The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.
Methods
This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV1 recorded 6 months after acute infection was also evaluated.
Results
A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1 % of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV1 after 6 months from the infection was +1.8 % (95 % CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8 %, 95 % CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1 %, 95 % CI: 0.6-1.9).
Conclusions
In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults.
{"title":"COVID-19 in people with Cystic Fibrosis beyond the pre-omicron era: a prospective study with a specific focus on long COVID","authors":"Carla Colombo , Paola Medino , Marco Cipolli , Francesca Lucca , Giulia Cucchetto , Federico Alghisi , Fabiana Ciciriello , Angela Sepe , Camilla Romano , Giovanni Taccetti , Michela Francalanci , Maura Ambroni , Valentina Donati , Giovanna Pizzamiglio , Maura Spotti , Novella Rotolo , Maria Cristina Lucanto , Simona Cristadoro , Francesca Ficili , Giuseppina Leonetti , Francesco Blasi","doi":"10.1016/j.jcf.2025.08.015","DOIUrl":"10.1016/j.jcf.2025.08.015","url":null,"abstract":"<div><h3>Background</h3><div>The long-term clinical consequences of COVID-19 in cystic fibrosis (CF) remain largely unexplored. This study aimed to assess the incidence of long COVID in a large population of people with CF.</div></div><div><h3>Methods</h3><div>This prospective, multicentre study enrolled individuals with confirmed SARS-CoV-2 infection between July 2021 and October 2022. Data collected included clinical features prior to infection, symptoms during the acute phase, hospitalization and symptom persistence after 1 and 6 months. Long COVID was defined according to CDC criteria as persistence of at least one COVID-related symptom for one or more months after diagnosis. The mean variation of FEV<sub>1</sub> recorded 6 months after acute infection was also evaluated.</div></div><div><h3>Results</h3><div>A total of 1102 people with CF were recruited (median age: 18 years, 520 younger than 18). The infection was symptomatic in 90.1 % of cases. During the acute phase, 8 subjects required oxygen support; 31 were hospitalized, one patient required intensive care. Complications included one thromboembolic event and two episodes of myocarditis, but no patient died. Mean variation of FEV<sub>1</sub> after 6 months from the infection was +1.8 % (95 % CI: 1.0-2.7). Long COVID was documented in 64 subjects (5.8 %, 95 % CI: 4.5-7.4) with a variety of symptoms which were still present in 12 cases 6 months after infection (1.1 %, 95 % CI: 0.6-1.9).</div></div><div><h3>Conclusions</h3><div>In the omicron phase of the pandemic, COVID-19 was relatively mild and did not negatively impact pulmonary function after 6 months. Long COVID was observed at all ages, but extrapulmonary symptoms were more frequent and persistent in adults.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 172-178"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000625","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}
We previously demonstrated that Tezacaftor inhibits the enzyme (DEGS) that converts dihydroceramides (dHCer) into ceramides, thus producing accumulation of dHCer in various cells and tissues. We here conducted an in-vivo safety study, by administering ETI to CD-1 mice during pregnancy and breastfeeding.
Methods
ETI was incorporated into mouse food (in a high-fat diet regimen). Pups' behavior was measured with SHIRPA tests. ETI and dHCer levels in plasma and tissues, as well as changes in the global lipidome were measured by tandem mass spectrometry coupled to liquid chromatography.
Results
At 10 days after birth, we observed a significant accumulation of dHCer in the brains of pups born from ETI-fed dams compared to controls. No accumulation was observed in the sciatic nerve of these animals, likely due to much lower levels of ETI compared to the brain. We also conducted an untargeted lipidomics survey, which revealed other alterations in lipid metabolism associated with exposure to ETI during pregnancy. During breastfeeding, given the negligible exposure to the drug, these alterations revert and virtually disappear at P28, together with other differences in the phenotype and behavior of the pups observed earlier during development.
Conclusions
We here demonstrate that exposure to ETI during pregnancy is associated with observable molecular changes in the brain lipidome, which are not likely limited to the inhibition of DEGS. These changes are reverted when exposure to ETI ceases.
{"title":"Exposure of dams to Elexacaftor/ Tezacaftor/Ivacaftor during pregnancy and breastfeeding induces reversible alterations in newborn wild type CD-1 mice","authors":"Angelica Squarzoni , Gaia Boschetti , Sine Mandrup Bertozzi , Maria Summa , Angelo Serani , Elisa Milandri , Roberto Mandrioli , Michele Protti , Laura Mercolini , Caterina Montani , Giovanna Capodivento , Giuliana Cangemi , Nicoletta Pedemonte , Tiziano Bandiera , Fabio Benfenati , Lucilla Nobbio , Rosalia Bertorelli , Andrea Armirotti","doi":"10.1016/j.jcf.2025.11.004","DOIUrl":"10.1016/j.jcf.2025.11.004","url":null,"abstract":"<div><h3>Background</h3><div>We previously demonstrated that Tezacaftor inhibits the enzyme (DEGS) that converts dihydroceramides (dHCer) into ceramides, thus producing accumulation of dHCer in various cells and tissues. We here conducted an <em>in-vivo</em> safety study, by administering ETI to CD-1 mice during pregnancy and breastfeeding.</div></div><div><h3>Methods</h3><div>ETI was incorporated into mouse food (in a high-fat diet regimen). Pups' behavior was measured with SHIRPA tests. ETI and dHCer levels in plasma and tissues, as well as changes in the global lipidome were measured by tandem mass spectrometry coupled to liquid chromatography.</div></div><div><h3>Results</h3><div>At 10 days after birth, we observed a significant accumulation of dHCer in the brains of pups born from ETI-fed dams compared to controls. No accumulation was observed in the sciatic nerve of these animals, likely due to much lower levels of ETI compared to the brain. We also conducted an untargeted lipidomics survey, which revealed other alterations in lipid metabolism associated with exposure to ETI during pregnancy. During breastfeeding, given the negligible exposure to the drug, these alterations revert and virtually disappear at P28, together with other differences in the phenotype and behavior of the pups observed earlier during development.</div></div><div><h3>Conclusions</h3><div>We here demonstrate that exposure to ETI during pregnancy is associated with observable molecular changes in the brain lipidome, which are not likely limited to the inhibition of DEGS. These changes are reverted when exposure to ETI ceases.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 13-20"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530608","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.12.012
Rebecca A Dobra
{"title":"News article","authors":"Rebecca A Dobra","doi":"10.1016/j.jcf.2025.12.012","DOIUrl":"10.1016/j.jcf.2025.12.012","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 1-2"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957773","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.10.005
Mariangela Retucci , Andrea Gramegna , Simone Gambazza , Martina Santambrogio , Gianmarco Putti , Alessandra Mariani , Maria Chiara Russo , Marco Vicenzi , Valeria Daccò , Francesco Blasi
Background
Elexacaftor/Tezacaftor/Ivacaftor (ETI) is changing life quality and expectancy of people with Cystic Fibrosis (pwCF). Exercise has a pivotal role in improving health of pwCF and proved to be a reliable indicator of health status. This study aims at describing the effects of 6 months of ETI therapy on pwCF exercise-related health and giving insight on the conditions predisposing to better treatment response.
Methods
In this observational prospective multicentric study were consecutively enrolled pwCF aged ≥16 who started ETI between May 2021 and April 2022 at Milan Children and Adult CF centres. Exercise performance at Cardiopulmonary Exercise Test (CPET), indicated by maximum workload (Wmax), and other functional outcomes were assessed before starting and after 6 months of ETI.
Results
101 pwCF were enrolled in the study, mean age 28.4 (8.7) years, 38.6 % females. 20.8 % were affected by CF-related diabetes (CFRD) and 46.5 % had a previous exposure to CFTR modulators. Wmax significantly improved across timepoints (151.0 [38.6] W to 156.6 [41.1] W, p = 0.008), baseline characteristics associated with such improvement were being more physically active, male sex, CFRD, higher lung clearance index, baseline exercise limitation. No significant change in peak oxygen consumption was observed, while patients experienced an overall improvement in functional outcomes. Fitted regression model showed male subjects and those affected by CFRD are expected to have better exercise performance.
Conclusion
While participants who started ETI treatment experienced some improvement in exercise capacity, the gains were limited. Therefore, integrating physical exercise training remains an essential and impactful strategy to enhance physical fitness.
背景：elexaftor /Tezacaftor/Ivacaftor （ETI）正在改变囊性纤维化（pwCF）患者的生活质量和预期。运动在改善pwCF的健康状况中具有关键作用，被证明是健康状况的可靠指标。本研究旨在描述6个月的ETI治疗对pwCF运动相关健康的影响，并深入了解易导致更好治疗反应的条件。方法：在这项观察性前瞻性多中心研究中，连续入组了2021年5月至2022年4月在米兰儿童和成人CF中心开始ETI治疗的年龄≥16岁的pwCF患者。在ETI开始前和6个月后评估心肺运动测试（CPET）的运动表现，以最大工作量（Wmax）表示，以及其他功能结果。结果：101例pwCF入组，平均年龄28.4（8.7）岁，女性占38.6%。20.8%的人患有cf相关性糖尿病（CFRD）， 46.5%的人以前接触过CFTR调节剂。Wmax在不同时间点显著改善（151.0 [38.6]W至156.6 [41.1]W, p = 0.008），与这种改善相关的基线特征是更活跃的身体活动、男性、CFRD、更高的肺清除率指数、基线运动限制。观察到峰值耗氧量没有显著变化，而患者的功能预后总体改善。拟合的回归模型显示，男性受试者和受CFRD影响的受试者有望有更好的运动成绩。结论：虽然开始ETI治疗的参与者在运动能力方面有一定的改善，但这种改善是有限的。因此，整合体育锻炼训练仍然是提高身体素质的必要和有效的策略。
{"title":"Limited impact of Elexacaftor/Tezacaftor/Ivacaftor on CPET outcomes in an Italian cohort of people with Cystic Fibrosis: reinforcing the essential role of exercise training","authors":"Mariangela Retucci , Andrea Gramegna , Simone Gambazza , Martina Santambrogio , Gianmarco Putti , Alessandra Mariani , Maria Chiara Russo , Marco Vicenzi , Valeria Daccò , Francesco Blasi","doi":"10.1016/j.jcf.2025.10.005","DOIUrl":"10.1016/j.jcf.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor/Tezacaftor/Ivacaftor (ETI) is changing life quality and expectancy of people with Cystic Fibrosis (pwCF). Exercise has a pivotal role in improving health of pwCF and proved to be a reliable indicator of health status. This study aims at describing the effects of 6 months of ETI therapy on pwCF exercise-related health and giving insight on the conditions predisposing to better treatment response.</div></div><div><h3>Methods</h3><div>In this observational prospective multicentric study were consecutively enrolled pwCF aged ≥16 who started ETI between May 2021 and April 2022 at Milan Children and Adult CF centres. Exercise performance at Cardiopulmonary Exercise Test (CPET), indicated by maximum workload (Wmax), and other functional outcomes were assessed before starting and after 6 months of ETI.</div></div><div><h3>Results</h3><div>101 pwCF were enrolled in the study, mean age 28.4 (8.7) years, 38.6 % females. 20.8 % were affected by CF-related diabetes (CFRD) and 46.5 % had a previous exposure to CFTR modulators. Wmax significantly improved across timepoints (151.0 [38.6] W to 156.6 [41.1] W, <em>p</em> = 0.008), baseline characteristics associated with such improvement were being more physically active, male sex, CFRD, higher lung clearance index, baseline exercise limitation. No significant change in peak oxygen consumption was observed, while patients experienced an overall improvement in functional outcomes. Fitted regression model showed male subjects and those affected by CFRD are expected to have better exercise performance.</div></div><div><h3>Conclusion</h3><div>While participants who started ETI treatment experienced some improvement in exercise capacity, the gains were limited. Therefore, integrating physical exercise training remains an essential and impactful strategy to enhance physical fitness.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 63-69"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313036","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.11.013
Rachel G. Sinkey , Bryan Garcia , Christopher Miles Fowler , Stefanie Krick , Kevin J. Ryan , Edward P. Acosta , Jennifer S. Guimbellot
There are a paucity of data regarding the pharmacokinetics (PK) of elexacaftor (ELX)/tezacaftor(TEZ)/ivacaftor(IVA)(ETI) in pregnant and/or lactating mothers and their offspring. We conducted a PK assessment of ETI and their metabolites in maternal/neonatal/cord blood and breast milk from a cystic fibrosis (CF) carrier mother/affected fetus dyad, collecting specimens at delivery, 1 and 4 weeks after birth. The infant received on-label direct dosing after 1 month of life; all PK samples were collected prior to initiation of neonatal dosing and analyzed using LC-MS/MS. Measured metabolites were IVA-M1, IVA-M6, ELX-M23 and TEZ-M1. The female infant was born at 37 weeks gestation with successful meconium passage on the first day of life. Sweat chloride at 15 days (16 and 17 mmol/L) and immunoreactive trypsinogen (27.5 ng/mL) were normal. Neonatal genetics confirmed F508del/P67L genotype. Parent drug concentrations were measurable in cord blood and capillary heel sticks, indicating they cross the placenta. After delivery, the infant’s only source of modulators was via breast milk. Breast milk concentrations were measured at 1 and 4 weeks of life. Relative to maternal concentrations, ETI and their metabolites were present at lower concentrations. Heel stick specimens revealed undetectable IVA, but ELX and TEZ were below the assay limit. IVA-M1 and IV-M6 concentrations were lower at 1 and 4 weeks relative to delivery. To our knowledge, this is the first report of ETI metabolite concentrations following in utero administration.
{"title":"Pharmacokinetic assessment of elexacaftor/tezacaftor/ivacaftor and their metabolites in maternal blood, cord blood, the neonate, and breastmilk of a cystic fibrosis carrier mother/affected fetus dyad","authors":"Rachel G. Sinkey , Bryan Garcia , Christopher Miles Fowler , Stefanie Krick , Kevin J. Ryan , Edward P. Acosta , Jennifer S. Guimbellot","doi":"10.1016/j.jcf.2025.11.013","DOIUrl":"10.1016/j.jcf.2025.11.013","url":null,"abstract":"<div><div>There are a paucity of data regarding the pharmacokinetics (PK) of elexacaftor (ELX)/tezacaftor(TEZ)/ivacaftor(IVA)(ETI) in pregnant and/or lactating mothers and their offspring. We conducted a PK assessment of ETI and their metabolites in maternal/neonatal/cord blood and breast milk from a cystic fibrosis (CF) carrier mother/affected fetus dyad, collecting specimens at delivery, 1 and 4 weeks after birth. The infant received on-label direct dosing after 1 month of life; all PK samples were collected prior to initiation of neonatal dosing and analyzed using LC-MS/MS. Measured metabolites were IVA-M1, IVA-M6, ELX-M23 and TEZ-M1. The female infant was born at 37 weeks gestation with successful meconium passage on the first day of life. Sweat chloride at 15 days (16 and 17 mmol/L) and immunoreactive trypsinogen (27.5 ng/mL) were normal. Neonatal genetics confirmed F508del/P67L genotype. Parent drug concentrations were measurable in cord blood and capillary heel sticks, indicating they cross the placenta. After delivery, the infant’s only source of modulators was via breast milk. Breast milk concentrations were measured at 1 and 4 weeks of life. Relative to maternal concentrations, ETI and their metabolites were present at lower concentrations. Heel stick specimens revealed undetectable IVA, but ELX and TEZ were below the assay limit. IVA-M1 and IV-M6 concentrations were lower at 1 and 4 weeks relative to delivery. To our knowledge, this is the first report of ETI metabolite concentrations following <em>in utero</em> administration.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 28-31"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145633957","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.11.009
Yuxin Chen , Daan Caudri , Eleni-Rosalina Andrinopoulou , Catherine A Byrnes , Joyce Cheney , Peter J Cooper , Keith Grimwood , John Massie , Colin F Robertson , Peter D Sly , Suzanna Vidmar , Claire E Wainwright , Harm A.W.M. Tiddens , Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) and Follow-up of the ACFBAL (CF-FAB) study groups
Background
Cystic fibrosis (CF) lung disease begins early in life and progresses throughout childhood into adolescence. Children completing the Australasian CF Bronchoalveolar Lavage (ACFBAL) trial were followed longitudinally (CF-FAB study) to determine progression of CF lung disease during adolescence using visual and automatic methods and to correlate CT-derived metrics with spirometry outcomes.
Methods
CTs from start and end visits of CF-FAB (mean 24 [SD 12] months apart) were analysed using visual PRAGMA-CF scoring and automatic bronchus-artery (BA) analysis. PRAGMA-CF assessed %Disease by summing %Bronchiectasis, %Mucus plugging, % Airway wall thickening on inspiratory scans and %Trapped air on expiratory scans. The BA-analysis segments the bronchial tree, identifies segmental bronchi (G0) and distal generations (G1, G2, G3…), measures diameters of bronchial outer wall (Bout), inner wall (Bin), wall thickness (Bwt), and artery (A), and computes BA-ratios (Bout/A, Bin/A, Bwt/A, Bwa/Boa[=bronchial wall area/bronchial outer area]) to evaluate bronchial dilatation and wall thickening.
Results
120 children (median age 13 years, IQR 11.4-14) contributed 115 start and 105 end scans. Eleven children were treated with CFTR modulators prior to the start of the study and four received the treatment during the study. Progression was found in PRAGMA-CF %Bronchiectasis (p=0.02) and %Mucus plugging (p=0.02), and Bout/A (p=0.01), Bwt/A (p<0.001), and Bwa/Boa (p<0.001). Spirometry outcomes showed no significant decline. BA-metrics correlated more strongly with spirometry outcomes than PRAGMA-CF scores.
Conclusion
Heterogeneous progression of structural lung disease in children with CF during adolescence was detected using visual PRAGMA-CF scores and automatic BA-analysis. Spirometry outcomes showed no significant decline.
{"title":"Progression of structural lung disease and lung function in adolescents with cystic fibrosis","authors":"Yuxin Chen , Daan Caudri , Eleni-Rosalina Andrinopoulou , Catherine A Byrnes , Joyce Cheney , Peter J Cooper , Keith Grimwood , John Massie , Colin F Robertson , Peter D Sly , Suzanna Vidmar , Claire E Wainwright , Harm A.W.M. Tiddens , Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) and Follow-up of the ACFBAL (CF-FAB) study groups","doi":"10.1016/j.jcf.2025.11.009","DOIUrl":"10.1016/j.jcf.2025.11.009","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis (CF) lung disease begins early in life and progresses throughout childhood into adolescence. Children completing the Australasian CF Bronchoalveolar Lavage (ACFBAL) trial were followed longitudinally (CF-FAB study) to determine progression of CF lung disease during adolescence using visual and automatic methods and to correlate CT-derived metrics with spirometry outcomes.</div></div><div><h3>Methods</h3><div>CTs from start and end visits of CF-FAB (mean 24 [SD 12] months apart) were analysed using visual PRAGMA-CF scoring and automatic bronchus-artery (BA) analysis. PRAGMA-CF assessed %Disease by summing %Bronchiectasis, %Mucus plugging, % Airway wall thickening on inspiratory scans and %Trapped air on expiratory scans. The BA-analysis segments the bronchial tree, identifies segmental bronchi (G<sub>0</sub>) and distal generations (G<sub>1</sub>, G<sub>2</sub>, G<sub>3</sub>…), measures diameters of bronchial outer wall (B<sub>out</sub>), inner wall (B<sub>in</sub>), wall thickness (B<sub>wt</sub>), and artery (A), and computes BA-ratios (B<sub>out</sub>/A, B<sub>in</sub>/A, B<sub>wt</sub>/A, B<sub>wa</sub>/B<sub>oa</sub>[=bronchial wall area/bronchial outer area]) to evaluate bronchial dilatation and wall thickening.</div></div><div><h3>Results</h3><div>120 children (median age 13 years, IQR 11.4-14) contributed 115 start and 105 end scans. Eleven children were treated with CFTR modulators prior to the start of the study and four received the treatment during the study. Progression was found in PRAGMA-CF %Bronchiectasis (p=0.02) and %Mucus plugging (p=0.02), and B<sub>out</sub>/A (p=0.01), B<sub>wt</sub>/A (p<0.001), and B<sub>wa</sub>/B<sub>oa</sub> (p<0.001). Spirometry outcomes showed no significant decline. BA-metrics correlated more strongly with spirometry outcomes than PRAGMA-CF scores.</div></div><div><h3>Conclusion</h3><div>Heterogeneous progression of structural lung disease in children with CF during adolescence was detected using visual PRAGMA-CF scores and automatic BA-analysis. Spirometry outcomes showed no significant decline.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 78-85"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596476","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.10.011
Tatiana Yuzyuk , Catherine M. McDonald , Kayode Balogun , Lauren M. Zuromski , Irene De Biase , Nicole Williams , Suzanne Meihls , Fadi Asfour
Background
Essential fatty acid deficiency (EFAD) is a common complication in people with cystic fibrosis (pwCF). While CFTR modulators (CFTRm) have become the standard of care, their effect on EFAD has been minimally explored. This study assesses the impact of CFTRm on fatty acid (FA) profiles in a large cohort of children/adolescents with CF and examines correlations with clinical outcomes.
Methods
227 blood samples were collected from 163 pwCF (median age: 9.7 years). Most participants were F508del homozygous/compound heterozygous, clinically stable, pancreatic insufficient on enzyme replacement therapy, and receiving CFTRm. FAs were measured by gas chromatography-mass spectrometry.
Results
FA abnormalities in CF were more pronounced in RBCs than in plasma. Low omega-6 linoleic acid (LA) was observed in 4.5 % and 11 % of plasma and RBC samples, respectively. 14.1 % of plasma and 33.9 % of RBC samples had elevated EFAD biomarkers (mead acid (MA) and/or T/T ratio). LA was lower in the participants ≥10 years old. Severe CFTR genotypes were associated with lower LA and higher MA and T/T ratio. In contrast, none of the pwCF with mild genotypes had laboratory findings suggestive of EFAD. There was no improvement in FAs on CFTRm. Elexacaftor/tezacaftor/ivacaftor was no more effective in correcting FA abnormalities than the older generation CFTRm.
Conclusion
Despite therapeutic and nutritional advances in CF treatment, EFAD remains prevalent and underrecognized in the CF population. The high risk of developing EFAD in pwCF with severe CFTR genotypes warrants the inclusion of the FA testing as a standard of care of these individuals.
{"title":"Persistent plasma and RBC fatty acid abnormalities in children and adolescents with cystic fibrosis on highly effective CFTR modulators","authors":"Tatiana Yuzyuk , Catherine M. McDonald , Kayode Balogun , Lauren M. Zuromski , Irene De Biase , Nicole Williams , Suzanne Meihls , Fadi Asfour","doi":"10.1016/j.jcf.2025.10.011","DOIUrl":"10.1016/j.jcf.2025.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Essential fatty acid deficiency (EFAD) is a common complication in people with cystic fibrosis (pwCF). While CFTR modulators (CFTRm) have become the standard of care, their effect on EFAD has been minimally explored. This study assesses the impact of CFTRm on fatty acid (FA) profiles in a large cohort of children/adolescents with CF and examines correlations with clinical outcomes.</div></div><div><h3>Methods</h3><div>227 blood samples were collected from 163 pwCF (median age: 9.7 years). Most participants were F508del homozygous/compound heterozygous, clinically stable, pancreatic insufficient on enzyme replacement therapy, and receiving CFTRm. FAs were measured by gas chromatography-mass spectrometry.</div></div><div><h3>Results</h3><div>FA abnormalities in CF were more pronounced in RBCs than in plasma. Low omega-6 linoleic acid (LA) was observed in 4.5 % and 11 % of plasma and RBC samples, respectively. 14.1 % of plasma and 33.9 % of RBC samples had elevated EFAD biomarkers (mead acid (MA) and/or T/T ratio). LA was lower in the participants ≥10 years old. Severe CFTR genotypes were associated with lower LA and higher MA and T/T ratio. In contrast, none of the pwCF with mild genotypes had laboratory findings suggestive of EFAD. There was no improvement in FAs on CFTRm. Elexacaftor/tezacaftor/ivacaftor was no more effective in correcting FA abnormalities than the older generation CFTRm.</div></div><div><h3>Conclusion</h3><div>Despite therapeutic and nutritional advances in CF treatment, EFAD remains prevalent and underrecognized in the CF population. The high risk of developing EFAD in pwCF with severe CFTR genotypes warrants the inclusion of the FA testing as a standard of care of these individuals.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 38-46"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458715","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.12.005
Edith T. Zemanick , Manesha Putra , Hannah Elfman , Michael V. Zaretsky , Jordana E. Hoppe
{"title":"Response to Wynn et al. re: “False reassurance following single gene non-invasive prenatal testing for cystic fibrosis”","authors":"Edith T. Zemanick , Manesha Putra , Hannah Elfman , Michael V. Zaretsky , Jordana E. Hoppe","doi":"10.1016/j.jcf.2025.12.005","DOIUrl":"10.1016/j.jcf.2025.12.005","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 183-184"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743050","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.09.009
Paolo Pezzella , Mario Brandon Russo , Angela Sepe , Antonella Tosco , Paolo Buonpensiero , Giovanna Izzo , Teodoro Aragona , Elena Cantone
Background
Chronic rhinosinusitis (CRS) is common in cystic fibrosis (CF) and affects quality of life (QoL), especially in children. Objective tools like Peak Nasal Inspiratory Flow (PNIF) may aid in assessing nasal obstruction and monitoring treatment, but their role in CF is not well established.
Methods
This prospective cohort study included 49 children (mean age: 11.4 ± 3.3 years) with CF or CFTR-related disorder (CFTR-RD) from a regional referral center. All underwent nasal endoscopy scored via the Lund-Kennedy (LK) system, spirometry (FEV₁), PNIF measurement, and QoL assessment using the Sinus and Nasal Quality of Life Survey questionnaire (SN-5) and a Visual Analogue Scale (VAS). Correlations between PNIF, clinical parameters, and subjective scores were analyzed.
Results
The mean age of participants was 11.4 ± 3.3 years; 53 % were male. All patients had CRS (mean LK score: 5.6 ± 4.2). The mean PNIF was 79.1 ± 32.3 L/min (z-score ≈ 0.00), and mean FEV₁ was 98.6 % ± 18 of predicted. PNIF was significantly higher in males than females (p = 0.003). A significant inverse correlation was found between PNIF and LK score (r = –0.538, p < 0.001), and a positive correlation between PNIF and FEV₁ (p = 0.001). No correlations were observed between PNIF and QoL scores (VAS, SN-5) or between LK score and QoL. Genotype did not significantly influence PNIF-age trajectories. In a subgroup of patients on CFTR modulators, PNIF did not differ significantly from the rest of the cohort.
Conclusion
PNIF is a feasible, well-tolerated, and non-invasive method for assessing nasal airflow in children with CF. It correlates significantly with both sinonasal inflammation and pulmonary function, supporting its potential role as a surrogate marker of global airway health. Given its simplicity and physiological relevance, PNIF may serve as a valuable adjunct in clinical and research settings to monitor upper and lower airway interactions in pediatric CF. Further longitudinal studies are warranted to validate its sensitivity to therapeutic interventions.
{"title":"Peak nasal inspiratory flow as an adjunct measure of respiratory function in paediatric cystic fibrosis","authors":"Paolo Pezzella , Mario Brandon Russo , Angela Sepe , Antonella Tosco , Paolo Buonpensiero , Giovanna Izzo , Teodoro Aragona , Elena Cantone","doi":"10.1016/j.jcf.2025.09.009","DOIUrl":"10.1016/j.jcf.2025.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis (CRS) is common in cystic fibrosis (CF) and affects quality of life (QoL), especially in children. Objective tools like Peak Nasal Inspiratory Flow (PNIF) may aid in assessing nasal obstruction and monitoring treatment, but their role in CF is not well established.</div></div><div><h3>Methods</h3><div>This prospective cohort study included 49 children (mean age: 11.4 ± 3.3 years) with CF or CFTR-related disorder (CFTR-RD) from a regional referral center. All underwent nasal endoscopy scored via the Lund-Kennedy (LK) system, spirometry (FEV₁), PNIF measurement, and QoL assessment using the Sinus and Nasal Quality of Life Survey questionnaire (SN-5) and a Visual Analogue Scale (VAS). Correlations between PNIF, clinical parameters, and subjective scores were analyzed.</div></div><div><h3>Results</h3><div>The mean age of participants was 11.4 ± 3.3 years; 53 % were male. All patients had CRS (mean LK score: 5.6 ± 4.2). The mean PNIF was 79.1 ± 32.3 L/min (z-score ≈ 0.00), and mean FEV₁ was 98.6 % ± 18 of predicted. PNIF was significantly higher in males than females (<em>p</em> = 0.003). A significant inverse correlation was found between PNIF and LK score (<em>r</em> = –0.538, <em>p</em> < 0.001), and a positive correlation between PNIF and FEV₁ (<em>p</em> = 0.001). No correlations were observed between PNIF and QoL scores (VAS, SN-5) or between LK score and QoL. Genotype did not significantly influence PNIF-age trajectories. In a subgroup of patients on CFTR modulators, PNIF did not differ significantly from the rest of the cohort.</div></div><div><h3>Conclusion</h3><div>PNIF is a feasible, well-tolerated, and non-invasive method for assessing nasal airflow in children with CF. It correlates significantly with both sinonasal inflammation and pulmonary function, supporting its potential role as a surrogate marker of global airway health. Given its simplicity and physiological relevance, PNIF may serve as a valuable adjunct in clinical and research settings to monitor upper and lower airway interactions in pediatric CF. Further longitudinal studies are warranted to validate its sensitivity to therapeutic interventions.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 47-51"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400943","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}
Pub Date : 2026-01-01DOI: 10.1016/j.jcf.2025.11.007
Nazanin Abolhassani , Kim Dao , Roberta Noseda , Francesca Bedussi , Alessandro Ceschi , Alice Panchaud , Ursula Winterfeld
Background
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed the management of cystic fibrosis (CF), but evidence on their safety during pregnancy remains limited and pregnancy-related adverse drug reactions (ADRs) are not well characterized.
Methods
We analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to identify signals of disproportionate reporting (SDRs) for pregnancy-related ADRs associated with elexacaftor, ivacaftor, tezacaftor and lumacaftor, reported until 15 December 2024.
Results
Of 1035 pregnancy-related ICSRs with CFTR modulators, 280 met inclusion criteria. Two SDRs were identified: spontaneous abortion (n = 96 events, reporting odds ratio [ROR] 2.43; 95% confidence interval [CI] 1.99–2.97) and pre-eclampsia (n = 17 events, ROR 4.29; 95% CI 2.66–6.92). Reported birth defects were heterogeneous, with no recurring patterns. There was no SDR for prematurity. These findings align with recent observational studies and preclinical data indicating no teratogenic effects of CFTR modulators.
Conclusion
CFTR modulators were not associated with the reporting of consistent patterns of congenital anomalies or prematurity in this large pharmacovigilance analysis. SDRs for spontaneous abortion and pre-eclampsia should be interpreted cautiously given the limitations inherent to the used study design and require confirmation in prospective pregnancy registries and controlled studies.
{"title":"CFTR during pregnancy and adverse drug reactions: A pharmacovigilance disproportionality analysis in VigiBase","authors":"Nazanin Abolhassani , Kim Dao , Roberta Noseda , Francesca Bedussi , Alessandro Ceschi , Alice Panchaud , Ursula Winterfeld","doi":"10.1016/j.jcf.2025.11.007","DOIUrl":"10.1016/j.jcf.2025.11.007","url":null,"abstract":"<div><h3>Background</h3><div>Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed the management of cystic fibrosis (CF), but evidence on their safety during pregnancy remains limited and pregnancy-related adverse drug reactions (ADRs) are not well characterized.</div></div><div><h3>Methods</h3><div>We analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to identify signals of disproportionate reporting (SDRs) for pregnancy-related ADRs associated with elexacaftor, ivacaftor, tezacaftor and lumacaftor, reported until 15 December 2024.</div></div><div><h3>Results</h3><div>Of 1035 pregnancy-related ICSRs with CFTR modulators, 280 met inclusion criteria. Two SDRs were identified: spontaneous abortion (<em>n</em> = 96 events, reporting odds ratio [ROR] 2.43; 95% confidence interval [CI] 1.99–2.97) and pre-eclampsia (<em>n</em> = 17 events, ROR 4.29; 95% CI 2.66–6.92). Reported birth defects were heterogeneous, with no recurring patterns. There was no SDR for prematurity. These findings align with recent observational studies and preclinical data indicating no teratogenic effects of CFTR modulators.</div></div><div><h3>Conclusion</h3><div>CFTR modulators were not associated with the reporting of consistent patterns of congenital anomalies or prematurity in this large pharmacovigilance analysis. SDRs for spontaneous abortion and pre-eclampsia should be interpreted cautiously given the limitations inherent to the used study design and require confirmation in prospective pregnancy registries and controlled studies.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"25 1","pages":"Pages 21-27"},"PeriodicalIF":6.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564195","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}
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