Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype.

BACKGROUND: Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters. METHODS: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method. RESULTS: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005). CONCLUSIONS: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.

Serum growth differentiation factor-15 (GDF-15) is a biomarker of cardiac manifestations in children with COVID-19.

BACKGROUND: COVID-19 leads to severe overwhelming inflammation in some patients mediated by various cytokines (cytokine storm) that usually leads to severe illness accompanied by cardiovascular manifestations. Growth differentiation factor-15 is a cytokine induced by stress and is associated with inflammatory processes in the lung and heart. This study aimed to measure the level of serum growth differentiation factor (GDF-15) in children with COVID-19 and to correlate it with the disease severity, cardiac affection, and the outcome of COVID-19. METHODS: A cross-sectional study was conducted on 144 children; 72 children diagnosed with COVID-19, and 72 healthy children. The severity of COVID-19 was assessed clinically, laboratory, and radiologically. Echocardiography was done within 48 h of admission for COVID-19 patients. Serum GDF-15 was measured by ELISA for both patients and controls. RESULTS: Serum GDF-15 level was significantly higher in patients with COVID-19 than in controls (p < 0.01). In COVID-19 patients with severe clinical grading, those who were hospitalized in the PICU, and those who died, serum GDF-15 levels were greater. individuals with cardiac manifestations exhibited significantly higher serum GDF-15 levels than individuals without them. In children with COVID-19, increased GDF-15 was correlated to poorer ejection fraction and higher INR using multivariate linear regression analysis. CONCLUSION: Serum GDF-15 is a promising biomarker of COVID-19, it can be used as a predictor of cardiac manifestations in children with COVID-19 and severe disease.

Autophagy-related 5 gene mRNA expression and ATG5 rs510432 polymorphism in children with bronchial asthma.

PURPOSE: Bronchial asthma is a common chronic respiratory disease in children with complex pathogenesis, characterized by airway hyper-responsiveness, obstruction, mucus hyperproduction, and airway remodeling. Autophagy is important for cellular physiology, and the ATG5 rs510432 has recently been implicated in several fundamental characteristics of childhood asthma pathogenesis and may play a role in the disease progression. This study aims to assess the expression of ATG5 messenger RNA (mRNA) according to rs510432 polymorphism in asthmatic children and to evaluate their possible relation with the development of the disease. METHODS: ATG5 mRNA expression and rs510432 polymorphism were measured using real-time polymerase chain reaction in 57 asthmatic children patients and 46 healthy controls. RESULTS: ATG5 level was significantly higher in asthmatic children than in controls and a significant increase in the frequency of TT and CC genotype of ATG5 rs510432 gene polymorphism was found in asthmatic patients when compared to control subjects (p < 0.001; and p = 0.01, respectively), and there was a statistically significant decrease in the frequency of CT genotype of ATG5 rs510432 gene polymorphism in asthmatic patients when compared to control subjects (p < 0.001). CONCLUSION: ATG5 rs510432 gene polymorphism plays an important role in childhood asthma pathogenesis.

Prevalence of common sensitizing aeroallergens in Egyptian asthmatic patients.

BACKGROUND: Aeroallergens and food allergens play a key role in the pathogenesis of asthma; they are the target for future immunotherapy worldwide. Food allergens have been studied often in Egypt, but data are defective concerning the prevalent Egyptian aeroallergens that can be affected by the climatic conditions in Egypt. So, our study aimed to explore the dominant sensitizing aeroallergens in Egyptian patients with bronchial asthma. METHODS: Cross-sectional study performed on 122 Egyptian asthmatic patients. Sera from all patients were examined by enzyme allegro sorbent test (EAST) method for specific IgE to a panel of 18 inhaled allergens. RESULTS: Positive specific IgE to aeroallergens was detected in 43.44% of our patients. German cockroach (18.9%) was the most frequent sensitizing aeroallergen amongst our asthmatic patients, followed by the fungal allergens (15.57%) and house dust mites (HDMs) (13.93%). CONCLUSION: German cockroach, fungi, and house dust mite are the chief sensitizing aeroallergens in Egyptian asthmatic patients.