Retrospective Observational Study to Assess Safety and Tolerability of Nebulized Colistin for the Treatment of Patients With Pneumonia in Real-World Settings in Respiratory ICU.

INTRODUCTION: Colistin is used to treat hospital-acquired pneumonia and ventilator-associated pneumonia. However, direct drug deposition at the site of infection may improve its efficacy and reduce systemic exposure. The aim of this study was to assess the safety and tolerability of nebulized colistin among Indian patients diagnosed with pneumonia caused by multidrug-resistant gram-negative bacilli in real-world settings. METHODOLOGY: We retrospectively reviewed the medical records of patients treated with nebulized colistin for pneumonia. We assessed the adverse events and relevant abnormal laboratory findings of nebulized colistin therapy. RESULTS: All enrolled patients (N=30, males: 22, females: 8; average age: 71.06 years) were treated for 13.36 days. Almost 80% of patients had a history of shortness of breath, which was a major symptom when they were admitted to the hospital. The patients were administered nebulized colistin for an average of six days (8 hours per day). The most common dosing schedule was 1 million international units (MIU)/8 hours. No serious adverse event was observed, and only one patient died while on the treatment but the death was not related to colistin treatment. The average sequential organ failure assessment score for all patients was 6.5. CONCLUSION: Our study demonstrated the efficient clinical utility and well-tolerated safety profile of nebulized colistin in the treatment of patients with pneumonia. Neurotoxicity and nephrotoxicity were not reported. Since a significant percentage of patients were with chronic respiratory diseases, our study further indicates the safety and effectiveness of nebulized colistin in chronic obstructive pulmonary disease (COPD) patients too.

An additional simultaneous magnetic ordering and magneto-capacitive behavior with dielectric relaxation besides multiferroicity in Fe1-xTexVO4.

Here we report the evidence of an additional magnetic ordering and frequency dispersive magneto-dielectric (MD) permittivity besides multiferroic behavior in Te4+(S= 0) doped FeVO4. Two antiferromagnetic transitions similar to FeVO4at ∼21.86 K (TN1) and 16.03 K (TN2) were observed in all samples. An additional novel defect clusters based magnetic ordering at relatively higher temperature (TAMO) ∼ 203 K is also observed from the magnetization. Evaluated magnetic moments show systematic decrease and the magnetic frustration factors show an increase with the increasing of Te4+(S= 0) content. MD studies show stable ferroelectric ordering at spiral magnetic transition (TN2) and the multiferroic order persists to the largest doping of Te (x= 0.10). The MD studies also reveal a magneto-capacitive (MC) behavior at TAMO(∼203 K) with a high dielectric constant and loss, and the possible reason for the magnetic ordering and MC behavior is ascribed to short range magnetic clustering arising out of defect based mechanisms. Mössbauer spectroscopic studies confirm local structural correlation with magnetic and ferroelectric ordering.

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.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis With Pirfenidone and Nintedanib: A Friend or Foe.

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is unfortunate a deadly event with a very high mortality rate. Its occurrence is highly unpredictable, though few baseline risk factors have been identified. The revised definition of AE is more precise with clarity on defined parameters. However, no clear guidelines exist on treatment, with most therapies showing inconsistent benefits. Both the approved anti-fibrotic (pirfenidone and nintedanib) have shown equal efficacy in reducing the decline in lung functions, with few studies suggesting a drop in AE. We report a case of a patient with IPF with mildly impaired lung functions who was initiated on pirfenidone with dose titrated on a weekly basis but developed AE-IPF on day 10 of starting pirfenidone and after four days of doubling the dose from 600 mg/day to 1,200 mg/day. This raised the suspicion of whether pirfenidone played any role in this unfortunate event. With no response to conventional therapy of steroids and non-invasive ventilation for AE-IPF, initialization of nintedanib led to recovery with discharge of the patient in two weeks of hospitalization. This case highlights inadequacy in knowledge about the effects of these anti-fibrotics in IPF and recommends close monitoring in the future.

Pulmonary-Renal Syndrome: A Real-World Experience From a Tertiary Care Pulmonary Center in North India.

BACKGROUND: Pulmonary renal syndrome (PRS) is a simultaneous occurrence of diffuse alveolar hemorrhage (DAH) and glomerulonephritis (GN). The diagnosis of PRS not only requires a high index of clinical suspicion and prompt management, but it is often fatal due to rapidly progressive clinical deterioration despite aggressive treatment. The authors, therefore, share the real-world experience of PRS presenting to tertiary care pulmonary center in north India. AIMS: The objectives of the study were to identify etiology, clinical manifestations, treatment modalities and outcomes of patients presenting with PRS. MATERIALS & METHODS: This was a retrospective observational study undertaken at Metro Centre for Respiratory Diseases of patients diagnosed with PRS during the last two years between 2019 and 2021. The patients diagnosed with PRS based on clinical manifestations, serology and biopsies were included in the study. All cases of non-immunological causes of PRS were excluded from the study. Chi-square and Mann-Whitney U tests were done to look for associations obtained between survivors and non-survivors. Cox regression analysis was done to estimate the hazard ratios of clinical variables on survival in PRS patients. RESULTS: A total of 12 patients of PRS were included in the study and diagnosis was made based on clinical manifestations, serology as well as biopsies. The mean age of presentation was 45.4 (± 17.8) years and 66.7% of the patients were females. The most common etiology was anti-nuclear cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) seen in 83.3% of the cases. The most common symptoms were coughing and fever (80%) followed by dyspnea and hemoptysis (70%) with the mean duration of symptoms being 17.1 (±8.9) days. The mortality of PRS patients in our study was 41.6% and these patients had a higher acute physiology and chronic health evaluation (APACHE) score (median-26) compared to those patients who survived (median - 15.8). CONCLUSION: The occurrence of PRS, although rare, presents with rapid clinical deterioration leading to a high mortality rate. AAV was the most common cause of PRS as observed in our study. Early recognition and prompt aggressive management strategies with immunosuppressant therapies are essential for better outcomes for the patients.

Real world efficacy and safety of nintedanib in idiopathic pulmonary fibrosis: A single center, observational study from India.

BACKGROUND: Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis (IPF) has been established by multiple clinical trials. This study aims to assess the efficacy and safety of nintedanib in real-world IPF patients in India. METHODS: Clinical records of IPF patients (prescribed with nintedanib) visiting tertiary pulmonary care center, between June 2016 and December 2019, were analyzed retrospectively. Data were analyzed for forced vital capacity (FVC), Diffusing capacity of lung for carbon monoxide(DLCO), 6-min walk distance (6-MWD). Acute exacerbations and adverse events were also analyzed. RESULTS: A total of 76 IPF patients were prescribed with nintedanib. Drug was prescribed at 100 and 150 mg BD dose to 37 and 39 patients. Ten patients (13.1%), of which eight were over the age of 60 years, died during the study period. Only 42 patients visited for follow-up. Mean baseline FVC was 1.67 L and mean annualized absolute change in FVC and FVC % predicted was -0.07 L and -1.80%, respectively. Mean baseline DLCO was 37.21% and mean annualized absolute change in DLCO % predicted was-2.20%. At follow-up, 1 (2.38%), 17 (40.47%), and 24 (57.14%) patients were at Deparatment of Internal Medicine stage I, II, and III, respectively. Acute exacerbations and adverse events were reported by 48 and 6 patients, respectively. CONCLUSION: Our results support the findings from previous studies, that nintedanib leads to annual decline in parameters such as FVC and DLCO and increased 6-MWD. It was found to be well tolerated in the Indian patients with IPF.

A retrospective observational study on pheno-endotypes of severe asthma among adults attending asthma clinic in a tertiary care centre in India.

Background and Objective: Severe asthma phenotyping based on invasive and non-invasive bio-markers assists in a better understanding of heterogeneity of clinical presentations and thereby using targeted therapies. Therefore, the current study was conducted to evaluate phenotypes based on non-invasive bio-markers of severe asthma patients attending a tertiary care hospital in North India. Methods: This was a retrospective, observational study conducted on the patients who visited the respiratory department of a tertiary care hospital in North India. Patients aged 18 years and above diagnosed with severe asthma were classified into distinct phenotypes, namely, atopic asthma, eosinophilic asthma, and Type 2 low asthma. Patients with their clinical and functional parameters were classified based on the levels of bio-chemical and hematological results [such as total/specific IgE, blood absolute eosinophil count (AEC)], skin prick tests, history of allergy, and the presence of allergic symptoms. Results: Out of total 100 severe asthmatics, the majority of the patients had an eosinophilic asthma (49%) phenotype, followed by atopic (allergic) asthma (36%) and Type 2 low asthma (15%) phenotypes. However, it was found that 29% of these patients had overlap of both atopy and eosinophilia. The atopic phenotype showed allergic symptoms, positive skin prick tests, and elevated IgE levels. The eosinophilic phenotype had high AEC (≥300 cells/uL) and low IgE (< 30 IU/ml) levels. The Type 2 low phenotype showed low AEC and IgE levels along with the absence of allergic symptoms. However, among these 100 patients, overlapping traits of both atopy and eosinophilia were labelled as overlap phenotypes. 50% of type 2 low severe asthma cases had eosinophils >150 cells/cmm and were eligible for mepolizumab. Conclusions: Identification of severe asthma pheno-endotypes based on simple non-invasive bio-markers is feasible in Indian settings, and it is of utmost importance for future treatment planning in these patients with available biologicals. Overlap of eosinophilic and atopic endotypes in one-third cases would challenge physicians to choose upfront appropriate biologicals in our country. Type 2 low asthma was least common with only <10% cases of severe asthma being ineligible for any biological.

Polar state in polycrystalline BaSn0.3Ti0.7O3thin film determined from ac- & dc-field studies.

The present work reports polarization response and the effects ofac- &dc-fields on 30% Sn doped BaTiO3polycrystalline relaxor thin films as a function of temperature. Apart from the low temperature frequency dispersion in dielectric data, a frequency independent local maxima in dielectric constant and a concomitant peak in dielectric loss atT* ∼ 245 K is observed, which is unusual of bulk relaxor systems. BelowT*, dispersion in dielectric constant becomes quite evident showing signatures of non-ergodic behavior. Subsequently, the dielectric and polarization responses in ergodic (>T*) and non-ergodic (

Lattice assisted dielectric relaxation in four-layer Aurivillius Bi5FeTi3O15ceramic at low temperatures.

We have investigated magnetic, structural and dielectric properties of Bi5FeTi3O15(BFTO) in the temperature range 5K-300 K. Using diffraction, Raman spectroscopy and x-ray absorption fine structure measurements, iso-structural modifications are observed at low temperatures (≈100 K). The analysis of dielectric constant data revealed signatures of dielectric relaxation, concomitant with these structural modifications in BFTO at the same temperatures. Further, employing complementary experimental methods, it is shown that the distribution of Fe/Ti ions in BFTO is random. With the help of techniques that probe magnetism at various length and time scales, it is shown that the phase-pure BFTO is non-magnetic down to the lowest temperatures.

Tracheobronchial amyloidosis: an uncommon disease with a common presentation.

Amyloidosis is an uncommon heterogeneous and multi-systemic disease characterized by extracellular amyloid deposition. The size of proteins varies and forms a part of local disease or systemic process. Light chain amyloidosis (AL) is the most prevalent form of systemic amyloidosis which may also be seen in localized disease. Isolated tracheobronchial amyloidosis (TBA) is rather unusual with local amyloid deposition which may pose a diagnostic dilemma with subsequent therapeutic challenge. Awareness of such a presentation is crucial in the diagnosis of this rare disease. We describe three cases who presented with haemoptysis, which on further evaluation were diagnosed as isolated TBA, and a review of literature.

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.

Refractory bronchovascular pleuropulmonary mucormycosis: Case report and difficulties in management.

Pulmonary mucormycosis is a life-threatening opportunistic fungal infection. It is considered as a disease of immunocompromised state and is rarely seen in immunocompetent patients. We here report a case of refractory bronchovascular pleuropulmonary mucormycosis, who despite early detection, optimal management with liposomal amphotericin B, and posaconazole therapy followed by surgery, progressed further and led to a fatal outcome. Dual antifungal therapy combined with surgery is the only definitive treatment option available in the literature. Many new therapeutic options for mucormycosis treatment have become available but none have shown promising results, and larger studies are required to assess their efficacy.

Hemoptysis: Beyond routine chest computed tomography and bronchoscopy.

Hemoptysis is considered as a medical emergency which requires urgent stabilization with identification and correction of underlying etiology. Diagnosis of the cause of hemoptysis is not always readily identified after bronchoscopy and conventional computed tomography (CT) chest. Arteriovenous malformation (AVM) is a rare but important cause of massive hemoptysis which can be easily picked up by the use of double turn contrast CT chest. We here report a rare congenital AVM anomaly called Klippel-Trenaunay-Parks-Weber syndrome as a cause of massive hemoptysis and utility of double turn CT in diagnosing AVM as a cause of hemoptysis.

Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association.

Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%), but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently.

Tracheal compression due to anomalous innominate artery in an adult.

A 47-year-old-female presented with dyspnea and unproductive cough for 4 months. General examination revealed pulsatile swelling in the midline below the thyroid cartilage present since childhood. Computed tomography-angiography of the neck showed right innominate artery dilated, elongated and coursing above downward, anterior to the trachea below the thyroid, compressing the trachea and origin of the right subclavian artery higher up. A case of anomalous innominate artery causing symptomatic compression of the trachea in adults is a rare entity.