Naomi Potter
Doctor of Philosophy in Experimental Medicine (PhD)
Research Topic
Patient-derived model systems to assess the in vitro efficacy of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapies in cystic fibrosis
Bradley Quon
Associate Professor
Research Classification
Cystic Fibrosis
Epidemiology
Respiratory System
Proteomics
Immune Mediators: Cytokines and Chemokines
Research Interests
biomarker discovery and development
clinical epidemiology
health care economics
medication adherence
Relevant Thesis-Based Degree Programs
Affiliations to Research Centres, Institutes & Clusters
Research Methodology
single-cell western blot
mesoscale discovery immunoassays
cystic fibrosis blood and sputum biorepository
Exercise Physiology
lung imaging (MRI)
Recruitment
Master's students
Doctoral students
Postdoctoral Fellows
Any time / year round
Cystic Fibrosis blood biomarker research and development - proteomics and transcriptomics Health outcomes research using the Canadian Cystic Fibrosis Registry - clinical epidemiology
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Graduate Student Supervision
Doctoral Student Supervision
Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
The burden of cystic fibrosis in British Columbia (2023)
The landscape of Cystic fibrosis (CF) is changing. Historically, it was a disease mainly affecting children, but now there are more adults living with CF with many additional health problems and evolving needs. The thesis aims to assess the impact and burden of CF in British Columbia (BC).The Canadian CF Registry (CCFR) and multiple administrative data sources were utilized to evaluate an annual, open provincial CF cohort from 2000 to 2017. Epidemiological and clinical trends were summarized. The Global Burden of Disease methodology was used to quantify the overall burden of CF attributed to lung impairment, complications/comorbidities, and mortality. Health care resource use and costs were summarized. A fixed CF cohort was followed from 2009 to 2017 to evaluate characteristics associated with frequent high-cost CF users.The incidence rate of CF has slightly increased (average annual percentage change [AAPC]: +2.9%, 95% CI: -0.1 to +5.9) while the birth incidence rate declined (AAPC: -2.4%, 95% CI: -4.2% to -0.5%) since 2000. The prevalence rate has grown over time (AAPC: +2.1%, 95% CI: +1.7% to +2.5%). Survival outcomes have improved and more growth in the prevalence of CF (up to 50%), specifically in the adult CF population is expected. The clinical status has also improved with less occurrence of severe or advanced lung disease and an overall improvement in lung function over time. The total burden of CF has declined over time (Disability Adjusted Life Year [DALY] rate: -12.3%, 95% CI: -2.7% to -20.9%) primarily due to a reduction in premature mortality. Despite this progress, morbidity due to other CF-related complications and comorbidities has been slowly rising (AAPC: +1.0%, 95% CI: -1.4% to +3.5%) and disproportionately affects adults. Health care resource use and inflation-adjusted costs have also increased during this time, driven by the rising costs of adult care and medications. Frequent high-cost users represent 17% of the cohort but accounted for 32% to 45% of the overall total health care costs. Moderate-to-severe lung impairment, transplantation, liver cirrhosis with portal hypertension, and female sex were the main factors associated with frequent high-costing CF individuals.
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Predictive biomarkers of pulmonary exacerbations in cystic fibrosis (2022)
Pulmonary exacerbations (PEx) are common in cystic fibrosis (CF) and are significant risk factors for lung disease progression. PEx are often diagnosed when a patient presents to clinic with increased respiratory symptoms and decreased lung function. However, changes can sometimes be subtle or the patient can be a poor perceiver of their symptoms, potentially leading to missed or delayed diagnosis of PEx. Blood-based biomarkers reflective of the host immune response and inflammatory activity have the potential to predict PEx in CF. However, due to the poorly defined pathophysiology of PEx, individual candidate biomarkers are unlikely to capture the full spectrum of immune and inflammatory responses in CF. The central hypothesis of this thesis is that by profiling molecules (protein, transcripts, and modifier genes) in blood with unbiased high-throughput ‘omics’ technologies, we can identify blood-based biomarkers to predict PEx risk and PEx-related treatment outcomes in CF. First, I assessed changes in blood proteins in response to IV antibiotic treatment for PEx. Early changes in IGFR2 were associated with symptom improvement by the end of treatment, suggesting its potential to act as a predictive marker of symptomatic treatment response in CF PEx. I further identified blood biomarker candidates (genes and proteins) from CF individuals with paired stable and PEx samples. Based on these candidates, a 16-gene panel and a 9-protein panel were developed predictive of imminent PEx risk (AUCs of 0.88 and 0.83, respectively). I then evaluated blood proteins to predict azithromycin treatment response in CF individuals. Early changes in serum calprotectin were predictive of PEx risk by day 168, indicating that serum calprotectin represents a promising predictive biomarker to identify individuals who derive benefit from azithromycin treatment. Finally, I investigated genetic modifiers of PEx risk in pre-school children with CF and identified the SLC9A3 variant as significantly associated with the risk of PEx. In summary, I showed that blood-based biomarkers could reliably predict response to treatment and PEx risk in CF individuals, which allows for more personalized monitoring and earlier diagnosis and treatment of CF PEx.
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Master's Student Supervision
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Evaluation of host genetic susceptibility to predict nontuberculous mycobacteria pulmonary disease in patients with cystic fibrosis (2022)
Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Infection with NTM can be associated with faster decline in lung function for people living with CF. Diagnosis and treatment of pulmonary NTM disease (NTM-PD) remains challenging as there are no accurate estimates of the burden, there is no way to predict progression to disease and the therapeutic guidelines lack high quality evidence for recommendations. In this thesis, we began by estimating the overall burden of NTM infection and disease in the CF population through a systematic review of prevalence and incidence. We included all available data from registries and observational studies and found a pooled estimate of NTM infection point prevalence of 8%. We identified geographical region and sample size as determinants of heterogeneity in our analysis. Also, we found that estimates were more accurate for NTM infection caused by the Mycobacterium avium and Mycobacterium abscessus complexes individually. However, we could not identify other sources of heterogeneity due to the lack of primary reporting of microbial identification methods and screening approaches. Next, we explored the impact of host gene expression on the progression to pulmonary NTM disease (NTM-PD) in a cohort of patients with NTM infection (n = 42). We conducted an RNAseq experiment using whole blood close to the time of first NTM growth and conducted differential gene expression using DESeq2. Our results show that patients who progressed to NTM-PD had higher expression of genes that are associated with innate immunity and inflammation. These findings contrast with results of non-cystic fibrosis studies in humans that show decreased lymphocyte and immune responses in NTM-PD. However, the pro-inflammatory state of the CF lung and the higher bacterial burden observed in CF, could explain this contradictory result. Overall, in this biomarker discovery study, we identified several functional pathways that may play a role in progression to NTM-PD n the CF population, providing a basis for future biomarker discovery studies.
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