ORCID Profile
0000-0001-7102-1712
Current Organisations
Royal College of Physicians of Ireland
,
Royal College of Surgeons in Ireland
,
Children's Health Ireland at Crumlin
,
Children's Health Ireland
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Publisher: MDPI AG
Date: 26-02-2021
DOI: 10.3390/MICROORGANISMS9030492
Abstract: The cystic fibrosis (CF) lung harbours a erse microbiome and reduced ersity in the CF lung has been associated with advancing age, increased inflammation and poorer lung function. Data suggest that the window for intervention is early in CF, yet there is a paucity of studies on the lung microbiome in children with CF. The objective of this study was to thoroughly characterise the lower airway microbiome in pre-school children with CF. Bronchoalveolar lavage (BAL) s les were collected annually from children attending the three clinical centres. Clinical and demographic data were collated on all subjects alongside BAL inflammatory markers. 16S rRNA gene sequencing was performed on the Illumina MiSeq platform. Bioinformatics and data analysis were performed using Qiime and R project software. Data on 292 sequenced BALs from 101 children with CF and 51 without CF show the CF lung microbiome, while broadly similar to that in non-CF children, is distinct. Alpha ersity between the two cohorts was indistinguishable at this early age. The CF diagnosis explained only 1.1% of the variation between the cohort microbiomes. However, several key genera were significantly differentially abundant between the groups. While the non-CF lung microbiome ersity increased with age, ersity reduced in CF with age. Pseudomonas and Staphylococcus were more abundant with age, while genera such as Streptococcus, Porphyromonas and Veillonella were less abundant with age. There was a negative correlation between alpha ersity and interleukin-8 and neutrophil elastase in the CF population. Neither current flucloxacillin or azithromycin prophylaxis, nor previous oral or IV antibiotic exposure, was correlated with microbiome ersity. Consecutive annual BAL s les over 5 years from a subgroup of children demonstrated erse patterns of development in the first years of life.
Publisher: BMJ
Date: 07-04-2020
DOI: 10.1136/THORAXJNL-2019-214027
Abstract: Mutations in the cystic fibrosis transmembrane regulator ( CFTR ) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways. To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF. EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs. A significantly higher level of EVs were released from CFBE41o- (p .0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p .001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p .001–0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls. This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.
Publisher: American Thoracic Society
Date: 09-2021
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.JCF.2017.10.016
Abstract: Bronchoalveolar lavage (BAL) is a potentially useful outcome measure for clinical trials in children with CF but its use is limited by variations in approach internationally. We sought to determine if pooling adversely affected the diagnostic properties of BAL. Children undergoing bronchoscopy for clinical reasons were included. A multi-step study protocol ensured BAL was collected and analysed both separately and as a pooled fluid. Eighty-five children (53 CF, 32 control) were recruited. There was a high level of concordance between pooled and non-pooled s les in terms of organism identification (76%). There was good agreement (Bland Altman) between the two methods in terms of detection of inflammation independent of centre, microbiological concordance or disease status. Bi-directional variability in IL-8 levels between pooled and non-pooled s les was seen. Free neutrophil elastase (NE) was detected in 4 cases in pooled lavage when absent in non-pooled lavage. Levels of interleukin-8 (IL-8) were similar between the two groups with pooled s les showing a greater spread of values. Pooling of BAL in children does not negatively impact on either the detection of pulmonary infection or inflammation or the observed relationship between infection and inflammation. Intra-patient variability in BAL IL-8 levels suggests regional differences in inflammation.
Publisher: Massachusetts Medical Society
Date: 16-07-2015
No related grants have been discovered for Paul McNally.