GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30-3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43-5.87, P = 0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

Association of IL4RA and IL-8 polymorphism in predicting susceptibility towards tuberculosis.

Mycobacterium tuberculosis is an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The aetiology of tuberculosis has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphism on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. PCR RFLP was performed to identify the genotype of the IL4RAQ576R and IL-8 +781C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p= 0.03) in tuberculosis. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781C/T, showed a significant association. Moreover, different combinations of the SNPS were made, and the 3 risk allele shows a significant protective role (p=0.02). There is considerable evidence which shows that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against tuberculosis, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with tuberculosis. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing tuberculosis.

Correlation of Serum Selenium in Asthma Patients with Severity of the Disorder.

Asthma is characterized by reversible airway obstruction, increased bronchial hyper-responsiveness and chronic inflammation, as well as higher levels of oxidative stress mainly due to decreased antioxidant defenses. Our primary aim was to investigate the correlation of serum selenium (Se) levels with the severity of asthma across gender, age, family history, and prevalence from childhood. Selenium levels in blood samples in 103 asthmatic patients and 103 healthy individuals were evaluated. The obtained data indicated that the mean serum Se levels in asthma patients were found to be twofold lower as compared to the controls (p < 0.001). However, there were no significant differences in the asthmatic patients when gender and age were considered. Patients characterized by family history of asthma and inhaler usage had 8% and 7% lower serum Se concentrations, although the difference was only border significant (p = 0.05). Multiple regression analysis demonstrated a significant inverse association of inhaler usage (ß = - 0.226; p < 0.001) with serum Se levels even after adjustment for asthma severity (ß = - 0.644; p < 0.001). While this report clearly necessitates a more detailed study, it is plausible that Se deficiency leads to impaired immune response, and therefore, Se supplementation might modulate oxidative stress in the lung and could potentially alleviate asthma pathophysiology.

Another rare presentation of allergic bronchopulmonary aspergillosis in a high burden tuberculosis country.

Mediastinal lymphadenopathy is often associated with tuberculosis, especially in a high burden country like India. We present a case of an asymptomatic female, who had mediastinal lymphadenopathy and middle lobe collapse, both of which pointed towards a diagnosis of tuberculosis. Patient was later diagnosed as a case of allergic bronchopulmonary aspergillosis (ABPA) on basis of clinical, radiological and serological findings. Hence, even in a high burden country and in background of bronchial asthma, ABPA should be kept as a differential diagnosis in patients presenting with mediastinal lymphadenopathy.

Prevalence of aspergillus skin hypersensitivity in allergic rhinitis.

Allergic rhinitis (AR) is a chronic allergen specific, IgE-mediated hypersensitivity disorder which significantly impairs the quality of life in affected patients. Many aeroallergens and molds are responsible for AR. This study was  conducted to find prevalence of Aspergillus fumigatus skin hypersensitivity in patients of AR by skin prick test (SPT).  150 clinically diagnosed AR patients visiting our OPD were enrolled. Skin hypersensitivity for Aspergillus f. was done by SPT in all the enrolled patients. Chi square test and Student’s t-test were applied for statistical analysis. Out of 150 patients, 60 (40%) were positive for Aspergillus fumigatus SPT. Majority of the positive patients had persistent AR and among those 39/60 (65%) had moderate to severe persistent AR and 12/60 (20%) had mild persistent AR.  Our study concluded that there is high (40%) prevalence of Aspergillus f. skin hypersensitivity among AR patients. The hypersensitivity to Aspergillus f. was found more in severe AR patients and it was statistically significant.