OTO Open. 2025 Feb 20;9(1):e70064. doi: 10.1002/oto2.70064. eCollection 2025 Jan-Mar.

ABSTRACT

OBJECTIVE: Given the recent dramatic changes in medical therapy for cystic fibrosis (CF), this study aims to describe temporal changes in chronic rhinosinusitis (CRS) and endoscopic sinus surgery (ESS) rates.

METHODS: National Inpatient Sample (2004-2019; weighted estimates for 119,067 pediatric and 202,407 adult patients) was used to analyze adult (age ≥18 years) and pediatric patients with CF with pulmonary manifestations. Comorbid CRS, ESS rates, and extended length of stay (LOS, ≥75th percentile) were analyzed.

RESULTS: The rate of CRS in both pediatric (14.1% vs 21.1%, P < .001) and adult (16.5% vs 40.9%, P < .001) patients increased. Rate of ESS in pediatric patients with CRS decreased from 25.3% to 3.4% (P < .001). A similar decline occurred in adults with CRS (12.3% vs 3.6%, P < .001). In multivariate analysis from 2015 to 2019, ESS and extended LOS were associated with admission in the Western United States (P < .001). CRS (OR 1.14, P = .002) and ESS (OR 1.78, P = .002) were independent predictors of extended LOS. Elective admission, primary insurance, race, and hospital teaching/location were significantly associated with ESS and extended LOS (P < .05).

CONCLUSION: Despite the increased prevalence of CRS in adults and pediatric patients with CF, rates of inpatient ESS have declined from 2004 to 2019. Patient and hospital factors affect undergoing ESS in 2015 to 2019. CRS and ESS are associated with extended LOS in recent years.

PMID:39981143 | PMC:PMC11840695 | DOI:10.1002/oto2.70064

Respir Med Case Rep. 2025 Jan 25;53:102171. doi: 10.1016/j.rmcr.2025.102171. eCollection 2025.

ABSTRACT

Lung cancer is uncommon among people with cystic fibrosis (pwCF). We describe the case of a 35-year-old man with mild, stable CF disease who presented with severe respiratory distress, systemic symptoms, elevated liver enzymes and hypereosinophilia along with a lung mass and pleural effusion. The patient was subsequently diagnosed with non-small cell lung carcinoma (NSCLC), featuring anaplastic lymphoma kinase (ALK) translocation. Following treatment with a targeted tyrosine kinase inhibitor (TKI) there was a rapid tumor regression, however, his dyspnea and hypoxemia subsequently worsened. A trial of Elexacaftor/Tezacaftor/Ivacaftor (ETI) led to significant clinical improvement and enhanced pulmonary function. In vitro testing using patient-derived intestinal organoids was performed in parallel and also demonstrated a significant response to ETI. The deterioration observed following the initiation of ALK inhibitor treatment and subsequent improvement with CFTR modulators suggest that ALK inhibitor therapy may potentially impair CFTR activity. A better understanding of the relationship between these pathways could provide valuable insights and contribute to the development of more effective and tailored treatment strategies for patients with coexisting conditions. To our knowledge, this is the first reported case of ALK-translocated lung cancer in a CF patient, underscoring the necessity for a high degree of clinical suspicion in atypical presentations of pulmonary exacerbation and potentially linking ALK-EML4 activation pathways, TKI therapy and CFTR. Care for pwCF with lung cancer requires a unique multi-disciplinary approach to optimize their complex multifactorial treatment.

PMID:39980610 | PMC:PMC11841201 | DOI:10.1016/j.rmcr.2025.102171

SAGE Open Med. 2025 Feb 19;13:20503121251320849. doi: 10.1177/20503121251320849. eCollection 2025.

ABSTRACT

INTRODUCTION: Bronchiectasis is a chronic respiratory disease caused by various respiratory and systemic conditions. It is now considered a potentially reversible disease, particularly when diagnosed early and managed with appropriate respiratory care strategies. Although rare in children, it typically develops in patients with recurrent lower respiratory tract infections. The etiology of bronchiectasis in children differs from that in adults. This study aims to identify the clinical features, causes, and outcomes of non-cystic fibrosis bronchiectasis in children at a tertiary center.

METHODS: A retrospective review was conducted among children with non-cystic fibrosis bronchiectasis who attended a university-affiliated hospital between January 2007 and December 2021. Clinical outcomes were assessed based on pulmonary function tests, exacerbation, and mortality.

RESULTS: The study included 35 children with non-cystic fibrosis bronchiectasis. The median age at diagnosis was 36 months (IQR: 24-170 months). Bronchiectasis was linked to underlying conditions in 22 cases (62.9%), such as primary immunodeficiency, chronic aspiration, and primary ciliary dyskinesia. Thirteen children had infectious-associated bronchiectasis (37.1%), with four cases related to pulmonary tuberculosis. At diagnosis, cystic bronchiectasis was most common (n = 17, 48.6%), followed by varicose (n = 13, 37.1%) and cylindrical bronchiectasis (n = 5, 14.3%). Pulmonary exacerbation occurred in 28 (80%) children, with a higher rate in noninfectious bronchiectasis than postinfectious bronchiectasis (90.9% vs 61.5%, p = 0.036). Hospitalization was required for 26 (77.1%) children, with a higher rate of noninfectious bronchiectasis than postinfectious bronchiectasis (86.3% vs 53.8%, p = 0.033).

CONCLUSIONS: Primary immune deficiency and chronic aspiration are the most common non-infective causes of non-cystic fibrosis bronchiectasis. Noninfectious bronchiectasis leads to higher exacerbation and hospitalization rates.

PMID:39980590 | PMC:PMC11840848 | DOI:10.1177/20503121251320849

J Cyst Fibros. 2025 Feb 19:S1569-1993(25)00059-1. doi: 10.1016/j.jcf.2025.02.008. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is caused by mutation of the CFTR gene, encoding an epithelial anion channel. Here we evaluated the effect of the modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) on the function of four rare, poorly characterized CFTR variants: L383S, I507del, L1065P and R1066H.

METHODS: Intestinal organoids were obtained from subjects carrying the CFTR variants L383S, I507del, L1065P or R1066H in trans of a minimal function allele (class I mutation). Organoids and epithelial monolayers were used to assess the effect of ETI on CFTR protein abundance and CFTR-mediated chloride, bicarbonate, and fluid transport.

RESULTS: In L383S-CFTR expressing cells, normal levels of fully glycosylated CFTR protein (C-band) were detected. In contrast, in I507del, L1065P or R1066H organoids, only partially glycosylated CFTR (B-band) was detected. Chloride/bicarbonate transport was severely impaired in epithelial monolayers prepared from these latter three variants, while anion transport of the L383S variant was affected to a moderate extent. ETI, but not ivacaftor alone, significantly enhanced CFTR-mediated chloride and bicarbonate transport in L1065P and R1066H monolayers, and stimulated fluid transport. A corresponding increase in the abundance of C-band protein was observed in both variants. ETI also modestly improved L383S-CFTR function, with a marginal effect on I507del-CFTR.

CONCLUSIONS: The I507del, L1065P and R1066H variants display severely impaired function. ETI treatment markedly enhanced L1065P- and R1066HCFTR function, whereas its effect on L383S- CFTR was less pronounced. Consequently, ETI may ameliorate disease symptoms in individuals carrying the L1065P or R1066H variant. More tentative, it may also benefit those carrying the L383S variant.

PMID:39979195 | DOI:10.1016/j.jcf.2025.02.008

J Cyst Fibros. 2025 Feb 19:S1569-1993(25)00064-5. doi: 10.1016/j.jcf.2025.02.014. Online ahead of print.

NO ABSTRACT

PMID:39979194 | DOI:10.1016/j.jcf.2025.02.014

Asian J Endosc Surg. 2025 Jan-Dec;18(1):e70036. doi: 10.1111/ases.70036.

ABSTRACT

Cholelithiasis is increasing in the pediatric population, and there are currently no guidelines for the management of asymptomatic patients with both cholelithiasis and a predisposing condition. This study seeks to highlight situations where prophylactic cholecystectomy may be desirable. We retrospectively reviewed the medical records of children who underwent elective laparoscopic cholecystectomy between October 2011 and September 2022. Thirty-two patients were included in the study. Five different groups of patients were identified based on associated pathologies. Twenty-six patients were symptomatic (81.25%), and six were asymptomatic (18.75%). All patients underwent a laparoscopic cholecystectomy. Hematologic and cystic fibrosis patients with asymptomatic cholelithiasis had a shorter length of hospital stay than patients with the same condition who progressed from asymptomatic to symptomatic gallstone disease. Consequently, patients with associated diseases (particularly hematologic diseases and cystic fibrosis) may benefit from early laparoscopic cholecystectomy, which could reduce the probability of surgical difficulties and shorten the length of hospital stay.

PMID:39978935 | DOI:10.1111/ases.70036

Am J Transplant. 2025 Feb 18:S1600-6135(25)00092-9. doi: 10.1016/j.ajt.2025.02.009. Online ahead of print.

ABSTRACT

Lung transplant candidates who are highly sensitized against human leucocyte antigen have a lower likelihood of graft allocation and a higher risk of dying while on the waiting list. C1-esterase inhibitor, an inhibitor of the classical and lectin pathways of complement activation, has been used successfully to prevent and treat acute antibody-mediated rejection in kidney and heart transplantation. Here, we report three cases of C1-esterase inhibitors used perioperatively in highly sensitized lung transplant candidates, with successful bilateral lung transplants despite severe primary graft dysfunction and/or hyperacute antibody-mediated rejection.

PMID:39978596 | DOI:10.1016/j.ajt.2025.02.009

Pulm Pharmacol Ther. 2025 Feb 18:102345. doi: 10.1016/j.pupt.2025.102345. Online ahead of print.

ABSTRACT

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor (ETI) therapy has shown improvement in lung function, BMI and reduction in pulmonary exacerbations but the impact of genotype and severity of lung disease on heterogeneity of ETI efficacy in real life is not known.

METHODS: This is a prospective observational study. Clinical data at baseline and at one-year of therapy were compared for the total cohort and for two subgroups; genotype [homozygous vs. heterozygous for F508del], and severity of lung disease at ETI initiation (ppFEV1 <80% vs. ≥80%).

RESULTS: Among the total cohort of 115 pwCF, median age of 23 (17, 32) years, 66 (58%) were homozygous, 76 (66%) had ppFEV1 <80%. Significant increases in mean ppFEV1 and mean BMI and decrease in MRSA and Pa culture positivity on sputum/throat swab were observed at one year of ETI therapy in the total cohort, and in groups based on either genotype or disease severity (p<0.05 in all). Comparing one-year prior to one-year on ETI therapy, significant improvements were noted in pulmonary exacerbations, hospital admissions, antibiotic courses, number of pwCF receiving daily chest therapy, dornase alfa and hypertonic saline in the total cohort and in all four subgroups (p<0.05 for all). Though improvements were not dependent on genotype, we noted larger mean differences in ppFEV1, BMI, pulmonary exacerbations and antibiotic use in the group with more severe lung disease (ppFEV1 <80%) after one year of ETI therapy.

CONCLUSION: ETI therapy improved clinical outcomes in pwCF which were impacted by severity of underlying lung disease.

PMID:39978537 | DOI:10.1016/j.pupt.2025.102345

J Clin Endocrinol Metab. 2025 Feb 20:dgaf099. doi: 10.1210/clinem/dgaf099. Online ahead of print.

ABSTRACT

BACKGROUND: Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI impact on glucose tolerance remains controversial.

METHODS: All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible. The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.

RESULTS: We included 106 adolescents with CF (age 14.1±1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1 and 2-h OGTT in the AGT group. ETI induced an increase in BMIz-score and in Forced Expiratory Volume in 1 second (FEV1) (p<0.001). After 12 months, participants with NGT did not experience any change of 1-h and 2-h glucose. By contrast, those with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). 15out of the 31 (48%) adolescents in the AGT group reversed to NGT but 9/75 (17%) in the NGT group progressed to AGT. 3 participants with CF related diabetes at baseline reversed to AGT. 1-hour glucose concentrations at or above 8.7 mmol/L (157mg/dL) during baseline OGTT had 80% sensitivity to identify those with AGT at 12 months (OR 1.51 [1.20, 1.92], p=0.001). 20 participants had a 24-month OGTT that confirmed preserved insulin secretion.

CONCLUSION: ETI may improve glucose tolerance in adolescents with CF by preserving insulin secretion. 1-hour glucose during the OGTT helps to detect risk for AGT after ETI treatment.

PMID:39977216 | DOI:10.1210/clinem/dgaf099

Microbiology (Reading). 2025 Feb;171(2). doi: 10.1099/mic.0.001536.

ABSTRACT

Obtaining sputum samples from people with cystic fibrosis (pwCF) for microbiology has become challenging due to the positive clinical effects of the cystic fibrosis transmembrane conductance regulator modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI). Although ETI improves lung function and reduces sputum production, recent data shows that bacterial pathogens persist, making continued monitoring of infection important. As an alternative to sputum sampling, this study developed a non-invasive technique called 'Cough Breath' (CB) to identify volatile organic compounds (VOCs) in exhaled breath condensate (EBC) and link them to cystic fibrosis (CF) bacterial pathogens using purge and trap GC-MS. The CB culturing approach was able to isolate pathogens from expectorated particulates simultaneously with EBC collection; however, culturing positivity was low, with 6% of samples collected (n=47) positive for either Pseudomonas aeruginosa or Staphylococcus aureus. From EBC, we identified VOCs matching those uniquely produced by P. aeruginosa (7), S. aureus (12), Achromobacter xylosoxidans (8) and Granulicatella adiacens (2); however, the overall detection rate was also low. Expanding to VOCs produced across multiple pathogens identified 30 frequently detected in the EBC of pwCF, including 2,3-pentanedione, propyl pyruvate, oxalic acid diallyl ester, methyl isobutyl ketone, methyl nitrate, 2-propenal, acetonitrile, acetoin and 2,3-butanedione. Comparing isolate volatilomes and EBC samples from the same pwCF enhanced detection rates with key VOCs, such as 2,3-pentanedione (86%) and propyl pyruvate (83%), in P. aeruginosa isolates. Further investigation showed that VOC production differed across strains and at different growth phases, creating variability that may explain the overall low EBC detection rate. Although this study successfully cultured CF pathogens from cough particulates and matched their unique VOCs in EBC samples, our results indicate that microbial volatiles more generally indicative of infection, such as 2,3-pentanedione, may have the most utility in aiding diagnostics in pwCF on ETI who have reduced sputum production in the clinic.

PMID:39976612 | DOI:10.1099/mic.0.001536

Eur J Gastroenterol Hepatol. 2025 Jan 21. doi: 10.1097/MEG.0000000000002917. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis-related liver disease (CFRLD) is a health problem that can affect as many as 30-40% of cystic fibrosis patients by the age of 12 years. We studied the epidemiology of CFRLD thanks to the first exclusively pediatric CFRLD patient registry to date.

METHODS: Descriptive cross-sectional study. Information from medical records from January 2018 to December 2020 is collected. CFRLD was classified according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition 2017 criteria.

RESULTS: Data were collected from 168 pediatric patients diagnosed with CFRLD (90.5% liver involvement without cirrhosis and 8.5% multinodular cirrhosis).

CONCLUSION: In this national registry, including exclusively pediatric population, liver disease is diagnosed around 7 years of age. Liver involvement without cirrhosis is the most frequent finding among our patients but about 9% of the patients already had cirrhosis. CFRLD is one of the challenges faced by pediatric gastroenterologists in the future and national registries give us the opportunity to further study and broaden our knowledge.

PMID:39976013 | DOI:10.1097/MEG.0000000000002917

bioRxiv [Preprint]. 2025 Feb 8:2025.02.03.636268. doi: 10.1101/2025.02.03.636268.

ABSTRACT

Constipation causes significant morbidity in Cystic Fibrosis (CF) patients. Using CF patient (F508del) derived ex vivo ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells . While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP) which was ∼48%, and ∼67% of the response in healthy enteroids, respectively and was prevented by a CFTR inhibitor. Also, linaclotide and a general PDE inhibitor independently enhanced combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP.

PMID:39975121 | PMC:PMC11838475 | DOI:10.1101/2025.02.03.636268

bioRxiv [Preprint]. 2025 Jan 27:2025.01.24.634747. doi: 10.1101/2025.01.24.634747.

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) studies identified a novel subpopulation of epithelial cells along the rostrocaudal axis of human intestine specifically marked by bestrophin 4 (BEST4) that are enriched for genes regulating pH, GPCR acid-sensing receptors, satiety, cGMP signaling, HCO3 - secretion, ion transport, neuropeptides, and paracrine hormones. Interestingly, BEST4+ cells in the proximal small intestine express CFTR but have not been linked to the previously described CFTR High Expresser Cell (CHE) subpopulation in rat and human intestine. ScRNA-seq studies in rat jejunum identified CHEs and a gene expression profile consistent with human small intestinal BEST4+ and neuropod cells. Protein immunolocalization confirmed that CHEs express CFTR, BEST4, neuropod proteins, high levels of intracellular uroguanylin (UGN), guanylyl cyclase-C (GC-C), and the proton channel otopetrin 2 (OTOP2), and display long basal processes connecting to neurons. OTOP2, GC-C, and CFTR traffic robustly into the apical domain of CHEs in response to acidic luminal conditions, indicating their roles in luminal pH regulation. In the ΔF508 cystic fibrosis (CF) rat jejunum, the loss of apical CFTR did not affect BEST4 protein expression in CHEs. However, there was an increased abundance of CHE cells in the ΔF508 rat jejunum compared to wild-type animals. Furthermore, ΔF508 rat CHEs expressed higher levels of GC-C at the apical domain compared to wild-type. These data implicate CHEs in intestinal CF disease pathogenesis.

NEW & NOTEWORTHY: This is the first study to identify CFTR High Expresser cells in the rat small intestine as neuropod cells capable of sensing and responding to luminal pH. This study also provides the first characterization of CFTR and relevant mRNA and proteins in CHEs in CF rat models that provide insights into the significance of CHEs to CF intestinal disease.

PMID:39974899 | PMC:PMC11838207 | DOI:10.1101/2025.01.24.634747

Lancet Reg Health Eur. 2024 Sep 15;45:101061. doi: 10.1016/j.lanepe.2024.101061. eCollection 2024 Oct.

NO ABSTRACT

PMID:39974772 | PMC:PMC11838078 | DOI:10.1016/j.lanepe.2024.101061

FEBS Lett. 2025 Feb 20. doi: 10.1002/1873-3468.70013. Online ahead of print.

ABSTRACT

The arachidonic acid (AA) pathway promotes tumor progression by modulating the complex interactions between cancer and immune cells within the microenvironment. In this Review, we summarize the knowledge acquired thus far concerning the intricate mechanisms through which eicosanoids either promote or suppress the antitumor immune response. In addition, we will discuss the impact of eicosanoids on immune cells and how they affect responsiveness to immunotherapy, as well as potential strategies for manipulating the AA pathway to improve anticancer immunotherapy. Understanding the molecular pathways and mechanisms underlying the role played by AA and its metabolites in tumor progression may contribute to the development of more effective anticancer immunotherapies.

PMID:39973474 | DOI:10.1002/1873-3468.70013

Int Forum Allergy Rhinol. 2025 Feb 19. doi: 10.1002/alr.23549. Online ahead of print.

NO ABSTRACT

PMID:39972960 | DOI:10.1002/alr.23549

Nat Rev Cardiol. 2025 Feb 19. doi: 10.1038/s41569-025-01130-5. Online ahead of print.

ABSTRACT

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.

PMID:39972009 | DOI:10.1038/s41569-025-01130-5

Curr Gastroenterol Rep. 2025 Feb 19;27(1):14. doi: 10.1007/s11894-025-00959-7.

ABSTRACT

PURPOSE OF REVIEW: Common indications to evaluate exocrine pancreatic function in children include chronic diarrhea, steatorrhea, failure to thrive, cystic fibrosis and those with chronic abdominal pain due to chronic pancreatitis where imaging studies are normal [1]. Exocrine Pancreatic Insufficiency (EPI) has a spectrum of severity. In children often remains an underdiagnosed condition, particularly in its mild, partial, and isolated enzyme deficiency forms. The purpose of this review is to help understand the different varieties of EPI including isolated pancreatic enzyme deficiencies as possible causes of malnutrition and growth failure in pediatric patients.

RECENT FINDINGS: Among the indirect diagnostic methods, the fecal elastase-1 (FE-1) testing is the most widely used one. While it has good sensitivity and specificity in severe pancreatic damage, like cystic fibrosis in children, its performance in the diagnosis of mild, partial, and isolated enzyme deficiencies is poor. Direct pancreatic function testing performed during endoscopy (ePFT), has emerged as a more sensitive and specific method for assessing all forms of exocrine pancreatic function. Notably, recent guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) emphasize the importance of ePFT in pediatric patients. Most of the pediatric practitioners taught that the pancreas has only two diseases, cystic fibrosis and pancreatitis. They are missing the fact that pancreas, like other digestive organs, can have different, many times secondary, dysfunctions that influence the growth of children. Most pediatric gastroenterologists still use the fecal elastase-1 (FE-1) test, however, this lacks sufficient specificity and sensitivity [2-5] especially in patients with mild or early pancreatic disease or those with isolated enzyme deficiencies [5]. The most accurate diagnostic modality to explore these conditions is ePFT. In this review we highlighted the critical importance of direct pancreatic function testing. Enhancing clinical awareness and incorporating direct testing methods can ultimately improve outcomes for affected children.

PMID:39971805 | DOI:10.1007/s11894-025-00959-7

J Cyst Fibros. 2025 Feb 18:S1569-1993(25)00063-3. doi: 10.1016/j.jcf.2025.02.012. Online ahead of print.

ABSTRACT

The year 2024 marks a pivotal moment in the field of cystic fibrosis (CF) treatment, characterised by significant advancements in clinical care and an expanding body of literature on CF transmembrane conductance regulator (CFTR) modulators. These CFTR therapies have transformed the landscape of CF management, offered systemic benefits, and established new guidelines for assessing clinical manifestations and therapies. Additionally, progress has been made in newborn screening (NBS), diagnosis, and understanding outcomes for individuals with CF-related metabolic syndrome or inconclusive diagnostic results. However, amidst these clinical milestones, disparities in global access to CFTR modulators (CFTRm) persist, threatening to exacerbate existing inequities in CF care. This review provides a focused overview of the most impactful articles from 2024, highlighting both the clinical advancements and the pressing global accessibility challenges that define this transformative era in CF research and treatment.

PMID:39971692 | DOI:10.1016/j.jcf.2025.02.012

J Cyst Fibros. 2025 Feb 18:S1569-1993(25)00062-1. doi: 10.1016/j.jcf.2025.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: AI-aided home stethoscopes offer the opportunity of continuous remote monitoring of cystic fibrosis (CF) patients, reducing the need for clinic visits.

AIM: This study aimed to analyze the possibility of detecting CF pulmonary exacerbations (PEx) at home using an AI-aided stethoscope (AIS).

MATERIALS AND METHODS: In a six-month study, 129 CF patients (85 children, 44 adults) used AIS for at least weekly self-examinations, recording various parameters: wheezes, rhonchi, crackles intensity, respiratory and heart rate, and inspiration-to-expiration ratio. Health state surveys were also completed. Physicians evaluated 5160 examinations to identify PEx. Machine learning models were trained using those parameters, and AUCs were calculated for PEx detection.

RESULTS: 522 self-examinations were diagnosed clinically as exacerbated. AI-aided home stethoscopes detected 415 exacerbated self-examinations (sensitivity 79.5 % at specificity 89.1 %). Among the single-parameter discriminators, coarse crackles intensity exhibited an AUC of 70 % (95% CI: 65-75) for young children, fine crackles intensity demonstrated an AUC of 75 % (95 % CI: 72-78) for older children, and an AUC of 93 % (95 % CI: 92-93) was achieved for adults using fine crackles intensity. The combination of parameters yielded the highest efficacy, with AUC exceeding 83% for objective parameters from the AI module alone and exceeding 90 % when incorporating both objective and subjective parameters across all groups.

CONCLUSIONS: The AI-aided home stethoscope has proven to be a reliable tool for detecting PEx with greater accuracy than self-assessment alone. Implementing this technology in healthcare systems has the potential to provide valuable insights for timely intervention and management of PExes.

PMID:39971691 | DOI:10.1016/j.jcf.2025.02.011