Doaa Mostafa Gad

Impact of glutathione-S-transferase gene polymorphisms on enzyme activity, lung function and bronchial asthma susceptibility in Egyptian children.

BACKGROUND Asthma is a complex multifactorial disease with an obvious genetic predisposition. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. The aim of the present study was to investigate the role of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes and asthma susceptibility in Egyptian children, and to analyze their effect on GST activity and lung function. METHODS GSTT1 and GSTM1 gene polymorphism was genotyped using the multiplex polymerase chain reaction (PCR) and GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 healthy and 126 asthmatic children (82 atopic and 44 nonatopic). Also GST enzyme activity and lung function were evaluated. RESULTS Asthmatic children had a significant higher prevalence of the GSTM1 null (P=0.003) and significant lower prevalence of GSTP1 Val/Val genotypes (P=0.02) than control group. Lung function was significantly decreased in GSTM1 null genotype and GSTP1 Ile/Ile genotype. GSTP1 Val/Val genotypes and GSTM1 null genotype had a significant decrease in plasma GST activity. CONCLUSIONS GST genes polymorphisms may play an important role in pathogenesis and susceptibility to asthma in children.

CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk.

OBJECTIVE Lung cancer remains the most prevalent malignancy worldwide. Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes. Several metabolic enzymes are currently under investigation for their possible role in lung cancer susceptibility, including members of the cytochrome P450 (CYP) superfamily. The aim of this work was to identify the correlation between CYP1A1 m1 and m2 polymorphisms and lung cancer risk and figure its interactions with smoking as genetic modifiers in the etiology of lung cancer in the Egyptian population. MATERIALS AND METHODS One hundred and ten patients with lung cancer and one hundred and ten controls were enrolled in the study. CYP1A1 m1 and m2 polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS Subjects carrying TC and CC genotypes of CYP1A1 m1 and AG and GG genotypes of CYP1A1 m2 were significantly more likely to develop lung cancer especially squamous cell carcinoma. The proportion of lung cancer attributable to the interaction of smoking and CYP1A1 m1 and CYP1A1 m2 polymorphisms was 32% and 52% respectively. CONCLUSION Our results revealed that CYP1A1 m1 and m2 polymorphisms contribute to smoking related lung cancer risk in the Egyptian population.

Clinical and Microbiological Characteristics of Metallo β-lactamase producing Pseudomonas aueroginosa in a sample of Egyptian Patients with Bronchiectasis

Background : Metallo-β-lactamases producing Pseudomonas aueroginosa represents a challenging concern especially in chronic colonization of bronchiectasis cases owing to progressive tissue damage, inflammation, frequent exacerbation and lack of response to antimicrobial agents. Objectives: This cross-sectional study was conducted to high-lighten the antimicrobial and molecular pattern of Pseudomonas aueroginosa isolates from bronchiectasis cases and assess their clinical outcome. Methodology: ninety-eight sputum and endotracheal aspirates were collected from bronchiectasis inpatients of Chest Department, Zagazig University Hospitals. Conventional identification and API20 NE were performed. Combined disc test and E-test were done, confirmed by PCR, to detect metallo-β-lactamases. Results : A total of 43 (43.9%) Pseudomonas were isolated, 16 (37.2%) were metallo β-lactamases and multidrug resistant. E. test had the best sensitivity and specificity. Both IMP-1 and VIM-1 genes were detected. The majority of isolates were IPM-1 positive. Conclusion : P. aeruginosa, is blamable for infection in more than 40% of bronchiectactic patients being a high-risk group. Combined disk test is a reliable, cheap and simple screening tool especially in low-resources laboratories. This study raised the concern of co-existing mechanism for both quinolone and carbapenem resistance for more investigation. Current results linked lab detection of MβL P. aeruginosa with inferior spirometry and lengthy hospital stay.

Role of serum proadrenomedullin in assessment of the severity and outcome of hospitalized healthcare-associated pneumonia patients

Background Clinical judgment of healthcare-associated pneumonia ( HCAP ) represents a major concern as these fragile patients have an unusual presentation that frequently misleads severity assessment and results in poor clinical outcome. The aim of this study was to evaluate the role of proadrenomedullin (proADM) in predicting disease severity and outcome in HCAP patients in comparison with community-acquired pneumonia (CAP) patients. Patients and methods Thirty-one HCAP patients and twenty-five CAP patients were enrolled in this study. Measurement of serum proADM level was performed in the first 24-h of admission. Assessment of severity was carried out using the CURB-65 scoring system. Finally, the outcome of the patients was assessed. Results Serum proADM level was higher in HCAP patients than that in CAP patients, this difference was statistically significant. Also, serum proADM level increased significantly with increasing severity of HCAP patients guided by CURB-65, with a cut-off value of more than 1.8 nmol/l, with a sensitivity of 91.7%, a specificity of 95%, a positive predictive value of 91.7%, and a negative predictive value of 95%. However, a higher value (>2.9 nmol/l) was detected in HCAP patients who died, with high sensitivity and negative predictive value (100%) and low specificity (42.3%) and positive predictive value (25%). Conclusion The use of proADM as a novel biomarker enhances the performance of the CURB-65 scoring system for risk stratification of HCAP patients.