Journal of Cystic Fibrosis最新文献

{"title":"WS11.03Infectious dynamics of bacteriophages that lyse diverse cystic fibrosis Stenotrophomonas maltophilia isolates","authors":"C. Crisan ,&nbsp;D. Van Tyne ,&nbsp;J. Goldberg","doi":"10.1016/j.jcf.2025.03.554","DOIUrl":"10.1016/j.jcf.2025.03.554","url":null,"abstract":"<div><h3>Objectives</h3><div>Bacterial pulmonary infections are an important health burden for people with cystic fibrosis (pwCF), even for those taking the CFTR modulator, elexacaftor/tezacaftor/ivacaftor (ETI). <em>Stenotrophomonas maltophilia</em> complex (Smc) is a bacterial pathogen that infects ∼5-30% of pwCF. Infections can lead to increased mortality, more frequent pulmonary exacerbations, and a higher probability of hospitalization. Isolates are often multidrug-resistant, and infections persist even after ETI treatment. Therefore, alternative therapies for Smc are urgently needed. Bacteriophages (phages) are viruses that infect bacteria but do not affect human cells. Lytic phages are efficient at killing specific bacteria (generally from a single species or genus) but leave the healthy microbiome unharmed. Phage therapy uses lytic phages to eradicate bacterial infections and has been successfully administered to pwCF. Smc CF isolates are genomically diverse, and this diversity could impact the ability of phages to target multiple strains. Few phages that lyse CF Smc isolates have been described.</div></div><div><h3>Methods</h3><div>We isolated lytic Smc phages from soil (Lsmp1) and from wastewater (STM02, STM03, STM04, STM05, and STM06). We performed infection assays to determine the host range of these phages on 25 genomically diverse Smc isolates (12 from pwCF). We also analyzed the genomes of the phages we isolated.</div></div><div><h3>Results</h3><div>We observed that Lsmp1 and STM06 are specialists, and each only lyse a single, but distinct Smc strain. By contrast, STM02, STM03, STM04, and STM05 are generalists and lyse multiple genetically distinct strains. Lsmp1 has a genome of ∼42 kilobases and is distantly related to the other five phages we studied, which all have genomes of ∼60-61 kilobases.</div></div><div><h3>Conclusions</h3><div>In this study, we identified both specialist and generalist phages that infect diverse Smc isolates. These results could lead to the development of novel therapies for pwCF infected by multidrug-resistant Smc strains.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S22"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205588","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":"WS14.03Novel pharmacological inhibitors of the NMD mechanism to rescue CFTR function in cystic fibrosis patients with nonsense mutations","authors":"A. Venturini ,&nbsp;A. Borrelli ,&nbsp;F. Ciciriello ,&nbsp;L. Galietta","doi":"10.1016/j.jcf.2025.03.572","DOIUrl":"10.1016/j.jcf.2025.03.572","url":null,"abstract":"<div><h3>Objectives</h3><div>The pharmacological treatment for cystic fibrosis (CF) patients with premature termination codons (PTCs) requires a combinatorial approach that includes inhibitors of the nonsense-mediated RNA decay (NMD) mechanism as well as compounds that promote the ribosomal readthrough. NMD inhibitors can also be effective in the absence of a readthrough agent for PTCs localized at the carboxy-terminus of the CFTR sequence such as W1282X. The aim of our project was to identify novel molecules able to modulate the NMD mechanism.</div></div><div><h3>Methods</h3><div>We screened a chemical library of more than 9,000 compounds using the 16HBE14o^– cell line expressing W1282X-CFTR and the halide-sensitive yellow fluorescent protein (HS-YFP). Cells were incubated for 24 with test compounds plus CFTR correctors. The functional assay allowed to identify compounds enhancing CFTR function. The most effective molecules were characterized by secondary biochemical and functional assays to assess their mechanism of action.</div></div><div><h3>Results</h3><div>75 primary hits were identified by the screening. Molecules with largest effect on CFTR rescue were further tested in the presence/absence of CFTRinh-172 to confirm a direct activity on CFTR channel and not on other anion channels/transporters. We focused our attention on three different compounds: NMDi-01, NMDi-02, NMDi-03. They induced more than 10-fold increase in CFTR-mRNA transcripts and promoted the appearance of a signal for CFTR protein. NMDi-01 and NMDi-02, together with CFTR correctors, generated a marked increase in CFTR channel activity in short-circuit current recordings experiments. NMDi-03 <em>per se</em> elicited a significant increase in CFTR function that was further amplified when it was combined with correctors.</div></div><div><h3>Conclusions</h3><div>We identified three possible candidates acting as NMD inhibitors/modulators that could increase CFTR rescue in patients with PTCs.</div><div><em>This project is supported by CFF (GALIET22I0) and the ECFS (post-doctoral research fellowship to Arianna Venturini)</em></div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S28"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204956","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":"WS08.06Integrative computational analysis of longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum microbiome and proteome in patients with cystic fibrosis","authors":"L. Schaupp ,&nbsp;R.L. Knoll ,&nbsp;K. Fentker ,&nbsp;J. Nazat Martinez Medina ,&nbsp;M. Riabchenko ,&nbsp;V.H. Jarquín-Díaz ,&nbsp;A. Löwe ,&nbsp;J. Duerr ,&nbsp;M. Stahl ,&nbsp;P. Mertins ,&nbsp;S. Boutin ,&nbsp;S.Y. Graeber ,&nbsp;S.K. Forslund-Startceva ,&nbsp;M.A. Mall","doi":"10.1016/j.jcf.2025.03.539","DOIUrl":"10.1016/j.jcf.2025.03.539","url":null,"abstract":"<div><h3>Objectives</h3><div>Despite beneficial effects of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) on the airway microbiome and inflammation in CF patients, residual airway infection and inflammation persist at a level expected to contribute to progressive lung damage over time. The aim of this project was therefore to initiate an integrative computational analysis to identify novel biomarkers and therapeutic targets for persisting airway infection and inflammation.</div></div><div><h3>Methods</h3><div>Sputum samples were collected from CF patients with at least one <em>F508del</em> allele, aged 12 years and older, before and at 1, 3 and 12 months after ETI initiation and subjected to microbiome, proteomic and inflammation marker analysis. An integrative data analysis was used to determine the relationship between clinical covariates, proteomic and inflammatory measures and the microbial composition.</div></div><div><h3>Results</h3><div>Sputum mesh-pore size, free NE activity (<em>P</em>≤0.01), sweat chloride concentration and free CatG activity (<em>P</em>≤0.05) most strongly influenced the airway microbiota composition. Commensal bacteria correlated positively with FEV₁ and negatively with inflammation markers and sputum viscoelasticity. CF pathogens, like <em>Pseudomonas</em>, showed opposite associations and could be linked to immune/inflammatory processes. PERMANOVA revealed that time after treatment had a more significant effect on proteomic (R2=6.2%, <em>P</em>=0.001) than on microbiome profiles (R2=2.5%, <em>P</em>=0.004).</div></div><div><h3>Conclusion</h3><div>Our integrated multi-omics analysis provides initial insights into bacteria-protein associations on ETI therapy. Distinctive association patterns between pathogens and commensals with clinical parameters were observed. Further exploration is required to identify novel biomarkers linked to persisting airway infection and inflammation in CF patients treated with ETI.</div><div>Funded by the German Research Foundation (SFB 1449 – project ID 431232613) and German Federal Ministry of Education and Research (82DZL009C1).</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S17"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205226","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":"WS14.05Effect of vanzacaftor/tezacaftor/ivacaftor on cystic fibrosis airway epithelial cells","authors":"L. Borek Dohalska ,&nbsp;S. Novotna ,&nbsp;E. Furstova ,&nbsp;Z. Varenyiova ,&nbsp;M. Modrak ,&nbsp;T. Dousova ,&nbsp;P. Drevinek","doi":"10.1016/j.jcf.2025.03.574","DOIUrl":"10.1016/j.jcf.2025.03.574","url":null,"abstract":"<div><h3>Objectives</h3><div>The latest triple-component CFTR modulator drug, consisting of vanzacaftor (V), tezacaftor (T) and deutivacaftor (D), is becoming a new treatment alternative to the established combination of elexacaftor (E), tezacaftor (T) and ivacaftor (I) in people with cystic fibrosis (pwCF). While the clinical trial data showed a comparable effect of VTD on FEV1% when compared to ETI, the superiority was reported in terms of improvement of sweat chloride concentrations. Therefore, the aim of our study was to investigate the potential of vanzacaftor to further improve CFTR function by measuring short-circuit current (I_SC).</div></div><div><h3>Methods</h3><div>Primary human nasal epithelial cells (HNEC) derived from 12 F508del/F508del pwCF were analysed in Ussing chamber. HNEC were untreated or pretreated with CFTR modulators (either 3 μM E+3 μM T, or 3 μM V+3 μM T) 48 hours prior Ussing experiments. I_SC was measured after sequential addition of 100 μM amiloride, 10 μM forskolin (Fsk) and 100 μM 3-isobutyl-1-methylxanthine (IBMX), 10 μM I, 10 μM CFTRinhibitor-172 (CFTRinh172) and 100 μM ATP. CFTR activity was calculated as ΔFsk/IBMX+I I_SC and ΔCFTRinh172 I_SC. Spontaneous CFTR activity was determined as difference between I_SC after addition of amiloride and I_SC after addition of CFTRinh172.</div></div><div><h3>Results</h3><div>I_SC measurements demonstrate significant CFTR function improvement after VTI treatment. Compared to ETI, VTI showed significant increase of ΔFsk/IBMX I_SC (difference: 5.36 μA/cm², p &lt; 0.001) as well as significant increase of ΔCFTRinh 172 I_SC (difference: 9.84 μA/cm², p &lt; 0.001). Moreover, spontaneous CFTR activity was improved in VT-treated over ET-treated cultures by 6.27 μA/cm² (p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Our results show significantly greater restoration of CFTR function in F508del/F508del HNEC treated with VTI compared to ETI. These results are in line with the improved sweat chloride values seen in the clinical trial.</div><div>Supported by Ministry of Health of the Czech Republic, grant no NU23-07-00079.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S29"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205337","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":"WS11.02Lack of sirB2 gene stimulates virulence, invasion, and small colony variants emergence in Pseudomonas aeruginosa","authors":"V. Baldelli ,&nbsp;S.J. Carrasco Aliaga ,&nbsp;C.A. Colque ,&nbsp;S. Ravishankar ,&nbsp;H.K. Johansen ,&nbsp;S. Molin ,&nbsp;P. Landini ,&nbsp;E. Rossi","doi":"10.1016/j.jcf.2025.03.553","DOIUrl":"10.1016/j.jcf.2025.03.553","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Pseudomonas aeruginosa</em> is the leading cause of death in cystic fibrosis (CF) patients. The production of virulence factors and the complex adaptation to the host play a crucial role in its pathogenesis. However, knowledge of the genetic determinants that drive <em>P. aeruginosa</em> persistence in the host environment is limited. Based on previously collected transcriptional data from human samples, in this study was investigated the role of <em>sirB2</em>, a <em>P. aeruginosa</em> PA14 gene with unknow function and whose expression is enhanced in the CF lung environment.</div></div><div><h3>Methods</h3><div><em>In silico</em> promoter analysis, molecular genetics and biochemical approaches were used to decipher the <em>sirB2</em> gene regulation. The generation of PA14 mutants and whole-genome sequencing analysis allowed to investigate the role of <em>sirB2</em> on heterogenous phenotypes known to be essential for <em>P. aeruginosa</em> persistence (<em>i.e</em>. biofilm formation, <em>in vitro</em> and <em>in vivo</em> virulence assays on different infection models).</div></div><div><h3>Results</h3><div>In <em>P. aeruginosa, sirB2</em> gene belongs to the Vfr and AmrZ regulons, and its inactivation increases <em>P. aeruginosa</em> pathogenic potential in <em>Galleria melonella</em>. Similarly, gene deletion stimulates transepithelial migration and biofilm formation in an infection model based on air-liquid interface cultures of the airway epithelium. In this context the lack of <em>sirB2</em> promotes the production of virulence determinants and the emergence of rugose small colony variants (RSCVs). RSCVs appearance depends on an increased rate of mutations in the <em>wsp</em> regulatory circuit, leading to increased c-di-GMP levels.</div></div><div><h3>Conclusions</h3><div>Our data identified the <em>sirB2</em> gene as a novel genetic determinant underlying the appearance of heterogenous phenotypes typical of infections, through a mechanism involving specific genetic rearrangement in the PA14 genome.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S22"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205587","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":"WS09.05Potential antimicrobial effects induced in cultured human bronchial epithelia by IL-17/TNF-alpha","authors":"D. Guidone ,&nbsp;M. De Santis ,&nbsp;M. Stabile ,&nbsp;E. De Gregorio ,&nbsp;L.J. Galietta","doi":"10.1016/j.jcf.2025.03.544","DOIUrl":"10.1016/j.jcf.2025.03.544","url":null,"abstract":"<div><div>Defective bacterial eradication and inflammation is an hallmark of many respiratory diseases, including cystic fibrosis (CF). In our previous study (Guidone et al., 2022), we found that treatment of human bronchial epithelia (HBE) with IL-17A/TNF-a, an inflammatory stimulus associated with neutrophilic infiltration, impact on cell transcriptome, with upregulation of genes involved in antimicrobial response, neutrophil recruitment and transepithelial ion transport. The consequence of ion transport changes is a hyperviscosity of the airway surface, that is reversed by b-adrenergic stimulation with isoproterenol. The switch from the hyperviscous to fluid state is dependent on CFTR. Our aim was to evaluate how this affects bacteria viability and motility. We deposited on HBE PAO1 and RP73 P. aeruginosa strains on a selected spot of the apical surface. After incubation, we pressed the snapwells on agar plates. Under control conditions, the bacteria were distributed all over the epithelial surface. Instead, in HBE treated with IL-17/TNF-a, bacteria remained in the area in which they were deposited. These findings indicate that the hyperviscosity elicited by the cytokines strongly limits the diffusion of bacteria. To identify antimicrobial molecules released by HBE, we decided to characterize their secretome. Mass spectrometry of fluid collected from the apical surface of epithelia treated with IL-17/TNF-a revealed an increased abundance of many defense molecules and chemoattractants for immune cells (IL-19, CSF3, CXCL17, CCL20). Surprisingly, we also found a specific set of membrane proteins including ATP12A, SLC26A4, DUOX2, SLC5A1, but not CFTR or ENaC. FACS experiments revealed an increased abundance of EVs upon treatment with IL-17A/TNF-a and the presence of EVs markers. We hypothesize that the presence of EVs may be involved in antimicrobial activity or in communication of regulatory stimuli to epithelial and immune cells.</div><div><em>Work supported by FFC#9/2022 and GMRF#1/2024.</em></div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S19"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203906","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":"WS02.02Experience and needs of children who have a parent with cystic fibrosis","authors":"A. Jacob ,&nbsp;C. Brain ,&nbsp;C. Flahault ,&nbsp;D. Grenet ,&nbsp;D. Hubert","doi":"10.1016/j.jcf.2025.03.499","DOIUrl":"10.1016/j.jcf.2025.03.499","url":null,"abstract":"<div><h3>Objectives</h3><div>To document the experience and needs of children who have a parent with CF.</div></div><div><h3>Methods</h3><div>We conducted focus groups and interviews with persons (minimum 6 years old) who had one parent with CF, followed in Parisian CF centres. Meetings were audio-recorded, transcribed and underwent a thematic analysis.</div></div><div><h3>Results</h3><div>We met 27 participants (6 males), aged from 6 to 38 years old (m=15.4 - 11 children, 7 teenagers and 9 adults) during one group of adults and one of teenagers, two interviews of siblings and 13 individual interviews. The analysis revealed 9 themes: The parent's disease; CF impact and consequences; Lived experience of CF; Conception and adoption; Emotional experience of CF; To talk about CF; Adjustments to CF; Perception of the parent with CF; Needs and expectations.</div><div>Participants appeared well informed on their parents’ CF, the treatments and the consequences. Most of them considered CF as a normal thing in their daily life, something they became used to, although not normal compared to other families. Nonetheless, many parents with CF were described as normal parents. Participants described different impacts on daily life (limitations in activities, reinforced hygiene, organisation around treatments), on how they felt, compared to other children (more responsible or armed for life), and how CF could impact their own parenthood. Many participants described emotional distresses, mainly fears and stress towards the parent's health, and diverse coping strategies such as oblivion of CF, detachment, focusing on the present, or speaking about CF with others. Many expressed needing to be informed about CF (by parents and professionals) in order to better deal with the situation. Some said they would have liked to speak with other children of parents with CF.</div></div><div><h3>Conclusion</h3><div>Although children of parents with CF are used to the disease, they should receive more dedicated attention from healthcare teams, to help them deal with the challenges and emotional distresses.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S3"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204926","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":"WS06.03Towards consensus guidelines: an international survey of follow-up practices for babies exposed to CFTR modulators (CFTRm) in utero and/or via lactation","authors":"I. Bokobza ,&nbsp;A. Downes ,&nbsp;I. Felton ,&nbsp;L. Thomson ,&nbsp;J.C. Davies","doi":"10.1016/j.jcf.2025.03.524","DOIUrl":"10.1016/j.jcf.2025.03.524","url":null,"abstract":"<div><h3>Objectives</h3><div>Limited evidence exists on risks to babies exposed to CFTRm in utero/via lactation. Our objective was to survey CF centre practices to inform consensus guidelines.</div></div><div><h3>Methods</h3><div>Clinicians in two UK centres devised 27 SurveyMonkey questions (max 14/respondent, adult/paediatric specific stems) exploring referral pathways and follow-up. A pilot UK survey and three independent clinicians optimised design. The link was emailed to ECFS and working group members.</div></div><div><h3>Results</h3><div>168 responses, with 28 incomplete removed, resulted in 140 analysed (75 adult, 65 paediatric) from 33 countries, majority from Europe (127). Across 71 adult centre responses, 367 pregnancies were estimated for 2023, with median ∼90% expectant mothers continuing CFTRm. Most adult sites (62%) referred CFTRm-exposed babies, either to general paediatrics (57%) or paediatric CF (43%). 38% do not refer or had no pregnancies. Among paediatric responses 38% always, 34% sometimes, and 22% never follow up these babies (6% unsure). Of those followed-up, 46% reported on-going review, 29% single review, 25% dependent on case. Table 1 specifies investigations offered:</div><div>60% of adult respondents perform a targeted <em>CFTR</em> panel in partner, 30% full <em>CFTR</em> sequencing. Partner genetics dictated baby genetic screening in 29%.</div></div><div><h3>Conclusion</h3><div>The data shows significant variability in practice. Some agreement exists, with most adult sites referring, and paediatric sites reviewing CFTRm exposed babies, with liver tests and cataract reviews most frequently offered. A desire for guidance was frequently expressed. These responses will inform the development of interim guidelines in parallel with a Delphi process to capture consensus.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S12"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204934","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":"WS06.06Exploring experiences of people with cystic fibrosis who have become mothers in the CFTR modulator era","authors":"R. Dobra ,&nbsp;A. Downes ,&nbsp;S. Madge ,&nbsp;R. Robinson ,&nbsp;R. Scott ,&nbsp;J.C. Davies ,&nbsp;I. Felton","doi":"10.1016/j.jcf.2025.03.527","DOIUrl":"10.1016/j.jcf.2025.03.527","url":null,"abstract":"<div><h3>Objectives</h3><div>The increasing number of pregnancies in pwCF reflects the changing landscape. We aimed to explore the motherhood journey experienced by pwCF in the CFTR modulator era.</div></div><div><h3>Method</h3><div>Semi-structured interviews were conducted with pwCF who had received care under the new CF Reproductive &amp; Maternal Health Service at The Royal Brompton. Interviews were recorded, transcribed, coded &amp; analysed using thematic analysis in NVivo.</div></div><div><h3>Findings</h3><div>Thematic saturation was reached at 8 interviews, Nov22-Nov 23. Example concepts which illustrate the experiences of pwCF planning pregnancy &amp; motherhood are outlined here:</div><div><u>ETI &amp; family planning</u></div><div><strong>1) ETI as main facilitator to pursue family planning.</strong> Subthemes a)Perception that ETI supports safer pregnancy, b)More energy to devote to motherhood, c)anticipated increase in life expectancy allowing mothers to see a child mature.</div><div><strong>2) Complex decisions about continuation vs discontinuation of ETI during pregnancy/breastfeeding (BF)</strong> a)balancing risks of continuation/discontinuation on maternal/fetal health, b)wish for dedicated research in this area.</div><div><strong>3) Gratitude for ETI</strong> &amp; life opportunities/milestones previously thought unlikely.</div><div><strong>4) Motherhood intensifying emotions regarding ETI</strong> including fear funding may be withdrawn &amp; survivor guilt.</div><div><u>CF-identity &amp; motherhood</u></div><div><strong>1) Multiple identity shifts</strong> with dynamic changes in level of CF-significance &amp; internal tension as to CF's significance.</div><div><strong>2) CF influence on maternal-identity</strong> particularly pride at overcoming CF-related challenges &amp; growing-up not having considered motherhood possible leading to increased levels of joy &amp; anxiety.</div><div><strong>3) Importance of peer support</strong> from other CF mothers.</div></div><div><h3>Conclusions</h3><div>Dedicated CF-maternal research is needed to optimise reproductive health &amp; wellbeing for pwCF. Stakeholders affirm desire for more evidence to support decisions about ETI/pregnancy/BF; work has begun to understand biological outcomes &amp; qualitative experiences with prospective studies MATRIARCH-CF(UK) &amp; MAYFLOWERS(US).</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":"144204937","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":"WS07.03Expiratory lung proton magnetic resonance imaging is a simple sensitive method to detect gas trapping in cystic fibrosis?","authors":"A.V. Simmons ,&nbsp;L.J. Smith ,&nbsp;Z. Somerville ,&nbsp;H. Faulke ,&nbsp;D. Hughes ,&nbsp;N. West ,&nbsp;A.M. Biancardi ,&nbsp;N.J. Stewart ,&nbsp;J.M. Wild","doi":"10.1016/j.jcf.2025.03.530","DOIUrl":"10.1016/j.jcf.2025.03.530","url":null,"abstract":"<div><h3>Objectives</h3><div>End-expiratory narrowing and obstruction of smaller airways in the lungs of people with Cystic Fibrosis (pwCF) causes “gas trapping” distal to airway closure. Early detection of CF lung disease is crucial for long-term lung health. Lung proton Magnetic Resonance Imaging (¹H-MRI) with a standard spoiled gradient echo recalled (SPGR) sequence offers a non-ionising alternative to Computed Tomography (CT) for visually assessing gas trapping. We aimed to develop a method to quantify gas trapping and compare it to other clinical metrics of lung function, including hyperpolarised xenon (¹²⁹Xe) ventilation MRI, body plethysmography, and spirometry.</div></div><div><h3>Methods</h3><div>Fifteen healthy children and 27 pwCF underwent 3D SPGR ¹H-MRI at approximately residual volume (RV) and total lung capacity (TLC) during a short breath hold. The lung cavity was segmented in all images using a semi-automated approach. A threshold was derived from the TLC images, based on the assumption that gas trapping regions in the RV images should have similar MR signal intensities (SIs) to the lungs at TLC, as both are filled with air. This threshold was applied to the RV images to determine the proportion of lung below it, enabling quantification of gas-trapping volume (GTV%) as a percentage of total lung volume. The upper limit of normal (ULN) was defined at mean +1.64SD of healthy cohort GTV%.</div></div><div><h3>Results</h3><div>Healthy participants (61.5% M) had a median (range) age of 10.64 (8.71-11.92) years and GTV% 1.52% (0.21-2.42%). PwCF (40.7% M) had a median (range) age of 16.90 (6.40-47.50) years, GTV% 20.45% (4.22-83.09%) and FEV₁ z-score -1.14 (-5.43, 2.17), with 14 having normal FEV₁ z-scores. Healthy participants had homogeneous SIs throughout the lungs, while pwCF had heterogeneous areas of increased and decreased SIs, with darker regions corresponding to gas trapping. In pwCF, GTV% strongly correlated with FEV₁ z-scores (p&lt;0.001, ρ=-0.7851) and ventilation defect percentage (VDP) (p&lt;0.001, ρ=0.9223), derived from ¹²⁹Xe-MRI. GTV% correlated with gas trapping measured during body plethysmography (RV/TLC%) (p&lt;0.001, ρ=0.7594). The ULN of GTV% was 2.32%. All pwCF exceeded this, including those with normal FEV₁, highlighting that GTV% is a sensitive metric of early lung function impairment.</div></div><div><h3>Conclusions</h3><div>Using a standard, easily implementable 3D SPGR ¹H-MRI breath-hold sequence, gas trapping in CF is visually apparent and can be quantified to detect lung function impairment with high sensitivity, even when FEV1 is normal. These images can be obtained in children aged &gt;5 years and have the potential to be routinely utilised to assess for early lung disease.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 ","pages":"Page S14"},"PeriodicalIF":5.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204938","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}