Journal of Cystic Fibrosis最新文献

{"title":"WS15.05Elexacaftor/tezacafor/ivacaftor improves bronchial dilatation in a real-world cohort of adolescents with cystic fibrosis","authors":"A.-S. Bonnel ,&nbsp;I. Sermet-Gaudelus ,&nbsp;A. Letierce ,&nbsp;L. Berteloot ,&nbsp;P. Makani ,&nbsp;D. Caudri ,&nbsp;H. Tiddens ,&nbsp;Y. Chen ,&nbsp;Modul-CF Study Group","doi":"10.1016/j.jcf.2025.03.580","DOIUrl":"10.1016/j.jcf.2025.03.580","url":null,"abstract":"<div><h3>Objective</h3><div>Elexacaftor/ tezacaftor/ivacaftor (ETI) improves clinical status of adolescents with cystic fibrosis (aCF). The impact on lung structure is unclear in the pediatric population.</div></div><div><h3>Methods</h3><div>MODUl-CF is a real-world study of the French pediatric cohort treated by ETI over 5 years. Pulmonary Function Tests include Forced Expiratory Volume in 1 second (FEV₁), Forced Expiratory Flow at 25-75 (FEF_25-75), Residual Volume/Total Lung Capacity (RV/TLC) and, for a subset of patient, Lung Clearance Index and sputum inflammatory markers. Low dose inspiratory controlled chest CT images are assessed using the LungQ^TM platform (Thirona, Nijmegen) bronchus-artery (BA) analysis, automated PRAGMA-CF analysis, and the Mucus Plugging (MP) analysis. The BA-analysis measures the dimensions of all detectable bronchi and their adjacent arteries e.g; the bronchial outer diameter (B_out), the bronchial wall thickness (B_wt) all calculated relative to the adjacent artery diameter (A). A transformation back calculates the volume of bronchiectasis (%Bx), bronchial wall thickening (%Bwt), all expressed as percentage of total lung volume (TLV). Bronchiectasis are defined by B_out/A &gt;1.5.</div></div><div><h3>Results</h3><div>All B/A ratios improved significantly in 188 patients who had a chest CT at baseline and M12. Markers of bronchial wall thickening, %Bwt, B_wtA decreased by -0.6 (-1.23; 0.08) (median(Q1; Q3); -0.08(-0.15; -0.01) (p&lt;0.0001). Mucus plugs number and volume decreased substantially to a value approaching 0<strong>.</strong> Measures of bronchiectasis (%Bx and B_outA ratio) decreased significantly by -1.42 (-3.84; -0.1) and -0.09 (-0.2; -0.01); p&lt; 0.0001<strong>.</strong> This correlated with improvement in bronchial pro-inflammatory parameters, RV/TLC and LCI. The number of BA pairs with B_out/A &gt;1.5 decreased significantly from 40%(19) at M0 to 28%(17) at M12 (p&lt;0.0001). This decrease was positively correlated with M0 and M12 B_out/A, B_wtA, mucus plug volume, ppRV/TLC and ppTLV (p&lt;0.0001). The decrease at M12 in number of pairs &gt; 1.5 was correlated with the variation of FEF_25-75 at M1 and M12.</div></div><div><h3>Conclusions</h3><div>ETI improves significantly bronchial dilatation and bronchial wall thickness in aCF. Our data suggest a decrease in the number of bronchiectasis at 1 year ETI in correlation with improvement in bronchial inflammation, lung distension and mucus distal bronchial obstruction.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S30-S31"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205353","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":"WS10.01Microbial tolerance in cystic fibrosis airways is imprinted by a new type of immune memory and can be countered by novel host-directed therapy","authors":"B. Dobosh ,&nbsp;D. Luthra ,&nbsp;J. Hosten ,&nbsp;P. Kumar ,&nbsp;D. Moncada Giraldo ,&nbsp;J. Coppinger ,&nbsp;R. Tirouvanziam","doi":"10.1016/j.jcf.2025.03.546","DOIUrl":"10.1016/j.jcf.2025.03.546","url":null,"abstract":"<div><h3>Objectives</h3><div>Chronic infections in cystic fibrosis (CF) airways are not efficiently countered by antibiotics and CFTR modulators. Our prior studies showed that neutrophils conditioned by the CF airway milieu actively repress microbial killing (Margaroli, Cell Rep Med 2021). Here, we asked if extracellular vesicles (EVs) may underlie this microbial tolerance.</div></div><div><h3>Methods</h3><div>EVs from CF airway supernatant (CF ASN, obtained from sputum by homogenization and removal of cells, bacteria and debris) were characterized by nanoparticle tracking analysis, Western blot, proteomics, qRT-PCR and RNASeq. CF ASN either whole or EV-depleted was used in a transmigration model to recapitulate airway leukocyte conditioning (Dobosh, STAR Prot 2021). EVs from transmigrated neutrophils were used in sequential transmigrations to evaluate signaling recursivity. Microbial killing was assessed by incubation of leukocytes with <em>Pseudomonas aeruginosa</em>.</div></div><div><h3>Results</h3><div>Unlike neutrophils recruited to full CF ASN, those recruited to CF ASN devoid of neutrophil EVs showed normal bacterial killing and their EVs had normal content and did not induce bacterial tolerance in the next wave of transmigrated cells. Like neutrophils, monocytes recruited to CF ASN and differentiated into macrophages also repressed bacterial killing. By omics analysis, we identified the long non-coding RNA MALAT1 in neutrophil EVs, and the histone deacetylase HDAC11 in airway leukocytes as key to this pathological loop. Clinically, MALAT1 levels in CF sputum was negatively correlated with lung function. Therapeutically, HDAC11 inhibitor SIS-17 normalized microbial killing by leukocytes in CF ASN and abrogated EV-mediated tolerance imprinting.</div></div><div><h3>Conclusion</h3><div>Neutrophil EVs mediate a new type of recursive immune memory in CF airways, which forces leukocytes to tolerate microbes and can be countered by host-directed therapy.</div><div><strong>Acknowledgments:</strong> CF Biospecimen Repository, Emory Cytometry and Genomics Cores; R01HL159058 (NIH), TIROUV22G0-CFRD (CFF).</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S19-S20"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203919","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":"WS02.03Cracking the code of CF: empowering children with cystic fibrosis through peer-created resources","authors":"E. Lee Mindel","doi":"10.1016/j.jcf.2025.03.500","DOIUrl":"10.1016/j.jcf.2025.03.500","url":null,"abstract":"<div><h3>Objectives</h3><div>Cystic Fibrosis Trust's Youth Advisory Group are aged 14-25, and have CF or a close family member with the condition. The young people expressed that as children they often felt confused about what was happening to their bodies and were left out of conversations about their care. The group decided to create a CF dictionary of medical terms for 6–9-year-olds. The dictionary aims to empower children and reduce their anxiety, by explaining words that they hear in hospital in child-friendly, compassionate and engaging ways.</div></div><div><h3>Methods</h3><div>The young people met online twice a month to write the dictionary, with the support of the Trust's Lead for Children and Young People. The group wrote over eighty definitions, which balance science and facts with their lived-experiences. Content was checked by a paediatric CF Consultant and CF Psychologist.</div></div><div><h3>Results</h3><div>The group produced a detailed and exciting resource, with child-friendly illustrations and layout. The dictionary engages children by presenting its young authors as CF ‘special agents’, who take the reader on a journey to ‘crack the code of CF’.</div><div>Young people who created the dictionary feel proud that they have created something that will benefit children with CF. By working together to create something impactful and meaningful, the young people have forged valuable friendships and a sense of community. One young person said:</div><div><em>“It has been such an incredible experience, it has increased my confidence with my CF. I really hope it can make a huge difference for children trying to understand their CF.”</em></div></div><div><h3>Conclusions</h3><div>Informing children with CF about their condition and treatments is vitally important. Young people are passionate about this issue, think of innovative ways to address it, and are willing to work diligently to help younger members of the community. By tapping into young people's experience, compassion and creativity we can establish relevant and affective ways of engaging with young children about their CF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S3-S4"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204927","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":"WS06.05Fetal drug exposure after maternally administered elexacaftor/tezacaftor/ivacaftor in a rat model","authors":"E. Schneider-Futschik,&nbsp;D. Li,&nbsp;M. Habgood","doi":"10.1016/j.jcf.2025.03.526","DOIUrl":"10.1016/j.jcf.2025.03.526","url":null,"abstract":"<div><h3>Background</h3><div>The potential effects of the very effective cystic fibrosis triple combination drug, Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pregnancy on prenatal development of offspring remain largely unknown. We aimed to investigate the fetal tissue distribution pattern of maternally administered ETI by placental transfer in the rat fetuses.</div></div><div><h3>Study Design and Methods</h3><div>Sprague Dawley pregnant rats were administered ETI (6.7 mg/kg/d elexacaftor + 3.5 mg/kg/d tezacaftor + 25 mg/kg/d ivacaftor) traced with [3H]-ivacaftor in single dose acute experiments (intraperitoneal injection) or treated orally with ETI (the same dose) for 7 days in sub-chronic experiments. Fetal tissue samples were collected at embryonic day (E) 19 and analyzed using liquid scintillation counting for acute experiments or liquid chromatography-mass spectrometry for sub-chronic experiments.</div></div><div><h3>Results</h3><div>On day E19, after acute exposure, the entry of ivacaftor into fetal brain (brain/plasma concentration ratios &lt;50%) was significantly lower than to other tissues (&gt;100%).</div><div>However, after sub-chronic exposure, the entry of all 3 components into the developing brain was comparably extensive as into other tissues (tissue/plasma ratios, 260 – 1000%). Each component of ETI accumulated in different fetal tissues to approximately equal extent. Inter-litter differences on fetal drug distribution were found in cortex for ivacaftor, muscle for tezacaftor and cortex and mid/hindbrain for elexacaftor. Fetal plasma concentrations of ETI (ng/mL) were variable between litters. The entry of ivacaftor and tezacaftor into adult brain appeared to be restricted (&lt;100%).</div></div><div><h3>Conclusion</h3><div>Fetal rats are exposed to maternally ingested ETI after sub-chronic exposure, potentially impacting fetal development. The brain entry data highlights the need for attention be paid to any long-term potential effects ETI exposure could have on normal brain development.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S13"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204936","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":"WS01.03Factors associated with persistent Pseudomonas aeruginosa infection following elexacaftor/tezacaftor/ivacaftor treatment: insights from the European Cystic Fibrosis Society Patient Registry","authors":"M. Pollak ,&nbsp;S. Gambazza ,&nbsp;A. Orenti ,&nbsp;V. De Rose ,&nbsp;D. Prais ,&nbsp;E. Kerem ,&nbsp;M. Mei-Zahav ,&nbsp;ECFSPR Steering Group","doi":"10.1016/j.jcf.2025.03.494","DOIUrl":"10.1016/j.jcf.2025.03.494","url":null,"abstract":"<div><h3>Objective</h3><div>Elexacaftor/tezacaftor/ivacaftor (ETI) treatment was shown to reduce airway colonization rate of <em>P. aeruginosa</em> (Pa). We aimed to identify factors associated with sustained Pa infection, while on ETI therapy.</div></div><div><h3>Methods</h3><div>Using the European Cystic Fibrosis Society Patient Registry, people with CF (pwCF) who initiated ETI therapy in 2019-2021 were identified. Multivariable logistic regression was used to explore clinical and demographic factors associated with the probability of remaining Pa chronic, while changes in clinical data from one year before to one year after ETI initiation were assessed using multivariable semiparametric models.</div></div><div><h3>Results</h3><div>In total, 6048 pwCF from 30 countries were Pa positive one year prior to ETI initiation. Of these, 3708 remained positive one year after ETI initiation, while 2340 shifted to Pa negative. Female sex (Odds Ratio (OR) 1.51, p&lt;001), age (OR 1.56, P&lt;0.001), D508F heterozygous (OR 1.38, P&lt;0.001) or other genotype vs D508F homozygous (OR 2.38, P&lt;0.001), BMI Z-score (OR 0.82, P&lt;0.001), ppFEV₁ (OR 0.66, P&lt;0.001), GNI (OR 1.06, P=0.02), chronic Burkholderia (OR 0.45, P&lt;0.001) and CF related diabetes (OR 0.82, P=0.001) were factors found associated with the probability of remaining Pa chronic. Change in ppFEV₁ following ETI was similar between those who remained Pa positive (12.0, 95% CI: 11.2–12.7) and those who did not (12.3, 95% CI: 11.5–13.0, p=0.31). BMI Z score change also showed no significant difference (0.40, 95% CI: 0.36–0.44 vs. 0.42, 95% CI: 0.38–0.46, p=0.08). The expected mean hospital days after ETI were higher in those who remained Pa positive: 1.8 (95%CI: 1.4 to 2.2) versus 1.2 (95%CI: 0.9 to 1.4, p&lt;0.001).</div></div><div><h3>Conclusion</h3><div>Several factors specific of more severe CF disease were linked to a higher probability of remaining Pa positive despite ETI. Nonetheless, most clinical parameters showed similar improvement regardless of Pa status changes.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S2"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204943","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":"WS12.01Final height in cystic fibrosis: what are the predictive factors?","authors":"B.E. Bar Aluma,&nbsp;D. Atrakchi,&nbsp;A. Dagan,&nbsp;D. Modan","doi":"10.1016/j.jcf.2025.03.558","DOIUrl":"10.1016/j.jcf.2025.03.558","url":null,"abstract":"<div><h3>Background</h3><div>Growth and nutrition are indexes of health status in people with cystic Fibrosis (pwCF). In this study we evaluated final height of pwCF and compared it to known final adult height in the general population in Israel, and to identify factors potentially affecting final height.</div></div><div><h3>Methods</h3><div>We retrieved data from files of 147 pwCF that were followed at Safra Children's Hospital since its establishment until present day and reached final height. Final height was compared to norms of the general healthy population in Israel. Potential factor that may affect final height were assessed including CFTR mutation severity, gender, weight, date of birth, glucocorticoid treatment, pancreatic insufficiency (PI), diabetes, renal and liver diseases, number of hospitalizations, microbial colonization, and FEV1 %predicted. Height data during growth was retrieved to describe growth patterns.</div></div><div><h3>Results</h3><div>Adult final height in CF is significantly lower in comparison to the healthy population in Israel (p&lt;0.001). When analyzed by gender, the difference in final height was significant in males with CF (172.4±7.6 cm) compared to healthy males in Israel (174.8±6.6 cm) (p&lt;0.001) but not lower in females with CF (161.2±6.5 cm vs 162.9±5.9 cm) (p=0.078). Contributing factors to lower final height in CF are Male sex (p=0.045) and minimal function mutation (p=0.009).</div><div>When examining growth during specific periods, we observed changes compatible with precocious puberty. People with CF had a lower height Z-score to begin with, however with time there was a gradual decrease in height Z-score, and finally, from adolescence to final height there was an increase, reaching final height Z-score similar to values measured during childhood.</div></div><div><h3>Conclusions</h3><div>People with CF had lower final height in comparison to the general healthy population in Israel. Predicting factors were male sex and minimal function CFTR mutations. Growth pattern in both sex were compatible with precious puberty.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S23"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204945","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":"WS13.02Two children homozygous for the complex allele p.Leu467Phe-p.Phe508del with reduced clinical response to elexacaftor/tezacaftor/ivacaftor but differences in nasal potential difference measurement","authors":"R. Dalferth ,&nbsp;K. Schütz ,&nbsp;J. Berger ,&nbsp;S.Y. Graeber ,&nbsp;A. Balázs ,&nbsp;M.A. Mall ,&nbsp;F. Stanke ,&nbsp;P. Maier ,&nbsp;S. Tamm ,&nbsp;N. Alfeis ,&nbsp;B. Tümmler ,&nbsp;A.-M. Dittrich","doi":"10.1016/j.jcf.2025.03.565","DOIUrl":"10.1016/j.jcf.2025.03.565","url":null,"abstract":"<div><h3>Objectives</h3><div>In vitro studies demonstrate that homozygosity for the complex allele p.Leu467Phe-p.Phe508del (L467F-F508del) is associated with failure to respond to Elexacaftor/Tezacaftor/Ivacaftor (ETI). The functional CFTR response in vivo in homozygous carriers of these mutations has not yet been investigated. We report clinical and functional responses towards ETI of two L467F-F508del homozygous children.</div></div><div><h3>Methods</h3><div>Both received functional assessments of CFTR responses via sweat chloride and nasal potential difference (nPD) measurements along with in vitro testing of responsiveness in primary nasal epithelial cell cultures before and during ETI and one child additionally during lumacaftor/ivacaftor (LUM/IVA) therapy.</div></div><div><h3>Results</h3><div>The diagnosis of CF was made in the 1st and 3rd year of life revealing F508del homozygosity in both cases. After initiation of LUM/IVA, no drop in sweat chloride was observed in either child. The girl was switched to ETI at the age of 11, and the boy at age 6 years. Lack of pronounced drop in sweat chloride after initiation of ETI in both children (- 18mmol/l to 85mmol/l and -15 mmol/l to 93 mmol/l, respectively) led to resequencing of CFTR, which revealed L467F homozygosity in both children. Both showed sub-par clinical responses with the girl experiencing continued decline in lung function and the boy demonstrating an above average number of pulmonary exacerbations. Both children received nPD measurements with and without ETI therapy, which showed discrepant responses. Whereas the boy did not have any activity-differences by nPD, the girl showed a sub-par, but notable response during ETI therapy. In vitro testing in nasal epithelial cell culture is pending.</div></div><div><h3>Conclusion</h3><div>The presence of L467F-F508del homozygosity does not lead uniformly abrogate CFTR's response towards modulation via ETI, but is associated with a significantly reduced response. Therefore further investigation of complex alleles on CFTR modulator responsiveness is important.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S25"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205077","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":"WS07.06Early change in forced vital capacity as a determinant of outcome in pulmonary exacerbations of cystic fibrosis","authors":"O.J. McElvaney ,&nbsp;S.L. Heltshe ,&nbsp;D.B. Sanders ,&nbsp;N.E. West ,&nbsp;T. Milinic ,&nbsp;B. Fogarty ,&nbsp;D.R. VanDevanter ,&nbsp;P.A. Flume ,&nbsp;C.H. Goss","doi":"10.1016/j.jcf.2025.03.533","DOIUrl":"10.1016/j.jcf.2025.03.533","url":null,"abstract":"<div><h3>Objectives</h3><div>To characterize the impact of acute pulmonary exacerbations (PEx) of CF on forced vital capacity (FVC, both absolute volume and percent of predicted), identify differences in FVC trajectory among exacerbating PwCF and clarify the association between FVC phenotypes and clinical outcomes.</div></div><div><h3>Methods</h3><div>We performed a secondary analysis of STOP2, a large randomized trial of antimicrobial treatment durations for PEx, that measured FVC at scheduled intervals (n=854). Patterns of FVC decline and trajectory of FVC response were evaluated, and multivariate logistic regression used to identify factors associated with pronounced loss of FVC, as well as with early FVC responses to antibiotics. Differences in absolute FVC recovery, residual FVC loss, symptomatic improvement, and time to next PEx by FVC phenotype were assessed among matched participants. The performance of FVC as a PEx endpoint was investigated via comparison with FEV₁.</div></div><div><h3>Results</h3><div>PEx-induced FVC loss varied within the cohort. Large FVC decreases were associated with <em>Pseudomonas aeruginosa</em> in sputum, circulating C-reactive protein (CRP) concentration ≥30mg/L and age &lt;30, and negatively associated with CFTR modulator use. Although participants with large FVC decreases recovered greater absolute volumes than those with smaller FVC decreases, their residual FVC deficit remained greater. An early FVC response was associated with large initial FVC loss, male sex, age &lt;30, and CRP &lt;30mg/L. Early FVC responders had more complete resolution to baseline FVC and greater symptomatic improvement compared to matched controls. For the overall cohort, the effects of antibiotic duration on FVC and FEV₁ were similar, however with larger variance FVC may be a less sensitive trial measure in certain populations.</div></div><div><h3>Conclusions</h3><div>Distinct FVC decline and FVC response phenotypes exist in acute CF PEx and are associated with differential clinical outcomes. The added utility of FVC as a clinical trial endpoint in PEx is uncertain.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S15"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205330","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":"WS08.02Specific Pseudomonas aeruginosa IgG levels before and after elexacaftor/tezacaftor/ivacaftor treatment","authors":"T. Bryrup ,&nbsp;D. Faurholt-Jepsen ,&nbsp;T. Katzenstein ,&nbsp;M. Skov ,&nbsp;J. Helweg-Larsen ,&nbsp;I.H.M. Mathiesen ,&nbsp;H.K. Johansen ,&nbsp;T. Qvist ,&nbsp;T. Pressler","doi":"10.1016/j.jcf.2025.03.535","DOIUrl":"10.1016/j.jcf.2025.03.535","url":null,"abstract":"<div><div>PA lung infection is a significant concern in people with cystic fibrosis (pwCF). Close monitoring with sputum samples is international standard, however this system of monitoring has become difficult after the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). In Denmark, routine analysis of specific PA immunoglobulin G (IgG) is used in combination with sputum samples. In this study we sought to examine specific PA IgG levels before and after ETI treatment among PA infected pwCF.</div><div>Data on IgG, modulator treatment and pulmonary infections were extracted from the Danish Cystic Fibrosis Cohort and national microbiology database. Data was grouped into four distinct time periods: One year before ETI initiation and the first, second and third year after. Based on sputum microbiology results, all individuals were grouped in accordance with Leeds criteria at each time period. A linear mixed effects model was used to estimate IgG levels.</div><div>236 pwCF were included. Distribution before ETI according to Leeds criteria was ‘<em>never infected’</em> 22 (9,3%), ‘<em>infection free’</em> 103 (44%), ‘<em>intermittent</em>’: 39 (17%) and ‘<em>chronic’</em>: 72 (31%). Among the 39 intermittently infected 24 shifted to ‘<em>infection free’</em> but IgG was unchanged with a difference of 0.6 ELISA units (-0.7; 2.0). Among the 72 chronically infected 19 dropped at least one level on Leeds criteria by year 3 while IgG decreased 2.0 ELISA units 95% CI (1.0; 3.0).</div><div>Our findings suggest that the use of IgG levels with conventional sputum analysis offers insights into the dynamics of PA infection status post-ETI. Among chronically infected individuals, a significant decrease in IgG levels was observed three years following ETI initiation, indicative of a reduction in bacterial load. Conversely, in intermittently infected individuals, no significant change in specific IgG levels was noted despite a large decrease in number of isolated PA, highlighting the need for continued vigilance in monitoring PA despite clinical stability.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S16"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205332","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":"WS08.04Analyzing the impact of elexacaftor/tezacaftor/ivacaftor treatment and Pseudomonas infection on gene expression in cystic fibrosis primary bronchial epithelial cultures","authors":"A. Chaubal,&nbsp;D. Cholon,&nbsp;M. Greenwald,&nbsp;S. Boyles,&nbsp;D. Hong,&nbsp;W. O'Neal,&nbsp;M. Wolfgang,&nbsp;M. Gentzsch","doi":"10.1016/j.jcf.2025.03.537","DOIUrl":"10.1016/j.jcf.2025.03.537","url":null,"abstract":"<div><div>Cystic Fibrosis (CF) is caused by mutations in the <em>CFTR</em> gene which encodes a chloride and bicarbonate ion channel. Ablation or impairment of CFTR function affects multiple organs however, the major pathological consequence affecting patient health is recurring bacterial lung infections, resulting in respiratory failure. <em>P. aeruginosa</em> is one of the predominant bacteria which causes chronic infection in 60-80% CF adults. Although highly effective CFTR modulator therapies are now available, they do not fully eliminate lung infections and their impact on bacterial infections in airway cell culture is not fully understood.</div><div><strong>Objective:</strong> Using our recently established model of diseased airway epithelium, we analyzed the effect of bacterial infection and CFTR modulators on gene expression in primary human bronchial epithelial (HBE) cultures.</div><div><strong>Methods:</strong> Fully differentiated HBE cultures obtained from 6 homozygous F508del donors were infected with <em>P. aeruginosa</em> strain PA01. Tobramycin was added 12 h post infection and cultures were treated with CFTR modulators VX-445, VX-661 and VX-770 for 48 h. RNA isolated from HBE ± bacterial infection and ± ETI was used for bulk RNAseq.</div><div><strong>Results:</strong> We successfully established a 72 h bacteria-epithelia co-culture model in airway cells to mimic persistent bacterial infection. In Pseudomonas infected HBE, RNAseq demonstrated significant changes in expression of genes involved in key biological pathways such as innate immune response, inflammation, hypoxia, cytoskeleton organization. Interestingly, HBE treated with ETI without any bacterial infection also exhibited more than 400 differentially expressed genes. Consistent with our previous report, we observed significant reduction in bacterial load in ETI-treated HBE cells.</div><div><strong>Conclusion:</strong> Our study underscores the importance of incorporating live bacteria to faithfully replicate the CF lung for investigating how bacterial infections and CFTR modulators impact gene expression in airway epithelia.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Pages S16-S17"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205334","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}