Evaluation of alpha-defensins as a marker of severity in chronic obstructive pulmonary disease.

BACKGROUND: Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples. METHODS: A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD. RESULTS: The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = -0.31, P < 0.001). CONCLUSION: Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients.

Decreased mRNA expression of NR1H3 and ABCA1 in pulmonary tuberculosis patients from population of Punjab, India.

BACKGROUND: Mycobacterium tuberculosis (MTB) is the causative organism of tuberculosis. Cholesterol is a crucial carbon source required for the survival of MTB in host cells. Transcription factor NR1H3 along with its important target genes ABCA1 and ApoE play important role in removal of extra cholesterol from cells. Changes in the gene expression of NR1H3, ABCA1 and ApoE can affect cholesterol homeostasis and thus the survival of MTB in host cells.Therefore, the present study was designed to analyze the mRNA expression of NR1H3, ABCA1 and ApoE in pulmonary TB (PTB) patients from the population of Punjab, India. METHODS AND RESULTS: In this study, mRNA expression of the transcription factor NR1H3 and its target genes ABCA1 and ApoE was analyzed in 89 subjects, including 41 PTB patients and 48 healthy controls (HCs) by real-time quantitative PCR. It was found that the mRNA expression of both NR1H3 and ABCA1 genes was significantly lower in TB patients than in HCs (p < 0.001). Even after sex-wise stratification of the subjects, mRNA expression of NR1H3 and ABCA1 was found to be down-regulated in both male and female TB patients. No significant difference was observed in expression of ApoE (p = 0.98). CONCLUSIONS: The present study found that the mRNA expression of NR1H3 and ABCA1 is down-regulated in TB patients from Punjab state of India.

Role of detailed psychological evaluation and treatment in pulmonary rehabilitation programs for patients with chronic obstructive pulmonary disease.

Psychological co-morbidities are common in chronic obstructive pulmonary disease (COPD) but remain overlooked. Psychosocial interventions are deemed to promote mental health and optimize management. This study aimed to determine the role of detailed psychological evaluation and treatment in the comprehensive management of COPD. COPD patients after screening with the general health questionnaire-12 (GHQ-12) for psychological co-morbidity were divided into three groups (26 patients each): i) group A [GHQ-12 score<3, received pulmonary rehabilitation (PR) and standard medical management]; ii and iii) group B and C (GHQ-12 score>3, in addition, received management by a psychiatrist and counseling by a pulmonologist, respectively). At baseline and 8 weeks of follow-up, all participants were evaluated for respiratory [forced expiratory volume in the first second (FEV1), six-minute walk distance (6-MWD), St. George's respiratory questionnaire (SGRQ), modified medical research council (mMRC) dyspnea scale], and psychological [GHQ-12, patient distress thermometer (PDT), coping strategy checklist (CSCL), World Health Organization-quality of life-brief (WHOQOL-Bref-26), and depression anxiety stress scales (DASS)] parameters. Psychological distress (GHQ-12>3) decreased significantly at follow-up, with 11.5% and 53.8% of patients having psychological distress in groups B and C, respectively, versus baseline (p<0.001). mMRC score, SGRQ score, FEV1 and 6-MWD significantly improved in all three groups. Improvement in mMRC and SGRQ was maximal in group B when compared with the other groups. PDT, CSCL, and WHO-QOL-Bref-26 scores improved significantly at follow-up in all three groups, with maximum improvement in group B, followed by group C, and then group A. The DASS score also improved maximally in group B. Patients should be screened for psychological co-morbidities using simple screening tools. PR plays an important role in improving the psychology of COPD patients. However, results are better with directed psycho-educative sessions by non-experts and best with definitive treatment by psychiatrists.

Persistent respiratory symptoms and lung function abnormalities in recovered patients of COVID-19.

Background and Objectives: COVID-19 is a disease caused by SARS-CoV-2 which belongs to a family of coronaviruses. After the acute phase of illness, the majority of the patients recover quickly but, in some cases, symptoms can persist for a variable duration, bringing into light another entity known as post-COVID syndrome. The objective was to estimate the burden of various persistent respiratory symptoms and lung function abnormalities among recovered patients of COVID-19 and also to correlate them with initial disease severity, demographic factors and comorbidities. Methods: Eighty-five post-COVID patients were recruited as per inclusion/exclusion criteria. Detailed history taking, physical examination and spirometry were done in all patients and data were correlated with baseline disease severity. Results: Fatigue and breathlessness were the most common symptoms followed by cough, chest pain and fever. Persistent symptoms and their severity were significantly higher in severe/moderate cases. Spirometry was abnormal in 45.88% of subjects and the most common pattern was restrictive type. It was seen that the likelihood of persistent symptoms and abnormal lung function increased significantly with the severity of COVID-19, age, comorbidities, hospital stay duration and steroid/oxygen therapy. Conclusion: The current study estimated the burden and array of various pulmonary sequelae encountered by post-COVID patients and elicited various risk factors associated with their occurrence after recovery from active infection. Awareness of these symptoms/sequelae and their risk factors is necessary for their follow-up and timely management, as the threat of this relatively new virus has still not abated.

Serial evaluation of antibody titres in patients recovered from COVID-19 and their correlation with disease severity.

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. According to the findings of various studies conducted around the world, the serological response varies greatly among different populations, with the determinants of variable response still unknown, including the role of disease severity, which is thought to have a definite correlation. The purpose of this study was to assess serial SARS-CoV-2 IgG antibody response in COVID-19 patients and correlate it with disease severity. It was a longitudinal observational study in which 45 patients (age >18 yrs), were enrolled who had recovered from COVID-19 and were reporting to the post-COVID Care OPD Clinic. Patients who had been on long-term immunosuppressive therapy prior to SARS-CoV-2 infection were not eligible. All patients had not been immunized against SARS-CoV-2 and had no history of contact with recent COVID-19 cases. The patients underwent serial blood tests to determine serum IgG titers specific for SARS-CoV-2 at 30, 60, and 90 days after being diagnosed with COVID-19. Chemiluminescence was used to perform a semi-quantitative evaluation of the SARS-CoV-2 IgG antibody. At 30 days after confirmed SARS-CoV-2 infection, 98.78% had detectable serum IgG levels, and sero-reversion (loss of previously detectable antibodies) occurred in 2.5% at 60 days and 90 days. Serum IgG was found to peak at 30 days out of the three time points of measurement (30, 60, and 90 days from diagnosis). Serum IgG levels at 90 days were significantly lower than those at 30 days (p<0.0001) and 60 days (p=0.002). The current study's findings shed light on the presence and persistence of serum SARS-CoV-2-specific IgG antibodies following a natural infection. The findings point to a long-lasting immune response with increasing severity of initial COVID-19 disease.

Cell wall and immune modulation by Rv1800 (PPE28) helps M. smegmatis to evade intracellular killing.

Rv1800 is predicted as PPE family protein found in pathogenic mycobacteria only. Under acidic stress, the rv1800 gene was expressed in M. tuberculosis H37Ra. In-silico study showed lipase/esterase activity in C-terminus PE-PPE domain having pentapeptide motif with catalytic Ser-Asp-His residue. Full-length Rv1800 and C-terminus PE-PPE domain proteins showed esterase activity with pNP-C4 at the optimum temperature of 40 °C and pH 8.0. However, the N-terminus PPE domain showed no esterase activity, but involved in thermostability of Rv1800 full-length protein. M. smegmatis expressing rv1800 (MS_Rv1800) showed altered colony morphology and a significant resistance to numerous environmental stresses, antibiotics and higher lipid content. In extracellular and membrane fraction, Rv1800 protein was detected, while C terminus PE-PPE was present in cytoplasm, suggesting the role of N-terminus PPE domain in transportation of protein. MS_Rv1800 infected macrophage showed higher intracellular survival and low production of ROS, NO and expression levels of iNOS and pro-inflammatory cytokines, while induced expression of the anti-inflammatory cytokines. The Rv1800, PPE and PE-PPE showed antibody-mediated immunity in MDR-TB and PTB patients. Overall, these results confirmed the esterase activity in the C-terminus and function of N-terminus in thermostabilization and transportation; predicting the role of Rv1800 in immune/lipid modulation to support intracellular mycobacterium survival.

Single nucleotide polymorphism rs2234711 of interferon gamma receptor 1 is associated with pulmonary tuberculosis in the population of North India.

Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine playing essential role in immunity against tuberculosis (TB). IFN-γ performs function by binding to its receptor complex, consisting of two polypeptide chains viz. IFN-γ receptor 1 (IFN-γR1) and IFN-γ receptor 2 (IFN-γR2). Structural and functional deficiencies in IFN-γR1 can make individual vulnerable to even weak mycobacterial infections. Studies from different populations of the world have reported the association of single nucleotide polymorphisms (SNPs) present in IFNGR1 gene with TB, however, there are no such studies from India. Thus, the present study was designed to analyse the association of rs2234711 (C/T), rs7749390 (C/T) and rs1327475 (C/T) SNPs of IFNGR1 with TB in the population of North India. For the present study, 263 TB patients (at zero day of anti-tuberculosis therapy) and 256 healthy controls (HCs) were recruited. The genotyping of selected SNPs was done by high-resolution melting (HRM) curve analysis. The mRNA and surface expression data of IFNGR1 was extracted from our previous study and was grouped according to the genotypes of studied SNPs. The genotype 'TT' and 'T' allele of SNP rs2234711 (C/T) were found to be associated with TB in studied population ['T' vs 'C': OR (CI) = 1.79 (1.39-2.29); p-value < 0.0001]. The haplotypes 'C-C-C' of rs2234711-rs7749390-rs1327475 confers protection, while haplotype 'T-C-C' is a risk factor for TB in studied population. It was also found that 'TT' genotype of rs2234711 in HCs is associated with lower surface expression of IFNGR1 (p-value = 0.0078). In conclusion, 'TT' genotype is associated with lower surface expression of IFNGR1 and is increasing the susceptibility to TB in North Indian population.

Prevalence of latent tuberculosis infection in household contacts of pulmonary tuberculosis, time to treat.

Treatment of latent pulmonary tuberculosis (TB) in household contacts has been included in the National Tuberculosis Elimination Program to achieve the target of TB elimination by the Government of India by 2025. However, there are no clear estimates of the prevalence of latent TB among the contacts that could suggest the impact of this intervention. The study was conducted to determine the prevalence of and factors predicting latent TB among household contacts with pulmonary TB. All microbiologically confirmed pulmonary TB patients registered between January 2020 and July 2021 and their household contacts were enrolled. All contacts underwent Mantoux testing to determine the prevalence of latent TB. All symptomatic patients also underwent chest radiographs and sputum examinations to diagnose active pulmonary TB. Thereafter, different demographic and clinical factors were evaluated to find predictors of latent TB using a logistic regression model. A total of 118 pulmonary TB cases and their 330 household contacts were enrolled. The prevalence of latent TB and active TB among the contacts was found to be 26.36% and 3.03%, respectively. The female gender of index TB cases was independently associated with a high proportion of latent TB cases in the family (adjusted odds ratio 2.32; 95% confidence interval 1.07-5.05; p=0.03). Neither the higher sputum smear positivity nor the severity of the chest radiograph of index TB cases had any association with the number of contacts being diagnosed as latent TB or active TB. The results showed a significant prevalence of latent TB among household contacts with pulmonary TB. The severity of the disease in the index patient had no association with the prevalence of latent TB.

N-terminal PPE domain plays an integral role in extracellular transportation and stability of the immunomodulatory Rv3539 protein of the Mycobacterium tuberculosis.

Multigene PE/PPE family is exclusively present in mycobacterium species. Only few selected genes of this family have been characterized till date. Rv3539 was annotated as PPE63 with conserved PPE domain at N-terminal and PE-PPE at C-terminal. An α/ß hydrolase structural fold, characteristic of lipase/esterase, was present in the PE-PPE domain. To assign the biochemical function to Rv3539, the corresponding gene was cloned in pET-32a (+) as full-length, PPE, and PE-PPE domains individually, followed by expression in E. Coli C41 (DE3). All three proteins demonstrated esterase activity. However, the enzyme activity in the N-terminal PPE domain was very low. The enzyme activity of Rv3539 and PE-PPE proteins was approximately same with the pNP-C4 as optimum substrate at 40 °C and pH 8.0. The loss of enzyme activity after mutating the predicted catalytic triad (Ser296Ala, Asp369Ala, and His395Ala) found only in the PE-PPE domain, confirmed the candidature of the bioinformatically predicted active site residue. The optimal activity and thermostability of the Rv3539 protein was altered by removing the PPE domain. CD-spectroscopy analysis confirmed the role of PPE domain to the thermostability of Rv3539 by maintaining the structural integrity at higher temperatures. The presence of the N-terminal PPE domain directed the Rv3539 protein to the cell membrane/wall and the extracellular compartment. The Rv3539 protein could generate humoral response in TB patients. Therefore, results demonstrated that Rv3539 demonstrated esterase activity. PE-PPE domain of Rv3539 is functionally automated, however, N-terminus domain played a role in protein stabilization and its transportation. Both domains participated in immunomodulation.

Revisiting the impact of serial therapeutic phlebotomy in polycythaemia on laboratory and clinical parameters using a fixed interval and fixed volume protocol.

OBJECTIVES: Therapeutic phlebotomy allows for a controlled and gradual decrease in red cell mass leading to improved blood flow and symptomatic relief in polycythaemia. The present study was aimed to determine the impact of serial fixed volume and fixed interval therapeutic phlebotomy protocol on the laboratory and clinical parameters in patients of polycythaemia. MATERIAL AND METHODS: This prospective longitudinal study was conducted over 18 months. The desired haematocrit for polycythemia vera and secondary polycythemia was 45% and 52% respectively. A fixed volume of 350 ml phlebotomy was performed every-three days till the achievement of desired haematocrit. Complete blood count was performed before and after each procedure and iron studies were done at the time of enrolment and after the achievement of desired haematocrit. Post-procedure symptomatic relief was assessed by a 10-point visual analogue scale (VAS). RESULTS: Of the 29 patients enrolled in the study, 3 patients were lost to follow up and data of 26 patients was analyzed. Mean Hb declined from 17.84 ± 1.88 gdL-1 to 14.67 ± 1.14 gdL-1 (p < 0.001) and mean haematocrit decreased from a baseline of 57.11 ± 5.47% to 46.27 ± 3.763% (p < 0.001) upon achievement of desired haematocrit. There was a significant decline in serum iron from the baseline of 132.85 ± 94.136 µg dL-1 to 69.41 ± 58.643 µg dL-1 at desired haematocrit. A significant change in VAS score of almost all clinical parameters was observed. Post phlebotomy hematocrit correlated negatively with the number of procedures (p = 0.015). CONCLUSION: Our protocol yielded rapid and marked improvement in patients of primary and secondary polycythemia with minimal adverse events and significant amelioration of clinical parameters.

Evaluating environmental quality in Rujigou coalfield, China, using analytic hierarchy process.

Coal is the major fossil fuel used for power generation. Coal mining activities lead to environmental changes to a large extent, such as degradation in the quality of air, water, and soil, changes in landform, land use/land cover, and vegetation distribution. Evaluating the environmental quality is therefore essential to study the nature and impact of mining activities on the environment. The present study attempts to use the analytic hierarchy process (AHP) to assess the environmental quality of Rujigou coalfield that lacked previous such analysis. The criteria used for evaluation were selected through a literature review and extensive field survey. A photo tour of the study area shows the current ground conditions. Weights were assigned to these criteria based on expert opinions, recommendations from published literature, and field investigation. The results indicate that mining activities in the study region most significantly impact the air quality, followed by soil, water, landform, and vegetation. The knowledge of environmental quality can forewarn policymakers and mine managers about impending environmental problems and improve their ability to manage and resolve them. Moreover, the systematic methodological process described in this research can be applied to any study area with similar features to the one investigated in this paper.

Assessment of the feasibility of 1-min sit-to-stand test in evaluating functional exercise capacity in interstitial lung disease patients.

Six-min walk test (6MWT) is widely used exercise test for the evaluation of interstitial lung disease (ILD). However, the long test duration and need for long and flat surface hinder its routine use. One-min sit-to-stand test (1-STST) is devoid of such limitations, but has been scarcely evaluated. The study was conducted to evaluate the performance of 1-STST by correlating it with 6MWT in ILD patients. Stable ILD patients were prospectively enrolled. After initial spirometry, all patients performed 6MWT and 1-STST following the standard recommendations. Exercise capacity and physiological parameters (heart rate, pulse oxygen saturation, blood pressure and dyspnea [modified Borg scale]) including peripheral oxygen saturation (SpO2) were correlated after the tests using Pearson correlation, Intraclass correlation coefficient (ICC) and kappa (κ) coefficient. The results showed that the mean age of the patients (n=60) was 58.8±11.5 years (male:female=1:1). Repetitions after 1-STST showed significant correlation with 6MWT (r=0.48; P<0.001). Changes in the physiological variables were similar (P>0.05) with good consistency (ICC=0.68-0.95) between 6MWT and 1-STST. Both lowest SpO2 and difference in SpO2 also showed good agreement (ICC=0.86; 95% confidence interval [CI], 0.77-0.92 and ICC=0.68; 95% CI, 0.47-0.81 respectively) and significant correlation (r=0.76 and r=0.52, respectively). 1-STST and 6MWT were consistent in identifying patients having oxygen desaturation ≥4% (κ=0.56; 96% CI, 0.30-0.82). The results demonstrated that the performance of 1-STST was consistent with 6MWT in terms of exercise capacity and change in physiological parameters. 1-STST can be a valid alternative to 6MWT in the assessment of ILD patients, especially in peripheral health centers.

Investigating the environmental impacts of coal mining using remote sensing and in situ measurements in Ruqigou Coalfield, China.

China is the largest producer and consumer of coal in the world. The extraction of coal is increasing intensively to meet the needs of the ever-increasing population and industries. However, coal mining has resulted in environmental changes, including deforestation, air, water, soil, and landform deterioration. This study investigates the impact of mining on the environment in Ruqigou coalfield by utilising in situ and remote sensing data. Field data collected include temperature, gas compositions, and water samples. Multi-temporal Landsat data of 1991, 2003, and 2019 were used in monitoring the impact of mining on different land covers, especially vegetation. A supervised classification was performed to assess the changes in land cover. In order to track the changes in vegetation, normalised difference vegetation index (NDVI) was employed. To study the changes in coal fire areas, thermal anomalies were extracted from the thermal infrared data using a dynamic thresholding technique. The results of in situ analyses show that water quality is unfit for domestic, industrial, and agricultural use. All the gas sampling sites emit noxious gases such as CO2, CO, NO2 and degrade the local air quality. The classified maps and vegetation indices show a significant decrease in vegetation. The thermal anomalies show an increase in fire areas over the years. Thus, it could be concluded that the conjunctive use of field-based measurements and remote sensing data can be a powerful tool for gaining a comprehensive understanding of the environmental impacts associated with large-scale mining.

Sex-dependent regulation of interferon-γ receptor expression in pulmonary tuberculosis.

Interferon-γ (IFN-γ) is an essential pro-inflammatory cytokine against tuberculosis (TB). To initiate immune response, IFN-γ binds to its receptor complex which consists of two subunits IFN-γ receptor 1 (IFN-γR1) and IFN-γ receptor 2 (IFN-γR2). The deficiency in either receptor subunit can alter IFN-γ signalling thus influencing host susceptibility to TB. In the present study IFN-γ receptor expression at transcriptional and translational level was analysed in pulmonary TB patients from North India. A total of 46 pulmonary TB patients (at 0 day of anti-tuberculosis therapy) and 48 healthy controls (HCs) were recruited. It was found that the mRNA expression of IFN-γR1 was decreased in male TB patients (p = 0.003). The surface expression of IFN-γR1 (p = 0.0005) and IFN-γR2 (p = 0.024) was also found to be decreased in male TB patients. In conclusion, we found sex-dependent regulation of IFN-γR1 and IFN-γR2 expression in pulmonary TB patients of studied population.

Pulmonary rehabilitation: A novel adjunct in management of obstructive sleep apnea.

Pulmonary rehabilitation (PR) is being used in the routine management of patients of obstructive sleep apnea (OSA) at some centers. However, the studies documenting benefits of PR in OSA lack standardization in terms of outcome measures. A study was hence planned to determine the efficacy of PR on exercise capacity, health related quality of life (HRQOL), day time sleepiness and sleep-quality of life (QOL) in patients of OSA. As a part of comprehensive therapy, patients diagnosed with OSA are managed with continuous positive airway pressure (CPAP), 8 weeks thrice weekly outpatient hospital-based PR and medical treatment at the Pulmonary Medicine Department, Government Medical College and Hospital, Chandigarh. However, some patients refuse for PR because of time constraints and travel issues. Patients with newly diagnosed OSA without co-existing respiratory disease, who agreed for the CPAP, PR and medical management were enrolled in group A. The patients who refused for PR but were ready for CPAP and medical management were enrolled in Group B; 30 patients were taken in each group. Exercise capacity, HRQOL, day time sleepiness and sleep-QOL were determined at baseline and at 8-weeks follow-up by 6-minute walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), Epworth Sleepiness Scale (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ) and compared amongst the two groups. Four patients from group A were excluded as they did not complete PR; 26 patients from group A and 30 patients from group B were finally analyzed. At baseline, both groups were matched with respect to age, gender, apnea-hypopnea index (AHI), body mass index (BMI), FEV1%predicted, 6MWD, SGRQ, ESS and FOSQ. At follow up at 8 weeks, BMI, 6MWD, SGRQ, ESS and FOSQ improved significantly from baseline in group A (p<0.001). FEV1%predicted also improved but non significantly. In group B, FEV1%predicted, BMI, 6MWD, SGRQ, ESS and FOSQ score did not improve significantly from baseline. Mean improvement from baseline in BMI, 6MWD, SGRQ, ESS and FOSQ was significantly more in group A than group B (p<0.001, p<0.001, p=0.041, p<0.001 and p<0.001, respectively). PR, being beneficial, should be incorporated in standard management of OSA.

Association of single nucleotide polymorphisms of interferon-γ with pulmonary tuberculosis in population of Himachal Pradesh, India.

Interferon-gamma (IFN-γ) plays an integral role in the host immunity against tuberculosis (TB). The gene encoding IFN-γ is polymorphic and several studies have reported the association of its genetic polymorphisms with TB in different populations of the world. The present study investigated the association of rs2069705 (C/T), rs1861494 (C/T), rs1861493 (A/G) and rs2069718 (C/T) single nucleotide polymorphisms (SNPs) of IFN-γ with pulmonary TB in a population of Himachal Pradesh, India. For present study, 210 pulmonary TB patients and 205 healthy controls (HCs) were recruited. The selected SNPs of IFN-γ were genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and plasma IFN-γ levels were measured by ELISA. The 'T' allele of rs1861494 SNP was found to increase susceptibility to TB in the studied population (OR = 2.18, 95%CI = 1.57-3.03; p < 0.001). After stratifying the subjects on basis of sex, males with 'T' allele of rs2069718 SNP were found to be at higher risk to TB (OR = 1.55, 95%CI = 1.07-2.25; p = 0.02). We also found moderate linkage disequilibrium among the studied SNPs. The haplotypes C-T-A-T and T-T-G-T of rs2069705-rs1861494-rs1861493-rs2069718 were overrepresented in TB patients and found to increase susceptibility to TB (p = 0.012). The plasma IFN-γ levels in TB patients were around seven times higher in comparison to HCs (p < 0.0001). The HCs with genotype 'AA' of SNP rs1861493 were found with higher plasma IFN-γ levels than 'AG/GG' genotype (p = 0.023). In conclusion, the results suggest the association of rs1861494 (C/T) and rs2069718 (C/T) SNPs of IFN-γ with TB and genotype 'AA' of rs1861493 is associated with higher plasma IFN-γ levels in the population of Himachal Pradesh, India.

Therapeutic efficacy of oscillating positive expiratory pressure therapy in stable chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airway and the lung to noxious particles or gases. Sputum production is a cardinal feature in COPD. Airway clearance techniques have been the mainstay of management. Oscillating positive expiratory pressure (OPEP) devices are handheld devices that provide a combination of positive expiratory pressure (PEP) with high frequency oscillations which involve exhaling against a resistance that is fluctuating. It encourages airflow within secretions, whereas oscillations induce vibrations within airway wall to displace secretions into airway lumen and help in expectoration. Methods: A randomized control trial was conducted at the department of pulmonary medicine, Government Medical College & Hospital, Chandigarh, in which 50 patients with stable COPD were enrolled for one- and- half years. After taking proper history, they were subjected to spirometry, six- minute walk test, and were asked to fill the St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT). These patients were randomized into group A (intervention group) and group B (control group), where group A was prescribed Aerobika OPEP device for daily use for a period of three months. After three months of use of device, the patients were again subjected to assessment parameters and inquired about any exacerbation within the three- month period. Results: At the end of three months were compared with baseline results. The median change in FEV1, FVC, 6MWD from baseline in group A was significantly more as compared to group B (FEV1: P < 0.001; FVC: P < 0.001; 6MWD: P = 0.08), whereas SGRQ score showed a significant improvement in both the intervention and control groups (P < 0.001) and CAT score showed significant improvement in comparison to the control group (P < 0.001). The median change in 6MWD and CAT from baseline in group A was significantly more as compared to group B (SGRQ: P < 0.001; CAT: P < 0.001), whereas it was not significant in case of SGRQ (P = 0.233). There was no significant difference in the incidence of exacerbation in the two groups (P = 0.19). The device did not help in controlling the rate of exacerbation in the present study at three months. Conclusion: Stable COPD patients who were given OPEP therapy as an adjunct to the standard drug therapy showed improvement in the spirometry parameters, exercise capacity and symptom burden in comparison to the drug only group.

Role of interleukin-6 and insulin resistance as screening markers for metabolic syndrome in patients of chronic obstructive pulmonary disease. A hospital-based cross-sectional study.

Chronic obstructive pulmonary disease (COPD) is usually associated with various extra-pulmonary manifestations. Metabolic syndrome (MetS) is one such entity that has been scarcely studied in Indian patients. The availability of a good screening marker may help in the timely detection of this co-morbidity in COPD patients. We conducted a cross-sectional study to evaluate the prevalence of MetS among COPD patients and the role of Interleukin-6 and insulin resistance (as measured by HOMA-IR) as screening markers for MetS in COPD. One hundred stable COPD patients were evaluated for MetS using US National Cholesterol Education Program Adult Treatment Panel III (2005) guidelines. Interleukin-6 and HOMA-IR (for insulin resistance) were measured and compared between COPD patients with and without MetS. ROC analysis was done to find both the molecules' best cut-off value and sensitivity and specificity in detecting MetS. In the results, the mean age of the study cohort was 59.9±8.7yrs (males=93). Forty-five COPD patients (45%) fulfilled the criteria for MetS. Patients with MetS were comparatively younger (57.9+9.5 v/s 61.6+7.8 years; p=0.037) but had a longer duration of preceding COPD (9.9±2.8 v/s 6.0±2.2 years; p<0.001) as compared to those without MetS. Both IL-6 and HOMA index were statistically higher (p<0.05) in COPD-MetS patients compared to the other group. A cutoff value of 36.3 pg/ml for IL-6 and 1.61 for HOMA index, IL-6 and HOMA-IR had sensitivity of 91.1% and 82.2%, respectively in detecting MetS among COPD patients. To conclude, metabolic syndrome is common comorbidity seen in COPD patients. Interleukin-6 has a better sensitivity than HOMA-IR in screening MetS among COPD patients.

An Experience with Delamanid in an XDR TB Case - Case Report.

INTRODUCTION: Tuberculosis is an endemic infection and a serious public health problem in India. India constitutes one-fourth of the global TB population. The emerging drug resistance is a major threat to global tuberculosis care and control. CASE REPORT: We present a case of newly diagnosed microbiologically confirmed, extremely drugresistant primary pulmonary tuberculosis which was treated with Delamanid and was found to be cured of tuberculosis. DISCUSSION: Delamanid is a new anti-tubercular drug, which is thought to primarily inhibit the synthesis of methoxy-mycolic, and keto-mycolic acid, which are components of the mycobacterial cell wall. In our patient who was a newly diagnosed case of MDR-TB converted to XDR-TB in little course of time and we were successful in treating him with Delamanid therapy. His sputum culture conversion was achieved in 20 days. Even though the patient did not tolerate well because of the side effects of the drug, still he became microbiologically negative for tuberculosis. CONCLUSION: Delamanid fulfills many target criteria for new TB drugs and may be particularly useful for the treatment of MDR-TB. It can be administered orally and its bactericidal properties make it suitable in regimens designed to shorten treatment duration. Clinical efficacy data, while limited, are reassuring.