ORCID Profile
0000-0001-9263-7137
Current Organisations
University of Amsterdam
,
Assiut University Faculty of Pharmacy
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Publisher: Wiley
Date: 25-01-2021
DOI: 10.1111/ALL.14731
Publisher: Authorea, Inc.
Date: 29-12-2022
DOI: 10.22541/AU.167228469.92826361/V1
Abstract: Background. Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. Methods. Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data was analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). Results. α- ersity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α- ersity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis , respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella , Neisseria and Veillonella species and Haemophilus parainfluenzae . Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β- ersities were stable at one year. Conclusions. Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 Type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.
Publisher: American Thoracic Society
Date: 12-2022
Publisher: MDPI AG
Date: 23-02-2023
DOI: 10.3390/BIOMEDICINES11030676
Abstract: Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 s les from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal s les. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) 0.1 and a genome-wide significance threshold of p 9 × 10−8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood s les (coefficient= −0.015, p = 2.53 × 10−9) and nominally associated in nasal s les (coefficient = −0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.
Publisher: American Thoracic Society
Date: 15-07-2023
Publisher: European Respiratory Society (ERS)
Date: 25-11-2021
No related grants have been discovered for Mahmoud Abdel-Aziz.