Journal of Cystic Fibrosis最新文献

{"title":"CFTR modulator therapy reshapes airway inflammation in cystic fibrosis: Insights from proteomics and machine learning","authors":"Filip Årman,&nbsp;Stefanie Diemer,&nbsp;Lotta J. Happonen,&nbsp;Lisa I. Påhlman","doi":"10.1016/j.jcf.2026.05.002","DOIUrl":"10.1016/j.jcf.2026.05.002","url":null,"abstract":"<div><h3>Background</h3><div>CFTR modulators, including Elexacaftor/Tezacaftor/Ivacaftor (ETI), have markedly improved clinical outcomes for people with cystic fibrosis (pwCF), but the molecular impact on airway inflammation remains incompletely understood. This study aimed to characterise longitudinal changes in airway inflammation and sputum proteomes following ETI treatment.</div></div><div><h3>Methods</h3><div>Sputum from pwCF (<em>n</em> = 30) was collected before ETI initiation and after 3 and 9–12 months of treatment. Sputum from healthy controls (<em>n</em> = 7) were included for comparison. Proteomes were analysed using data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS), and cytokines using Mesoscale assays. Differential expression analysis and correlations between airway proteomes and inflammatory cytokines were performed. Machine learning (XGBoost with bootstrapping approach) was applied to identify proteins predictive of ETI response.</div></div><div><h3>Results</h3><div>ETI induced broad proteomic shifts, mainly related to decreased neutrophil degranulation and an increase in anti-proteases. Machine learning predicted proteins linked to RNA splicing, ER stress and lipid transport as contributors to treatment response. IL-1β, IL-8, and TNFα decreased with treatment, correlating with neutrophil-related proteins. In contrast, IL-6 levels increased and correlated with mucin O-glycosylation pathways. Despite these improvements, proteomic and cytokine profiles remained distinct from healthy controls.</div></div><div><h3>Conclusion</h3><div>ETI therapy reduces neutrophilic inflammation and restores the protease/antiprotease balance but does not fully normalise airway biology. Machine learning provides novel insights into molecular determinants of ETI response, suggesting a role for RNA splicing, ER stress and lipid metabolism. This dataset provides a valuable resource for further exploration of CF airway biology under ETI therapy.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 909-917"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929777","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":"Impact of ETI therapy on bone health, body composition and cardiopulmonary fitness in children with CF","authors":"A Holden,&nbsp;P Burns,&nbsp;A Devenny,&nbsp;L Thomson,&nbsp;R Langley,&nbsp;S Shepherd,&nbsp;A Mason","doi":"10.1016/j.jcf.2026.05.013","DOIUrl":"10.1016/j.jcf.2026.05.013","url":null,"abstract":"<div><h3>Background</h3><div>Improved survival in cystic fibrosis (CF) has shifted clinical focus toward late complications, including altered body composition, bone health and cardiopulmonary fitness. The effects of Elexacaftor/Tezacaftor/Ivacaftor (ETI) on these outcomes in paediatric patients remain unclear.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included paediatric CF patients undergoing dual-energy X-ray absorptiometry (DXA) at annual review before and 2 years after ETI initiation. Lean mass index (LMI), fat mass index (FMI), lumbar spine bone mineral apparent density (LS-BMAD) and total body less head bone mineral content (TBLH-BMC) were converted to age and sex-adjusted standard deviation scores (SDS). Spirometry and cardiopulmonary exercise testing (CPET) assessed lung function and cardiopulmonary fitness. A matched CF control group not receiving modulators was included.</div></div><div><h3>Results</h3><div>47 children were included (ETI <em>n</em> = 23, controls <em>n</em> = 24). LMI declined significantly following ETI (mean change -0.64, <em>p</em> = 0.02) but remained stable in controls (<em>p</em> = 0.36). LS-BMAD declined in the ETI group (mean change -0.45, <em>p</em> = 0.009) with no change in controls (<em>p</em> = 0.31). VO_2peak % predicted decreased in the ETI group (median change -12%, <em>p</em> = 0.0018) alongside reductions in anaerobic threshold (-14%, <em>p</em> &lt; 0.01) and increased breathing reserve (+15%, <em>p</em> &lt; 0.01), controls showed no significant changes. FEV1 % predicted remained stable in both groups.</div></div><div><h3>Conclusions</h3><div>Despite preserved lung function, ETI treated children exhibited declines in lean mass, trabecular bone density and cardiopulmonary fitness, consistent with deconditioning. DXA and CPET provide important complementary information beyond BMI and spirometry, supporting targeted physical activity and nutritional interventions in ETI treated paediatric CF patients.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 819-826"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042511","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":"Real-time breath metabolomics to assess early response to CFTR modulators in adults with cystic fibrosis: An open-label proof-of-concept study","authors":"Emmanuelle Bardin,&nbsp;Hélène Salvator,&nbsp;Camille Roquencourt,&nbsp;Elodie Lamy,&nbsp;Nicolas Hunzinger,&nbsp;Isabelle Sermet-Gaudelus,&nbsp;Sandra De Miranda,&nbsp;Dominique Grenet,&nbsp;Philippe Devillier,&nbsp;Stanislas Grassin-Delyle","doi":"10.1016/j.jcf.2026.06.013","DOIUrl":"10.1016/j.jcf.2026.06.013","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective CFTR modulators, particularly elexacaftor/tezacaftor/ivacaftor (ETI), produce rapid clinical improvements in people with cystic fibrosis. Yet early effects may be difficult to capture with spirometry or sweat test in patients with a mild disease or atypical mutations. Exhaled breath is rich in volatile organic compounds (VOCs) reflecting metabolic and inflammatory processes. We aimed to determine whether ETI induces early, measurable changes in breath composition and whether these relate to clinical outcomes.</div></div><div><h3>Methods</h3><div>Ten adults initiating ETI were enrolled in a prospective, open-label study with breath sampling at baseline, week one and month one. VOCs were measured using real-time proton-transfer-reaction - mass spectrometry (PTR-MS). Longitudinal changes were assessed using multilevel statistics, including univariate linear mixed-effects models, and multivariate repeated measures ANOVA-simultaneous component analysis plus (RM-ASCA+); repeated-measures correlations examined associations with lung function and sweat chloride concentration. Results were compared with a healthy cohort.</div></div><div><h3>Results</h3><div>Amongst the eight clinical responders, 11 features changed significantly after ETI initiation. Eight differed from healthy controls at baseline and shifted towards healthy levels over one month. RM-ASCA+ identified monotonous and non-monotonous patterns capturing various dynamics such as acute, progressive or delayed metabolic responses. A 11-feature PLS-DA model classified visits with high accuracy (AUC=0.84–0.96). Ten VOCs correlated with clinical readouts. Tentatively identified features pointed towards a shift in the microbiome and/or energy metabolism.</div></div><div><h3>Conclusions</h3><div>ETI induces rapid alterations in exhaled VOCs, many trending towards healthy values and correlating with clinical improvement. Real-time breath analysis offers a promising non-invasive surrogate for early monitoring of therapeutic response.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 796-804"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368572","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":"Normalization of total bilirubin after switch from elexacaftor/tezacaftor/ivacaftor to vanzacaftor/tezacaftor/deutivacaftor in patients with cystic fibrosis and Gilbert’s syndrome","authors":"Naehrig S,&nbsp;Breuling M","doi":"10.1016/j.jcf.2026.06.011","DOIUrl":"10.1016/j.jcf.2026.06.011","url":null,"abstract":"<div><ul><li><span>•</span><span><div>Treatment with ETI might unmask Gilbert’s syndrome in some patients with cystic fibrosis.</div></span></li><li><span>•</span><span><div>One possible explanation might be an interaction of elexacftor and its metabolite M23elexacaftor with the transport proteins OATP1B1 and OATP1B3.</div></span></li><li><span>•</span><span><div>The new triple modulator VTD seems to have less interactions with OATP1B1 and OATP1B3.</div></span></li><li><span>•</span><span><div>We recognized a normalization of total bilirubin levels in pwCF and Gilbert’s syndrome after the switch from ETI to VTD.</div></span></li><li><span>•</span><span><div>Larger subject numbers have to confirm that VTD might be better in pCF and Gilbert’s syndrome.</div></span></li></ul></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 5","pages":"Pages 817-818"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470877","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":"Publication Information","authors":"","doi":"10.1016/S1569-1993(26)03726-4","DOIUrl":"10.1016/S1569-1993(26)03726-4","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page iii"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964541","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: 83The NET effect on NF-κB–activation in CF epithelia and the impact of ETI","authors":"A. Dasgupta,&nbsp;S. Shanker,&nbsp;D. Baird,&nbsp;B. Ziegelmeyer,&nbsp;M. Imbrogno,&nbsp;R. Pasula,&nbsp;J. Meeker,&nbsp;H. Morgan,&nbsp;C. Black,&nbsp;P. Harrison,&nbsp;E. Kramer,&nbsp;J. Brewington,&nbsp;J. Clancy,&nbsp;K. Hudock","doi":"10.1016/j.jcf.2026.07.115","DOIUrl":"10.1016/j.jcf.2026.07.115","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Neutrophil extracellular traps (NETs) are web-like structures composed of DNA and associated proteins released by neutrophils as part of the innate immune response. In cystic fibrosis (CF), elevated NET burden has been strongly associated with severe structural lung disease. We previously demonstrated NETs stimulate human bronchial epithelial (HBE) cells to secrete increased levels of proinflammatory cytokines relevant to CF lung disease, however the mechanism by which this occurs is unknown. Elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to reduce the concentrations of several inflammatory cytokines in the lungs of people with CF. We hypothesize that NETs drive proinflammatory cytokine production in CF epithelia via NF-κB activation, and ETI only partially attenuates this response.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Neutrophil extracellular traps (NETs) are web-like structures composed of DNA and associated proteins released by neutrophils as part of the innate immune response. In cystic fibrosis (CF), elevated NET burden has been strongly associated with severe structural lung disease. We previously demonstrated NETs stimulate human bronchial epithelial (HBE) cells to secrete increased levels of proinflammatory cytokines relevant to CF lung disease, however the mechanism by which this occurs is unknown. Elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to reduce the concentrations of several inflammatory cytokines in the lungs of people with CF. We hypothesize that NETs drive proinflammatory cytokine production in CF epithelia via NF-κB activation, and ETI only partially attenuates this response.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;16HBEge CFTR F508del cell lines were exposed to freshly generated human NETs, produced from peripheral blood neutrophils stimulated with 25 nM PMA for 18 hours. Total and phosphorylated NF-κB protein expression was assessed by western blot. Cells were pretreated with the NF-κB inhibitor, BAY 11-7082 (2.5 μM) for 24 hours prior to NET exposure. Epithelial supernatants were analyzed for IL-8 and TNF-α levels by ELISA, while cytokine RNA expressions (e.g., IL-8, IL-1α, IL-1β, TNF-α) were quantified in cell lysates by q-PCR. To assess the impact of CFTR modulators, cells were pretreated with elexacaftor/tezacaftor for 24 hours, followed by addition of ivacaftor along with NET exposure for an additional 18 hours.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;16HBEge CFTR F508del cell lines were exposed to freshly generated human NETs, produced from peripheral blood neutrophils stimulated with 25 nM PMA for 18 hours. Total and phosphorylated NF-κB protein expression was assessed by western blot. Cells were pretreated with the NF-κB inhibitor, BAY 11-7082 (2.5 μM) for 24 hours prior to NET exposure. Epithelial supernatants were analyzed for IL-8 and TNF-α levels by ELISA, while cytokine RNA expressions (e.g., IL-8, IL-1α, IL-1β, TNF-α) were quantified in cell lysates by q-PCR. To assess the impact of CFTR modulators, cells were pretreate","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 42"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964803","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: 85Determining Mycobacterium abscessus factors required for infection by therapeutic phage Itos","authors":"S. Greenlund,&nbsp;G. Hatfull,&nbsp;K. Wetzel","doi":"10.1016/j.jcf.2026.07.117","DOIUrl":"10.1016/j.jcf.2026.07.117","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Mycobacterium abscessus&lt;/em&gt; is an opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF); these infections are difficult to treat due to multi-drug resistance and poor patient tolerance of approved antibiotics. Mycobacteriophages show promise as alternative therapeutic agents for these infections. However, &lt;em&gt;M. abscessus&lt;/em&gt; strains vary in phage susceptibility, and there is little known about how phages recognize mycobacteria cells, nor about mechanisms for phage resistance. Phages have been used to treat patients with &lt;em&gt;M. abscessus&lt;/em&gt; infections on a personalized, compassionate use basis, and about half of those treated have shown improvement [1]. Mechanisms of phage-mycobacteria interactions and mycobacteria determinants of phage susceptibility need to be better understood to broaden the application of phage therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Mycobacterium abscessus&lt;/em&gt; is an opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF); these infections are difficult to treat due to multi-drug resistance and poor patient tolerance of approved antibiotics. Mycobacteriophages show promise as alternative therapeutic agents for these infections. However, &lt;em&gt;M. abscessus&lt;/em&gt; strains vary in phage susceptibility, and there is little known about how phages recognize mycobacteria cells, nor about mechanisms for phage resistance. Phages have been used to treat patients with &lt;em&gt;M. abscessus&lt;/em&gt; infections on a personalized, compassionate use basis, and about half of those treated have shown improvement [1]. Mechanisms of phage-mycobacteria interactions and mycobacteria determinants of phage susceptibility need to be better understood to broaden the application of phage therapy.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We performed a genetic screen with a transposon mutagenesis library of clinical isolate &lt;em&gt;M. abscessus&lt;/em&gt; strain GD01 to obtain bacterial mutants resistant to therapeutic phage Itos. Twenty phage resistant mutants were isolated and analyzed by PCR to determine what bacterial gene(s) are essential for Itos infection. To determine if gene interruption prevents phage binding, we performed an adsorption assay with strain GD01 and an Itos-resistant mutant. We also grew &lt;em&gt;M. abscessus&lt;/em&gt; GD01 on standard lab media (7H9 broth and 7H10 agar) and synthetic CF sputum media (SCFM) that mimics the CF lung environment to determine differences in phage susceptibility.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;We performed a genetic screen with a transposon mutagenesis library of clinical isolate &lt;em&gt;M. abscessus&lt;/em&gt; strain GD01 to obtain bacterial mutants resistant to therapeutic phage Itos. Twenty phage resistant mutants were isolated and analyzed by PCR to determine what bacterial gene(s) are essential for Itos infection. To determine if gene interruption prevents phage binding, we performed an adsorption assay with strain GD01 and an Itos-resistant mutant. We also grew &lt;em&gt;M. abscess","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 43"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964805","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: 86Adaptative Staphylococcus aureus phenotypes in CF airways under modulator therapy","authors":"C. Rumpf,&nbsp;E. Braun,&nbsp;S. Deiwick,&nbsp;B. Kahl","doi":"10.1016/j.jcf.2026.07.118","DOIUrl":"10.1016/j.jcf.2026.07.118","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Staphylococcus aureus&lt;/em&gt; is one of the most prevalent pathogens in the airways of people with cystic fibrosis (pwCF), which can persist for years or even decades. To accomplish such an extended persistence, &lt;em&gt;S. aureus&lt;/em&gt; needs to adapt to this hostile environment. Adaptation of &lt;em&gt;S. aureus&lt;/em&gt; to the challenges of the CF lung have been described previously. Small colony variants and the mucoid phenotype with biofilm production represent adaptive strategies of the pathogen to withstand selective pressure, not just in &lt;em&gt;S. aureus&lt;/em&gt; isolated from respiratory samples of pwCF. Highly effective modulator therapy (HEMT, e.g. ETI) affects the frequency of CF pathogen detection, particularly &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; and, to a lesser extent, &lt;em&gt;S. aureus&lt;/em&gt;. Because ETI substantially changes the CF lung environment, pathogens now face different selective pressures. It remains unclear how these ETI-driven environmental shifts influence the adaptive strategies of &lt;em&gt;S. aureus&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;em&gt;Staphylococcus aureus&lt;/em&gt; is one of the most prevalent pathogens in the airways of people with cystic fibrosis (pwCF), which can persist for years or even decades. To accomplish such an extended persistence, &lt;em&gt;S. aureus&lt;/em&gt; needs to adapt to this hostile environment. Adaptation of &lt;em&gt;S. aureus&lt;/em&gt; to the challenges of the CF lung have been described previously. Small colony variants and the mucoid phenotype with biofilm production represent adaptive strategies of the pathogen to withstand selective pressure, not just in &lt;em&gt;S. aureus&lt;/em&gt; isolated from respiratory samples of pwCF. Highly effective modulator therapy (HEMT, e.g. ETI) affects the frequency of CF pathogen detection, particularly &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; and, to a lesser extent, &lt;em&gt;S. aureus&lt;/em&gt;. Because ETI substantially changes the CF lung environment, pathogens now face different selective pressures. It remains unclear how these ETI-driven environmental shifts influence the adaptive strategies of &lt;em&gt;S. aureus&lt;/em&gt;.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We retrospectively characterized &lt;em&gt;S. aureus&lt;/em&gt; isolated from airway specimen (sputum/throat swabs) routinely collected in our CF diagnostics lab. For further analysis, isolates (n=400) from 13 pwCF from two CF centers in Muenster, Germany, with and without ETI were included. From nine pwCF with ETI treatment, sequential isolates from at least 24 months before ETI and up to 60 months with ETI treatment were subject of investigation and also isolates from four pwCF without ETI during the same period of time. Analyses include identification of adaptive phenotypes on Columbia blood and Congo red agar, biofilm characterization and genotyping.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;We retrospectively characterized &lt;em&gt;S. aureus&lt;/em&gt; isolated from airway specimen (sputum/throat swabs) routinely collected in our CF diagnostics lab. For further analysis, isolates (n=400) from 13 pwCF from two CF centers in M","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 ","pages":"Page 43"},"PeriodicalIF":5.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964869","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: 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,&nbsp;J. Tame,&nbsp;H. Morgan,&nbsp;S. Mitchell,&nbsp;R. Dhillon,&nbsp;E. Mahenthiralingam,&nbsp;A. Aseeri,&nbsp;L. Thia,&nbsp;J. Forton","doi":"10.1016/j.jcf.2026.07.103","DOIUrl":"10.1016/j.jcf.2026.07.103","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Sputum induction (SI) in clinic is 2.5 times as effective at identifying pathogens as oropharyngeal sampling (OPS)&lt;sup&gt;1&lt;/sup&gt;, but time-commitment in clinic limits its universal application.&lt;/div&gt;&lt;div&gt;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). &lt;span&gt;&lt;span&gt;https://www.uhwchildren.com/respiratory/cf-homespit/&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Sputum induction (SI) in clinic is 2.5 times as effective at identifying pathogens as oropharyngeal sampling (OPS)&lt;sup&gt;1&lt;/sup&gt;, but time-commitment in clinic limits its universal application.&lt;/div&gt;&lt;div&gt;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). &lt;span&gt;&lt;span&gt;https://www.uhwchildren.com/respiratory/cf-homespit/&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Children age &gt;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: &lt;strong&gt;COUGH, HUFF, COUGH, CLEAR THROAT (hawk), and SPIT&lt;/strong&gt;. 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Children age &gt;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: &lt;strong&gt;COUGH, HUFF, COUGH, CLEAR THROAT (hawk), and SPIT&lt;/strong&gt;. 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.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;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,&nbsp;V. Calado Nogueira de Moura,&nbsp;S. Alper,&nbsp;B. Vestal,&nbsp;J. Nick,&nbsp;J. Honda","doi":"10.1016/j.jcf.2026.07.047","DOIUrl":"10.1016/j.jcf.2026.07.047","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Dominant circulating clone 1 (DCC1) of &lt;em&gt;Mycobacterium abscessus&lt;/em&gt; subsp. &lt;em&gt;abscessus&lt;/em&gt; (MABS) is a major pathogen in people with cystic fibrosis (pwCF) that can cause asymptomatic, indolent colonization or overt nontuberculous mycobacterial pulmonary disease (NTMPD)&lt;sup&gt;1&lt;/sup&gt;. 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 &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;ex vivo&lt;/em&gt; phenotypes may explain the fitness of DCC1 isolates and predict clinical outcomes (NTMPD vs indolent infections) in pwCF.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Dominant circulating clone 1 (DCC1) of &lt;em&gt;Mycobacterium abscessus&lt;/em&gt; subsp. &lt;em&gt;abscessus&lt;/em&gt; (MABS) is a major pathogen in people with cystic fibrosis (pwCF) that can cause asymptomatic, indolent colonization or overt nontuberculous mycobacterial pulmonary disease (NTMPD)&lt;sup&gt;1&lt;/sup&gt;. 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 &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;ex vivo&lt;/em&gt; phenotypes may explain the fitness of DCC1 isolates and predict clinical outcomes (NTMPD vs indolent infections) in pwCF.&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Intrinsic virulence was evaluated between DCC1 (&lt;em&gt;n&lt;/em&gt;=28) vs non-DCC1 (&lt;em&gt;n&lt;/em&gt;=20) MABS isolates that cause indolent (&lt;em&gt;n&lt;/em&gt;=20) or NTMPD (&lt;em&gt;n&lt;/em&gt;=28) using a variety of &lt;em&gt;in vitro&lt;/em&gt; phenotypic assays and &lt;em&gt;ex vivo&lt;/em&gt; 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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;Intrinsic virulence was evaluated between DCC1 (&lt;em&gt;n&lt;/em&gt;=28) vs non-DCC1 (&lt;em&gt;n&lt;/em&gt;=20) MABS isolates that cause indolent (&lt;em&gt;n&lt;/em&gt;=20) or NTMPD (&lt;em&gt;n&lt;/em&gt;=28) using a variety of &lt;em&gt;in vitro&lt;/em&gt; phenotypic assays and &lt;em&gt;ex vivo&lt;/em&gt; 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}