report spirometric data using minimal and most important variables is presented. The use of statistically valid lower limits of normality during interpretation is emphasized, and a listing of Indian reference equations is provided for this purpose. Other important issues such as peak expiratory flow, bronchodilator reversibility testing, and technician training are also discussed. We hope that this document will improve use of spirometry in a standardized fashion across diverse settings in India.

Background: Treatment of multidrug-resistant (MDR-TB) mainly focuses on bacteriological cure. However, only limited studies have evaluated the sequelae left after the completion of treatment among MDR-TB patients. Objective: To assess the persistent symptoms, radiological sequelae, pulmonary function impairment and quality of life at the completion of treatment among MDR-TB patients. Methods: Forty six MDR-TB patients were enrolled, who completed two years of treatment under programmatic management of Drug Resistant tuberculosis at a tertiary referral institute in Delhi, India. Detailed clinical history was taken. X-ray chest, 6 Minute Walk Test and pulmonary function tests were attempted in all patients. Quality of life was evaluated using Seattle obstructive lung disease questionnaire. Results: At the completion of MDR-TB treatment 95.7% patients had residual symptoms; 100% patients had residual bilateral chest x-ray abnormality with 82.6% patients showing far advanced disease. PFT was abnormal in 97.6% patients with mixed pattern being the commonest abnormality. Quality of Life was impaired with mean physical function of 46%. Conclusion: At the completion of MDR-TB treatment, significant numbers of patients are left with post treatment sequelae. The medical management and social support for these patients should be incorporated in the national programs.

One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%-50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%-3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases.

The COVID-19 pandemic caused by the highly infectious SARS-CoV-2 has affected over 15.9 million people across 200 countries and caused more than 643,000 deaths.[1] As on July 27, 2020, India has ~14.5 lakh cases of COVID-19 and the number is still increasing.[2] The coronavirus is a highly infectious virus and spreads through droplets generated during coughing, sneezing, talking, and even breathing. Indirect contact via contaminated surfaces is another possible cause of infection.[3] The virus may remain viable on plastic (polypropylene) and stainless steel for up to 3 days but does not survive on cardboard for >1 day or on copper for >4 h. The virus is inactivated by soap, which destabilizes its lipid bilayer.[4] Screening of patients with non-COVID respiratory disease poses special problems at the triage and fever clinics of the hospital, as it would be difficult if not impossible to rule out COVID. Transmission risks during pulmonary function testing (PFT) for COVID-19 are unknown at present as data available are sparse, but the prevalence of the virus in the community, old age, severity of lung disease, and presence of immunosuppression are significant risk factors determining the risk of infection. PFT is a valuable tool in the assessment of respiratory disease. Spirometry is the key diagnostic test for airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and is the most commonly performed test. The other tests include lung volumes and diffusing capacity measurement, impulse oscillometry (IOS), bronchoprovocation, and exercise physiology tests. Spirometry is an effort-dependent test wherein the patient takes a deep inhalation and blows forcefully into the spirometer flow sensor for at least 6 s. Many patients often cough during spirometry. Blowing forcefully and coughing are known to produce aerosol droplets that may contain millions of viruses from the respiratory tract, thereby significantly increasing the risk of transmitting SARS-CoV-2 viruses not only to people present in and around the spirometry room but also to other patients who subsequently perform the test in the same room. It is, therefore, important to avoid and postpone all spirometry tests as well as other PFTs unless it is absolutely necessary. Decisions regarding the conduct of PFTs need to balance the potential risks against the benefits from the test in making decisions. Several professional societies have advised to defer PFT still after the COVID-19 pandemic.[5,6,7,8] We concur with this recommendation and would recommend avoiding spirometry and other PFTs, during the COVID-19 pandemic. Physicians will have to rely more on taking a good history and, wherever possible, using validated diagnostic/screening questionnaires to arrive at a diagnosis and limit testing to the minimum required. In the following section, we have outlined the assessment of the need for testing, the precautions to be taken, and suggested approach to the clinical management of common respiratory conditions, without lung function testing.

Both tuberculosis and COVID-19 being communicable and prevalent diseases in India, the co-existence can lead to worse outcomes, as seen in this study, where there was high mortality among active as well as treated TB patients with COVID-19 co-infection https://bit.ly/3jHcGbQ

Contents: Executive Summary Introduction Methodology Definition, Epidemiology and Risk Factors Diagnosis of Asthma Management of Stable Asthma Management of Acute Exacerbations of Asthma Miscellaneous Issues in Asthma Management

Background Host genetic factors that influence predisposition to anti-tuberculosis drug-induced hepatotoxicity (DIH) are not clear in the Indian population. Objective To investigate the possible association of DIH with polymorphism at the RsaI site of the 5-prime untranslated region of CYP2E1 and GSTM1 'null' mutations. Methods In this prospective study, 113 tuberculosis (TB) patients with DIH and 201 TB patients receiving anti-tuberculosis treatment without developing hepatotoxicity (non-DIH) constituted cases and controls, respectively. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyse genetic polymorphisms of CYP450 2E1 at the RsaI site and 'null' GSTM1 mutations. PCR-RFLP results were compared between 185 non-DIH and 105 DIH patients Results A high frequency of c1c1 genotypes of CYP2E1 was commonly encountered, and the difference between DIH and non-DIH patients was not significant (75.14% vs. 77.14%). The genotypic distribution of c2c2 was significantly higher in the DIH than in the non-DIH group (4.8% vs. 0.5%, OR 8.58, P = 0.03). However, adjustment for age, sex and serum albumin differences yielded an OR of 2.75, making it non-significant (P = 0.26). Homozygous 'null' mutation frequencies at the GSTM1 gene in DIH and non-DIH patients were observed that were not significantly different (40% and 37%, respectively, P = 0.61). Conclusion RsaI variants of the CYP2E1 gene and GSTM1 'null' mutation were not associated with risk of DIH in a north Indian population.

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis.12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure).Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage 600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg.The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

SETTING: Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases (LRS), a tertiary level tuberculosis (TB) institute in Delhi, India. OBJECTIVE: To study the profile of TB among household contacts of multidrug-resistant TB (MDR-TB) patients. DESIGN: In a cross-sectional study, contacts of MDRTB patients were traced and clinical, radiological, bacteriological and pulmonary function tests were performed for evidence of TB infection and active disease. RESULTS: Between January 2005 and December 2008, 58 of 92 index MDR-TB patients could be traced. Of 302 contacts who could be studied, 16 (5.29%) developed TB: nine had pulmonary and seven had extra- pulmonary disease; two (0.66%) had MDR-TB. Of the 302 contacts, 137 reported to the LRS Institute and were investigated. The most common symptoms observed were cough, chest pain and fever. The tuberculin skin test was positive in 109 of 135 (80.7%) contacts; among these, bacille Calmette-Guerin scar was present in 86. Pulmonary function tests revealed obstruction, restriction and mixed abnormalities. CONCLUSION: The majority of contacts of MDR-TB patients had drug-susceptible TB and the rate of MDRTB was very low. Evaluation of contacts of MDR-TB cases may lead to early diagnosis and prevention of TB.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

Background: The audio signal in the conventionally accepted protocol of shuttle walk test (SWT) is not well-understood by the patients and modification of the audio signal may improve the performance of the test. Objectives: The aim of this study is to study the validity and reliability of an audio signal modified SWT, called the Singla-Richa modified SWT (SWTSR), in healthy normal adults. Patients and Methods: In SWTSR, the audio signal was modified with the addition of reverse counting to it. A total of 54 healthy normal adults underwent conventional SWT (CSWT) at one instance and two times SWTSR on the same day. The validity was assessed by comparing outcomes of the SWTSR to outcomes of CSWT using the Pearson correlation coefficient and Bland–Altman plot. Test-retest reliability of SWTSR was assessed using the intraclass correlation coefficient (ICC). The acceptability of the modified test in comparison to the conventional test was assessed using Likert scale. Results: The distance walked (mean ± standard deviation) in the CSWT and SWTSR test was 853.33 ± 217.33 m and 857.22 ± 219.56 m, respectively (Pearson correlation coefficient - 0.98; P < 0.001) indicating SWTSR to be a valid test. The SWTSR was found to be a reliable test with ICC of 0.98 (95% confidence interval: 0.97–0.99). The acceptability of SWTSR was significantly higher than CSWT. Conclusions: The SWTSR with modified audio signal with reverse counting is a reliable as well as a valid test when compared with CSWT in healthy normal adults. It better understood by subjects compared to CSWT.

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.

From the authors: We read with interest the comments by M.S. Bolhuis and co-workers on our article discussing the role of linezolid in treating multidrug-resistant (MDR) tuberculosis (TB) failures in India [1]. First, we would like to underline that our study was carried out in field conditions in a country with a high burden of MDR-TB cases and limited resources. We thank M.S. Bolhuis and co-workers for the opportunity to discuss the different perspectives of the Indian setting and those of a high-level tertiary hospital in a high-income country (India has one of the best existing TB control programmes). M.S. Bolhuis and co-workers correctly conclude that only a randomised trial comparing linezolid versus a placebo, in addition to an adequate background regimen using drug susceptibility testing (DST) and therapeutic drug monitoring (TDM), would provide comprehensive results on …

Background and Objectives: Tuberculosis (TB) is an important cause of childhood morbidity and mortality with different clinical presentations and outcomes as compared to TB in adults. The present study was designed to compare these differences and to determine if childhood TB was an important predictor of adverse outcome following treatment under the Revised National Tuberculosis Control Program (RNTCP). Materials and Methods: Retrospective record based study of cases registered between January 2008 and December 2011, at the Amdanga TB Unit (TU), West Bengal. Results: Of the total 1,508 cases notified, 3.4% were childhood TB. Differences with adult TB were noted in the number of cases categorized as cat II and III in children (P = 0.012 and 0.000, respectively). New smear positive pulmonary TB was significantly lower (21.6%, P = 0.000), while new extra-pulmonary TB (39.2%, P = 0.000) was significantly higher in children. Smear negative cases comprised 7.8 and 11.4% of the childhood and adult cases of TB, respectively. Retreatment cases were significantly higher in adults (P = 0.012). Among the registered new smear positive cases, the differences in favourable and adverse outcomes did not have a significant statistical difference (P = .100) . Childhood TB was not a significant risk factor for adverse outcome following treatment (adjusted odds ratio [AOR] = 0.80, 95% confidence interval [CI] = 0.28-2.32). Conclusions: The registration of childhood TB under the RNTCP in the TU was low. There were differences in the clinical presentation and treatment outcomes of TB among children and adults. Childhood TB was not a significant predictor of adverse treatment following treatment.

Lower respiratory tract infection is one of the common causes of morbidity in India which is occasionally undiagnosed. In this regard tracheobronchomegaly is one of those conditions which masquerade as chronic bronchitis and bronchiectasis and are usually undiagnosed. It is a well-defined clinical and radiologic entity characterized by marked dilatation of the trachea and the central bronchi and is frequently associated with recurrent lower respiratory tract infection. Tracheobronchomegaly has been described by a variety of names, including Mounier-Kuhn syndrome, tracheal diverticulosis, tracheobronchiectasis, tracheocele, tracheomalacia, and tracheobronchopathia malacia.