Journal of Cystic Fibrosis最新文献

{"title":"Poster: 71The CF Home Sputum-Induction Trial (CF-HomeSpIT): Primary outcome data for early morning sputum-induction at home compared to same-day sputum-induction in clinic","authors":"K. Ronchetti, J. Tame, H. Morgan, S. Mitchell, R. Dhillon, E. Mahenthiralingam, A. Aseeri, L. Thia, J. Forton","doi":"10.1016/j.jcf.2026.07.103","DOIUrl":"10.1016/j.jcf.2026.07.103","url":null,"abstract":"<div><h3>Background</h3><div>Sputum induction (SI) in clinic is 2.5 times as effective at identifying pathogens as oropharyngeal sampling (OPS)<sup>1</sup>, but time-commitment in clinic limits its universal application.</div><div>The CF-Home Sputum-Induction Trial (CF-HomeSpIT) [ISRCTN86523335] is a prospective internally-controlled interventional trial comparing home-sampling using spontaneous early morning cough-clear (emCC) and home sputum-induction (hSI) with matched same-day clinic sampling using cough swab (CS), spontaneous clinic cough-clear (cCC) and clinic sputum-induction (cSI). <span><span>https://www.uhwchildren.com/respiratory/cf-homespit/</span><svg><path></path></svg></span></div></div><div>Sputum induction (SI) in clinic is 2.5 times as effective at identifying pathogens as oropharyngeal sampling (OPS)<sup>1</sup>, but time-commitment in clinic limits its universal application.</div><div>The CF-Home Sputum-Induction Trial (CF-HomeSpIT) [ISRCTN86523335] is a prospective internally-controlled interventional trial comparing home-sampling using spontaneous early morning cough-clear (emCC) and home sputum-induction (hSI) with matched same-day clinic sampling using cough swab (CS), spontaneous clinic cough-clear (cCC) and clinic sputum-induction (cSI). <span><span>https://www.uhwchildren.com/respiratory/cf-homespit/</span><svg><path></path></svg></span></div><div><h3>Methods</h3><div>Children age >6yrs with CF at the Children’s Hospital for Wales already using Hypertonic saline (HS) were eligible for recruitment. Home sampling packs were provided by post. emCC was obtained on waking, using 3 rounds of a standardised approach to expectoration: <strong>COUGH, HUFF, COUGH, CLEAR THROAT (hawk), and SPIT</strong>. For hSI, patients used HS with their normal physiotherapy, and applied the same approach to expectoration for a minimum of 3 times during the procedure. Same-day clinic samples (cCC and cSI) were taken after routine cough swab (CS) by a physiotherapist using the same protocols and approach to expectoration. 8 mls of 7% HS was used for all sputum-induction events.</div></div><div>Children age >6yrs with CF at the Children’s Hospital for Wales already using Hypertonic saline (HS) were eligible for recruitment. Home sampling packs were provided by post. emCC was obtained on waking, using 3 rounds of a standardised approach to expectoration: <strong>COUGH, HUFF, COUGH, CLEAR THROAT (hawk), and SPIT</strong>. For hSI, patients used HS with their normal physiotherapy, and applied the same approach to expectoration for a minimum of 3 times during the procedure. Same-day clinic samples (cCC and cSI) were taken after routine cough swab (CS) by a physiotherapist using the same protocols and approach to expectoration. 8 mls of 7% HS was used for all sputum-induction events.</div><div><h3>Results</h3><div>64 patients were recruited and performed 96 sampling events. Median age was 11 years. Median FEV1% was 94%. 93% of patients were on m","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 35-36"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964941","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: 15Divergent virulence traits across Mycobacterium abscessus genetic subtypes contribute to clinical heterogeneity in cystic fibrosis","authors":"C. Vang, V. Calado Nogueira de Moura, S. Alper, B. Vestal, J. Nick, J. Honda","doi":"10.1016/j.jcf.2026.07.047","DOIUrl":"10.1016/j.jcf.2026.07.047","url":null,"abstract":"<div><h3>Background</h3><div>Dominant circulating clone 1 (DCC1) of <em>Mycobacterium abscessus</em> subsp. <em>abscessus</em> (MABS) is a major pathogen in people with cystic fibrosis (pwCF) that can cause asymptomatic, indolent colonization or overt nontuberculous mycobacterial pulmonary disease (NTMPD)<sup>1</sup>. This clinical variability raises unresolved questions about the relationship between MABS genetic subtype, virulence-associated phenotypes, and disease outcome. Understanding and characterizing DCC1 is central to addressing the growing burden of MABS infections in pwCF. We hypothesize that <em>in vitro</em> and <em>ex vivo</em> phenotypes may explain the fitness of DCC1 isolates and predict clinical outcomes (NTMPD vs indolent infections) in pwCF.</div></div><div>Dominant circulating clone 1 (DCC1) of <em>Mycobacterium abscessus</em> subsp. <em>abscessus</em> (MABS) is a major pathogen in people with cystic fibrosis (pwCF) that can cause asymptomatic, indolent colonization or overt nontuberculous mycobacterial pulmonary disease (NTMPD)<sup>1</sup>. This clinical variability raises unresolved questions about the relationship between MABS genetic subtype, virulence-associated phenotypes, and disease outcome. Understanding and characterizing DCC1 is central to addressing the growing burden of MABS infections in pwCF. We hypothesize that <em>in vitro</em> and <em>ex vivo</em> phenotypes may explain the fitness of DCC1 isolates and predict clinical outcomes (NTMPD vs indolent infections) in pwCF.</div><div><h3>Methods</h3><div>Intrinsic virulence was evaluated between DCC1 (<em>n</em>=28) vs non-DCC1 (<em>n</em>=20) MABS isolates that cause indolent (<em>n</em>=20) or NTMPD (<em>n</em>=28) using a variety of <em>in vitro</em> phenotypic assays and <em>ex vivo</em> experiments. Illumina short read sequencing was mapped to the MABS ATCC 19977 reference genome using Bowtie2 and sorted using Samtools. SNPs were determined by variant calling using BCFtools. Smooth and rough MABS were called based on visual morphological assessments and tested for pellicles as a surrogate indicator for biofilms, presence of glycopeptidolipids (GPL) by thin-layer chromatography, evasion of LL-37 antimicrobial peptide, and successful infection of primary immune cell models.</div></div><div>Intrinsic virulence was evaluated between DCC1 (<em>n</em>=28) vs non-DCC1 (<em>n</em>=20) MABS isolates that cause indolent (<em>n</em>=20) or NTMPD (<em>n</em>=28) using a variety of <em>in vitro</em> phenotypic assays and <em>ex vivo</em> experiments. Illumina short read sequencing was mapped to the MABS ATCC 19977 reference genome using Bowtie2 and sorted using Samtools. SNPs were determined by variant calling using BCFtools. Smooth and rough MABS were called based on visual morphological assessments and tested for pellicles as a surrogate indicator for biofilms, presence of glycopeptidolipids (GPL) by thin-layer chromatography, evasion of LL-37 antimicrobial peptide, and ","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 7"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965059","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":"Safety and efficacy of elexacaftor/tezacaftor/ivacaftor in children ≥2 years with cystic fibrosis: 96-week interim results from a phase 3 open-label extension study","authors":"Jennifer L. Goralski,&nbsp;Cori Daines,&nbsp;Jessica E. Pittman,&nbsp;Jonathan H. Rayment,&nbsp;Philip Robinson,&nbsp;Rebecca Thursfield,&nbsp;Florian Stehling,&nbsp;Felix Ratjen,&nbsp;Neil Ahluwalia,&nbsp;Peng Shi,&nbsp;Mengdi Lu,&nbsp;Tanya G. Weinstock,&nbsp;Marcus A. Mall","doi":"10.1016/j.jcf.2026.05.014","DOIUrl":"10.1016/j.jcf.2026.05.014","url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor/tezacaftor/ivacaftor(ELX/TEZ/IVA) was safe and efficacious in children with CF 2–5y with at least one <em>F508del</em> allele in 24-week phase 3 Trial 445–111. Children who completed 445–111 were eligible for the long-term safety and efficacy extension trial.</div></div><div><h3>Methods</h3><div>This 2-part (part A and B), open-label, phase 3, 192-week trial enrolled children ≥ 2y who completed 445–111. Primary endpoint: safety and tolerability. Secondary endpoints: absolute changes in sweat chloride(SwCl) concentration and lung clearance index 2.5(LCI_2.5). 96-week analysis (Part A) is reported.</div></div><div><h3>Results</h3><div>Seventy children received ELX/TEZ/IVA and mean exposure was 89.9 (SD: 17.0) weeks. All children had ≥1 adverse event(AE), most AEs were mild (35.7%) or moderate (52.9%) in severity. Most AEs were generally consistent with known manifestations of CF in children. Fifteen children had ≥1 serious AE, of which 1 (DIOS) was considered related to ELX/TEZ/IVA. Three children discontinued due to AEs. Decreases in SwCl (-57.0 mmol/L [95%CI: -61.5, -52.6]) and LCI_2.5 (-0.90 [95%CI: -1.14, -0.67]) were sustained from parent trial baseline, 80.8% of children achieved SwCl&lt;60 mmol/L (below diagnostic threshold) and 28.8% achieved SwCl&lt;30 mmol/L (normal). Growth remained in normal range throughout treatment period. Increases in fecal elastase-1 from parent trial baseline were maintained through Week 96, with 9 children above the pancreatic sufficiency threshold.</div></div><div><h3>Conclusions</h3><div>ELX/TEZ/IVA remained generally safe and well-tolerated in this extension trial. SwCl and lung function improvements reported in parent trial were maintained through additional 96 w of treatment. These results demonstrate long-term safety and efficacy, and CF disease-modifying potential of ELX/TEZ/IVA in children ≥2y.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 778-785"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in chronic therapies for cystic fibrosis following initiation of CFTR modulators: A UK retrospective cohort study 2009 - 2023","authors":"Jordan Busby,&nbsp;Tricia M McKeever,&nbsp;Andrew W Fogarty,&nbsp;Helen L Barr","doi":"10.1016/j.jcf.2026.06.003","DOIUrl":"10.1016/j.jcf.2026.06.003","url":null,"abstract":"<div><h3>Introduction</h3><div>People with Cystic Fibrosis have a significant treatment burden from large numbers of maintenance therapies required to manage this multi-organ condition. Currently, there are limited data on the impact of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator use, including Elexacaftor/Tezacaftor/Ivacaftor (ETI), on prescribing of traditional maintenance therapies in the UK.</div></div><div><h3>Methods</h3><div>Retrospective analysis of chronic medications obtained from UK CF registry data, from 2009 to 2023. Impact of starting ETI on maintenance therapies was analysed using descriptive statistics. For those on ETI, risk factors associated with stopping maintenance treatments were identified by logistic regression models, adjusted for age, sex, and percentage predicted FEV₁. Socioeconomic status (SES) was determined by Townsend score quintiles.</div></div><div><h3>Results</h3><div>Overall, chronic medication use decreased for both those prescribed and not prescribed CFTR modulators. Those on ETI, who previously were on dual modulator therapy, had an absolute reduction of 15.1% in inhaled antibiotics, 14.7% in dornase alfa and 9.8% in hypertonic saline by 3 years after ETI initiation. Older age, higher body mass index, and poorer lung function were associated with lower odds of stopping inhaled antibiotics and azithromycin for those on ETI. Those in the lowest SES quintile had significantly lower odds of discontinuing azithromycin (OR:0.61; CI:0.40–0.91) and flucloxacillin (OR:0.54; CI:0.33–0.86), compared to the highest SES quintile.</div></div><div><h3>Conclusions</h3><div>Overall, prescriptions of traditional maintenance therapies reduced, irrespective of CFTR modulator use. These data suggest deprescribing may have occurred, despite a limited evidence base to support safe antibiotic withdrawal in this population.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 851-858"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive colorectal cancer screening in cystic fibrosis: Promise, pitfalls, and future directions","authors":"Liron Birimberg-Schwartz,&nbsp;Eitan H Zlotnick,&nbsp;Lior H Katz","doi":"10.1016/j.jcf.2026.08.001","DOIUrl":"10.1016/j.jcf.2026.08.001","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 763-764"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813171","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: 21Leveraging genetic vulnerabilities to identify new antibiotic targets in Pseudomonas aeruginosa","authors":"J. Sullivan,&nbsp;J. Bagnall,&nbsp;A. Wang,&nbsp;N. Shoresh,&nbsp;T. Warrier,&nbsp;D. Hung","doi":"10.1016/j.jcf.2026.07.053","DOIUrl":"10.1016/j.jcf.2026.07.053","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Antibiotic resistant &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; accounts for significant mortality and morbidity in patients with cystic fibrosis, despite major advances made in treating the underlying genetic disease with therapies such as Trikafta. Among the key challenges in discovering new antibiotics against &lt;em&gt;P. aeruginosa&lt;/em&gt; is that currently used antibiotics target a limited set of bacterial processes, while &lt;em&gt;P. aeruginosa&lt;/em&gt; encodes more than 300 core essential genes under conditions relevant to human infection, representing a large pool of potential targets.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Antibiotic resistant &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; accounts for significant mortality and morbidity in patients with cystic fibrosis, despite major advances made in treating the underlying genetic disease with therapies such as Trikafta. Among the key challenges in discovering new antibiotics against &lt;em&gt;P. aeruginosa&lt;/em&gt; is that currently used antibiotics target a limited set of bacterial processes, while &lt;em&gt;P. aeruginosa&lt;/em&gt; encodes more than 300 core essential genes under conditions relevant to human infection, representing a large pool of potential targets.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To address this gap, we used a functional genomics approach using CRISPR interference (CRISPRi) to systematically identify the most vulnerable genes and prioritize targets for next-generation antibiotic development. We first engineered a tightly regulated CRISPRi system, enabling the construction of a pooled library of 12,697 strains targeting 839 conditionally essential genes in &lt;em&gt;P. aeruginosa&lt;/em&gt;. We then performed CRISPRi-Seq screens using this library in the reference strain PA14 and two clinical isolates grown under multiple conditions, including LB, synthetic cystic fibrosis media, and fetal bovine serum.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;To address this gap, we used a functional genomics approach using CRISPR interference (CRISPRi) to systematically identify the most vulnerable genes and prioritize targets for next-generation antibiotic development. We first engineered a tightly regulated CRISPRi system, enabling the construction of a pooled library of 12,697 strains targeting 839 conditionally essential genes in &lt;em&gt;P. aeruginosa&lt;/em&gt;. We then performed CRISPRi-Seq screens using this library in the reference strain PA14 and two clinical isolates grown under multiple conditions, including LB, synthetic cystic fibrosis media, and fetal bovine serum.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Gene vulnerability was inferred by measuring the rate at which individual CRISPRi strains were depleted during serial passaging of the pool. These analyses identified lipopolysaccharide (LPS) and peptidoglycan synthesis, as well as aminoacyl-tRNA synthetases, as among the most vulnerable pathways to genetic perturbation. In contrast, the ribosome was unexpectedly invulnerable. Within the LPS transport pathway, we identified the periplasmic bridge protein LptA as a unique point of ","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 10"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964742","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: 43Hypermutation accelerates the evolution of drug-resistant Mycobacterium avium during chronic CF infection","authors":"N. Bolden,&nbsp;Q. She,&nbsp;S. Rajagopal,&nbsp;P. Kaur,&nbsp;J. Logan,&nbsp;J. Mell,&nbsp;P. Planet","doi":"10.1016/j.jcf.2026.07.075","DOIUrl":"10.1016/j.jcf.2026.07.075","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Mycobacterium avium&lt;/em&gt; (MAC) is the leading cause of chronic nontuberculous mycobacterial pulmonary disease (NTM-PD) in people with underlying co-morbidities such as cystic fibrosis (pwCF). Chronic MAC lung infection is difficult to treat because of high levels of antibiotic resistance and host toxicity during treatment. Even in the advent of advanced treatment options such as CFTR modulator therapies, the incidence and prevalence of chronic NTM-PD in pwCF have steadily been increasing over the past few years. Although MAC can persist in the lung for years, there is a knowledge gap regarding the molecular mechanisms it can use to establish chronic infection. To address this deficit, we conducted a retrospective longitudinal analysis on 62 isolates from a single pwCF over 5 years of chronic MAC lung infection. Phylogenetic analysis revealed two clonal populations, with a multidrug-resistant population emerging later during infection. This latter emerging lineage (VAR) harbored more single-nucleotide polymorphisms (SNPs) than the initial infecting lineage (PRO). It also contained SNPs exclusively in the DNA repair genes &lt;em&gt;uvrA&lt;/em&gt; and &lt;em&gt;recR&lt;/em&gt;. These results led us to hypothesize that the identified DNA repair mutations result in hypermutation, a phenomenon in which DNA repair defects increase the mutation rate and produce genetic variants better adapted to the environment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Mycobacterium avium&lt;/em&gt; (MAC) is the leading cause of chronic nontuberculous mycobacterial pulmonary disease (NTM-PD) in people with underlying co-morbidities such as cystic fibrosis (pwCF). Chronic MAC lung infection is difficult to treat because of high levels of antibiotic resistance and host toxicity during treatment. Even in the advent of advanced treatment options such as CFTR modulator therapies, the incidence and prevalence of chronic NTM-PD in pwCF have steadily been increasing over the past few years. Although MAC can persist in the lung for years, there is a knowledge gap regarding the molecular mechanisms it can use to establish chronic infection. To address this deficit, we conducted a retrospective longitudinal analysis on 62 isolates from a single pwCF over 5 years of chronic MAC lung infection. Phylogenetic analysis revealed two clonal populations, with a multidrug-resistant population emerging later during infection. This latter emerging lineage (VAR) harbored more single-nucleotide polymorphisms (SNPs) than the initial infecting lineage (PRO). It also contained SNPs exclusively in the DNA repair genes &lt;em&gt;uvrA&lt;/em&gt; and &lt;em&gt;recR&lt;/em&gt;. These results led us to hypothesize that the identified DNA repair mutations result in hypermutation, a phenomenon in which DNA repair defects increase the mutation rate and produce genetic variants better adapted to the environment.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;To test this hypothesis, clinical MAC isolates and isogenic mutants of &lt;em&gt;M. smegmatis&lt;/em&gt; were subjecte","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 21-22"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964764","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: 44Reduced pathogens in bronchoalveolar lavage fluid from young children on elexacaftor/tezacaftor/ivacaftor","authors":"E. Zemanick,&nbsp;C. O'Rourke,&nbsp;R. Russell,&nbsp;J. Sullivan,&nbsp;J. Chmiel,&nbsp;R. Buckingham,&nbsp;K. Ode,&nbsp;B. Ramsey,&nbsp;S. Heltshe,&nbsp;L. Hoffman","doi":"10.1016/j.jcf.2026.07.076","DOIUrl":"10.1016/j.jcf.2026.07.076","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Elexacaftor/tezacaftor/ivacaftor (ETI) results in improved lung function and fewer pulmonary exacerbations for many people with cystic fibrosis (CF). In older children and adults with CF treated with ETI, airway infection with conventional pathogens are reduced but, particularly for those with preexisting chronic infection, airway infections often persist.[1] In young children with CF (CwCF), oropharyngeal cultures are used clinically to monitor for airway infections, but often do not correlate well with lower airway samples which are difficult to obtain.[2] BEGIN Part B (NCT04509050) is a longitudinal study of CwCF prior to and following initiation of ETI, including collection of bronchoalveolar lavage (BAL) fluid from a subset of participants. We sought to compare lower airway pathogens detected from BAL fluid before and after ETI initiation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Elexacaftor/tezacaftor/ivacaftor (ETI) results in improved lung function and fewer pulmonary exacerbations for many people with cystic fibrosis (CF). In older children and adults with CF treated with ETI, airway infection with conventional pathogens are reduced but, particularly for those with preexisting chronic infection, airway infections often persist.[1] In young children with CF (CwCF), oropharyngeal cultures are used clinically to monitor for airway infections, but often do not correlate well with lower airway samples which are difficult to obtain.[2] BEGIN Part B (NCT04509050) is a longitudinal study of CwCF prior to and following initiation of ETI, including collection of bronchoalveolar lavage (BAL) fluid from a subset of participants. We sought to compare lower airway pathogens detected from BAL fluid before and after ETI initiation.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The BEGIN BAL sub-study is enrolling up to 20 CwCF at 5 study sites for research bronchoscopy with BAL during clinical stability prior to and one and two years following ETI initiation. Local microbiologic laboratories culture BAL samples for CF pathogens. Aliquots are shipped frozen to the CFF Microbiologic Outcomes Advancement Core (MOAC) Laboratory at University of Washington for future microbiome analyses and to the CFF Center for Biochemical Markers at Children’s Hospital Colorado for future inflammatory marker analysis. Oropharyngeal swabs and reagent and bronchoscope control aliquots are also collected and shipped frozen to MOAC. Data are presented as counts/percentages or mean ± standard deviation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;The BEGIN BAL sub-study is enrolling up to 20 CwCF at 5 study sites for research bronchoscopy with BAL during clinical stability prior to and one and two years following ETI initiation. Local microbiologic laboratories culture BAL samples for CF pathogens. Aliquots are shipped frozen to the CFF Microbiologic Outcomes Advancement Core (MOAC) Laboratory at University of Washington for future microbiome analyses and to the CFF Center for Biochemical Markers at Children’s Hospi","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 22"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964765","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: 45Cell-type–resolved heterogeneity of early Mycobacterium abscessus infection in a human small airway epithelial model","authors":"A. Shiozawa,&nbsp;H. Murano,&nbsp;H. Dang,&nbsp;G. Crisp,&nbsp;S. Randell,&nbsp;W. O'Neal,&nbsp;K. Okuda,&nbsp;K. Olivier","doi":"10.1016/j.jcf.2026.07.077","DOIUrl":"10.1016/j.jcf.2026.07.077","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Nontuberculous mycobacterial infections, particularly &lt;em&gt;Mycobacterium abscessus&lt;/em&gt; (&lt;em&gt;M. abscessus&lt;/em&gt;), are increasingly recognized in patients with bronchiectasis, including those with cystic fibrosis (CF). Because epithelial dysfunction and mucus abnormalities shape host–pathogen interactions in CF airways, defining early epithelial responses to &lt;em&gt;M. abscessus&lt;/em&gt; is clinically important. However, how early infection distributes across epithelial populations, and whether this reflects cell-type–specific tropism or dynamic propagation remains unclear, even in well-controlled non-CF airway models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Nontuberculous mycobacterial infections, particularly &lt;em&gt;Mycobacterium abscessus&lt;/em&gt; (&lt;em&gt;M. abscessus&lt;/em&gt;), are increasingly recognized in patients with bronchiectasis, including those with cystic fibrosis (CF). Because epithelial dysfunction and mucus abnormalities shape host–pathogen interactions in CF airways, defining early epithelial responses to &lt;em&gt;M. abscessus&lt;/em&gt; is clinically important. However, how early infection distributes across epithelial populations, and whether this reflects cell-type–specific tropism or dynamic propagation remains unclear, even in well-controlled non-CF airway models.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Primary human small airway epithelial (SAE) cells from six non-CF donors were differentiated at an air–liquid interface under mucus-preserving conditions. Cells were infected apically with &lt;em&gt;M. abscessus&lt;/em&gt; (ATCC 19977) harboring a GFP-expressing plasmid at multiplicities of infection (MOI) of 100 and 1000 and analyzed at post-infection days (PID) 1 and 3. Bulk RNA sequencing and RT-qPCR were performed to characterize epithelial responses. In parallel, cytospin-based imaging analyses were conducted in a subset of samples using epithelial marker panels spanning basal, ciliated, and secretory compartments (TP63, FOXJ1, MUC5B, CCSP, SFTPB, and MUC5AC) in combination with bacterial detection to assess marker-defined epithelial infection patterns.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Primary human small airway epithelial (SAE) cells from six non-CF donors were differentiated at an air–liquid interface under mucus-preserving conditions. Cells were infected apically with &lt;em&gt;M. abscessus&lt;/em&gt; (ATCC 19977) harboring a GFP-expressing plasmid at multiplicities of infection (MOI) of 100 and 1000 and analyzed at post-infection days (PID) 1 and 3. Bulk RNA sequencing and RT-qPCR were performed to characterize epithelial responses. In parallel, cytospin-based imaging analyses were conducted in a subset of samples using epithelial marker panels spanning basal, ciliated, and secretory compartments (TP63, FOXJ1, MUC5B, CCSP, SFTPB, and MUC5AC) in combination with bacterial detection to assess marker-defined epithelial infection patterns.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Bulk transcriptomic profiling revealed early epithelial responses characterized by induction of inflammatory and stress-related pat","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Pages 22-23"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964766","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: 49Sublethal doses of the microbicidal compound hypothiocyanite convert methicillin-resistant Staphylococcus aureus to small colony variants","authors":"J. Fairholm,&nbsp;B. Rada","doi":"10.1016/j.jcf.2026.07.081","DOIUrl":"10.1016/j.jcf.2026.07.081","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Staphylococcus aureus&lt;/em&gt; lung infection is a hallmark of cystic fibrosis (CF), affecting up to 80% of all people with CF (PwCF) by their mid-teens. Additionally, antibiotic resistance also represents an increasing concern, with methicillin-resistant &lt;em&gt;S. aureus&lt;/em&gt; (MRSA) infecting up to 20% of all PwCF. One way &lt;em&gt;S. aureus&lt;/em&gt; can survive in the lungs of PwCF is through the formation of small colony variants (SCVs) which are characterized by colonies that are up to 10 times as small as normal colonies, are non-pigmented, and slower growing. SCVs arise due to alterations in metabolism and may increase resistance to antibiotics and environmental stressors. One way to treat antibiotic resistant infections is with hypothiocyanite (OSCN&lt;sup&gt;-&lt;/sup&gt;). OSCN&lt;sup&gt;-&lt;/sup&gt; is produced through the action of peroxidases such as lactoperoxidase (LPO) and myeloperoxidase (MPO) reacting with hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;) and thiocyanate (SCN&lt;sup&gt;-&lt;/sup&gt;). OSCN&lt;sup&gt;-&lt;/sup&gt; has known antimicrobial effects against a broad range of viral and bacterial pathogens. Our goal was to test the ability of OSCN&lt;sup&gt;-&lt;/sup&gt; to kill CF clinical isolates of MRSA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Staphylococcus aureus&lt;/em&gt; lung infection is a hallmark of cystic fibrosis (CF), affecting up to 80% of all people with CF (PwCF) by their mid-teens. Additionally, antibiotic resistance also represents an increasing concern, with methicillin-resistant &lt;em&gt;S. aureus&lt;/em&gt; (MRSA) infecting up to 20% of all PwCF. One way &lt;em&gt;S. aureus&lt;/em&gt; can survive in the lungs of PwCF is through the formation of small colony variants (SCVs) which are characterized by colonies that are up to 10 times as small as normal colonies, are non-pigmented, and slower growing. SCVs arise due to alterations in metabolism and may increase resistance to antibiotics and environmental stressors. One way to treat antibiotic resistant infections is with hypothiocyanite (OSCN&lt;sup&gt;-&lt;/sup&gt;). OSCN&lt;sup&gt;-&lt;/sup&gt; is produced through the action of peroxidases such as lactoperoxidase (LPO) and myeloperoxidase (MPO) reacting with hydrogen peroxide (H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;) and thiocyanate (SCN&lt;sup&gt;-&lt;/sup&gt;). OSCN&lt;sup&gt;-&lt;/sup&gt; has known antimicrobial effects against a broad range of viral and bacterial pathogens. Our goal was to test the ability of OSCN&lt;sup&gt;-&lt;/sup&gt; to kill CF clinical isolates of MRSA.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;OSCN&lt;sup&gt;-&lt;/sup&gt; was produced in vitro by combining LPO (175 µg/ml) with NaSCN (7.5 mM) and H&lt;sub&gt;2&lt;/sub&gt;0&lt;sub&gt;2&lt;/sub&gt; (5.6 mM) at 4°C. Any remaining H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; was removed by adding catalase (13.1 mg/ml) at 4°C. Catalase and LPO were removed through filtration with 10 kDa amicon spin filters and OSCN&lt;sup&gt;-&lt;/sup&gt; concentration was measured using a DTNB assay. OSCN&lt;sup&gt;-&lt;/sup&gt; was then incubated with 1 × 10&lt;sup&gt;5&lt;/sup&gt; CFU/ml of four CF clinical isolates of MRSA (MRSA24, MRSA25, MRSA47, and MRSA74) and two MRSA reference strains (USA300 and JE","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 24"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964802","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}