Julie Renwick - Academia.edu (original) (raw)

Papers by Julie Renwick

Reference Module in Life Sciences, 2019

Odds ratios are presented to determine the odds of a particular colonisation status being linked ... more Odds ratios are presented to determine the odds of a particular colonisation status being linked to development of CFRD and/ or ABPA. (PNG 75 kb)

Cystic Fibrosis (CF) lung damage begins early in life. Lung function decline is associated with p... more Cystic Fibrosis (CF) lung damage begins early in life. Lung function decline is associated with pulmonary infections, neutrophil infiltration and inflammation. In CF, neutrophils have an altered phenotype. In this pilot study, we aimed to determine if signals of dysfunctional neutrophil responses were evident early in life and whether these signals may be associated with lung damage in later childhood. We examined the pulmonary protein profiles of 14 clinical stable infants and pre-school children with CF employing the aptamer-based affinity platform, SOMAscan®. High resolution computed tomography (HRCT) was performed on all children after age 6 years and Brody score calculated. A Spearman's rank order correlation analysis and Benjamini-Hochberg adjustment was used to correlate protein concentrations in early life to Brody scores in later childhood. Early life concentrations of azurocidin and myeloperoxidase, were positively correlated with Brody score after age 6 (p = 0.0041 an...

Antibiotics, 2021

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disea... more Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping P. aeruginosa pathogenicity and resistance. P. aeruginosa can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic P. aeruginosa infection have poorer lung function, higher morbidity, and a reduced life expectancy. P. aeruginosa adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or ‘microbiome’ and that these microorganisms are known to intera...

Journal of Cystic Fibrosis, 2018

Journal of Cystic Fibrosis, 2017

B35. PATHOGENESIS AND CLINICAL ISSUES IN CYSTIC FIBROSIS, 2012

Microorganisms, 2021

The cystic fibrosis (CF) lung harbours a diverse microbiome and reduced diversity in the CF lung ... more The cystic fibrosis (CF) lung harbours a diverse microbiome and reduced diversity 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) samples 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 diversity between t...

Infections caused by opportunistic fungal pathogens are increasingly resistant to first-line azol... more Infections caused by opportunistic fungal pathogens are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about the extent to which susceptible patients acquire infection from drug resistant genotypes in the environment. Here, we present a population genomic analysis of the mouldAspergillus fumigatusfrom across the United Kingdom and Republic of Ireland. First, we show occurrences where azole resistant isolates of near identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Second, we find that the fungus is structured into two clades (‘A’ and ‘B’) with little interclade recombination and the majority of environmental azole resistance genetically clustered inside Clade A. Genome-scans show the impact of selective sweeps across multiple regions of the genome. These signatures of...

Journal of Microbiological Methods

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Frontiers in microbiology, 2018

Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe-microb... more Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe-microbe interactions may play an important role in disease pathology. and are the most prevalent bacterial and fungal pathogens isolated from the CF airway, respectively. We have previously shown that patients co-colonized with these pathogens had comparable outcomes to those chronically colonized with . Our objective was to examine the interactions between and , specifically the effects of co-colonization on biofilm formation, virulence and host pro-inflammatory responses. Our findings suggest that co-infections of and in the acute infection model showed that pre-exposure of larvae to sub-lethal inocula of increased the mortality caused by subsequent infection. Co-infection of human bronchial epithelial cells (CFBE41o) with both pathogens did not enhance IL-6 and IL-8 production beyond the levels observed following single infections. In addition, both pathogens stimulated cytokine secretion v...

BMC Pulmonary Medicine

Background: Pulmonary infection is the main cause of death in cystic fibrosis (CF). Aspergillus f... more Background: Pulmonary infection is the main cause of death in cystic fibrosis (CF). Aspergillus fumigatus (AF) and Pseudomonas aeruginosa (PA) are the most prevalent fungal and bacterial pathogens isolated from the CF airway, respectively. Our aim was to determine the effect of different colonisation profiles of AF and PA on the clinical status of patients with CF. Methods: A retrospective analysis of data from the Cystic Fibrosis Registry of Ireland from 2013 was performed to determine the effect of intermittent and persistent colonisation with AF or PA or co-colonisation with both microorganisms on clinical outcome measures in patients with CF. Key outcomes measured included forced expiratory volume in one second (FEV 1), number of hospitalisations, respiratory exacerbations and antimicrobials prescribed, and complications of CF, including CF related diabetes (CFRD) and allergic bronchopulmonary aspergillosis (ABPA). Results: The prevalence of AF and PA colonisation were 11% (5% persistent, 6% intermittent) and 31% (19% persistent, 12% intermittent) in the Irish CF population, respectively. Co-colonisation with both pathogens was associated with a 13.8% reduction in FEV 1 (p = 0.016), higher levels of exacerbations (p = 0.042), hospitalisations (p = 0.023) and antimicrobial usage (p = 0.014) compared to non-colonised patients and these clinical outcomes were comparable to those persistently colonised with PA. Intermittent and persistent AF colonisation were not associated with poorer clinical outcomes or ABPA. Patients with persistent PA had a higher prevalence of CFRD diagnosis (p = 0.012). Conclusions: CF patients co-colonised with AF and PA had poor clinical outcomes comparable to patients persistently colonised with PA, emphasising the clinical significance of co-colonisation with these microorganisms.

Journal of Allergy and Clinical Immunology, 2015

Colonization by Aspergillus fumigatus in patients with cystic fibrosis (CF) can cause A fumigatus... more Colonization by Aspergillus fumigatus in patients with cystic fibrosis (CF) can cause A fumigatus sensitization and/or allergic bronchopulmonary aspergillosis (ABPA), which affects pulmonary function and clinical outcomes. Recent studies show that specific allergens upregulate the surface-expressed basophil marker CD203c in sensitized subjects, a response that can be readily measured by using flow cytometry. We sought to identify A fumigatus sensitization in patients with CF by using the basophil activation test (BAT). Patients with CF attending Beaumont Hospital were screened for study inclusion. BAT was used to identify A fumigatus sensitization. Serologic (total and A fumigatus-specific IgE), pulmonary function, and body mass index measurements were performed. The BAT discriminates A fumigatus-sensitized from nonsensitized patients with CF. Persistent isolation of A fumigatus in sputum is a significant risk factor for A fumigatus sensitization. Levels of the A fumigatus-stimulated basophil activation marker CD203c inversely correlated with pulmonary function and body mass index in A fumigatus-sensitized but not nonsensitized patients with CF. Total and A fumigatus-specific IgE, but not IgG, levels are increased in A fumigatus-sensitized patients with CF and ABPA when compared with those in A fumigatus-sensitized and nonsensitized patients with CF without ABPA. Itraconazole treatment did not affect A fumigatus sensitization. Combining the BAT with routine serologic testing allows classification of patients with CF into 3 groups: nonsensitized, A fumigatus-sensitized, and ABPA. Accurate and prompt identification of A fumigatus-associated clinical status might allow early and targeted therapeutic intervention, potentially improving clinical outcomes.

Introduction:Aspergillus fumigatus is an opportunistic pathogen known to cause a spectrum of dise... more Introduction:Aspergillus fumigatus is an opportunistic pathogen known to cause a spectrum of diseases including Allergic Bronchopulmonary Aspergillosis and invasive aspergillosis. A. fumigatus is the most common agent causing fungal infections in Cystic Fibrosis (CF). Resistance to triazole antifungals in A. fumigatus isolates from CF patients has been reported [1], however to date there are no reports on antifungal drug resistance in Irish A. fumigatus isolates. In this study the epidemiology of A. fumigatus in CF patient populations from four Irish CF centres was investigated and antifungal drug susceptibility of all isolates collected was determined. Methods:A. fumigatus isolates from CF patients were collected. All isolates from the study were confirmed as A. fumigatus by PCR and sequencing of the ITS region. Isolates were genotyped using the Short Tandem Repeat assay for A. fumigatus (STRAf assay) [2]. Minimum Inhibitory Concentrations (MICs) of all A. fumigatus isolates to nin...

Medical Mycology Case Reports, 2015