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BackgroundBirt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma. Here, we comprehensively studied germline mutations in BHDS patients and asymptomatic members from 15 Indian families.MethodsTargeted amplicon NGS and Sanger sequencing was performed to detect germline mutations at FLCN in 31 clinically diagnosed patients and 74 asymptomatic family members. Functional effects and protein-protein interaction of FLCN variants were evaluated in-silico and molecular docking method. Family-based association study between pathogenic mutations and BHDS was also performed. Germline mutations at genes associated with phenotypically similar diseases were also addressed in few families.ResultsSix different types of pathogenic FLCN mutations were observed in the patients. Two of them: 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and splice acceptor mutation (c.1301-1G>A), were novel mutations. Two unreported Clinvar pathogenic mutations: stop-gain (c.634C>T) and 4-nucleotide duplication (c.1329_1332dupAGCC), and known mutations: hotspot mutation (c.1285delC) and splice donor mutations (c.1300+1G>A) were also detected. All these mutations greatly affected the protein stability and FLCN-FNIP2 protein interaction. Family-based association studies suggested pathogenic FLCN mutations are significantly associated with BHDS. Two pathogenic SNPs, rs1801133 and rs138189536, at MTHFR, associated with Homocystinuria, were found in one family.ConclusionPathogenic mutations at FLCN may play key roles in deregulating metabolic pathways leading to disease pathogenesis. Instead of FLCN mutations, MTHFR pathogenic SNPs were also detected in clinically diagnosed BHDS patients, therefore, genetic evaluation is necessary to avoid confounding diagnosis.

Background: Burden of Asthma-COPD Overlap Syndrome (ACO) is evolving especially with smoke- or nonsmoking risk factors in developing countries. The proportion of ACO varies from 12.1 to 55.2% according to diagnostic criteria applied. Once daily Glycopyrronium, offers persistent bronchodilation for complimentary action in Severe COPD or ACO. Aim: To assess COPD & ACO management with Glycopyrronium (50 mcg) addition. Methods: A prospective, observational, drug utilization study was planned on 160 cases of COPD & ACO defined by GOLD and ATS criteria at four centres during Jan’ to Dec ‘18 with IRB approval. Sample size calculation with Interim analyses was planned for Intergroup differences in FEV1 with Glycopyrrolate addition. Results: Interim analyses for COPD (n=64) and ACO (n=64) on Glycopyrronium 50 mcg OD & Formoterol/Budesonide DPI inhalation with follow-up at 12 wks were analyzed. Baseline demographics, Male/Female (119/09); Age 59.92 y; Wt 59.12 kg; FEV1 49.8%; Reversibility 15.03%, Exacerbation (≥2/y; 64%; Conclusion: Glycopyrronium 50 mcg offers Therapeutic synergy for incremental bronchodilation that is meaningfully clinically significant (MCID) in Severe COPD or ACO

Isolated cardiac sarcoidosis (ICS) accounts for 5%–10% of patients with sarcoidosis. It can involve atrioventricular node causing heart block, as well as the basal septum, papillary muscles, focal regions in the free wall, and the myocardium being more commonly involved. The diagnosis is achieved on magnetic resonance imaging (MRI) and endomyocardial biopsy. Recently, Fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (F-18 FDG PET) has been incorporated in the diagnosis as well as management algorithm. We describe an interesting case of ICS detected on F-18 FDG PET and MRI and discuss its role in the management of this rare presentation.

With improved imaging and early symptomatic diagnosis, a large number of patients are being diagnosed with interstitial lung diseases (ILD) in India. As ILD is a disease with limited response to conventional pharmacological treatment, pulmonary rehabilitation (PR) as a nonpharmacological approach is found to be promising in these patients. Despite the proven benefits of PR in patients with COPD, PR holds a weak recommendation for patients with ILD, with very few centers offering it to ILD patients in India. The study was aimed to assess the beneficial effects of an 8 week PR program in ILD patients at a private PR centre. A retrospective observational study analyzed over 2 years consisted of 100 patients (34% males and 66% females), 21 were lost to follow up. 24 patients required oxygen support (SpO2 We found significant improvement in 6MWTD, upper and lower limb muscle strength and CRDQ. Mean 6MWTD improved by 61.8 meters [p The 8 week PR program improved quality of life, muscle strength, functional capacity and proved beneficial in ILD patients.