Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Safe and effective liver-directed AAV-mediated homology-independent targeted integration in mouse models of inherited diseases.

Liver-directed adeno-associated viral (AAV) vector-mediated homology-independent targeted integration (AAV-HITI) by CRISPR-Cas9 at the highly transcribed albumin locus is under investigation to provide sustained transgene expression following neonatal treatment. We show that targeting the 3' end of the albumin locus results in productive integration in about 15% of mouse hepatocytes achieving therapeutic levels of systemic proteins in two mouse models of inherited diseases. We demonstrate that full-length HITI donor DNA is preferentially integrated upon nuclease cleavage and that, despite partial AAV genome integrations in the target locus, no gross chromosomal rearrangements or insertions/deletions at off-target sites are found. In line with this, no evidence of hepatocellular carcinoma is observed within the 1-year follow-up. Finally, AAV-HITI is effective at vector doses considered safe if directly translated to humans providing therapeutic efficacy in the adult liver in addition to newborn. Overall, our data support the development of this liver-directed AAV-based knockin strategy.

Knowledge, attitude and practices towards seasonal influenza vaccination among healthcare workers.

Background: Vaccination as a primary prevention strategy is a well-established public health policy for preventing influenza. Despite strong recommendation, vaccination coverage among health workers is still not satisfying. The intention of the current study is to evaluate the knowledge, attitudes and practices towards influenza vaccination among healthcare workers. Materials and Methods: In this cross-sectional, single-centre study, 789 healthcare workers (out of total 1380) participated. Institutional ethical committee clearance was obtained before the study. It was conducted in October 2021. A structured questionnaire in the form of Google sheet was sent to all healthcare professionals (HCPs) affiliated with the institution. Data collected was tabulated using MS Excel and analysed using appropriate statistical tools. Results: Of the 1380 approached, a total of 789 (57.17%) HCPs responded to the questionnaire. The overall vaccination coverage in the study population was 71.6%. The overall vaccination acceptance rate drops to 36.78% when those taken vaccine as a recommended pre-employment requisite and got never vaccinated again were excluded. Also, 88.21% of the respondents believed that influenza is a potentially dangerous disease and 93.16% believed that flu vaccination is effective against preventing influenza. Although 736 participants (93.28%) were aware that seasonal influenza vaccine is recommended for healthcare workers, irrespective of age and comorbidities, only 411 (52.1%) intended to take vaccine in the coming year. Also, 97.34% of the participants considered vaccine as safe. Conclusion: Influenza vaccination coverage among healthcare workers is still at an unsatisfactory level. This is despite majority of the HCPs accepting that the vaccine is safe and preventive against influenza. Efforts are still needed to improve the coverage.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Recurrent endobronchial actinomycosis following an interventional procedure.

Actinomycosis is an indolent, slowly progressive infection caused by anaerobic or microaerophilic bacteria, primarily from the genus Actinomyces. Thoracic involvement is observed in approximately 15% of cases of infection with actinomycosis. Here, we present a case of a 61-year-old male who presented with recurrent endobronchial actinomycosis. The case is being presented because of its rarity on three counts - endobronchial involvement, which is uncommon, recurrence in different sites in the bronchial tree, which is even rarer and development of the disease following an endobronchial procedure.

Aberrant right subclavian artery syndrome manifesting as focal tracheomalacia.

Tracheomalacia is one of the rarest etiologies of chronic cough. Herein, we present the case of an elderly woman with chronic cough who on detailed evaluation was found to have focal (localized) tracheomalacia due to compression by an aberrant right subclavian artery (arteria lusoria). The absence of dysphagia in this patient also deserves particular mention.

An uncommon congenital anomaly of the ribs.

Intrathoracic rib is an extremely rare congenital anomaly of the ribs. Here, we present the case of a 10-year-old boy with asthma who, on routine evaluation, was found to have this anomaly.

Dual diaphragmatic anomalies.

Although diaphragmatic anomalies such as an eventration and hiatus hernia are commonly encountered in incidental chest X-ray imaging, the presence of concomitant multiple anomalies is extremely rare. This is all the more true in adults. Herein, we present the case of a 75-year-old female, while undergoing a routine chest X-ray imaging, was found to have eventration of right hemidiaphragm along with a hiatus hernia as well.

Disseminated nocardiosis masquerading as metastatic malignancy.

Nocardiosis is an uncommon gram-positive bacterial infection caused by aerobic actinomycetes of the genus Nocardia. It can be localized or systemic and is regarded as an opportunistic infection that is commonly seen in immunocompromised hosts. We report a case of disseminated nocardiosis caused by Nocardia cyriacigeorgica in a patient with underlying malignancy in whom the clinical presentation was highly suggestive of a metastatic disease.

An undiagnosed cause of chronic cough.

Tracheomalacia (TM) refers to loss of tracheal rigidity and resulting susceptibility to collapse. It is usually an incidental finding during investigations of other illness. The main symptoms are dyspnoea, cough, sputum production and hemoptysis. Most cases are considered as respiratory infection and are treated symptomatically. Acquired TM results from damage to trachea due to various conditions such as inflammation, chronic pressure, or medical/surgical procedures. The diagnosis is done by end-expiratory dynamic tracheal imaging, which demonstrates typical crescentric narrowing of trachea and reduced antero-posterior diameter <50% of normal. Management include conservative measures like cough suppressants or surgical measures like tracheoplasty, stenting or surgical repair. We are reporting a case of chronic cough, which was subsequently diagnosed as TM.