PLoS One. 2025 Feb 24;20(2):e0318249. doi: 10.1371/journal.pone.0318249. eCollection 2025.

ABSTRACT

OBJECTIVE: The autosomal recessive disease congenital chloride diarrhea (CLD), caused by loss-of-function mutations in the solute carrier family 26 member 3 (SLC26A3) gene, shows association with inflammatory bowel disease (IBD). However, it is unclear whether IBD risk is associated with genetic or immune signatures. SLC26A3 interacts with several ion transporters linked to intestinal inflammation, such as cystic fibrosis transmembrane conductance regulator (CFTR) and solute carrier family 9 member 3 (SLC9A3) causing congenital sodium diarrhea. We hypothesized that other epithelial channels affecting intestinal salt balance might modulate CLD phenotype or IBD risk.

MATERIALS AND METHODS: We analyzed 495 gene variants within 33 ion transporters among 28 patients with CLD and 44,443 population controls.

RESULTS: We found three intronic variants at or near the CFTR locus (rs17132543, rs2283054 and rs76622533) showing statistically significant (P < 1.42x10-5) associations with CLD.

CONCLUSIONS: These data demonstrate enrichment of rare variants at the CFTR locus in chromosomes harboring the Finnish founder mutation for CLD.

PMID:39992989 | DOI:10.1371/journal.pone.0318249

Med J Armed Forces India. 2024 Nov-Dec;80(6):731-734. doi: 10.1016/j.mjafi.2022.11.006. Epub 2023 Jan 4.

ABSTRACT

Infantile refractory diarrhea presents after first few days of life leading to intestinal insufficiency. It is a diagnostic challenge due to varied etiologies like food senstive enteropathy, anatomical defects and dysmotility disorders, transport and enzymatic defects, pancreatic malabsorption - cystic fibrosis (CF), primary epithelial causes like microvillus inclusion disease (MVID), tufting enteropathy and heparan sulfate deficiency, immunodeficiencies, metabolic diseases and autoimmune enteropathy. It is refractory to treatment making the patient dependent on total parenteral nutrition. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), is one of the rarest causes of intractable diarrhea. It occurs due to mutations in the FOXP3 gene, leading to dysfunction of T-regulatory cells and is characterised by diarrhoea, diabetes, and dermatitis. We aim to evaluate various causes of infantile refractory chronic diarrhea, and to present one such case of IPEX syndrome from this part of the world due to mutation not been reported in literature so far.

PMID:39990538 | PMC:PMC11842919 | DOI:10.1016/j.mjafi.2022.11.006

Intern Med J. 2025 Feb 24. doi: 10.1111/imj.16658. Online ahead of print.

ABSTRACT

The role of non-invasive ventilation (NIV) in patients with cystic fibrosis (pwCF) includes use in both the management of hypercapnic respiratory failure and as an adjunct to airway clearance techniques. We performed a retrospective review of the Australian Cystic Fibrosis Data Registry to analyse the characteristics of pwCF requiring NIV. We demonstrated that despite improvements in overall health in pwCF there is still a significant role of NIV in this population.

PMID:39989367 | DOI:10.1111/imj.16658

Sci Rep. 2025 Feb 22;15(1):6520. doi: 10.1038/s41598-025-91368-3.

ABSTRACT

The study of key Pseudomonas aeruginosa (PA) virulence factors, the molecular basis of pathogenicity, as well as their correlation with the immune response during exacerbations in patients with non-cystic fibrosis bronchiectasis can help to identify novel targets and biomarkers for clinical management. The objective was to compare P. aeruginosa virulence and the patient's immune response during stable phases and exacerbations of bronchiectasis. We used polymerase chain reaction (PCR) and real-time quantitative PCR (qRT-PCR) to perform molecular characterization of the genomic islands and virulence genes present in 42 P. aeruginosa strains obtained from the sputum of patients with bronchiectasis during stability and exacerbations. Immunoglobulin (Ig) and interleukin (IL) levels in 32 serum samples were analyze by ELISA and Luminex assay. A greater presence of the conjugative element pKLC102, specific virulence genes (exoS, exoY) and pyoverdine production characterize the P. aeruginosa strains obtained during exacerbations. The expression levels of type III secretion system (exoS, exoY) showed an important role in the humoral immune response during exacerbations. Exacerbations were associated with high levels of IL-6. The presence of specific genomic islands, virulence genes, and increased IL-6 levels provide an accurate characterization on bronchiectasis exacerbations. These targets could be useful in the prevention, management and treatment of these exacerbations.

PMID:39987197 | DOI:10.1038/s41598-025-91368-3

J Cyst Fibros. 2025 Feb 21:S1569-1993(25)00066-9. doi: 10.1016/j.jcf.2025.02.016. Online ahead of print.

ABSTRACT

BACKGROUND: Symptoms of depression and anxiety can contribute to lower medical treatment adherence. Given that people with cystic fibrosis (PWCF) have higher rates of depressive and anxiety symptoms than those without cystic fibrosis (CF), this study examined factors that mediated the association between mental health and adherence.

METHODS: Participants were 294 adults (M age=25 years) with CF who were enrolled in the Daily Care Check-in Validation Study. Participants completed in-clinic questionnaires that assessed depressive and anxiety symptoms, perceived barriers to self-management, and medication self-efficacy. Medication adherence was measured by pharmacy refill data. Parallel mediation models assessed perceived barriers and medication self-efficacy as mediators between depressive symptoms and adherence, and between anxiety symptoms and adherence.

RESULTS: Perceived interference of barriers to self-management significantly mediated the association between depressive symptoms and adherence (β =-0.005, SE=0.002, 95 % CI [-0.009, -0.001]), and between anxiety symptoms and adherence (β=-0.005, SE=0.003, 95 % CI [-0.008, -0.001]). Additionally, self-efficacy significantly mediated the association between depressive symptoms and adherence (β=-0.004, SE=0.001, 95 % CI [-0.007, -0.002]), and between anxiety symptoms and adherence (β=-0.004, SE=0.001, 95 % CI [-0.007, -0.001]).

CONCLUSIONS: This study found that when PWCF experienced mental health symptoms (either anxiety or depression), they were likely to report more interference from barriers to disease management or experience less medication self-efficacy, which was related to worse adherence. Building self-efficacy around taking medications may reduce the impact that mental health symptoms have on adherence. Care teams should also work with PWCF to minimize the impact of barriers on daily therapies.

PMID:39986976 | DOI:10.1016/j.jcf.2025.02.016

J Cyst Fibros. 2025 Feb 21:S1569-1993(25)00057-8. doi: 10.1016/j.jcf.2025.02.010. Online ahead of print.

ABSTRACT

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. 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. 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.

PMID:39986975 | DOI:10.1016/j.jcf.2025.02.010

BMC Pulm Med. 2025 Feb 21;25(1):85. doi: 10.1186/s12890-025-03553-9.

ABSTRACT

BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) poses substantial diagnostic and management challenges, particularly among individuals with pre-existing lung conditions and/ or immunodeficiencies. NTM-PD can severely impair lung function and quality of life, potentially leading to both increased healthcare costs and mortality. There is a lack of comprehensive understanding of the disease burden and healthcare gaps from the patients' perspective. The European NTM-PD Patient Disease Experience (ENPADE) survey aimed to collect insights into these aspects.

METHODS: The survey aim was addressed by several methods. First, an online questionnaire was carried out from July 2021 to February 2022 across eight European countries for quantitative data collection. Additionally, semi-structured qualitative patient interviews were conducted with a subset of patients, eliciting their insights on the aspects surveyed. Descriptive statistics were used for quantitative analysis and interview outcomes were categorised along the online questionnaire for qualitative analysis.

RESULTS: A total of 543 patients participated in the survey and 23 patients were interviewed. Satisfaction with care received before and after diagnosis was scored, on average, moderate with 32% "highly satisfied" patients and 25% "highly dissatisfied" patients across the aspects surveyed. Dissatisfaction was expressed particularly regarding referral and access to expert care, and information received on their disease and its management. Patients reported high restrictions in daily life (49%), work (31%), and social activities (43%), often leading to substantial emotional distress, such as experiencing an increase in feeling depressed or anxious (82%). Interviews with patients highlighted a need for improved disease information, faster diagnosis, and enhanced physician-patient relationships.

CONCLUSIONS: The ENPADE survey outcomes revealed dissatisfaction among patients with care and restrictions in daily life, work, and social activities, often leading to emotional distress. These findings underscore the need for improved disease information, standardised care, and enhanced physician-patient relationships with appropriate support measures.

PMID:39984983 | DOI:10.1186/s12890-025-03553-9

Dig Dis Sci. 2025 Feb 21. doi: 10.1007/s10620-025-08932-0. Online ahead of print.

NO ABSTRACT

PMID:39984786 | DOI:10.1007/s10620-025-08932-0

J Cyst Fibros. 2025 Feb 20:S1569-1993(25)00053-0. doi: 10.1016/j.jcf.2025.02.004. Online ahead of print.

ABSTRACT

BACKGROUND: As the lifespan of people with cystic fibrosis (pwCF) improves, more individuals are pursuing pregnancy. Historically, pregnancy was not recommended in this population; however, more recent evidence has revealed inconsistent survival and lung function outcomes. Our aim was to assess the differences in survival and lung function between pregnant and never-pregnant pwCF and to provide updated recommendations for contemporary clinical practice.

METHODS: In this retrospective matched parallel cohort study, data was collected from the American Cystic Fibrosis Foundation Patient Registry (CFFPR) from 1999 to 2019. 1743 adult pwCF with a reported pregnancy were matched with 1743 never-pregnant patients. Regression models were developed to estimate associations between patient characteristics, pregnancy, and outcomes. The primary endpoint was the probability of survival comparing pregnant and never-pregnant pwCF, while the secondary endpoint was lung function over time.

RESULTS: The study cohort (n = 3486) had a mean age of 24.96 years. There was no significant difference in survival probabilities between pregnant and never-pregnant pwCF (56.2 %, CI95 %: 51.3 %-61.5 % vs. 55.8 %, CI95 %: 52.1 %-59.7 %, p = 0.5). The multivariable time-dependent Cox regression analysis resulted in a significantly lower mortality hazard rate for pregnant cohorts (HR:0.78, p < 0.01). There was no significant association between pregnancy and lung function over time (0.99, p = 0.21).

CONCLUSION: Pregnancy was associated with a reduced hazard of death compared to never-pregnant pwCF and did not demonstrate a significant impact on lung function. Therefore, pregnancy should not be generally discouraged in pwCF and clinicians should evaluate pregnancy risks and benefits on an individualized basis.

PMID:39984374 | DOI:10.1016/j.jcf.2025.02.004

Epilepsy Behav. 2025 Feb 20;165:110292. doi: 10.1016/j.yebeh.2025.110292. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess documentation of pregnancy-related counseling and care for people with epilepsy of childbearing potential (PWECP) in pediatric and adult neurology who became pregnant.

METHODS: We reviewed health records for primigravida PWECP prescribed an antiseizure medication (ASM) who delivered between June 2014 and May 2024 within one academic medical center. We used chi-squared tests to compare counseling, ASM prescriptions, and recommendations for supplemental folic acid between individuals in pediatric and adult neurology care before pregnancy. We performed logistic regression for these outcomes of pre-pregnancy counseling associated with type of neurology care, race, ethnicity, intellectual disability (ID), teratogenic profile of ASMs prescribed, and ASM polytherapy.

RESULTS: 173 PWECP (84 % White non-Hispanic, 9 % with intellectual disability (ID) were included. Twenty-one (12 %) transferred from pediatric to adult neurology care due to pregnancy ("pediatric group") and 152 (88 %) were previously established with adult neurology ("adult group"). PWECP in the pediatric group compared to the adult group had lower rates of documentation of clinician discussion of ASM teratogenicity (43 % vs 66 %, p = 0.041) and folic acid use (24 % vs 63 %, p = 0.001) before pregnancy. PWECP established with adult neurology prior to pregnancy were significantly more likely to have been taking folic acid before pregnancy (OR 5.21, 95 % CI 1.78-15.3). Individuals with ID were significantly less likely to have documentation of discussion of ASM teratogenicity (OR 0.18, 95 % CI 0.05-0.62).

CONCLUSION: Our findings suggest a need for improvement in providing pre-pregnancy guidance and care for PWECP, especially for PWECP in pediatric neurology care and those with ID.

PMID:39983588 | DOI:10.1016/j.yebeh.2025.110292

Am J Physiol Lung Cell Mol Physiol. 2025 Feb 21. doi: 10.1152/ajplung.00293.2024. Online ahead of print.

ABSTRACT

Bronchial epithelial cells derived from the tracheo-bronchial regions of human airways (HBECs) provide a valuable in vitro model for studying pathological mechanisms and evaluating therapeutics. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media: airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and Pneumacult Ex plus (PEx+). Analysis through RNA sequencing, immune assays and impedance measurements revealed that PEx+ media significantly drove cell proliferation and a broad pro-inflammatory phenotype in BCs. In contrast, BCs expanded in AECGM, displayed increased expression of structural and extracellular matrix components at higher passage. AECGM increased expression of some cytokines at high passage, while DSI suppressed inflammation implicating the involvement TGF-β in BC inflammatory processes. Differentiation capacity of BCs declined with time in culture irrespective of expansion media. This was associated with an increase in PLUNC expressing secretory cells in AECGM and PEx+ media consistent with the known immune modulatory role of PLUNC in the airways. These findings highlight the profound impact of media conditions on inflammatory niche established by, and function of, in vitro expanded BCs. The broad pro-inflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic application.

PMID:39982813 | DOI:10.1152/ajplung.00293.2024

Int J Neonatal Screen. 2025 Jan 27;11(1):10. doi: 10.3390/ijns11010010.

ABSTRACT

The Portuguese Newborn Screening Program currently includes 28 pathologies: congenital hypothyroidism, cystic fibrosis, 24 inborn errors of metabolism, sickle cell disease and spinal muscular atrophy. This pilot study for sickle cell disease newborn screening, including 188,217 samples, was performed between May 2021 and December 2023, with phase I, including 24,130 newborns, in the Lisbon and Setubal districts and phase II, including 164,087 newborns, in the whole country. DBS samples were analyzed through capillary electrophoresis. In phase I, a high birth incidence of sickle cell disease was found (1:928 NBs), resulting from the identification of 24 HbSS and 2 HbSC patients. This birth incidence decreased but remained significant when the pilot study for sickle cell disease newborn screening was expanded to a national level, with the identification of 67 sickle cell disease patients (59 HbSS and 8 HbSC), revealing a birth incidence of 1:2449 NBs. These data suggest that this condition is becoming increasingly relevant in Portugal, thus reflecting a general European trend, where sickle cell disease is already recognized as a public health problem. Therefore, it highlights the importance of its integration into the Portuguese National Newborn Screening Program panel in January 2024, thus allowing the early identification and clinical follow-up of these patients.

PMID:39982344 | DOI:10.3390/ijns11010010

Antibodies (Basel). 2025 Feb 14;14(1):18. doi: 10.3390/antib14010018.

ABSTRACT

Immunoglobulin Y (IgY) is the primary antibody found in the eggs of chicken (Gallus domesticus), allowing for large-scale antibody production with high titers, making them cost-effective antibody producers. IgY serves as a valuable alternative to mammalian antibodies typically used in immunodiagnostics and immunotherapy. Compared to mammalian antibodies, IgY offers several biochemical advantages, and its straightforward purification from egg yolk eliminates the need for invasive procedures like blood collection, reducing stress in animals. Due to the evolutionary differences between birds and mammals, chicken antibodies can bind to a broader range of epitopes on mammalian proteins than their mammalian counterparts. Studies have shown that chicken antibodies bind 3-5 times more effectively to rabbit IgG than swine antibodies, enhancing the signal in immunological assays. Additionally, IgY does not interact with rheumatoid factors or human anti-mouse IgG antibodies (HAMA), helping to minimize interference from these factors. IgY obtained from egg yolk of hens immunized against Pseudomonas aeruginosa has been used in patients suffering from cystic fibrosis and chronic pulmonary colonization with this bacterium. Furthermore, IgY has been used to counteract streptococcus mutans in the oral cavity and for the treatment of enteral infections in both humans and animals. However, the use of avian antibodies is limited to pulmonary, enteral, or topical application and should, due to immunogenicity, not be used for systemic administration. Thus, IgY expands the range of strategies available for combating pathogens in medicine, as a promising candidate both as an alternative to antibiotics and as a valuable tool in research and diagnostics.

PMID:39982233 | DOI:10.3390/antib14010018

Immunol Rev. 2025 Mar;330(1):e70009. doi: 10.1111/imr.70009.

ABSTRACT

Cystic fibrosis (CF) is a common autosomal recessive disease resulting from mutations of the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR). Although severe pulmonary neutrophilic inflammation is a primary pathologic feature of CF, more recent studies reveal a role for type 2 inflammation that is characterized by eosinophilia directed by both the innate and adaptive immune systems through ILC2 and CD4+ Th2 cells, respectively. We have published that a clear type endotype exists within CF subjects stratified by Th2 inflammation, defined by increased obstructive pulmonary disease and a distinct phenotypic signature of increased allergic disease, infections, and burden of CF complications. Further, we showed an increased risk of death among CF subjects with type 2 inflammatory signatures compared to CF subjects lacking significant type 2 inflammation. The mechanisms of this heightened type 2 inflammatory signature in CF are still being defined, but it is clear that airway epithelial cells from CFTR-deficient mice have increased expression and release of IL-33, a key activator of ILC2 and Th2 cells, compared to persons with normal CFTR function. Further, there is strong evidence that CF regulates CD4+ Th2 function in a cell-intrinsic fashion. These concepts are explored in this review article.

PMID:39981881 | DOI:10.1111/imr.70009

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