Journal of Cystic Fibrosis最新文献

{"title":"Microbial content versus microbial interaction: the impact of medications on CF airway microbial ecosystems.","authors":"Pok-Man Ho, Rahan Rudland Nazeer, Isabel Askenasy, Robert A Quinn, Martin Welch","doi":"10.1016/j.jcf.2026.08.011","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.08.011","url":null,"abstract":"<p><strong>Background: </strong>The airways of people with cystic fibrosis (pwCF) are often colonized by a variety of different microbes. Although much effort has been put into cataloguing the impact of medication on the identities and abundances of these microbes, far less has been directed towards examining this from an ecological perspective, i.e., examining how medications affect the network and types of interactions between microbes.</p><p><strong>Methods: </strong>In the current work, we generated an ecological model of the CF airway microbiome and examined how medications affect interactions between co-habiting airway microbiota in six pwCF. Ecological interactions were inferred from a generalized Lotka-Volterra model, and the impact of medications was determined by principal component(s) regression analysis.</p><p><strong>Results: </strong>For the majority of the subjects studied, antimicrobial interventions had relatively little impact on the CF airway microbial ecology, and even appeared to stabilize ecological interactions between the microbiota. However, the microbial ecosystem in some individuals was more sensitive to external perturbations. More surprisingly, we found that some non-antimicrobial medications, and also certain carriers and excipients affect the ecosystem.</p><p><strong>Conclusions: </strong>Medications affect the ecology of the CF airway microbiota. These impacts appear to be very patient-specific. We also note that some nominally non-bioactive ingredients in medications can also potentially impact the CF airway ecosystem. Our data highlight the importance of collecting patient-specific data and in employing suitable computational frameworks for disentangling medication-microbiota interactions in vivo.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891886","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":"The cystic fibrosis gut microbial dysbiosis index (CF-GMDI): a quantitative measure of gut microbial imbalance in children with cystic fibrosis.","authors":"B L D Uthpala Pushpakumara, Michael J Coffey, Jennifer Hudson, Jessica Halim, Sandra Chuang, Bernadette Prentice, Adam Jaffe, Robert Edwards, Andrew S Day, Mark Oliver, Sarath Ranganathan, Claire Wainwright, Hiran Selvadurai, Josie van Dorst, Chee Y Ooi","doi":"10.1016/j.jcf.2026.08.007","DOIUrl":"https://doi.org/10.1016/j.jcf.2026.08.007","url":null,"abstract":"<p><strong>Background: </strong>Gut dysbiosis is a hallmark of cystic fibrosis (CF), typically characterised using non-specific diversity metrics and study-specific taxonomic lists, limiting comparability across studies. We aimed to develop a metagenomic, species-level CF Gut Microbial Dysbiosis Index (CF-GMDI) to standardise measurement of gut microbial imbalance in children with CF (cwCF) METHODS: CF-GMDI was derived using stool metagenomic data from the PEARL-CF study (70 cwCF; 67 healthy controls (HC); 0-6 years). Differentially abundant taxa were identified between cwCF and HC using MaAsLin2. The index was calculated as the log₁₀ ratio of the summed relative abundances of taxa enriched in CF vs HC to those depleted in CF vs HC. Reproducibility was assessed in the independent EARTH cohort (56 cwCF; 56 HC; 0-18 years). Responsiveness to therapy was evaluated using publicly available metagenomic data from an Elexacaftor/Tezacaftor/Ivacaftor (ETI) study (39 cwCF; 6-18 years).</p><p><strong>Results: </strong>CF-GMDI was significantly higher in cwCF than HC (p < 0.001), inversely correlated with species richness (ρ = -0.74, p < 0.001), and higher in pancreatic-insufficient vs pancreatic-sufficient cwCF in the PEARL-CF cohort (p = 0.01). Key ecological and clinical associations were replicated in the EARTH cohort. In the ETI study, CF-GMDI decreased significantly at 6 and 12 months post-treatment, whereas alpha diversity remained unchanged.</p><p><strong>Conclusions: </strong>CF-GMDI is a CF-associated metric that captures clinically relevant gut microbiome restructuring not detected by standard diversity measures in cwCF (0-18 years). It differentiates disease and pancreatic status and tracks therapeutic modulation, supporting its use as a novel endpoint in CF intervention studies.</p>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887679","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: 78Closer than expected: Environmental exposures in people with CF infected with ST398 Staphylococcus aureus","authors":"J. Krogh,&nbsp;J. Zapata,&nbsp;M. Boyle,&nbsp;T. Zaputil,&nbsp;A. Rozen,&nbsp;H. Shin,&nbsp;D. Kanwischer,&nbsp;M. Teresi,&nbsp;D. Cwiertny,&nbsp;P. Planet,&nbsp;A. Fischer","doi":"10.1016/j.jcf.2026.07.110","DOIUrl":"10.1016/j.jcf.2026.07.110","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;In CF, thickened airway mucus predisposes to chronic bacterial respiratory infections, including &lt;em&gt;Staphylococcus aureus&lt;/em&gt;. In 2017, we isolated a tetracycline-resistant strain of &lt;em&gt;S. aureus&lt;/em&gt; belonging to sequence type 398 (ST398). This lineage is found in livestock, and it infects some farm workers. We prospectively isolated &lt;em&gt;S. aureus&lt;/em&gt; from respiratory cultures of patients with CF from August 2020 to July 2024 and used whole genome sequencing (WGS) to determine the prevalence of this &lt;em&gt;S. aureus&lt;/em&gt; lineage, and issued questionnaires to identify environmental risk factors for ST398 infection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;In CF, thickened airway mucus predisposes to chronic bacterial respiratory infections, including &lt;em&gt;Staphylococcus aureus&lt;/em&gt;. In 2017, we isolated a tetracycline-resistant strain of &lt;em&gt;S. aureus&lt;/em&gt; belonging to sequence type 398 (ST398). This lineage is found in livestock, and it infects some farm workers. We prospectively isolated &lt;em&gt;S. aureus&lt;/em&gt; from respiratory cultures of patients with CF from August 2020 to July 2024 and used whole genome sequencing (WGS) to determine the prevalence of this &lt;em&gt;S. aureus&lt;/em&gt; lineage, and issued questionnaires to identify environmental risk factors for ST398 infection.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The IRB of the University of Iowa approved this study and the parent study SA Risk Factors. We isolated &lt;em&gt;S. aureus&lt;/em&gt; from people with CF at routine clinic appointments and performed short read WGS. We used Bactopia to analyze sequence type and we used RAxML and BEAST for phylogenetic analysis. We surveyed patients with CF to assess environmental risks, including questions pertaining to employment, home location, proximity to livestock operations, antibiotic usage, contact with animals and their feces, drinking water type, home sewage system type, and contact with raw meat. Sample collections included water from patients’ homes and raw meat purchased from local stores.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;The IRB of the University of Iowa approved this study and the parent study SA Risk Factors. We isolated &lt;em&gt;S. aureus&lt;/em&gt; from people with CF at routine clinic appointments and performed short read WGS. We used Bactopia to analyze sequence type and we used RAxML and BEAST for phylogenetic analysis. We surveyed patients with CF to assess environmental risks, including questions pertaining to employment, home location, proximity to livestock operations, antibiotic usage, contact with animals and their feces, drinking water type, home sewage system type, and contact with raw meat. Sample collections included water from patients’ homes and raw meat purchased from local stores.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ST398 &lt;em&gt;S. aureus&lt;/em&gt; infected 16 patients (of N = 254 cultured) at the University of Iowa CF center. Phylogenetically, ST398 included two types; markers for these types included tetracycline resistance (type 1, n = 5 subjects) and the bacteriophage PhiStau4 w","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":"148964695","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: 38Racial disparities in microbiological profiles of people with cystic fibrosis","authors":"G. Hernandez Romero,&nbsp;F. Haque,&nbsp;O. Okubadejo,&nbsp;T. Frantzen,&nbsp;K. Papia,&nbsp;J. Javor,&nbsp;S. Islam,&nbsp;J. Wang","doi":"10.1016/j.jcf.2026.07.070","DOIUrl":"10.1016/j.jcf.2026.07.070","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Racial minorities with cystic fibrosis (CF) experience greater morbidity and mortality than non-Hispanic White individuals, even after adjustment for socioeconomic factors. [1] Although elexacaftor/tezacaftor/ivacaftor reduces airway pathogen burden, infections often persist. Minority people with CF (PwCF) have higher rates of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) infection, lower lung function, reduced modulator eligibility, and worse clinical outcomes. [2, 3] Data describing longitudinal microbiologic changes before and after CFTR modulator therapy remain limited. We evaluated longitudinal respiratory microbiology across racial groups in adults with CF.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Racial minorities with cystic fibrosis (CF) experience greater morbidity and mortality than non-Hispanic White individuals, even after adjustment for socioeconomic factors. [1] Although elexacaftor/tezacaftor/ivacaftor reduces airway pathogen burden, infections often persist. Minority people with CF (PwCF) have higher rates of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) infection, lower lung function, reduced modulator eligibility, and worse clinical outcomes. [2, 3] Data describing longitudinal microbiologic changes before and after CFTR modulator therapy remain limited. We evaluated longitudinal respiratory microbiology across racial groups in adults with CF.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective cohort study of adults with CF enrolled in the Cystic Fibrosis Foundation Patient Registry at the Adult CF Center of Long Island Jewish Medical Center. Respiratory microbiology was evaluated from 2017–2026 using registry and electronic medical record data. Eligible patients had confirmed CF, ≥3 years of follow-up, and no lung transplantation before 2017. The final analytic cohort included 45 matched PwCF (30 White [W] and 15 Non-White [NW]) matched by sex and age (±2 years). Primary outcomes were longitudinal changes in the prevalence of PA, methicillin-sensitive S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA). Secondary outcomes included microbiologic changes following CFTR modulator initiation and P. aeruginosa–S. aureus coinfection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;We conducted a retrospective cohort study of adults with CF enrolled in the Cystic Fibrosis Foundation Patient Registry at the Adult CF Center of Long Island Jewish Medical Center. Respiratory microbiology was evaluated from 2017–2026 using registry and electronic medical record data. Eligible patients had confirmed CF, ≥3 years of follow-up, and no lung transplantation before 2017. The final analytic cohort included 45 matched PwCF (30 White [W] and 15 Non-White [NW]) matched by sex and age (±2 years). Primary outcomes were longitudinal changes in the prevalence of PA, methicillin-sensitive S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA). Secondary outcomes included microbiologic changes following CFTR modulator initiation and","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 19"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964740","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: 70Defining the physiological differences between Mycobacteroides abscessus morphotypes in synthetic sputum media","authors":"I. Abdullaeva,&nbsp;F. Diggle,&nbsp;B. Ross","doi":"10.1016/j.jcf.2026.07.102","DOIUrl":"10.1016/j.jcf.2026.07.102","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Mycobacteroides abscessus&lt;/em&gt; (MAB) is an emerging multidrug-resistant pathogen with increasing incidence in people with Cystic Fibrosis [1, 2]. MAB adapts in the CF lung in real time through a single point mutation that confers a loss of a cell wall lipid, glycopeptidolipid (GPL) [3, 4]. This modulation of GPL expression gives rise to two distinct colony morphotypes: Smooth (GPL&lt;sup&gt;+&lt;/sup&gt;) which can cause a silent infection and Rough (GPL&lt;sup&gt;-&lt;/sup&gt;) associated with symptomology and increased mortality. This study aims to investigate physiological differences between these morphotypes beyond GPL expression under CF lung-mimicking conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Mycobacteroides abscessus&lt;/em&gt; (MAB) is an emerging multidrug-resistant pathogen with increasing incidence in people with Cystic Fibrosis [1, 2]. MAB adapts in the CF lung in real time through a single point mutation that confers a loss of a cell wall lipid, glycopeptidolipid (GPL) [3, 4]. This modulation of GPL expression gives rise to two distinct colony morphotypes: Smooth (GPL&lt;sup&gt;+&lt;/sup&gt;) which can cause a silent infection and Rough (GPL&lt;sup&gt;-&lt;/sup&gt;) associated with symptomology and increased mortality. This study aims to investigate physiological differences between these morphotypes beyond GPL expression under CF lung-mimicking conditions.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Both morphotypes of MAB strain ATCC 19977 strain were grown in Synthetic Cystic Fibrosis Sputum Medium (SCFM) lacking mucin and DNA. Growth rates were monitored by OD&lt;sub&gt;600&lt;/sub&gt; over 60 hours and paired samples were collected at early log, mid log, late log, and stationary phase for metabolic consumption and RNA and protein profiling analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Both morphotypes of MAB strain ATCC 19977 strain were grown in Synthetic Cystic Fibrosis Sputum Medium (SCFM) lacking mucin and DNA. Growth rates were monitored by OD&lt;sub&gt;600&lt;/sub&gt; over 60 hours and paired samples were collected at early log, mid log, late log, and stationary phase for metabolic consumption and RNA and protein profiling analyses.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In SCFM, both morphotypes were observed to grow at the same rate and consumed the same metabolites. However, both the RNA and protein profiles show differentially expressed genes between the two morphotypes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;In SCFM, both morphotypes were observed to grow at the same rate and consumed the same metabolites. However, both the RNA and protein profiles show differentially expressed genes between the two morphotypes.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Consistent differences in RNA and proteins between the two morphotypes were observed, highlighting unexplored physiological differences between the two morphotypes beyond GPL expression. The physiological roles of the most upregulated RNA/proteins of each morphotype are currently under investigation. These findings suggest that morphotypes have unique physiology in the lung which may impact ","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 34-35"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964749","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: 4Evolution and pathoadaptation of Pseudomonas aeruginosa through the gut-lung axis in cystic fibrosis","authors":"R. Valls,&nbsp;R. Wills,&nbsp;C. Armbruster,&nbsp;J. Baker,&nbsp;Y. Hilliam,&nbsp;A. Kohan,&nbsp;J. Bomberger","doi":"10.1016/j.jcf.2026.07.036","DOIUrl":"10.1016/j.jcf.2026.07.036","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;People with cystic fibrosis (pwCF) face significant gastrointestinal challenges with fat absorption linked to chronic lung complications, implicating the gut-lung axis in disease pathogenesis. Dietary fatty acids are packaged into chylomicrons in the small intestine and traffic to the lungs via lymph. Despite advances with highly effective modulator therapy (HEMT), pathogens like &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; (&lt;em&gt;Pa&lt;/em&gt;) persist along with local inflammation, and systemic lipid levels remain dysregulated even after HEMT initiation. The role of gut-derived lipids in shaping the airway nutritional environment and driving &lt;em&gt;Pa&lt;/em&gt; adaptation in the lungs remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;People with cystic fibrosis (pwCF) face significant gastrointestinal challenges with fat absorption linked to chronic lung complications, implicating the gut-lung axis in disease pathogenesis. Dietary fatty acids are packaged into chylomicrons in the small intestine and traffic to the lungs via lymph. Despite advances with highly effective modulator therapy (HEMT), pathogens like &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; (&lt;em&gt;Pa&lt;/em&gt;) persist along with local inflammation, and systemic lipid levels remain dysregulated even after HEMT initiation. The role of gut-derived lipids in shaping the airway nutritional environment and driving &lt;em&gt;Pa&lt;/em&gt; adaptation in the lungs remains unclear.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To investigate how gut-derived lipids, which are changing with HEMT, shape the airway nutritional environment and drive &lt;em&gt;Pa&lt;/em&gt; adaptation, we established a mouse model to study lipid transport via the gut-lung axis, studied &lt;em&gt;Pa&lt;/em&gt; adaptation in pwCF before and after HEMT and established an experimental evolution model to study how dietary lipids instigate &lt;em&gt;Pa&lt;/em&gt; adaptation in the airways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;To investigate how gut-derived lipids, which are changing with HEMT, shape the airway nutritional environment and drive &lt;em&gt;Pa&lt;/em&gt; adaptation, we established a mouse model to study lipid transport via the gut-lung axis, studied &lt;em&gt;Pa&lt;/em&gt; adaptation in pwCF before and after HEMT and established an experimental evolution model to study how dietary lipids instigate &lt;em&gt;Pa&lt;/em&gt; adaptation in the airways.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;To identify adaptive mutations in persistent &lt;em&gt;Pa&lt;/em&gt; populations, we whole-genome sequenced pre and post-HEMT clinical airway &lt;em&gt;Pa&lt;/em&gt; populations of pwCF and found significant enrichment and fixation of mutations in lipid metabolism pathways. Importantly, recurrent variants in fatty acid degradation (&lt;em&gt;fad&lt;/em&gt;) and synthesis (&lt;em&gt;fab&lt;/em&gt;) pathways mirrored mutations independently identified in our chylomicron-evolved &lt;em&gt;Pa&lt;/em&gt; populations. To confirm gut-to-lung trafficking of dietary lipids, we oral-gavaged mice with &lt;sup&gt;3&lt;/sup&gt;H-oleate and detected radiolabeled lipid in plasma, BALF, and lung tissue&lt;strong&gt;.&lt;/strong&gt; To define the functional consequences of &lt;em&gt;fad&lt;/em&gt;","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":"148964789","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: 53Highly effective modulator therapies repair neutrophil's dysfunction in people with cystic fibrosis","authors":"F. Robledo-Avila,&nbsp;R. Rascon,&nbsp;A. Montanez-Barragan,&nbsp;B. Kopp,&nbsp;S. Partida-Sanchez","doi":"10.1016/j.jcf.2026.07.085","DOIUrl":"10.1016/j.jcf.2026.07.085","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Cystic Fibrosis (CF) is a channelopathy of the respiratory system that causes severe lung damage and leads to life-threatening infections. CF is produced by mutations in the &lt;em&gt;cftr&lt;/em&gt; gene, leading to the production of a defective protein. CF has no cure, but novel therapeutic drugs have emerged targeting defects in the CFTR channel, including highly effective CFTR modulators (HEMT), in which the triple combination Elexacaftor/tezacaftor/ivacaftor (ETI) has been the most successful FDA approved HEMT for people with CF (pwCF). Despite recent increase in HEMT, some bacterial infections and clinical exacerbations persist in pwCF. Thus, the effects of those treatments on the functional expression of CFTR channel in phagocytic cells or the antimicrobial functions of these cells, remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Cystic Fibrosis (CF) is a channelopathy of the respiratory system that causes severe lung damage and leads to life-threatening infections. CF is produced by mutations in the &lt;em&gt;cftr&lt;/em&gt; gene, leading to the production of a defective protein. CF has no cure, but novel therapeutic drugs have emerged targeting defects in the CFTR channel, including highly effective CFTR modulators (HEMT), in which the triple combination Elexacaftor/tezacaftor/ivacaftor (ETI) has been the most successful FDA approved HEMT for people with CF (pwCF). Despite recent increase in HEMT, some bacterial infections and clinical exacerbations persist in pwCF. Thus, the effects of those treatments on the functional expression of CFTR channel in phagocytic cells or the antimicrobial functions of these cells, remain unclear.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We collected peripheral blood from pwCF carrying &lt;em&gt;delF508-CFTR&lt;/em&gt; mutation and healthy donors (non-CF). Neutrophils were treated with ETI combination and then stimulated with PMA or with &lt;em&gt;Burkholderia cenocepacia&lt;/em&gt; (&lt;em&gt;B. cenocepacia)&lt;/em&gt;. The cellular expression and function of CFTR was assessed by confocal microscopy, flow cytometry and patch clamp. Furthermore, neutrophils’ antimicrobial functions including, bacterial killing, ROS production and the release of Neutrophil Extracellular Traps (NETs), were also evaluated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;We collected peripheral blood from pwCF carrying &lt;em&gt;delF508-CFTR&lt;/em&gt; mutation and healthy donors (non-CF). Neutrophils were treated with ETI combination and then stimulated with PMA or with &lt;em&gt;Burkholderia cenocepacia&lt;/em&gt; (&lt;em&gt;B. cenocepacia)&lt;/em&gt;. The cellular expression and function of CFTR was assessed by confocal microscopy, flow cytometry and patch clamp. Furthermore, neutrophils’ antimicrobial functions including, bacterial killing, ROS production and the release of Neutrophil Extracellular Traps (NETs), were also evaluated.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We observed that CF and non-CF neutrophils increased the expression and function of the CFTR channel, when treated in vitro with ETI. The CFTR protein was detected in subcellular compar","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 26"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964794","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: 46Do not overestimate: Incorporating lung tissue–limited antibiotic penetration for more accurate antibiotic selection than MIC in patients with cystic fibrosis","authors":"G. Tetz,&nbsp;V. Tetz,&nbsp;K. Kardava,&nbsp;M. Vecherkovskaya","doi":"10.1016/j.jcf.2026.07.078","DOIUrl":"10.1016/j.jcf.2026.07.078","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Conventional antimicrobial susceptibility testing (AST) relies on MIC values and susceptibility breakpoints, which reflect antibiotic concentrations in the blood. But for many infections, antibiotic penetration into lungs is limited. This results in false-positive errors in antibiotic selection by standard methods, because antibiotics may not reach relevant concentrations at the infection site.&lt;/div&gt;&lt;div&gt;AtbFinder is a novel, non–MIC-based phenotypic test for antibiotic selection under patient-representative conditions. It preserves the complete polymicrobial biofilm communities from biosamples and tests antibiotics at clinically achievable, site-specific concentrations based on known tissue penetration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Conventional antimicrobial susceptibility testing (AST) relies on MIC values and susceptibility breakpoints, which reflect antibiotic concentrations in the blood. But for many infections, antibiotic penetration into lungs is limited. This results in false-positive errors in antibiotic selection by standard methods, because antibiotics may not reach relevant concentrations at the infection site.&lt;/div&gt;&lt;div&gt;AtbFinder is a novel, non–MIC-based phenotypic test for antibiotic selection under patient-representative conditions. It preserves the complete polymicrobial biofilm communities from biosamples and tests antibiotics at clinically achievable, site-specific concentrations based on known tissue penetration.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This open-label, single-arm, investigator-initiated clinical study compared sensitivity to 24 commonly used antibiotics when tested against (1) a single “primary pathogen” and (2) complete polymicrobial biofilms under two conditions:&lt;/div&gt;&lt;div&gt;(i) MIC-based breakpoint concentrations, and&lt;/div&gt;&lt;div&gt;(ii) pharmacokinetically achievable lung concentrations.&lt;/div&gt;&lt;div&gt;22 patients with cystic fibrosis chronically colonized with &lt;em&gt;P.aeruginosa&lt;/em&gt; for over 5 years, and with over 2 hospitalizations per year due to pulmonary exacerbations, were enrolled. AtbFinder panels tested 24 antibiotics in agar-containing plates at concentrations lung-achievable concentrations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;This open-label, single-arm, investigator-initiated clinical study compared sensitivity to 24 commonly used antibiotics when tested against (1) a single “primary pathogen” and (2) complete polymicrobial biofilms under two conditions:&lt;/div&gt;&lt;div&gt;(i) MIC-based breakpoint concentrations, and&lt;/div&gt;&lt;div&gt;(ii) pharmacokinetically achievable lung concentrations.&lt;/div&gt;&lt;div&gt;22 patients with cystic fibrosis chronically colonized with &lt;em&gt;P.aeruginosa&lt;/em&gt; for over 5 years, and with over 2 hospitalizations per year due to pulmonary exacerbations, were enrolled. AtbFinder panels tested 24 antibiotics in agar-containing plates at concentrations lung-achievable concentrations.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;For monobacterial &lt;em&gt;P. aeruginosa&lt;/em&gt; testing, 74% of antibiotics selected as effective by MIC-based testi","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 23"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964799","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: 9The candid truth of Candida in cystic fibrosis","authors":"J. Burke-Gaffney,&nbsp;K. Strayer,&nbsp;M. Stephens,&nbsp;B. Waddell,&nbsp;A. Sombolestani,&nbsp;A. Simon,&nbsp;C. MacKenzie,&nbsp;M. Gillrie,&nbsp;M. Parkins,&nbsp;S. Znaidi,&nbsp;B. McDonald,&nbsp;R. Somayaji,&nbsp;C. Thornton","doi":"10.1016/j.jcf.2026.07.041","DOIUrl":"10.1016/j.jcf.2026.07.041","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Although bacterial pathogens are well-established contributors to pulmonary exacerbations (PEx) in people with cystic fibrosis (pwCF), the role of fungi such as &lt;em&gt;Candida&lt;/em&gt; spp. remains poorly defined. Current guidelines classify &lt;em&gt;Candida&lt;/em&gt; as a benign colonizer; however, emerging evidence links its airway presence to greater bacterial virulence, inflammation, and poorer clinical outcomes [1]. We hypothesized that &lt;em&gt;Candida&lt;/em&gt; adopts a more pathogenic phenotype during PEx compared with clinical stability.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Although bacterial pathogens are well-established contributors to pulmonary exacerbations (PEx) in people with cystic fibrosis (pwCF), the role of fungi such as &lt;em&gt;Candida&lt;/em&gt; spp. remains poorly defined. Current guidelines classify &lt;em&gt;Candida&lt;/em&gt; as a benign colonizer; however, emerging evidence links its airway presence to greater bacterial virulence, inflammation, and poorer clinical outcomes [1]. We hypothesized that &lt;em&gt;Candida&lt;/em&gt; adopts a more pathogenic phenotype during PEx compared with clinical stability.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We evaluated frozen, biobanked sputum-derived &lt;em&gt;Candida&lt;/em&gt; isolates from 21 pwCF, collected between 2010 and 2021, with each contributing at least three longitudinal specimens from periods of clinical stability and PEx (clinician-defined). Isolates were identified to the strain-phenotype level using Fourier-transform infrared spectroscopy (FTIR), cultured in Synthetic Cystic Fibrosis Medium (SCFM) and yeast extract peptone dextrose (YPD) to model host-relevant conditions, assessed for morphology by light microscopy, and characterized transcriptionally by bulk RNA sequencing. Morphology was classified on an ordinal scale as yeast, mixed, or hyphae. Results were descriptively summarized; group differences in morphology were assessed using Fisher’s exact test and cumulative link mixed models (CLMM) for ordinal outcomes; strain similarity was evaluated using the Wilcoxon signed-rank test; and transcriptional profiles were analyzed by differential expression analysis and principal component analysis (PCA).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;We evaluated frozen, biobanked sputum-derived &lt;em&gt;Candida&lt;/em&gt; isolates from 21 pwCF, collected between 2010 and 2021, with each contributing at least three longitudinal specimens from periods of clinical stability and PEx (clinician-defined). Isolates were identified to the strain-phenotype level using Fourier-transform infrared spectroscopy (FTIR), cultured in Synthetic Cystic Fibrosis Medium (SCFM) and yeast extract peptone dextrose (YPD) to model host-relevant conditions, assessed for morphology by light microscopy, and characterized transcriptionally by bulk RNA sequencing. Morphology was classified on an ordinal scale as yeast, mixed, or hyphae. Results were descriptively summarized; group differences in morphology were assessed using Fisher’s exact test and cumulative link mixed models (CLMM) for ordinal outcomes; st","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 4-5"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964848","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: 58Evaluating CFTR G551D transgenic ferrets as an animal model for Mycobacteroides abscessus lung infection in CF","authors":"N. Gokanapudi,&nbsp;T. Gupta,&nbsp;K. Sakamoto,&nbsp;B. Ross,&nbsp;A. Stecenko,&nbsp;J. Engelhardt,&nbsp;F. Quinn,&nbsp;B. Rada","doi":"10.1016/j.jcf.2026.07.090","DOIUrl":"10.1016/j.jcf.2026.07.090","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Mycobacteroides abscessus&lt;/em&gt; has emerged as a multidrug resistant pathogen within the cystic fibrosis (CF) population. This bacterium exhibits morphological dimorphism: smooth (S) or rough (R) colony variants. Despite its clinical urgency, the study of &lt;em&gt;M. abscessus&lt;/em&gt; pathogenesis and the development of novel therapeutics have been hindered by the lack of relevant animal models. Conventional murine models fail to achieve sustained bacterial colonization. To address this gap, we utilized the transgenic CFTR-G551D ferret model to establish chronic &lt;em&gt;M. abscessus&lt;/em&gt; pulmonary infection. Ferrets are uniquely suited for CF research due to their anatomical and physiological similarities to human lungs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Mycobacteroides abscessus&lt;/em&gt; has emerged as a multidrug resistant pathogen within the cystic fibrosis (CF) population. This bacterium exhibits morphological dimorphism: smooth (S) or rough (R) colony variants. Despite its clinical urgency, the study of &lt;em&gt;M. abscessus&lt;/em&gt; pathogenesis and the development of novel therapeutics have been hindered by the lack of relevant animal models. Conventional murine models fail to achieve sustained bacterial colonization. To address this gap, we utilized the transgenic CFTR-G551D ferret model to establish chronic &lt;em&gt;M. abscessus&lt;/em&gt; pulmonary infection. Ferrets are uniquely suited for CF research due to their anatomical and physiological similarities to human lungs.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To evaluate the longitudinal dynamics of infection, CFTR G551D ferrets (N=11) were infected intratracheally with either smooth or rough morphotype of &lt;em&gt;M. abscessus&lt;/em&gt; isolated from the same CF patient (Emory IRB#00042577). Baseline physiological parameters were established via the collection of pre-infection sera and nasal lavage fluid. Following a 4-week stabilization period, serial nasal wash and blood samples were collected bi-weekly to perform ELISA for the quantification of the humoral immune response (anti-&lt;em&gt;M. abscessus&lt;/em&gt; antibodies) against heat-killed, gamma-irradiated, and whole-cell lysates of each bacterial morphotype. At the 12-week study endpoint, a comprehensive necropsy was performed to harvest nasal wash, blood, bronchoalveolar lavage, spleen, lungs, and liver. To assess systemic dissemination, tissue samples were homogenized and quantitatively cultured on selective media. To distinguish &lt;em&gt;M. abscessus&lt;/em&gt; from microflora endemic to the G551D ferrets, recovered colonies were validated via PCR using species-specific primers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;To evaluate the longitudinal dynamics of infection, CFTR G551D ferrets (N=11) were infected intratracheally with either smooth or rough morphotype of &lt;em&gt;M. abscessus&lt;/em&gt; isolated from the same CF patient (Emory IRB#00042577). Baseline physiological parameters were established via the collection of pre-infection sera and nasal lavage fluid. Following a 4-week stabilization period, serial na","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 28-29"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964853","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}