Journal of Cystic Fibrosis最新文献

{"title":"Poster: 3Identification, characterization, and clinical use of bacteriophages against Achromobacter infection in cystic fibrosis","authors":"J. Massey, N. Wallace, K. Hughes Kramer, G. Haidar, D. Van Tyne","doi":"10.1016/j.jcf.2026.07.035","DOIUrl":"10.1016/j.jcf.2026.07.035","url":null,"abstract":"<div><h3>Background</h3><div><em>Achromobacter</em> is a genus of gram-negative bacteria which are clinically relevant as a pulmonary pathogen in persons with cystic fibrosis (pwCF). <em>Achromobacter</em> is prevalent, correlated with negative clinical outcomes, and difficult to manage in pwCF. Due to its intrinsically multidrug-resistant nature and ability to rapidly acquire additional resistance, there are very few treatment options available for pwCF suffering from <em>Achromobacter</em> infection. Thus, <em>Achromobacter </em>is an ideal candidate for the development of new treatment options.</div><div>Bacteriophages (phages) are naturally occurring, ubiquitous viruses that specifically infect and kill bacteria. With the growing antibiotic resistance crisis, there has been newfound interest in utilizing phages to treat bacterial infections. However, there is currently little data surrounding phage therapy for <em>Achromobacter</em> infections. Therefore, we set out to isolate and characterize phages with activity against <em>Achromobacter</em> to evaluate their potential role as a therapeutic agent in pwCF.</div></div><div><em>Achromobacter</em> is a genus of gram-negative bacteria which are clinically relevant as a pulmonary pathogen in persons with cystic fibrosis (pwCF). <em>Achromobacter</em> is prevalent, correlated with negative clinical outcomes, and difficult to manage in pwCF. Due to its intrinsically multidrug-resistant nature and ability to rapidly acquire additional resistance, there are very few treatment options available for pwCF suffering from <em>Achromobacter</em> infection. Thus, <em>Achromobacter </em>is an ideal candidate for the development of new treatment options.</div><div>Bacteriophages (phages) are naturally occurring, ubiquitous viruses that specifically infect and kill bacteria. With the growing antibiotic resistance crisis, there has been newfound interest in utilizing phages to treat bacterial infections. However, there is currently little data surrounding phage therapy for <em>Achromobacter</em> infections. Therefore, we set out to isolate and characterize phages with activity against <em>Achromobacter</em> to evaluate their potential role as a therapeutic agent in pwCF.</div><div><h3>Methods</h3><div>Wastewater samples from environmental sources were filtered and then plated on enriched media with clinical <em>Achromobacter</em> isolates. Individual plaques were passaged, purified, then sequenced to identify and characterize each phage. Concurrently, we gathered clinical isolates of <em>Achromobacter</em> from pwCF at our hospital system, sequenced their genomes, and established a host range of the isolated phages against the clinical <em>Achromobacter</em> isolates. Phage-resistant <em>Achromobacter</em> mutants were generated by growing bacteria in phage-containing medium. Whole-genome sequencing was conducted on phage-resistant mutants to identify mutations associated with phage resistance.</div></div><div","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 2"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 34Bile acids as potential immunomodulatory signals","authors":"S. Durfey, J. Maaskant, J. Moran, I. Miralda, M. Shrestha, H. Ozuna, X. Ji, P. Dawson, J. Chandler, R. Tirouvanziam, B. Kopp","doi":"10.1016/j.jcf.2026.07.066","DOIUrl":"10.1016/j.jcf.2026.07.066","url":null,"abstract":"<div><h3>Background</h3><div>Plasma and sputum from people with CF (pwCF) suppress macrophage functions and it is unknown what induces this suppression. This suppression could be mediated by bile acids (BA), as BA are dysregulated in CF in metabolomic studies of clinical samples and mechanistic studies showing direct CFTR effects on BA regulation. Importantly, some BA species and their derivatives can regulate gut and liver immune cell function by reducing pro-inflammatory cytokine production and phagocytosis. However, it remains unclear whether systemic and airway macrophages respond to BAs, and whether BA dysregulation persists with CFTR modulator therapy.</div></div><div>Plasma and sputum from people with CF (pwCF) suppress macrophage functions and it is unknown what induces this suppression. This suppression could be mediated by bile acids (BA), as BA are dysregulated in CF in metabolomic studies of clinical samples and mechanistic studies showing direct CFTR effects on BA regulation. Importantly, some BA species and their derivatives can regulate gut and liver immune cell function by reducing pro-inflammatory cytokine production and phagocytosis. However, it remains unclear whether systemic and airway macrophages respond to BAs, and whether BA dysregulation persists with CFTR modulator therapy.</div><div><h3>Methods</h3><div>Plasma samples from pwCF pre- and post-elexacaftor/tezacaftor/ivacaftor (ETI) were assessed for BAs and related metabolites. Single-cell RNA sequencing data from the Chan-Zuckerberg CellxGene database were mined to determine if BA receptors are expressed in lung-resident macrophages. Human monocyte-derived macrophages (MDMs) from healthy and CF donors were differentiated with 20% human serum, exposed to BA for 24hrs, and BA effects on phagocytosis and intracellular killing were assessed.</div></div><div>Plasma samples from pwCF pre- and post-elexacaftor/tezacaftor/ivacaftor (ETI) were assessed for BAs and related metabolites. Single-cell RNA sequencing data from the Chan-Zuckerberg CellxGene database were mined to determine if BA receptors are expressed in lung-resident macrophages. Human monocyte-derived macrophages (MDMs) from healthy and CF donors were differentiated with 20% human serum, exposed to BA for 24hrs, and BA effects on phagocytosis and intracellular killing were assessed.</div><div><h3>Results</h3><div>Untargeted metabolomics revealed two BAs in the top 10 most elevated metabolites in CF plasma (vs healthy), and this difference persisted following ETI. We further investigated BA levels using a quantitative panel of 64 BA species. Hyocholic, cholic, and chenodeoxycholic acids were all significantly elevated in plasma from pwCF pre-ETI. This difference persisted with ETI, with a further increase in hyocholic acid. As BA alterations can influence other signaling molecules, such as the production of fatty acids like oxylipins, we also quantified both esterified and non-esterified versions of 50 different oxyli","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 17"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 36Longitudinal changes in the airway microbiome following elexacaftor/tezacaftor/ivacaftor treatment in cystic fibrosis","authors":"A. Hughes, T. DeFor, A. Moen, J. Dunitz, J. Billings, P. Ferrieri, K. Mahan","doi":"10.1016/j.jcf.2026.07.068","DOIUrl":"10.1016/j.jcf.2026.07.068","url":null,"abstract":"<div><h3>Background</h3><div>In cystic fibrosis (CF), airway microbial composition is closely associated with clinical outcomes, and pathogen predominance has been linked to disease progression. The use of elexacaftor/tezacaftor/ivacaftor (ETI) may modify the airway environment and thereby influence the respiratory microbiome, although its impact remains incompletely understood. We therefore aimed to characterize longitudinal changes in the respiratory microbiome following ETI initiation in a large real-world cohort.</div></div><div>In cystic fibrosis (CF), airway microbial composition is closely associated with clinical outcomes, and pathogen predominance has been linked to disease progression. The use of elexacaftor/tezacaftor/ivacaftor (ETI) may modify the airway environment and thereby influence the respiratory microbiome, although its impact remains incompletely understood. We therefore aimed to characterize longitudinal changes in the respiratory microbiome following ETI initiation in a large real-world cohort.</div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of 461 people with CF (pwCF) who had microbiologic culture data both before and after ETI initiation. Associations between ETI exposure and organism detection were evaluated using generalized linear mixed-effects models with a binomial distribution, logit link, and random intercept for patient to account for repeated measures. ETI exposure was modeled as a time-varying variable. Outcomes included detection of <em>Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus</em> species, <em>Burkholderia</em> species, <em>Haemophilus influenzae</em>, and <em>Stenotrophomonas maltophilia</em>. Odds ratios (ORs) compared ETI with non-ETI exposure, with OR < 1 indicating lower odds and OR >1 indicating higher odds of organism detection during ETI treatment.</div></div><div>We conducted a retrospective cohort study of 461 people with CF (pwCF) who had microbiologic culture data both before and after ETI initiation. Associations between ETI exposure and organism detection were evaluated using generalized linear mixed-effects models with a binomial distribution, logit link, and random intercept for patient to account for repeated measures. ETI exposure was modeled as a time-varying variable. Outcomes included detection of <em>Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus</em> species, <em>Burkholderia</em> species, <em>Haemophilus influenzae</em>, and <em>Stenotrophomonas maltophilia</em>. Odds ratios (ORs) compared ETI with non-ETI exposure, with OR < 1 indicating lower odds and OR >1 indicating higher odds of organism detection during ETI treatment.</div><div><h3>Results</h3><div>Among the 461 pwCF, the median age was 20.8 years (IQR [10.6–31.4]); 48.4% were female, 96.2% were White, and 54.2% had homozygous F508del genotype. Relative to non-ETI therapy, ETI was associated with lower odds of detection of <em>Pseudomonas aeruginosa</em> (OR 0.25","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 18"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 84Large-scale aggregation of Pseudomonas aeruginosa in cystic fibrosis sputum despite reduced airway burden after CFTR modulator therapy","authors":"A. Morris, S. Eisha, Y. Yau, S. Goel, M. Shaw, W. DePas, I. Martin, A. Selvarajah, M. Gaudet, E. Tullis, D. Nguyen, V. Waters","doi":"10.1016/j.jcf.2026.07.116","DOIUrl":"10.1016/j.jcf.2026.07.116","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies have transformed care for people with cystic fibrosis (pwCF), improving lung function and reducing airway bacterial burden. However, chronic <em>Pseudomonas aeruginosa</em> (Pa) infection often persists despite treatment, suggesting that factors beyond bacterial load contribute to infection chronicity. One such factor is bacterial aggregation, which is associated with increased antibiotic tolerance and the evasion of host immune defenses. Yet, clinical evaluations of CFTR modulator efficacy focus largely on bacterial quantity, often overlooking structural changes within the airway microbial community. We therefore evaluated the impact of CFTR modulation on Pa burden and aggregation directly in expectorated CF sputum.</div></div><div>Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies have transformed care for people with cystic fibrosis (pwCF), improving lung function and reducing airway bacterial burden. However, chronic <em>Pseudomonas aeruginosa</em> (Pa) infection often persists despite treatment, suggesting that factors beyond bacterial load contribute to infection chronicity. One such factor is bacterial aggregation, which is associated with increased antibiotic tolerance and the evasion of host immune defenses. Yet, clinical evaluations of CFTR modulator efficacy focus largely on bacterial quantity, often overlooking structural changes within the airway microbial community. We therefore evaluated the impact of CFTR modulation on Pa burden and aggregation directly in expectorated CF sputum.</div><div><h3>Methods</h3><div>In this three-year prospective longitudinal study, pwCF with chronic Pa infection were enrolled at three Canadian CF centers (2022-2025). Sputum samples were embedded in hydrogels using the Microbial Identification after Passive CLARITY Technique (MiPACT), followed by visualization via fluorescence <em>in situ</em> hybridization (FISH) and three-dimensional confocal laser scanning microscopy. Image analyses quantified Pa biovolume, aggregate number, maximum aggregate size, and the proportion of large aggregates (>20 µm) relative to planktonic or small aggregates (0.5-20 µm). Mixed-effects models were applied to assess longitudinal and cross-sectional differences between participants receiving CFTR modulators and those not on therapy.</div></div><div>In this three-year prospective longitudinal study, pwCF with chronic Pa infection were enrolled at three Canadian CF centers (2022-2025). Sputum samples were embedded in hydrogels using the Microbial Identification after Passive CLARITY Technique (MiPACT), followed by visualization via fluorescence <em>in situ</em> hybridization (FISH) and three-dimensional confocal laser scanning microscopy. Image analyses quantified Pa biovolume, aggregate number, maximum aggregate size, and the proportion of large aggregates (>20 µm) relative to plankton","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 42-43"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 64A critical review and meta-analysis of C. difficile infection in people with cystic fibrosis","authors":"E. Gill, C. Dill, C. Hodges","doi":"10.1016/j.jcf.2026.07.096","DOIUrl":"10.1016/j.jcf.2026.07.096","url":null,"abstract":"<div><h3>Background</h3><div><em>Clostridioides difficile</em> is a Gram-positive, spore forming, toxin-producing, anaerobic bacterium that is the most common cause of antibiotic-associated diarrhea. CF is an autosomal recessive genetic disorder that requires frequent antibiotic use. Despite being at high risk for developing <em>C. diff</em> infection (CDI), it is rarely reported in people with CF (PwCF). The purpose of this critical review of the literature and meta-analysis is two part: 1) determine the prevalence and incidence of CDI in PwCF, and 2) describe the clinical signs of CDI in PwCF and report therapies used to treat CDI in PwCF.</div></div><div><em>Clostridioides difficile</em> is a Gram-positive, spore forming, toxin-producing, anaerobic bacterium that is the most common cause of antibiotic-associated diarrhea. CF is an autosomal recessive genetic disorder that requires frequent antibiotic use. Despite being at high risk for developing <em>C. diff</em> infection (CDI), it is rarely reported in people with CF (PwCF). The purpose of this critical review of the literature and meta-analysis is two part: 1) determine the prevalence and incidence of CDI in PwCF, and 2) describe the clinical signs of CDI in PwCF and report therapies used to treat CDI in PwCF.</div><div><h3>Methods</h3><div>Medline, SCOPUS, Web of Science, and PubMed were searched for studies that were published in English. The search included any article published by or prior to April 13<sup>th</sup>, 2024 that reported on <em>C. diff</em> in PwCF. Poster abstracts, literature reviews, and editorial reviews were excluded. Inclusion criteria was if studies provided quantitative evidence of colonization rate, prevalence, or incidence rate of <em>C. diff</em>, or if studies detailed traits, characteristics, or treatment of CDI in PwCF. Two independent reviewers performed the data abstraction and quality analysis. Incidence data were pooled only when the denominators used the same units.</div></div><div>Medline, SCOPUS, Web of Science, and PubMed were searched for studies that were published in English. The search included any article published by or prior to April 13<sup>th</sup>, 2024 that reported on <em>C. diff</em> in PwCF. Poster abstracts, literature reviews, and editorial reviews were excluded. Inclusion criteria was if studies provided quantitative evidence of colonization rate, prevalence, or incidence rate of <em>C. diff</em>, or if studies detailed traits, characteristics, or treatment of CDI in PwCF. Two independent reviewers performed the data abstraction and quality analysis. Incidence data were pooled only when the denominators used the same units.</div><div><h3>Results</h3><div>Two authors reviewed 497 abstracts and 115 full-text articles. Thirty-two articles met the selection criteria. Eight articles were retrospective reviews, 11 were prospective studies, and 13 were case study reports. Total, there were 42,533 PwCF and across 32 studies, with 1007 PwCF posi","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 31-32"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 24Mycobacterium abscessus-chelonae prophages have the potential to inhibit phage superinfection threatening phage therapy treatments","authors":"I. Dauphinais, W. Shymko, S. McCallister, J. Kelley, S. Molloy","doi":"10.1016/j.jcf.2026.07.056","DOIUrl":"10.1016/j.jcf.2026.07.056","url":null,"abstract":"<div><h3>Background</h3><div>Non-tuberculosis mycobacteria, such as those in the M. abscessus-chelonae (Mab-chel) complex, cause pulmonary and soft tissue infections posing a major global health threat. Mab-chel infections are common in patients that are elderly, immunocompromised or have chronic pulmonary disease such as cystic fibrosis (CF). Most clinical strains are multi- or completely drug resistant making phage therapy an important alternative treatment strategy. Clinical Mab-chel strains typically carry one or more prophages, integrated bacteriophage genomes, that likely increase the bacterium's resistance to lytic infection by superinfecting phage [1]. Secreted toxin systems encoded by the majority of Mab-chel prophages, potentially interfere with treatment by increasing bacterial virulence, drug resistance and resistance to phage infection. To better understand the effect of prophage-encoded toxins on the lytic dynamics of superinfecting phages, a fluorophage will be engineered that allows the monitoring of early and late lytic gene expression in single cells over time. This project investigates how the presence of a Mab-chel prophage affects the lytic dynamics of superinfecting phage to gain deeper insight into phage lytic dynamics necessary to improve future phage therapy treatments.</div></div><div>Non-tuberculosis mycobacteria, such as those in the M. abscessus-chelonae (Mab-chel) complex, cause pulmonary and soft tissue infections posing a major global health threat. Mab-chel infections are common in patients that are elderly, immunocompromised or have chronic pulmonary disease such as cystic fibrosis (CF). Most clinical strains are multi- or completely drug resistant making phage therapy an important alternative treatment strategy. Clinical Mab-chel strains typically carry one or more prophages, integrated bacteriophage genomes, that likely increase the bacterium's resistance to lytic infection by superinfecting phage [1]. Secreted toxin systems encoded by the majority of Mab-chel prophages, potentially interfere with treatment by increasing bacterial virulence, drug resistance and resistance to phage infection. To better understand the effect of prophage-encoded toxins on the lytic dynamics of superinfecting phages, a fluorophage will be engineered that allows the monitoring of early and late lytic gene expression in single cells over time. This project investigates how the presence of a Mab-chel prophage affects the lytic dynamics of superinfecting phage to gain deeper insight into phage lytic dynamics necessary to improve future phage therapy treatments.</div><div><h3>Methods</h3><div>To investigate the effect of Mab-chel prophage, McProf, on superinfection by secondary phage, BPs, CRISPY-BRED will be used to recombineer the genome of BPs to fluorescently report both early and late lytic phage infection. A GFP fluorophage strain of BPs that reports late lytic gene expression will be modified in a recombineering strain of Mycobac","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 12"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 77Metabolism in flux: How CFTR loss disrupts mast cell mitochondrial function","authors":"I. Miralda, K. Crotty, J. Moran, J. Chandler, B. Kopp","doi":"10.1016/j.jcf.2026.07.109","DOIUrl":"10.1016/j.jcf.2026.07.109","url":null,"abstract":"<div><h3>Background</h3><div>The role of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells is well understood; however, its function in immune cells, which also express CFTR, is less characterized. Mast cells (MC) are tissue-resident immune cells with critical roles in lung homeostasis and disease. Our data shows that primary human MC express CFTR, and loss of CFTR function results in significant changes to MC phenotype and function. For example, transmission electron microscopy (TEM) imaging showed that CF MC have enlarged mitochondria. We examined this phenotype and assessed functional consequences associated with activation and inflammation.</div></div><div>The role of dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells is well understood; however, its function in immune cells, which also express CFTR, is less characterized. Mast cells (MC) are tissue-resident immune cells with critical roles in lung homeostasis and disease. Our data shows that primary human MC express CFTR, and loss of CFTR function results in significant changes to MC phenotype and function. For example, transmission electron microscopy (TEM) imaging showed that CF MC have enlarged mitochondria. We examined this phenotype and assessed functional consequences associated with activation and inflammation.</div><div><h3>Methods</h3><div>Peripheral blood CD34+ cells from healthy controls (HC) and people with CF (pwCF) were differentiated into primary MC <em>in vitro</em>. Mitochondrial biomass was quantified and mitochondrial function was assessed by Seahorse. Using HC MC and CF MC ± culture with CFTR inhibitor 172 or elexacaftor/tezacaftor/ivacaftor (ETI), we assessed different MC functions to assess increases in inflammatory potential. MC intracellular calcium influx, degranulation, and cytokine production were used as readouts for MC activation. Genes associated with mitochondrial biogenesis (PPARGC1A, NRF1, TFAM, TOMM20) and mitophagy (PINK1, PRKN, BNIP3) were assessed in lung resident mast cells from single cell RNAseq datasets in the Chan Zuckerberg CellxGene Explorer.</div></div><div>Peripheral blood CD34+ cells from healthy controls (HC) and people with CF (pwCF) were differentiated into primary MC <em>in vitro</em>. Mitochondrial biomass was quantified and mitochondrial function was assessed by Seahorse. Using HC MC and CF MC ± culture with CFTR inhibitor 172 or elexacaftor/tezacaftor/ivacaftor (ETI), we assessed different MC functions to assess increases in inflammatory potential. MC intracellular calcium influx, degranulation, and cytokine production were used as readouts for MC activation. Genes associated with mitochondrial biogenesis (PPARGC1A, NRF1, TFAM, TOMM20) and mitophagy (PINK1, PRKN, BNIP3) were assessed in lung resident mast cells from single cell RNAseq datasets in the Chan Zuckerberg CellxGene Explorer.</div><div><h3>Results</h3><div>We determined that CF MC have greater m","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 39"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 16Utility of lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis: Preliminary results from the Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) Trial","authors":"J. Nick, K. Poch, E. Armantrout, S. Caceres, K. Malcolm, B. Vestal, N. Rysavy, J. Manzer, I. Aboellail, D. Chatterjee","doi":"10.1016/j.jcf.2026.07.048","DOIUrl":"10.1016/j.jcf.2026.07.048","url":null,"abstract":"<div><h3>Background</h3><div>Routine screening for nontuberculous mycobacterial (NTM) lung infection in people with cystic fibrosis (CF) is dependent on sputum cultures. This is challenging in a CFTR-modulator treated population due to reduced sputum availability and low culture sensitivity. Non-sputum biomarkers may reduce the need for sputum samples, leading to an earlier diagnosis and a better understanding of disease pathogenesis. The presence of the mycobacterial cell wall component lipoarabinomannan (LAM) in urine has been shown to accurately reflect the history of NTM infections in a cohort of adults with CF, and as marker of NTM treatment response.</div></div><div>Routine screening for nontuberculous mycobacterial (NTM) lung infection in people with cystic fibrosis (CF) is dependent on sputum cultures. This is challenging in a CFTR-modulator treated population due to reduced sputum availability and low culture sensitivity. Non-sputum biomarkers may reduce the need for sputum samples, leading to an earlier diagnosis and a better understanding of disease pathogenesis. The presence of the mycobacterial cell wall component lipoarabinomannan (LAM) in urine has been shown to accurately reflect the history of NTM infections in a cohort of adults with CF, and as marker of NTM treatment response.</div><div><h3>Methods</h3><div>A prospective, single-center, non-randomized observational study was conducted in adults with CF (NCT04579211). Participants had >3 years of negative NTM cultures and no known history of NTM. Participants were followed during routine clinical care visits, with sputum and urine samples obtained annually, across a three-year period. Urine was analyzed for LAM by GC/MS. <strong>We hypothesize</strong> that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value (NPV) to identify individuals at low risk of positive NTM sputum culture. The primary endpoint was a positive NTM sputum culture within a year of a positive urine LAM result, with multiple secondary and exploratory endpoints.</div></div><div>A prospective, single-center, non-randomized observational study was conducted in adults with CF (NCT04579211). Participants had >3 years of negative NTM cultures and no known history of NTM. Participants were followed during routine clinical care visits, with sputum and urine samples obtained annually, across a three-year period. Urine was analyzed for LAM by GC/MS. <strong>We hypothesize</strong> that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value (NPV) to identify individuals at low risk of positive NTM sputum culture. The primary endpoint was a positive NTM sputum culture within a year of a positive urine LAM result, with multiple secondary and exploratory endpoints.</div><div><h3>Results</h3><div>Enrollment started late 2020 with follow-up ending in late 2025. Subjects were reflective of the current CF population, with 90.5% receiving a CFTR m","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 7-8"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 6Impact of Haemophilus influenzae in children with cystic fibrosis undergoing elexacaftor/tezacaftor/ivacaftor therapy","authors":"E. Tiller, R. Boone, M. Kiedwroski, T. Poore","doi":"10.1016/j.jcf.2026.07.038","DOIUrl":"10.1016/j.jcf.2026.07.038","url":null,"abstract":"<div><h3>Background</h3><div><em>Haemophilus influenzae</em> (<em>Hflu</em>) is one of the most common pathogens isolated in children with cystic fibrosis (CF). With the initiation of elexacaftor/tezacaftor/ivacaftor (ETI), CF pathogen density in the airway has changed, yet how this effects children with CF and how <em>Hflu</em> is adjusting to this microbiome shift is poorly understood. In the post ETI CF airway, there is an emerging belief that greater microbial diversity and increased commensal bacteria isolation is indicative of less infection and pathogen virulence. Given this, <strong>our main hypothesis</strong> is that ETI is resulting in increased <em>Hflu</em> isolation, restoration of commensal bacteria, and reduction of the isolation of virulent <em>Hflu</em> strains in children with CF. To address this, we will perform a multilevel study investigating both clinical and lab data to determine <em>Hflu</em> infectivity. With this data we hope to provide a more thorough picture of <em>Hflu</em> acquisition, describe how ETI alters <em>Hflu</em> co-infections in children with CF, and determine whether post modulator <em>Hflu</em> is still considered pathogenic or if it is shifting towards a more commensal profile.</div></div><div><em>Haemophilus influenzae</em> (<em>Hflu</em>) is one of the most common pathogens isolated in children with cystic fibrosis (CF). With the initiation of elexacaftor/tezacaftor/ivacaftor (ETI), CF pathogen density in the airway has changed, yet how this effects children with CF and how <em>Hflu</em> is adjusting to this microbiome shift is poorly understood. In the post ETI CF airway, there is an emerging belief that greater microbial diversity and increased commensal bacteria isolation is indicative of less infection and pathogen virulence. Given this, <strong>our main hypothesis</strong> is that ETI is resulting in increased <em>Hflu</em> isolation, restoration of commensal bacteria, and reduction of the isolation of virulent <em>Hflu</em> strains in children with CF. To address this, we will perform a multilevel study investigating both clinical and lab data to determine <em>Hflu</em> infectivity. With this data we hope to provide a more thorough picture of <em>Hflu</em> acquisition, describe how ETI alters <em>Hflu</em> co-infections in children with CF, and determine whether post modulator <em>Hflu</em> is still considered pathogenic or if it is shifting towards a more commensal profile.</div><div><h3>Methods</h3><div>We will prospectively and retrospectively review patients followed at UAB CF center with sputum cultures positive for <em>Hflu</em>, looking at the time of modulator initiation AND time of <em>Hflu</em> growth, as well as <em>Hflu</em> quantity as reported in the electronic medical record (EMR). We will then define each individual’s first <em>Hflu</em> isolation and modulator initiation date(s) along with subsequent <em>Hflu</em> isolation on modulator therapy. We will determine patient’s clin","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 3"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster: 12Mucus and Pseudomonas aeruginosa exopolysaccharides impair sensory neuron-mediated immune defense in cystic fibrosis","authors":"D. Aguilar, S. Fernandes, A. Milesi Galindo, E. Scandinari Manzolli, N. Jendzjowsky, P. Jorth","doi":"10.1016/j.jcf.2026.07.044","DOIUrl":"10.1016/j.jcf.2026.07.044","url":null,"abstract":"<div><h3>Background</h3><div>The loss of function of the Cystic Fibrosis transmembrane conductance regulator (CFTR) leads to mucus accumulation and impaired mucociliary clearance, creating an advantageous environment for bacterial colonization. Despite advancements in CFTR modulators, <em>Pseudomonas aeruginosa</em> remains persistent in people with cystic fibrosis (CF). A key feature of <em>P. aeruginosa</em> persistence in the CF lung environment is its ability to produce biofilms. Previous studies have shown that the vagal transient receptor potential vanilloid 1 (TRPV1) afferent neurons release specific neuropeptides that suppress neutrophils and γδ T cells, improving survival in response to <em>Staphylococcus aureus</em> infection [1]. More recently, exopolysaccharide (EPS) produced by <em>P. aeruginosa</em> was found to block lipopolysaccharide binding to toll-like receptor 4, preventing activation of the lung-brain sensory pathway [2]. In CF, abundant mucins may further amplify EPS-mediated evasion through biofilm formation. Here, we aim to determine whether mucus and <em>P. aeruginosa</em> EPS obstruct sensory neuron detection of the pathogen, disrupting neuropeptide release and leading to an impaired immune response.</div></div><div>The loss of function of the Cystic Fibrosis transmembrane conductance regulator (CFTR) leads to mucus accumulation and impaired mucociliary clearance, creating an advantageous environment for bacterial colonization. Despite advancements in CFTR modulators, <em>Pseudomonas aeruginosa</em> remains persistent in people with cystic fibrosis (CF). A key feature of <em>P. aeruginosa</em> persistence in the CF lung environment is its ability to produce biofilms. Previous studies have shown that the vagal transient receptor potential vanilloid 1 (TRPV1) afferent neurons release specific neuropeptides that suppress neutrophils and γδ T cells, improving survival in response to <em>Staphylococcus aureus</em> infection [1]. More recently, exopolysaccharide (EPS) produced by <em>P. aeruginosa</em> was found to block lipopolysaccharide binding to toll-like receptor 4, preventing activation of the lung-brain sensory pathway [2]. In CF, abundant mucins may further amplify EPS-mediated evasion through biofilm formation. Here, we aim to determine whether mucus and <em>P. aeruginosa</em> EPS obstruct sensory neuron detection of the pathogen, disrupting neuropeptide release and leading to an impaired immune response.</div><div><h3>Methods</h3><div>We utilized <em>Scnn1b</em>-Tg (CF mice) that overexpresses the ENaC sodium channel, which mimics hyperinflammation and mucus accumulation phenotype seen in CF [3], and C57BL/6-WT mice. TRPV1<sup>+</sup> sensory neurons were chemically ablated using resiniferatoxin (RTX). 5-week-old WT and CF mice received subcutaneous injections of escalating RTX doses (30, 70, and 100 mg/kg); control mice received vehicle. 21 days after the final RTX treatment, WT and CF mice were intratracheally ino","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 6"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}