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.

Clinical and Laboratory Diagnosis of Cryptosporidiosis among Children with Acute Gastroenteritis at a Tertiary Hospital, Cairo, Egypt.

BACKGROUND: Most studies on gastroenteritis have focused on viral and bacterial infections, while gastroenteritis where intestinal protozoan parasites may have played a role has not been well studied. This study was therefore, designed to assess the frequency and several potential risk factors for Cryptosporidium infection among children suffering from acute gastroenteritis and presented to a tertiary hospital in Cairo, Egypt. Effectiveness of modified Ziehl-Neelsen (MZN) and nested polymerase chain reaction (nPCR) for Cryptosporidium detection were evaluated as well. METHODS: A cross-sectional study was performed during the period from July 2018 to December 2018, where 100 human diarrheic stool samples were collected from children aged 3 months up to 12 years old presented to Ain Shams University Pediatrics Hospital, Cairo, Egypt with acute gastroenteritis. Demographic and clinical data were obtained from the participants. Initial parasite screening was done using the MZN staining method, and microscopically examined for Cryptosporidium infection, while genotyping was based on molecular diagnostic assays using nPCR and sequencing for selected samples. RESULTS: The overall frequency of Cryptosporidium infection was 5% using light microscopy, while 19% of samples were positive by nPCR. Cryptosporidium hominis was the only detected genotype. Clinical picture among cases were not significant in comparison to patients with other causes of gastroenteritis. CONCLUSION: Cryptosporidium infection is more common below 5 years of age; however, clinical data are not enough for suspicion of infection. Nucleic acid-based methods are more sensitive and specific despite the high cost in developing countries. However, real estimation of Cryptosporidium disease burden is of an outmost importance to achieve prevention and detection of the Cryptosporidium species genetic diversity. Lay summaryCryptosporidium is a protozoan, which causes gastroenteritis in humans. It is most common below 5 years of age; however, diarrhea and vomiting characteristics are not different from other causes of gastroenteritis. General diagnostic methods are inadequate for detection of these infections. Nested polymerase chain reaction (nPCR) and sequencing are accurate methods for pathogen detection and species verification. Our study included 100 Egyptian children with acute gastroenteritis. The overall frequency of Cryptosporidium infection was 5% using light microscopy, while 19% of samples were positive by nPCR. The clinical picture of the children presenting with this disease was not significantly different from those presenting with gastroenteritis due to other causes. This emphasizes the importance of proper diagnosis to know the true burden of the disease.