Publications by authors named "Julie Avolio"
Article Synopsis
- Primary human nasal epithelial cell (HNEC) cultures are valuable for research on respiratory health, diseases, and treatments.
- The chapter outlines step-by-step protocols for collecting samples and culturing HNECs.
- Culturing is done under air-liquid interface (ALI) conditions to create functional airway cultures with characteristics like beating motile cilia.
Article Synopsis
- Ivacaftor, a drug for cystic fibrosis (CF), significantly improves lung function and weight gain, but its long-term effects on weight, resting energy expenditure (REE), and body composition need more investigation.* -
- A study involving 18 participants showed that after 24 months of ivacaftor treatment, there was a noticeable increase in BMI and fat mass, but no change in fat-free mass or REE.* -
- The findings suggest that weight gain in patients on ivacaftor is mostly due to increased fat mass, emphasizing the importance of diet and exercise counseling for those undergoing CFTR-modulating treatment.*
Article Synopsis
- Highly effective drugs that target the defective CFTR protein have transformed cystic fibrosis treatment, allowing for more personalized therapies.
- This study is the first to demonstrate consistent CFTR responses to modulator treatments across patients with different CFTR gene variants using various human cell culture methods (2D HIO, 3D HIO, and human nasal epithelial cells).
- The results revealed that 2D HIO, which offers better functional range and access to the cell membrane, is a valuable tool for preclinical drug testing in cystic fibrosis.
Article Synopsis
- Phasing of heterozygous alleles is essential for interpreting the effects of genetic variations related to cystic fibrosis (CF), and researchers sequenced 477 CF individuals to construct haplotypes using linked-read sequencing.
- The resulting haplotypes are visualized in an interactive web app called CFTbaRcodes, allowing for exploration of complex CF gene variations.
- Fine-mapping revealed that a specific 20-kb deletion and a missense variant are linked to an increased risk of CF-related meconium ileus and pancreatic issues, providing insights into the genetic mechanisms involved in both CF and non-CF pancreatitis.
Article Synopsis
- - Over 400 variants in the CFTR gene cause cystic fibrosis (CF), and while CFTR modulators can help improve lung function, they don't work for everyone and don't address all variants.
- - The study examines the SLC26A9 gene marker (rs7512462) and its relationship to lung function in CF patients before and after treatment, finding that certain genetic variants linked to SLC26A9 lead to better lung function and response to CFTR modulators.
- - The research suggests that targeting SLC26A9 could offer new therapeutic options not just for CF but also for individuals with other lung conditions like chronic obstructive pulmonary disease (COPD).
Article Synopsis
- The study investigates the comparability of CF lung disease modifier gene expressions between cultured human nasal epithelia (HNE) and the established model of cultured human bronchial epithelia (HBE), which is important for testing cystic fibrosis therapies.* -
- RNA-sequencing was performed on both types of cultured and fresh cells from individuals with cystic fibrosis, revealing that over 90% of expressed genes have similar expression levels in HNE and HBE, indicating the culturing process had minimal impact on these genes.* -
- The findings suggest that cultured HNE can serve as an effective surrogate for HBE in research, as the co-expression relationships of CFTR and other modifier genes are consistent between the two models.*
Article Synopsis
- - Aquagenic wrinkling of palms (AWP) is a common symptom in cystic fibrosis (CF) patients, especially linked to CFTR mutations.
- - A study monitored 16 CF patients before and after they started ivacaftor therapy, finding that most had mild to moderate AWP at the beginning.
- - After six months of treatment, AWP showed improvement, indicating a potential relationship between AWP severity and CFTR function in CF patients.
Article Synopsis
- RSV infections in early life can lead to more serious lung function decline in children with cystic fibrosis (CF).
- In CF cells, RSV replicates more efficiently and triggers a stronger inflammatory response compared to healthy cells.
- The increased cytokine production in CF cells correlates negatively with lung function, indicating that a dysfunctional response to RSV may worsen airway inflammation and lung health.
Article Synopsis
- Cystic fibrosis (CF) affects various organs, including the pancreas, which can lead to cystic fibrosis-related diabetes (CFRD), impacting survival rates if untreated.
- Researchers built a CFRD prediction model using genetic data from a Canadian study and validated it with data from a French study, highlighting key predictors like sex and certain genetic variants.
- The final model successfully identifies individuals at high risk for CFRD and has led to the creation of a web-based tool that helps doctors monitor and treat patients based on their specific risk levels.
Article Synopsis
- Researchers are exploring gene replacement therapy using helper-dependent adenoviral vectors (HD-CFTR) to restore CFTR function in individuals with class I mutations where no functional protein is made.
- They found that HD-CFTR can significantly restore CFTR function in cultured nasal cells from CF patients, and the efficacy of this approach can help in testing other CFTR-modulating drugs.
Article Synopsis
- *Research involving over 6,500 participants from the International CF Gene Modifier Consortium pinpointed new genetic loci related to meconium ileus on chromosomes 1, 7, and 13, highlighting their impact on gene expression in the pancreas.
- *The study employed a new colocalization method to analyze gene expression across different tissues, revealing connections between CF-related genetic loci and airway regulation specific to lung disease.
Article Synopsis
- * A study observed that treatment with ivacaftor, a CFTR potentiator, led to a significant decrease in the inflammatory marker calprotectin and an increase in beneficial gut bacteria (Akkermansia) among 16 CF patients over approximately 6 months.
- * The findings suggest that ivacaftor may improve gut health in CF patients by promoting a healthier microbiome and reducing intestinal inflammation in those with specific CFTR mutations.
Background: Therapies targeting certain CFTR mutants have been approved, yet variations in clinical response highlight the need for in-vitro and genetic tools that predict patient-specific clinical outcomes. Toward this goal, the CF Canada-Sick Kids Program in Individual CF Therapy (CFIT) is generating a "first of its kind", comprehensive resource containing patient-specific cell cultures and data from 100 CF individuals that will enable modeling of therapeutic responses.
Methods: The CFIT program is generating: 1) nasal cells from drug naïve patients suitable for culture and the study of drug responses in vitro, 2) matched gene expression data obtained by sequencing the RNA from the primary nasal tissue, 3) whole genome sequencing of blood derived DNA from each of the 100 participants, 4) induced pluripotent stem cells (iPSCs) generated from each participant's blood sample, 5) CRISPR-edited isogenic control iPSC lines and 6) prospective clinical data from patients treated with CF modulators.
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations.
View Article and Find Full Text PDFTesting gene therapy vectors in human primary nasal epithelial cultures.
Mol Ther Methods Clin Dev
January 2016
Article Synopsis
- - Cystic fibrosis (CF) is caused by mutations in the CFTR gene, leading to severe lung disease and other health issues due to faulty chloride/bicarbonate channels in epithelial cells.
- - Researchers are exploring gene therapy to potentially cure CF by correcting or replacing the defective CFTR gene, necessitating testing in preclinical models.
- - Using primary human nasal epithelial cultures (HNECs) from CF patients, a study found that a helper-dependent adenoviral vector effectively delivered and expressed the CFTR gene, indicating HNECs are suitable for testing gene therapy methods for CF.
Article Synopsis
- * After 4 weeks of ivacaftor treatment, a group of 15 patients showed a significant increase in exhaled nitric oxide levels and improved pulmonary function, particularly in younger patients.
- * In contrast, treatments like inhaled dornase alfa or hypertonic saline did not influence nitric oxide levels, suggesting that ivacaftor may enhance airway nitric oxide production, contributing to its positive effects on cystic fibrosis.
Article Synopsis
- - The study aimed to analyze infants with inconclusive cystic fibrosis diagnoses, identified through newborn screening, to understand disease manifestations and outcomes.
- - It involved 82 infants with CFSPID and 80 with confirmed cystic fibrosis, comparing various health data including sweat tests and genetic information, revealing that some CFSPID infants eventually received a cystic fibrosis diagnosis.
- - Results showed that CFSPID infants had lower immunoreactive trypsinogen levels and that a significant number were likely to be diagnosed with cystic fibrosis within the first three years, indicating the need for close monitoring and repeat testing.
Article Synopsis
- Averaging nasal potential difference (NPD) results from both nostrils helps minimize differences among individuals but may underestimate individual CFTR function in cystic fibrosis (CF) patients.
- The study compared the best NPD response from each nostril to the average result among 113 subjects, including CF patients, those who may have CF, and healthy controls, revealing significant variability in individuals.
- Findings indicate that averaging NPD results can lead to a lower assessment of chloride response and misinterpretation of CF diagnosis in nearly 27% of cases, suggesting a need to rethink current averaging practices.
β-adrenergic sweat secretion as a diagnostic test for cystic fibrosis.
Am J Respir Crit Care Med
October 2012
Article Synopsis
- β-Adrenergic sweat secretion testing is a quick way to evaluate the function of the CFTR protein involved in cystic fibrosis (CF).
- The study found that β-adrenergically stimulated sweat rates were significantly lower in CF patients compared to healthy subjects, with high diagnostic accuracy (0.99) and reliability (0.90).
- Results showed that while the test effectively distinguished between healthy individuals, heterozygotes, and CF patients, women had lower sweat secretion rates than men.
Article Synopsis
- The study aimed to explore how living with inflammatory bowel disease (IBD) affects the quality of life for children and adolescents aged 7 to 19.
- Eighty participants shared their experiences, revealing that IBD significantly impacts their daily lives, leading to feelings of vulnerability and being "different" from peers.
- Despite these challenges, many found coping strategies, with family and friend support playing a crucial role in maintaining a positive outlook and quality of life.
The IMPACT questionnaire: a valid measure of health-related quality of life in pediatric inflammatory bowel disease.
J Pediatr Gastroenterol Nutr
October 2002
Article Synopsis
- The IMPACT questionnaire is a health-related quality-of-life tool designed for children and teens with inflammatory bowel disease, developed through patient interviews to ensure relevance.
- A study on 147 patients showed that the questionnaire had high readability, with only a tiny percentage of unanswered questions, indicating it was easy for participants to understand and complete.
- Results demonstrated that the questionnaire is both reliable (with a high Cronbach's alpha of 0.96) and valid in distinguishing quality of life based on disease activity, with patients in remission reporting significantly better quality of life scores compared to those with active disease.