Journal of Cystic Fibrosis最新文献

{"title":"Racial disparities in lung transplantation for cystic fibrosis in the era of highly effective modulator therapy","authors":"Jessica M. Ruck ,&nbsp;Shi Nan Feng ,&nbsp;Alexandra H. Toporek ,&nbsp;Pali D. Shah ,&nbsp;Erin Tallarico ,&nbsp;Noah Lechtzin ,&nbsp;Allan B. Massie ,&nbsp;Dorry L. Segev ,&nbsp;Errol L. Bush ,&nbsp;Christian A. Merlo","doi":"10.1016/j.jcf.2025.01.006","DOIUrl":"10.1016/j.jcf.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.</div></div><div><h3>Methods</h3><div>Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005–12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005–1/30/2012), IVA (1/31/2012–10/30/2019), ETI (10/31/2019–12/31/2022)]. We compared the percentage of patients listed, delisted/died, or transplanted by race/ethnicity and era.</div></div><div><h3>Results</h3><div>34,659 lung transplants were performed: 10,521 pre-HEMT, 15,944 in IVA era, and 7,888 in ETI era. Over the three eras, the percentage of lung recipients with CF of White race decreased (94.5 % to 92.4 % to 78.4 %) and of Black race (1.7 % to 2.4 % to 5.7 %) or Hispanic ethnicity increased (3.5 % to 4.6 % to 14.2 %; <em>p</em> &lt; 0.001). Similarly, among candidates listed for CF over the three eras, the percentage that were of White race decreased (82.0 % vs. 78.6 % vs. 71.0 %) and of Black race (9.2 % vs. 10.0 % vs. 10.3 %) or Hispanic ethnicity increased (6.4 % vs. 8.6 % vs. 13.6 %; <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>The introduction of HEMT appears to have benefitted CF lung transplant candidates and recipients of Black race or Hispanic ethnicity less than those of White race. This is likely due to the higher prevalence of HEMT-ineligible CFTR mutations among Black and Hispanic patients and underscores the need for therapies aimed at non-HEMT-responsive mutations prevalent in these racial/ethnic populations.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 278-283"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006157","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":"Real-world outcomes of generic elexacaftor/tezacaftor/ivacaftor (gETI) in South Africans (SA) with CF using standard versus clarithromycin-boosted gETI, modulator-sparing strategies to reduce cost","authors":"Marco Zampoli ,&nbsp;Janine Verstraete ,&nbsp;Cathy Baird ,&nbsp;Tony Biebuyck ,&nbsp;Greg Calligaro ,&nbsp;Marina Coetzee ,&nbsp;Carla Els ,&nbsp;Marlize Frauendorf ,&nbsp;Paul Gebers ,&nbsp;Brenda Morrow ,&nbsp;Dave Richards ,&nbsp;Hanri Truter ,&nbsp;Andrew Hill","doi":"10.1016/j.jcf.2025.02.002","DOIUrl":"10.1016/j.jcf.2025.02.002","url":null,"abstract":"<div><h3>Objective</h3><div>Access to highly effective modulator therapies (HEMT) in resource-limited countries is limited by prohibitive cost and restrictive patents. We report the clinical outcomes of a cost-reduction strategy in South Africa (SA), where generic elexacaftor/tezacaftor/ivacaftor (gETI) was pharmacokinetically enhanced with clarithromycin (gETI/c) for people with CF (pwCF) eligible for HEMT.</div></div><div><h3>Methods</h3><div>A multi-center observational study from December 2021 to May 2024. Analysis of variance (ANOVA) and linear mixed effects analyses were conducted to describe and compare change in sweat chloride (SC), FEV1pp, BMI (m/kg²) and adverse events (AE) over 18-months follow-up for different gETI dose categories: a) standard, full or b) modulator sparing dose (gETI/c at 25–50 % recommended dose, twice/thrice weekly).</div></div><div><h3>Results</h3><div>70/413 (17 %) eligible pwCF [median age 27 years (range 6–52); 68 (97 %) with ≥ one copy F508del] received gETI with standard (<em>n</em> = 38) or modulator-sparing doses (<em>n</em> = 32); 29 changed dosing regimens across the study period. The overall mean (SD) reduction in SC after 1-month of treatment was -52.9 (16.9) mmol/L (<em>p</em> &lt; 0.001), with no evidence of difference between dose groups (<em>p</em> = 0.2). Overall mean (SD) FEV1pp and BMI increased at 1-month by 14.9 (95 % CI 11.49–18.40) and 0.84 (95 % CI 0.16–1.49), respectively. Improvements in FEV1pp and BMI were sustained throughout follow-up, with no evidence of difference between dosing groups. No serious AEs were reported.</div></div><div><h3>Conclusion</h3><div>Our experience with gETI is similar to real-world reports using the originator product. Boosting ETI with CYP3A-inhibitors is a safe and effective strategy to increase access to ETI in settings where access to HEMT is restricted.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 284-289"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies used to access CFTR modulators in countries without reimbursement agreements","authors":"Jonathan Guo ,&nbsp;Grace Hennessy ,&nbsp;Benedict Young ,&nbsp;Andrew Hill","doi":"10.1016/j.jcf.2025.02.010","DOIUrl":"10.1016/j.jcf.2025.02.010","url":null,"abstract":"<div><div>CFTR modulators represent the international standard of care for the treatment of cystic fibrosis (CF). Yet due to prices of over $250,000 per year they are functionally inaccessible for people with CF (pwCF) unless reimbursed by healthcare systems. Current prices are unaffordable for payors in almost all low- and middle-income countries (LMICs) worldwide, and resulting disparities in access are widening existing global health inequities. In comparable situations in other therapeutic areas, patients have successfully developed strategies to bypass national reimbursement systems and gain access to treatment. We therefore undertook an international survey of CF clinicians in 15 countries where CFTR modulators are not reimbursed, to characterise alternative means of accessing modulator therapy.</div><div>Successful methods were identified in 11 countries, and could broadly be categorised into legal challenges to access originator modulators, use of generic formulations, and access via donations. Aside from domestically produced generics used in Argentina and an originator-led donation program in Ukraine, these methods were only able to provide treatment to limited proportions of the local CF population due to significant associated financial costs. Accordingly, they are generally not sustainable or widely applicable, and fail to address the underlying structural issues driving international disparities in access.</div><div>Twelve years after the initial marketing of CFTR modulators, pwCF in LMICs are being forced to take extraordinary measures to access disease-modifying treatment. Corrective measures are urgently required to overcome barriers posed by restrictive patents and prohibitively high prices, and to promote global health equity for pwCF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 290-294"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring cystic fibrosis airway infections with Pseudomonas aeruginosa with anti-OprF serum antibodies","authors":"Burkhard Tümmler ,&nbsp;Christiane Bürger ,&nbsp;Peter Kubesch","doi":"10.1016/j.jcf.2024.06.001","DOIUrl":"10.1016/j.jcf.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><div>The management of cystic fibrosis (CF) requires knowledge of the patient's microbiological status. The serology of anti-<em>Pseudomonas aeruginosa</em> antibodies against exoenzymes or water-soluble antigens has gained diagnostic value, particularly to detect the onset of colonization with <em>P. aeruginosa.</em> However, the diversity and variable expression of these antigens, which was unknown when the ELISAs became common diagnostic procedures at CF clinics, prohibits the quantitative evaluation of bacterial antigen load during intermittent and chronic infection.</div></div><div><h3>Methods</h3><div>An ELISA was developed to measure the serum IgG antibody levels against <em>P. aeruginosa</em> porin OprF, a species-specific, conserved, immunogenic and constitutively expressed protein present in the outer membrane and extracellular vesicles.</div></div><div><h3>Results</h3><div>Serial serum samples were collected from 310 people with CF (pwCF) over a period of up to 15 years. Compared to a reference of <em>P. aeruginosa</em> – negative CF sera set to 1, OprF antibody titers ranged from 0.3 to 13.2 (median: 1.7) in 56 intermittently colonized patients and from 0.5 to 51.2 (median: 11.8) in 176 chronically colonized pwCF showing higher anti-OprF antibody levels during chronic than during intermittent colonization with <em>P. aeruginosa</em> (<em>P</em> = 0, <em>Z</em> = - 21.7, effect size 0.62). Inhalation with twice daily 80 mg tobramycin decreased OprF antibody titers (<em>P</em> = 5 × 10⁻⁵), particularly during the third and fourth year of chronic colonization.</div></div><div><h3>Conclusion</h3><div>The OprF ELISA should be an appropriate tool to monitor Pseudomonas serology at all stages of infection and disease severity and to study the impact of short- and long-term therapeutic interventions.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 353-358"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of race and ethnicity with the development of cystic fibrosis-related diabetes","authors":"Maria S. Rayas ,&nbsp;Blessed Mbogo ,&nbsp;Andrea Kelly ,&nbsp;Phuong Vu ,&nbsp;Amalia Magaret ,&nbsp;Tanicia Daley","doi":"10.1016/j.jcf.2024.07.018","DOIUrl":"10.1016/j.jcf.2024.07.018","url":null,"abstract":"<div><h3>Background</h3><div>CF-related diabetes (CFRD) is a common, life-expectancy limiting complication of CF. While Black race and Hispanic ethnicity in youth-onset type 1 and type 2 diabetes are well-recognized risk factors for worse diabetes complications, the potential for racial/ethnic disparities in CFRD has received limited attention.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study utilizing the CF Foundation Patient Registry from 2010 to 2019 to determine the prevalence and incidence of CFRD by race/ethnicity. Three age cohorts were identified at baseline in 2010 (11–20y, 21–30y, and 31–40y). Logistic regression and Cox regression stratified by age group were used to determine the prevalence and incidence, respectively, among Hispanic, non-Hispanic Blacks (NHB), and non-Hispanic whites (NHW) after adjustment for relevant confounders, including demographics, socioeconomic status, clinical factors, and chronic medication use.</div></div><div><h3>Results</h3><div>Among 14,660 registry participants, 510 were NHB and 890 Hispanic. NHB associated with higher odds of CFRD baseline prevalence in all age cohorts (11–20y: OR 2.53 (95 % CI: 1.88–3.41, <em>P</em> &lt; 0.05), 21–30y: OR 1.80 (1.25–2.59, <em>P</em> &lt; 0.05), and 31–40y: OR 1.93 (1.00–3.73, <em>P</em> &lt; 0.05)) relative to NHW. In the 11–20y cohort, the hazard of new-onset CFRD was 40 % higher in NHB (HR 1.40 (1.09–1.8, <em>P</em> &lt; 0.05)) and 19 % higher in Hispanics (HR 1.19 (1.01–1.41, <em>P</em> &lt; 0.05)).</div></div><div><h3>Conclusion</h3><div>NHB had a higher prevalence of CFRD across all age groups, with NHB and Hispanics showing higher incidence of CFRD in the youngest group. Multicenter studies performed in diverse CF populations are warranted to identify modifiable factors influencing earlier CFRD development in minoritized groups and their potential contribution to diabetes complication disparities.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 263-270"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889388","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":"GRASPing for answers: The shortfalls of our current understanding of the effects of GI-related aspiration on the lungs in CF (GRASP-CF)","authors":"Christopher Vélez ,&nbsp;Isabel Neuringer ,&nbsp;Jeffrey King","doi":"10.1016/j.jcf.2024.09.014","DOIUrl":"10.1016/j.jcf.2024.09.014","url":null,"abstract":"","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 398-400"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347592","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":"Pain in adults with cystic fibrosis – Are we painfully unaware?","authors":"Anastasia Ward ,&nbsp;Ramil Mauleon ,&nbsp;Gretel Davidson ,&nbsp;Chee Y. Ooi ,&nbsp;Nedeljka Rosić","doi":"10.1016/j.jcf.2025.01.009","DOIUrl":"10.1016/j.jcf.2025.01.009","url":null,"abstract":"<div><h3>Background</h3><div>A previous Australia-wide pilot study identified pain as a significant burden in people with CF (pwCF). However, the prevalence, frequency and severity have not been evaluated using validated tools.</div></div><div><h3>Methods</h3><div>Australian adults, pwCF and healthy controls (HC) were invited to complete an online questionnaire from July 2023 – February 2024, consisting of four validated tools: Brief Pain Inventory, Pain Catastrophising Scale, PAGI-SYM and PAC-SYM. The questionnaire, disseminated via Cystic Fibrosis Australia, CF Together and online social media groups, explored experiences surrounding pain and its management using closed and free text entries.</div></div><div><h3>Results</h3><div>There were 206 respondents, consisting of 117 CF patients and 89 HC. Over 70 % (<em>n</em> = 69) of pwCF reported pain compared to 28 % (<em>n</em> = 21) of HC (<em>p</em> = &lt;0.001). Further, significantly higher pain frequency per month was reported for pwCF than HC (40 % vs. 10 %; <em>p</em> &lt; 0.001). Symptom clustering was also observed where at least three other locations of pain were reported, and pain was reported to trigger other physiological and psychological symptoms. Notably, there was no significant difference in the locations, occurrence, frequency or severity of pain between those on a CFTR modulator or not (<em>p</em> = 0.625). PwCF also reported significantly lower relief from over-the-counter therapies (<em>p</em> = 0.002) and expressed themes of unmet symptom and management needs.</div></div><div><h3>Conclusions</h3><div>This study identified a high prevalence of pain affecting multiple body parts in pwCF compared to HC and suggests that pain is sub-optimally managed, impairing their quality of life. Increased awareness and early recognition within the CF clinics and the development of clinical pathways are critically needed to better manage and monitor pain in pwCF, leading to improved quality of life and health outcomes.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 236-245"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in outcomes by race and ethnicity in the Canadian cystic fibrosis population","authors":"Rachel Holland ,&nbsp;Hanna Stewart ,&nbsp;Stephanie Y. Cheng ,&nbsp;Miriam Schroeder ,&nbsp;Sanja Stanojevic","doi":"10.1016/j.jcf.2024.09.009","DOIUrl":"10.1016/j.jcf.2024.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Cystic Fibrosis has historically been described as a disease that affects people of European ancestry. Consequently, much of what we know about CF is based on evidence generated from data collected in white individuals. This may lead to systematic bias in how non-white people with CF are diagnosed and treated. In this study we compared clinical outcomes between the white and non-white people with CF in Canada.</div></div><div><h3>Methods</h3><div>Canadian CF Registry data collected between 2000 and 2019 were used in this population-based cohort study. Demographic characteristics and clinical outcomes of people with CF identified as white and those identified as non-white were compared. Analyses were adjusted for cohort effects but not socioeconomic status.</div></div><div><h3>Results</h3><div>Between 2000 and 2019, 5516 people with CF in the Registry were identified as white and 323 were identified as non-white. At diagnosis, the white and non-white groups were similar with respect to sex at birth, age at diagnosis, prevalence of pancreatic insufficiency, and meconium ileus. The non-white group had similar rates of CF-related complications and bacterial infections compared to the white, but worse lung function, worse nutritional status, lower treatment rates, and higher rate of hospitalizations. During the 20-year study period, the non-white group had a 1.85 higher risk of death compared to the white group (HR 95 %CI 1.39; 2.47).</div></div><div><h3>Interpretation</h3><div>There is an urgent need understand why outcomes for Canadians with CF differ between white and non-white individuals, including the role of socioeconomic circumstances.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 271-277"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection prevention and control in cystic fibrosis: An update of a systematic review of interventions","authors":"Nicola J Rowbotham ,&nbsp;Sherie Smith ,&nbsp;Nikki Jahnke ,&nbsp;Sarah Milczanowski ,&nbsp;Zoe C Elliott ,&nbsp;Andrew P Prayle ,&nbsp;Alan R Smyth","doi":"10.1016/j.jcf.2024.08.004","DOIUrl":"10.1016/j.jcf.2024.08.004","url":null,"abstract":"<div><div>Preventing transmissible infection is a priority in cystic fibrosis (CF) care. This is an update of a systematic review of the evidence for infection prevention and control interventions in CF.</div><div>Our full protocol can be found on PROSPERO (CRD42018109999). We searched for studies and guidelines which included interventions for infection prevention and control in CF.</div><div>We included 39 studies and 7 guidelines. Strategies included: cohort or individual segregation, hand hygiene, facemasks, equipment, enhanced adherence or a combination of these. Many studies showed a reduction in transmission with segregation. However, the certainty of evidence (using GRADE) was low or very low. Most guideline recommendations have little evidence to support them, with no updates since our original review.</div><div>Undertaking RCTs in this area is ethically difficult. Large-scale registry-based studies may be the best pragmatic approach. Benefits of infection control must be balanced against the intrusion in the lives of people with CF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 359-363"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pf bacteriophage is associated with decline in lung function in a longitudinal cohort of patients with cystic fibrosis and Pseudomonas airway infection","authors":"Elizabeth B. Burgener ,&nbsp;Aditi Gupta ,&nbsp;Kayo Nakano ,&nbsp;Sophia L. Gibbs ,&nbsp;Maya E. Sommers ,&nbsp;Arya Khosravi ,&nbsp;Michelle S. Bach ,&nbsp;Colleen Dunn ,&nbsp;Jacquelyn Spano ,&nbsp;Patrick R. Secor ,&nbsp;Lu Tian ,&nbsp;Paul L. Bollyky ,&nbsp;Carlos E. Milla","doi":"10.1016/j.jcf.2024.09.018","DOIUrl":"10.1016/j.jcf.2024.09.018","url":null,"abstract":"<div><h3>Background</h3><div>The Pseudomonas filamentous bacteriophage (Pf) infects <em>Pseudomonas aeruginosa</em> (<em>Pa</em>) and is abundant in the airways of many people with cystic fibrosis (CF) (pwCF). We previously demonstrated that Pf promotes biofilm growth, as well as generates liquid crystals that confer biofilms with adhesivity, viscosity and resistance to clearance. Consistent with these findings, the presence of Pf in sputum from pwCF has been linked to chronic <em>Pa</em> infection and more severe exacerbations in a cross-sectional cohort study.</div></div><div><h3>Methods</h3><div>We examined the relationships between Pf and clinical outcomes in a longitudinal study of pwCF. Sputum <em>Pa</em> and Pf concentrations were measured by qPCR, as well cytokines and active neutrophil elastase by standardized assays. Recorded clinical data, including spirometry and microbiological results, were analyzed for associations with Pf. Finally, lung explants from pwCF in this cohort who underwent lung transplantation were examined for presence of liquid crystals within secretions.</div></div><div><h3>Results</h3><div>In explanted lungs from pwCF with known Pf infection we demonstrate areas of birefringence consistent with liquid crystalline structures within the airways. We find that high concentration of Pf in sputum is associated with accelerated loss of lung function, suggesting a potential role for Pf in the pathogenesis of CF lung disease. We also find Pf to associate with increased airway inflammation and an anti-viral cytokine response.</div></div><div><h3>Conclusion</h3><div>Pf may serve as a prognostic biomarker and potential therapeutic target for <em>Pa</em> infections in CF.</div></div>","PeriodicalId":15452,"journal":{"name":"Journal of Cystic Fibrosis","volume":"24 2","pages":"Pages 345-352"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}