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 ( 6518 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\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). 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

Stenting for obstructive iliac vein lesions

Endovenous stenting has supplanted open surgery as the treatment of choice for iliocaval obstruction. This review provides a brief overview of such obstructive pathology and an in-depth assessment of femoroilio- caval stenting

Successful Wallstent exclusion of iliofemoral venous aneurysms—a new treatment paradigm

Treatment of venous aneurysms involving the iliac and femoral veins has generally been an open surgical approach, with a few case reports noting use of an endovascular approach. We report three cases: (1) a patient with an iliocaval occlusion involving an occluded TrapEase filter who presented with a large left external iliac vein aneurysm; (2) a patient with a left common femoral vein aneurysm; and (3) a patient with left profunda femoris vein aneurysms with associated pulmonary embolism. All three patients were successfully managed with the use of appropriately sized bare metal woven stents (Wallstents; Boston Scientific). Their clinical presentation, technical considerations, and outcomes are reviewed

Role of laser ablation in recalcitrant instent restenosis post iliofemoral venous stenting

Instent restenosis (ISR) represents the most common reason for recurrent symptoms requiring reintervention in patients who have undergone venous stenting for chronic iliofemoral venous obstruction. Treatment of ISR requires stent angioplasty typically using angioplasty balloons equal to or larger than the rated diameter of the stent. At times this does not yield the required result, and in these patients, utilization of a laser catheter supported by an angled sheath is helpful to ablate the ISR or make it more amenable to repeat balloon angioplasty. The authors report their experience with this technique for 18 patients with recurrent symptoms impacting quality of life as a result of recalcitrant ISR in this retrospective review of contemporaneously entered electronic medical record data. 12 (67%) limbs underwent laser ablation only, while 6 (33%) limbs underwent additional angioplasty post laser ablation. Post intervention for ISR, at 12 months, the venous clinical severity score improved from 5 to 3.5 (P = .0005) and the VAS pain score went from 7 to 5 (P = .0005). At 10 months, primary patency was 87% and primary assisted patency was 100%. There were no stent occlusions. Laser ablation of recalcitrant instent restenosis in patients presenting with recurrent chronic iliac venous obstruction post iliofemoral venous stenting is a safe and effective option. Corroboration from larger studies is warranted

A unique complication of double barrel Wallstent technique in iliac-caval stenting

The “double barrel” technique has been a popular option in reconstituting the iliac-caval confluence in bilateral stenting. It has been mostly used with the Wallstent (Boston Scientific, Marlborough, Mass). The technique, although generally trouble-free, has a unique long-term complication. One stent barrel was found to compress the other from a late developing compliance mismatch. The complication is easily missed unless an intravascular ultrasound examination is performed. A cross-fenestration between the two barrels supported by a Z stent might provide clinical relief if the double barrel extension into the vena cava is relatively short in length

Analysis of Notch signaling-dependent gene expression in developing airways reveals diversity of Clara cells.

Clara cells (CCs) are a morphologically and operationally heterogeneous population of Secretoglobin Scgb1a1-expressing secretory cells that are crucial for airway homeostasis and post-injury repair. Analysis of the extent and origin of CC diversity are limited by knowledge of genes expressed in these cells and their precursors. To identify novel putative markers of CCs and explore the origins of CC diversity, we characterized global changes in gene expression in embryonic lungs in which CCs do not form due to conditional disruption of Notch signaling (Rbpjk(CNULL)). Microarray profiling, Real Time PCR (qRT-PCR), and RNA in situ hybridization (ISH) identified eleven genes downregulated in the E18.5 airways of Rbpjk(cnull) compared to controls, nearly half not previously known to mark CCs. ISH revealed that several genes had overlapping but distinct domains of expression of in the normal developing lung (E18.5). Notably, Reg3g, Chad, Gabrp and Lrrc26 were enriched in proximal airways, Hp in the distal airways and Upk3a in clusters of cells surrounding Neuroepithelial Bodies (NEBs). Seven of the eleven genes, including Reg3g, Hp, and Upk3a, were expressed in the adult lung in CCs in a pattern similar to that observed in the developing airways. qRT-PCR-based analysis of gene expression of CCs isolated from different airway regions of B1-EGFP reporter mice corroborated the spatial enrichment in gene expression observed by ISH. Our study identifies candidate markers for CC-precursors and CCs and supports the idea that the diversification of the CC phenotype occurs already during embryonic development

Expression patterns of the genes identified by transcriptional profiling at E14.5.

<p><b>(A)</b> qRT-PCR analysis of gene expression in CTRL and Rbpjk^CNULL lungs from E14.5 <b>(B)</b> ISH showing expression of the eleven genes in lungs from control and Rbpjk^CNULL at E14.5. Genes expressed at E14.5 shown in left panel.</p