Eur Respir J. 2024 Jun 6;63(6):2400858. doi: 10.1183/13993003.00858-2024. Print 2024 Jun.

NO ABSTRACT

PMID:38843940 | DOI:10.1183/13993003.00858-2024

Eur Respir J. 2024 Jun 6:2302160. doi: 10.1183/13993003.02160-2023. Online ahead of print.

ABSTRACT

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. Also, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD. Many affected children will reach adulthood with minimal activity or clinical remission of the disease. They need continuing care and follow-up from childhood to adulthood if the disease persists and progresses over time but also if they are asymptomatic and in full remission. Therefore, for every chILD patient an active transition process from paediatric to adult care should be guaranteed. This ERS statement provides a review of the literature and current practice concerning transition of care in chILD. It draws on work in existing transition care programs in other chronic respiratory diseases, disease-overarching transition of care programs, evidence on the impact of these programs on clinical outcomes, current evidence regarding long-term remission of chILD as well as the lack of harmonisation between the current adult ILD and chILD classifications impacting on transition of care. While the transition system is well established in several chronic diseases, such as cystic fibrosis or diabetes mellitus, we could not find sufficient published evidence on transition systems in chILD. This statement summarises current knowledge but cannot yet provide evidence-based recommendations for clinical practice.

PMID:38843911 | DOI:10.1183/13993003.02160-2023

Eur Respir J. 2024 Jun 6:2301504. doi: 10.1183/13993003.01504-2023. Online ahead of print.

NO ABSTRACT

PMID:38843909 | DOI:10.1183/13993003.01504-2023

Respir Med Res. 2024 Apr 24;86:101107. doi: 10.1016/j.resmer.2024.101107. Online ahead of print.

ABSTRACT

BACKGROUND: Nebulized Hypertonic saline (HS) and positive expiratory pressure device (PEP) are often used in patients with bronchiectasis. We sought to describe the clinical characteristics in patients using HS and PEP, utilizing a large national database registry.

METHODS: Data from the US Bronchiectasis and NTM Research Registry were used in this study. Patients with a diagnosis of bronchiectasis were included. Eligible patients were assigned to one of four mutually exclusive groups: HS only, PEP only, HS & PEP, or no airway clearance or mucoactive agent. Descriptive statistics were computed for the overall study population and stratified by the four groups. One-way ANOVA and chi-square tests were used to test the difference in the means in continuous variables and the association between categorical variables (respectively) across the four groups.

RESULTS: A total of 2195 patients were included. Of those with bronchiectasis and a productive cough, a greater number of patients utilized HS only vs PEP only (17.5 % vs 9.1 %, p < 0.001). Similar association was found in those with Pseudomonas aeruginosa (22.3 % HS only vs 6.5 % PEP only, p < 0.001). There was a higher number of patients who used HS and PEP therapy in combination vs PEP therapy alone (25.0 % vs 9.1 %, p = 0.002), in those with a productive cough.

CONCLUSIONS: In patients with bronchiectasis and a productive cough or Pseudomonas aeruginosa, HS is used more often than PEP alone. There is a need for further analysis to compare these two modalities and explore the factors influencing their utilization.

PMID:38843603 | DOI:10.1016/j.resmer.2024.101107

Respir Med Res. 2024 Feb 29;86:101094. doi: 10.1016/j.resmer.2024.101094. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a muco-obstructive lung disease characterized by thick sputum with abnormal rheological properties. The intermittent intrapulmonary deflation (IID) is a new instrumental airway clearance technique (ACT) that aims to decrease the sputum viscoelastic properties. This study assessed the benefits of adding the IID technique to a conventional ACT in patients with CF hospitalized for intravenous antibiotic therapy.

METHODS: Participants with CF accustomed to autogenic drainage (AD) as their standard ACT received, in a randomized order, a 30-min session of either AD alone or AD combined with IID (AD+IID). Sputum was collected during each ACT regimens and for a 24-hour period following both sessions. Sputum wet weight, dry weight, solids content and rheological properties were analyzed. Cough events occurring during and over 2 h post ACT were compared between both regimens.

RESULTS: Seventeen patients with CF (aged 29 ± 11 years; FEV1%: 57.1 ± 20.1) were analysed. The sputum wet weight collected during AD alone was significantly higher than during AD+IID (8.11 ± 6.93 vs 5.40 ± 4.11 respectively, p = 0.01). The sputum rheological properties did not significantly differ between group. There were more cough episodes during AD alone compared to AD+IID (median [IQR]: 8 [5-15.5] vs 5 [3.5-11.0] respectively, p = 0.02).

CONCLUSIONS: In participants with CF accustomed to AD, adding the IID technique in combination to AD does not confer a clear benefit on airway clearance in the short term. Clinical Trials register: NCT04157972.

PMID:38843595 | DOI:10.1016/j.resmer.2024.101094

Respir Res. 2024 Jun 6;25(1):236. doi: 10.1186/s12931-024-02860-9.

ABSTRACT

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.

METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.

RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037.

CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.

PMID:38844921 | DOI:10.1186/s12931-024-02860-9

Am J Respir Crit Care Med. 2024 Jun 6. doi: 10.1164/rccm.202404-0787LE. Online ahead of print.

NO ABSTRACT

PMID:38843542 | DOI:10.1164/rccm.202404-0787LE

Am J Respir Crit Care Med. 2024 Jun 6. doi: 10.1164/rccm.202404-0852LE. Online ahead of print.

NO ABSTRACT

PMID:38843537 | DOI:10.1164/rccm.202404-0852LE

Prax Kinderpsychol Kinderpsychiatr. 2024 Jun;73(4):311-330. doi: 10.13109/prkk.2024.73.4.311.

ABSTRACT

The Protective Role of Self-Regulation for HRQOL of Adolescents with a Chronic Physical Health Condition A physical chronic condition comes with many challenges and negatively impacts the healthrelated quality of life (HRQOL) of those affected. Self-regulation plays an important role in successfully coping with the demands of a chronic condition. In line with a resource-oriented approach, this study aimed to investigate themoderating effect of self-regulation on the relationship between disease severity andHRQOL. For this, 498 adolescents with cystic fibrosis, juvenile idiopathic arthritis, or type-1 diabetes aged of 12-21 years (M= 15.43, SD= 2.07) were recruited through three patient registers. Subjective disease severity, self-regulation (Brief Self-Control- Scale), andHRQOL (DISABKIDSChronicGenericMeasure)were examined at two time points (T₁ and T₂, one year apart). Cross-sectional analysis showed significant effects of subjective disease severity and self-regulation on HRQOL. Prospective analysis, in which HRQOL at T₁ was controlled for, revealed that disease severity only predicted emotion-related HRQOL at T₂; selfregulation emerged as a predictor for HRQOL subscales independence, emotion, inclusion, exclusion, and treatment. A significantmoderation effect of self-regulation was found on the relationship between disease severity and HRQOL emotion. Our results highlight the positive impact of self-regulation on quality of life, specifically in the context of chronic conditions and represent a starting point for prevention and intervention approaches.

PMID:38840539 | DOI:10.13109/prkk.2024.73.4.311

BJOG. 2024 Jun 5. doi: 10.1111/1471-0528.17832. Online ahead of print.

ABSTRACT

Expanded carrier screening (ECS) is a genetic screening test carried out by analysing a blood sample. This screen can be used to detect whether the individual unknowingly carries gene variants associated with common genetic conditions, such as cystic fibrosis, that may be passed on to their children. It is typically performed in reproductive medicine for those who are considering having a family either naturally or via fertility treatment. Many donor sperm and egg banks, particularly in the USA and Europe, also perform blanket ECS testing on all their prospective sperm and egg donors. ECS is not currently routine practice in the UK, but a growing number of patients are requesting it before treatment. All of us carry gene variants of some sort that may cause autosomal recessive disease in their children if their partner or donor also carry a variant in the same gene. An autosomal recessive disease means two copies of an abnormal gene must be present in order for the disease or trait (such as cystic fibrosis or sickle cell disease) to develop. One copy of the variant means the person is a carrier but does not have the condition. Two copies, i.e. from the mother and father, means the child has a 25% chance of having the genetic disease. Carrying a gene variant does not mean that the individual would necessarily have any symptoms of the disease or any features of the condition. Genetic tests for specific conditions are currently available either before or during pregnancy for prospective parents who have a family or personal history of a genetic condition, or for those from ethnic backgrounds where certain conditions - such as haemoglobinopathies (blood disorders) - are common, prompting referral to a clinical genetics department. Expanded carrier screens may test for more than 100 genetic conditions. The list of conditions screened for is called a panel. Common panels are 250 or 600 genes. Not all expanded carrier screens that are available analyse the same genes. Some may test for genes that do not cause serious disease, or cause diseases that occur in later life; others test for genes that cause severe conditions in childhood. There is no agreement as to which panel of genes should be tested for in an ECS. Understanding the screening that is being offered, and the meaning of any results, is complicated and requires support from appropriately trained professionals to best inform the prospective parent or parents.

PMID:38839259 | DOI:10.1111/1471-0528.17832

Curr Probl Pediatr Adolesc Health Care. 2024 Jun 4:101635. doi: 10.1016/j.cppeds.2024.101635. Online ahead of print.

NO ABSTRACT

PMID:38839515 | DOI:10.1016/j.cppeds.2024.101635

Pediatr Pulmonol. 2024 Jun 5. doi: 10.1002/ppul.27069. Online ahead of print.

ABSTRACT

INTRODUCTION: Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores.

METHODS: This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit.

RESULTS: No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4).

CONCLUSIONS: We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires.

PMID:38838063 | DOI:10.1002/ppul.27069

Nutr Diet. 2024 Jun 5. doi: 10.1111/1747-0080.12882. Online ahead of print.

ABSTRACT

AIMS: This systematic review aims to describe the dietary quality, dietary intake and related behaviours of adults diagnosed with cystic fibrosis.

METHODS: A comprehensive literature search was conducted in four databases (Medline, CINAHL, EMBASE, CENTRAL); studies were included if they addressed dietary intake, diet quality or eating behaviours among adults (≥15 years) living with cystic fibrosis and were published from January 2000 to November 2022. The Mixed Methods Appraisal Tool was used to assess the risk of bias and quality of included studies. Findings were synthesised narratively.

RESULTS: Nineteen observational studies (n = 2236) were included and considered high to moderate quality. Most (13/19) studies reported that individuals with cystic fibrosis were consuming high-energy diets; where studies reported energy intake as a proportion of requirements met, energy intake was high, even when using individualised or cystic fibrosis-specific referents. In addition, fat intakes as a proportion of energy appeared high (29%-39% of total energy), particularly as current guidelines recommend macronutrient profile similar to the general population (<30% of total energy). There was considerable variation in the reporting of fatty acid profiles and other nutrients. Five studies reported on concerns regarding diet and eating in this population.

CONCLUSION: Findings from the current review suggest dietary intakes of adults with cystic fibrosis appear to be less than optimal and concerns about diet, weight and food may be emerging in this population. Future research utilising consistent measures of dietary assessment and reporting, reporting of medical therapies, and exploring potential concerns about diet and eating is warranted.

PMID:38837652 | DOI:10.1111/1747-0080.12882

J Cell Biol. 2024 Jul 1;223(7):e202405160. doi: 10.1083/jcb.202405160. Epub 2024 Jun 5.

ABSTRACT

During ER-associated decay, unfolded membrane-resident proteins are targeted for removal and degradation by ubiquitin ligases whose identities and precise operations remain unclear. In this issue, Guerriero and Brodsky discuss new results from Kamada et al. (https://doi.org/10.1083/jcb.202308003) showing the clearance of misfolded CFTR by the E3 ligase HERC3.

PMID:38836811 | DOI:10.1083/jcb.202405160

Front Immunol. 2024 May 21;15:1379754. doi: 10.3389/fimmu.2024.1379754. eCollection 2024.

ABSTRACT

An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.

PMID:38835761 | PMC:PMC11148260 | DOI:10.3389/fimmu.2024.1379754

Sleep Med. 2024 May 23;119:574-583. doi: 10.1016/j.sleep.2024.05.042. Online ahead of print.

ABSTRACT

OBJECTIVE: Sleep problems constitute a common and heterogeneous complaint in pediatric palliative care (PPC), where they often contribute to disease morbidity and cause additional distress to children and adolescents and their families already facing the burden of life-threatening and life-limiting conditions. Despite the significant impact of sleep problems, clinical evidence is lacking. The application of general pediatric sleep recommendations appears insufficient to address the unique challenges of the PPC dimension in terms of disease variability, duration, comorbidities, complexity of needs, and particular features of sleep problems related to hospice care. Therefore, we initiated an international project aimed at establishing a multidisciplinary consensus.

METHODS: A two-round Delphi approach was adopted to develop recommendations in the areas of Definition, Assessment/Monitoring, and Treatment. After selecting a panel of 72 worldwide experts, consensus (defined as ≥75% agreement) was reached through an online survey.

RESULTS: At the end of the two voting sessions, we obtained 53 consensus recommendations based on expert opinion on sleep problems in PPC.

CONCLUSIONS: This study addresses the need to personalize sleep medicine's approach to the palliative care setting and its peculiarities. It provides the first international consensus on sleep problems in PPC and highlight the urgent need for global guidance to improve sleep-related distress in this vulnerable population and their caregivers. Our findings represent a crucial milestone that will hopefully enable the development of guidelines in the near future.

PMID:38833942 | DOI:10.1016/j.sleep.2024.05.042

mBio. 2024 Jun 4:e0119824. doi: 10.1128/mbio.01198-24. Online ahead of print.

ABSTRACT

Stenotrophomonas maltophilia expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A S. maltophilia mutant lacking the gene for 20845 was impaired for killing Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant E. coli being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede E. coli, indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the S. maltophilia T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase.IMPORTANCEStenotrophomonas maltophilia is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to S. maltophilia infection. In hospital water systems and various types of infections, S. maltophilia co-exists with other bacteria, including other pathogens such as Pseudomonas aeruginosa. We previously demonstrated that S. maltophilia has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, S. maltophilia currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).

PMID:38832773 | DOI:10.1128/mbio.01198-24

J Clin Pharmacol. 2024 Jun 3. doi: 10.1002/jcph.2478. Online ahead of print.

ABSTRACT

The lack of data on drug-drug interactions in pediatrics represents a relevant problem in making appropriate therapeutic decisions. Our study aimed to investigate the incidence and risk factors for potential drug-drug interactions (pDDIs) in pediatric pneumonology units, including cystic fibrosis patients. We performed a 6-month prospective observational study during which clinical pharmacists, using the Lexicomp Drug Interactions checker, screened medical records to identify pDDIs. Spearman's rank coefficient, logistic regression, and the Mann-Whitney U test were used to identify correlations, analyze risk factors for pDDIs, and compare cystic fibrosis patients with the rest, respectively. Recommendations were provided for the D and X pDDIs categories. Within the 218 patients, 428 pDDIs were identified, out of which 237 were classified as clinically significant. Almost 60% of patients were exposed to at least one relevant interaction. The number of pDDIs correlated with the number of; drugs (rs = 0.53, P < .001), hospitalization length (rs = 0.20, P < .01), and off-label medicines (rs = 0.25, P < .001). According to the multivariate analysis, at least 6 administered medications (OR = 4.15; 95% CI = 2.21-7.78), 4 days of hospitalization (OR = 6.41; 95% CI = 2.29-17.97), and off-label therapy (OR = 3.37; 95% CI = 1.69-6.70) were the risk factor for pDDIs. Despite significant differences in the number of medications taken, comorbidities, and off-label drugs, cystic fibrosis patients were not more exposed to pDDI. Given the lack of data on pDDIs in the pediatric population, the need for close cooperation between clinicians and clinical pharmacists to improve the safety and efficacy of pharmacotherapy is highlighted.

PMID:38831707 | DOI:10.1002/jcph.2478

BMJ Open. 2024 Jun 3;14(6):e081560. doi: 10.1136/bmjopen-2023-081560.

ABSTRACT

INTRODUCTION: Families with children who have cystic fibrosis (CF) face a multitude of challenges. They require complex and time-consuming daily care, various forms of knowledge and intricate care responsibilities. One of the most critical challenges that Iranian families of children with CF face is the lack of adequate support from health teams in the early stages of diagnosis, frequent hospitalisation and the postdischarge process. Unfortunately, limited studies have been conducted in this field, and the Iranian society lacks a comprehensive support programme for these families after leaving treatment centres or home care teams. Therefore, it is necessary to identify and redefine the needs of these families for better care and support in Iran.

METHODS AND ANALYSIS: A mixed-method research design with an exploratory sequential approach will be used in this study. The study consists of three stages: stage (1) the qualitative phase (conventional content analysis and scoping review); stage (2) the programme design phase (development of a support programme) and stage (3) the quantitative phase (validation of the programme through the Delphi method). In the first stage, data will be collected through interviews. Key concepts, evidence and gaps in research will also be identified, collected and analysed through a scoping review. In the second stage, a support programme will be designed based on the results of the content analysis of interviews and the findings from the scoping review. In the final phase, the study will aim to validate the designed programme through a Delphi study.

ETHICS AND DISSEMINATION: This study formed part of a Ph.D. degree and was approved by the ethics committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1402.395). Informed consent will be obtained from all study participants. Findings will be published in a peer-reviewed journal.

PMID:38830739 | DOI:10.1136/bmjopen-2023-081560

Pflugers Arch. 2024 Jun 3. doi: 10.1007/s00424-024-02975-4. Online ahead of print.

ABSTRACT

The intestinal epithelium is covered by mucus that protects the tissue from the luminal content. Studies have shown that anion secretion via the cystic fibrosis conductance regulator (Cftr) regulates mucus formation in the small intestine. However, mechanisms regulating mucus formation in the colon are less understood. The aim of this study was to explore the role of anion transport in the regulation of mucus formation during steady state and in response to carbamylcholine (CCh) and prostaglandin E2 (PGE2). The broad-spectrum anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), CftrdF508 (CF) mice, and the slc26a3 inhibitor SLC26A3-IN-2 were used to inhibit anion transport. In the distal colon, steady-state mucus expansion was reduced by SLC26A3-IN-2 and normal in CF mice. PGE2 stimulated mucus expansion without de novo mucus release in wild type (WT) and CF colon via slc26a3 sensitive mechanisms, while CCh induced de novo mucus secretion in WT but not in CF colon. However, when added simultaneously, CCh and PGE2 stimulated de novo mucus secretion in the CF colon via DIDS-sensitive pathways. A similar response was observed in CF ileum that responded to CCh and PGE2 with DIDS-sensitive de novo mucus secretion. In conclusion, this study suggests that slc26a3 regulates colonic mucus expansion, while Cftr regulates CCh-induced de novo mucus secretion from ileal and distal colon crypts. Furthermore, these findings demonstrate that in the absence of a functional Cftr channel, parallel stimulation with CCh and PGE2 activates additional anion transport processes that help release mucus from intestinal goblet cells.

PMID:38829391 | DOI:10.1007/s00424-024-02975-4