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.

Miliary Sarcoidosis: does it exist? A case series and systematic review of literature.

BACKGROUND AND OBJECTIVES: Sarcoidosis typically presents with peribronchovascular and perilymphatic nodules on high-resolution computed tomography (HRCT); a miliary pattern is reported but not well described. DESIGN SETTING: We describe four patients with miliary sarcoidosis and results of a systematic review of all previously reported cases from 1985 onwards. RESULTS: We identified only 27 cases of "miliary" sarcoidosis in the HRCT era. These patients were older (85.2% older than 40 years), had more co-morbidities (72.7%) and were symptomatic compared to "typical" sarcoidosis. Respiratory symptoms were present in 61.9% at diagnosis. Hypercalcemia was seen in 28.5%. On review of HRCT images, only 34.6% (9/26) had a "true miliary" pattern without fissural nodules. In our series, prominent perivascular granulomas were seen on histopathology in all. 44.4% (12/27) had tuberculosis preceding or concurrent to miliary sarcoidosis. Of the eight true associations, tuberculosis preceded sarcoidosis by 52 (median, IQR 36) weeks in six and occurred concurrently in another two. The diagnosis of tuberculosis was clinical in all with concurrent diagnosis of tuberculosis and sarcoidosis. Treatment with steroids had 100% response and 14.2% relapse. CONCLUSIONS: A true miliary pattern in the HRCT era is very rare in sarcoidosis and subtle perilymphatic pattern is nearly always seen; this should be labeled "pseudo-miliary". Prominent perivascular granulomas are associated with true miliary pattern. Miliary sarcoidosis patients are older and symptomatic, needing treatment at diagnosis. "Miliary" sarcoidosis may follow treatment for tuberculosis; concurrent cases possibly indicate the difficulty in differentiating both or a "tuberculo-sarcoid" presentation. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 53-65).

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.

An unusual cause of breathlessness and profuse micronodules.

We describe a 21-year-old male with a history of smoking and subacute onset of breathlessness with normal cardiorespiratory examination. The presence of "track marks" and digital infarcts prompted evaluation for infective endocarditis and confrontational history taking revealed anorexia, weight loss over 3 months along with intravenous drug abuse of reconstituted tablets of tapentadol. Echocardiography was normal and blood cultures were sterile; computed tomography showed bilateral, diffuse, small centrilobular nodules with "tree-in-bud" appearance. In this clinicopathologic conference, we discuss the clinical and radiological differential diagnosis of centrilobular nodules, lung biopsy findings, and management options for patients with such a presentation.

Tuberculosis-Associated Chylothorax: Case Report and Systematic Review of the Literature.

Tuberculosis (TB) is a rare cause of chylothorax. We describe a case and the results of a systematic review of all reported cases of TB-chylothorax. We identified 37 cases of TB-chylothorax. The symptoms at presentation were constitutional (85.7%; 30/35), dyspnea (60.6%; 20/33), and cough (54.5%; 18/33). Chylothorax developed subsequent to the diagnosis of TB in 27.8% (10/36) of the patients, after a median of 6.75 weeks (IQR 4-9). Chylothorax developed during an immune reconstitution syndrome (IRS) in 16.7% (10/36) of the patients, including immunocompetent ones. TB was disseminated in 45.9% (17/37) of the patients at the diagnosis of chylothorax. Chylothorax developed in the absence of any mediastinal lymphadenopathy in 45.9% (17/37) of the patients; 13.5% (5/37) had isolated tubercular empyema alone. The diagnosis of TB was established microbiologically in 72.2% (26/36) and by biopsy alone in 27.8% (9/36) of the patients. Anti-TB treatment (ATT) was administered for a median of 7.57 months (IQR 6-9). Steroids were administered to 22.9% (8/35) of the patients, often for suspected IRS. Thoracic duct ligation and octreotide were required for only 17.1% (6/35) and 8.6% (3/35) of the patients, respectively. In all, 94.4% (34/36) of the patients had resolution of chylothorax and completed treatment successfully; only 5.6% (2/36) died. In conclusion, TB-chylothorax may develop without obvious mediastinal lymphadenopathy and be associated with tubercular empyema alone. TB-chylothorax can develop during treatment of TB due to IRS, even in immunocompetent patients. ATT and dietary manipulation are associated with good resolution and low mortality, and duct ligation is needed for only a small minority of patients.

Undiagnosed Obstructive Sleep Apnea and Postoperative Outcomes: A Prospective Observational Study.

BACKGROUND: The prevalence of undiagnosed obstructive sleep apnea (OSA) during preoperative evaluation and the best method to screen OSA and its association with postoperative complications remain unclear. OBJECTIVES: To determine the prevalence of undiagnosed OSA in preoperative Indian patients undergoing noncardiac surgery, to compare the diagnostic accuracy of the STOP-BANG questionnaire to a preoperative level III sleep study, and to assess the association of OSA with postoperative complications. METHODS: A prospective cohort of 245 consecutive adults with ≥2 risk factors for OSA who underwent noncardiac surgery between July 2011 and February 2013 were studied. The STOP-BANG questionnaire was administered to all patients, and 182/245 (74.2%) patients underwent a preoperative level III sleep study. Patients were followed for postoperative complications in hospital and contacted at 30 days after surgery. RESULTS: 70/182 (38.5%) obtained a new diagnosis of OSA, including 11/182 (6%) with moderate to severe OSA (apnea-hypopnea index ≥15/h). On logistic regression analyses, the presence of OSA was independently associated with postoperative oxygen desaturation (OR 5.96, 95% CI 2.35-15.1, p < 0.01), a postoperative complication within 7 days (OR 3.63, 95% CI 1.77-7.45, p < 0.01) and within 30 days (OR 3.5, 95% CI 1.74-7.1, p < 0.01). The STOP-BANG questionnaire did not identify 12/70 (17%) of the patients diagnosed with OSA and classified 28% of the cohort as OSA when the level III sleep study was negative. CONCLUSIONS: Unrecognized OSA is common in preoperative patients and is independently associated with postoperative complications. The STOP-BANG questionnaire had a lower performance in the diagnosis of OSA in a South Indian population than the level III sleep study.

Diffuse alveolar hemorrhage in IgA nephropathy: case series and systematic review of the literature.

OBJECTIVES: To describe the spectrum of pulmonary involvement in immunoglobulin A nephropathy (IgAN). METHODS: We describe two patients with pulmonary renal syndrome related to IgAN and a systematic review of previously reported cases of IgAN and lung involvement. RESULTS: We identified 23 reports of IgAN-related pulmonary disease, including 19 reports of alveolar hemorrhage and two cases of organizing pneumonia. Dyspnea (84%), hemoptysis (74%), cough (53%) and fever (47%) were common presenting complaints. Simultaneous involvement of kidneys and lung was the most common presentation (42%) but alveolar hemorrhage occurred independent of renal disease in one-fifth (21%). Azotemia was seen in 55.5% at presentation. Mesangio-proliferative glomerulonephritis was the most common biopsy finding and crescentic glomerulonephritis was seen in 27.7%. Among patients undergoing lung biopsy, capillaritis was seen in 72.7%; 37.5% of these had IgA deposits. Steroids with cyclophosphamide, followed by maintenance with methotrexate or azathioprine was used in 44%. Mechanical ventilation, dialysis and plasmapheresis were other adjunctive therapies used. IgAN-related alveolar hemorrhage was associated with a mortality of 26.3% and significant morbidity, with 52.7% having end-stage kidney disease despite immunosuppression. Organizing pneumonia with pulmonary IgA deposition is a well-described association of IgAN. CONCLUSION: These findings are similar to our previous observations of Henoch-Schonlein purpura (HSP)-related alveolar hemorrhage, highlighting the similarities of these related syndromes. Multicentric studies of IgAN and HSP-related pulmonary renal syndrome with a standard protocol are needed to define their similarities and differences, optimum suppression and its role in preventing renal progression in this setting.

Pulmonary-renal syndromes: Experience from an Indian Intensive Care Unit.

BACKGROUND: The etiology of patients presenting with pulmonary-renal syndrome (PRS) to Intensive Care Units (ICUs) in India is not previously reported. AIMS: The aim was to describe the prevalence, etiology, clinical manifestations, and outcomes of PRS in an Indian ICU and identify variables that differentiate immunologic causes of PRS from tropical syndromes presenting with PRS. MATERIALS AND METHODS: We conducted a prospective observational study of all patients presenting with PRS over 1-year. Clinical characteristics of patients with "definite PRS" were compared with those with "PRS mimics". RESULTS: We saw 27 patients with "provisional PRS" over the said duration; this included 13 patients with "definite PRS" and 14 with "PRS mimics". The clinical symptoms were similar, but patients with PRS were younger and presented with longer symptom duration. Ninety-two percent of the PRS cohort required mechanical ventilation, 77% required vasopressors and 61.5% required dialysis within 48 h of ICU admission. The etiologic diagnosis of PRS was made after ICU admission in 61.5%. Systemic lupus erythrematosus (54%) was the most common diagnosis. A combination of biopsy and serology was needed in the majority (69%, 9/13). Pulse methylprednisolone (92%) and cyclophosphamide (61.5%) was the most common protocol employed. Patients with PRS had more alveolar hemorrhage, hypoxemia and higher mortality (69%) when compared to "PRS mimics". CONCLUSION: The spectrum of PRS is different in the tropics and tropical syndromes presenting with PRS are not uncommon. Multicentric studies are needed to further characterize the burden, etiology, treatment protocols, and outcomes of PRS in India.

An unusual cause of type 2 respiratory failure.

We present a female patient who was referred for management of respiratory failure. She was being evaluated and managed as worsening chronic inflammatory demyelinating polyneuropathy with type 2 respiratory failure. Initial examination showed hypertrichosis, clubbing and papilledema along with severe distal and proximal motor-predominant weakness with impending respiratory failure. She was managed with noninvasive ventilation (NIV) and plasmapheresis awaiting diagnostic investigations. Immunofixation showed an "M band" and free lambda chain levels were elevated. Radiographs showed the classic osteosclerotic lesions of POEMS (polyradiculoneuropathy, organomegaly, endocrinopathy, M-protein and Skin abnormalities) syndrome. Six weeks after commencing radiotherapy to the osteosclerotic lesions, the patient responded favorably and remains off nocturnal NIV support.

Adrenal insufficiency in patients with stable non-cystic fibrosis bronchiectasis.

BACKGROUND & OBJECTIVES: Suppressed adrenal responses associated with inhaled steroid use have been reported in patients with bronchiectasis and have been shown to be associated with poor quality of life. This study was undertaken to examine the prevalence of suppressed cortisol responses in stable bronchiectasis and determine their correlation with the use of inhaled corticosteroids, radiologic severity of bronchiectasis and quality of life (QOL) scores. METHODS: In this case-control study, cases were patients with bronchiectasis and suppressed cortisol responses and controls were healthy volunteers, and patients with bronchiectasis without suppressed cortisol responses. Symptoms, lung function test values, exercise capacity, HRCT severity scores for bronchiectasis, exacerbations, inhaled corticosteroid use and quality of life scores were compared between patients with and without suppressed cortisol values. RESULTS: Forty consecutive patients with bronchiectasis and 40 matched controls underwent 1-µg cosyntropin testing. Baseline cortisol (mean difference -2.0 µg/dl, P=0.04) and 30-minute stimulated cortisol (mean difference -3.73 µg/dl, P=0.001) were significantly lower in patients with bronchiectasis. One patient had absolute adrenal insufficiency and 39.5 per cent (15/38) patients with bronchiectasis had impaired stimulated responses. Baseline and stimulated cortisol responses were unaffected by inhaled steroids (O.R 1.03, P=0.96). SGRQ scores were negatively correlated with body mass (r= -0.51, P=0.001) and bronchiectasis severity (r=0.37, P=0.019), but not related to baseline or stimulated cortisol responses. INTERPRETATION & CONCLUSIONS: Our results showed that the impaired adrenal responses to 1-µg cosyntropin were common in patients with bronchiectasis. This was not associated with the use of inhaled steroids or severity of bronchiectasis. Poor health status was associated with advanced disease and not with cortisol responses to the 1-µg cosyntropin test.

Tuberculosis in liver transplant recipients: experience of a South Indian liver transplant center.

Tuberculosis (TB) is a serious disease for liver transplant recipients (LTRs). Data on post-liver transplant TB from high-burden countries are scant. The aims of this study were to describe the prevalence of TB in LTRs from a high-prevalence area and to analyze the risk factors for the development of post-liver transplant TB. We performed a retrospective review of our database and a case-control study of identified cases with TB and age-matched LTRs without TB. The overall prevalence of TB in LTRs was comparable to the prevalence of TB in LTRs from low-prevalence countries (5/214 or 2.3%). A low rate of interferon-γ release assay (IGRA) testing before liver transplantation was observed (68/214 or 31%). Most patients were screened clinically and with chest radiography alone before transplantation. TB developed variably after transplantation [median = 72 days, interquartile range (IQR) = 534 days]. The presentation was mostly extrapulmonary and/or disseminated (4/5 or 80%). When cases with posttransplant TB were compared with matched healthy LTRs, the presence of unexplained granulomas in explants (2/5 or 40%, P = 0.01) was the only factor associated with the development of TB. When all explants showing granulomas were reviewed, TB (52.9%) remained the most common cause; however, in almost half (47.1%), other attributable causes were found. Patients were treated with a standard daily regimen for a median of 12 months (IQR = 7.5 months). Posttransplant TB was associated with a high mortality rate (2/5 or 40%). In conclusion, we observed a low prevalence of TB in LTRs from a high-prevalence region. The presence of granulomas suggestive of TB in liver explants warrants isoniazid prophylaxis in the absence of disease. Post-liver transplant TB is associated with a high mortality rate. The roles of routine IGRA testing and isoniazid prophylaxis in a high-prevalence setting urgently need to be studied.

Pulmonary hemorrhage in Henoch-Schönlein purpura: case report and systematic review of the english literature.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a rare complication of Henoch-Schönlein purpura (HSP) and data on its prevalence, management, and outcomes are scant. OBJECTIVES: To enable evidence-based management of DAH in HSP. METHODS: A case report and a systematic review were conducted of all reported cases of DAH complicating HSP in the English literature. RESULTS: DAH predominantly affects older male children and adults with HSP. The occurrence of DAH in HSP is rare and the reported prevalence ranged from 0.8% to 5%. DAH occurred variably after the diagnosis of HSP, ranging from 2 days to 18 years. Hemoptysis (75%), drop in hemoglobin (74%), and chest infiltrates (94%) were the most common clinical findings. Lung biopsy showed leukocytoclastic vasculitis with alveolar hemorrhage (69.2%) or only alveolar hemorrhage (31.8%) with variable IgA staining by immunofluorescence. DAH was frequently severe and 50% of the patients required mechanical ventilation. Cyclophosphamide and pulse methylprednisolone for DAH was associated with better outcomes, particularly in patients who were already receiving steroids at the time of DAH. Steroids and immunosuppressants were administered for a median duration of 9 and 4.5 months, respectively. Systemic recurrences (27.7%) and recurrences of DAH (8.3%) were frequent. DAH was associated with high mortality (27.6%) and morbidity (persistent urinary abnormalities, 12%; chronic renal failure, 9%; complications of therapy, 27%). CONCLUSIONS: DAH is a life-threatening complication in HSP. Current protocols use pulse methylprednisolone and cyclophosphamide for 6 months.

Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: systematic review from the Indian subcontinent.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic syndrome of unrestrained immune activation. Evaluation and management of HLH in the tropics is challenging. OBJECTIVES: To examine the reported etiologies and management of HLH reported from the sub-continent. METHODS: Systematic review of all published cases from the Indian sub-continent. RESULTS: We found only 156 published cases of HLH from the sub-continent. HLH was reported from the immediate perinatal period to 46 years of age. Infection-associated HLH (IAHS) constituted 46.8% of all cases of HLH (44% and 51% in children and adults respectively). In adults, tropical infections triggered 51% of these cases of IAHS. Steroids were used in 47% of children and 10% of adults. Etoposide and/or cyclosporine were used in 8% children and 8% of adults only. Intravenous immunoglobulin was used in another 30% of children and 4% of the adults. HLH-related mortality occurred in 31.8% and 28% of children and adults respectively. CONCLUSIONS: HLH is under-reported in the sub-continent and has high mortality. Cyclosporine and etoposide are seldom administered early despite diagnosis of HLH. Larger cohorts with IAHS triggered by tropical infections are urgently needed to understand its natural history and implications of this differing prescription pattern on mortality.

Pulmonary amyloidosis in Sjogren's syndrome: a case report and systematic review of the literature.

Amyloidosis is a heterogeneous group of disorders characterized by misfolding of extracellular proteins. The two most common forms are light-chain (AL) and reactive (AA) amyloidosis. Pulmonary amyloidosis secondary to Sjogren's syndrome (SS) is rare, and there is a paucity of data on its clinical and radiological features. We describe the case of a 41-year-old woman with diffuse septal pulmonary AL (lambda) amyloidosis related to SS, in the absence of systemic amyloidosis. A systematic search for pulmonary amyloidosis in SS yielded 37 cases. Amyloidosis occurred almost exclusively in women (96.5%). Cough and dyspnoea (56%) were the most common symptoms. The diagnosis of pulmonary amyloidosis was made subsequent to that of SS, with a median delay of 7 years. Radiologically, diffuse nodules with (45.5%) or without (33.3%) multiple cysts were the most common pattern. Most cases were related to nodular AL amyloidosis (both kappa and lambda). Diffuse septal AA amyloidosis has been reported in SS. The index patient is the first documented case of diffuse septal pulmonary AL amyloidosis in SS, without systemic amyloidosis. Surgical lung biopsy (78%) is usually required to establish the diagnosis and rule out lymphoma. There is no data to support any definitive therapeutic intervention for SS-related pulmonary amyloidosis. Observation is sufficient for nodular amyloidosis. Further studies are necessary to assess the efficacy of current therapies in diffuse septal amyloidosis secondary to SS.