Journal of Cystic Fibrosis最新文献

Background: The cystic fibrosis (CF) regimen is time-consuming and burdensome leading to barriers to self-management. This mixed-methods study developed the Daily Care Check-in (DCC) that is specific to the barriers faced by people with CF (PWCF) and evaluated its validity.

Methods: Qualitative methods were used to identify barriers to self-management and develop items, with "think aloud" cognitive interviews conducted to refine the items. A multisite, cross-sectional study was conducted to test the internal consistency, test-retest reliability, and validity of the DCC scores, comparing them to objective medication adherence (composite medication possession ratio (cMPR)) and psychosocial measures (self-efficacy, medication beliefs, executive functioning, depressive and anxiety symptoms, treatment burden, and treatment complexity).

Results: The DCC (18 items) includes two scales: Occurrence (score range 0-18) and Interference (score range 0-90). 405 participants completed the DCC, 344 (85 %) completed the survey, and 365 (90 %) had a cMPR calculated. On average, 6.8 barriers were reported (SD = 4.2 Occurrence Scale), and the Interference Scale had a mean score of 18.4 (SD = 14.0). Reliability was acceptable to good. cMPR was negatively correlated with the DCC (rho=-0.26, Occurrence and rho = -0.31, Interference, p-values<0.0001). A priori hypotheses between the DCC and the other measures were supported and demonstrated construct validity.

Conclusions: This study provides evidence supporting the validity of the DCC for assessing the presence and impact of barriers to CF self-management, including medication adherence. Formal screening of self-management barriers (e.g., using the DCC) should be considered to facilitate conversations with the care team and identify tailored interventions to support CF self-management.

This case report presents a 14-month-old boy with a history of cystic fibrosis (CF) carrier status, diagnosed following a positive newborn screening for CF (CF-NBS), who developed symptoms suggestive of Pseudo-Bartter syndrome (PBS). Despite initial evaluations not meeting CF diagnostic criteria, subsequent investigations revealed an intermediate sweat chloride concentration, a second CFTR mutation, and CFTR dysfunction through rectal organoid morphology analysis (ROMA) consistent with CFTR-related disorder (CFTR-RD). This case raises important considerations regarding the diagnosis and management of CFTR-RD. PBS can be considered as a rare presentation of CFTR-RD and can occur in children with sweat chloride below the CF range. Functional testing of CFTR by ROMA enabled a more accurate diagnosis. Despite the negative work-up after CF-NBS, this infant developed CFTR-RD, but this should not be considered as a screen failure. Follow-up of children with CFTR-RD at a CF centre is preferred, because of the risk of developing CF.

Background: The Pseudomonas filamentous bacteriophage (Pf) infects Pseudomonas aeruginosa (Pa) 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 Pa infection and more severe exacerbations in a cross-sectional cohort study.

Methods: We examined the relationships between Pf and clinical outcomes in a longitudinal study of pwCF. Sputum Pa 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.

Results: 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.

Conclusion: Pf may serve as a prognostic biomarker and potential therapeutic target for Pa infections in CF.

Background: Triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and impacts upon the respiratory microbiome in people with Cystic fibrosis (pwCF) with advanced lung disease. However, adolescents with cystic fibrosis (CF) are less colonized with bacterial pathogens than adult pwCF but their microbiota already differs from healthy individuals. The aim of this study was to longitudinally analyze the impact of ETI on the respiratory metagenome in adolescents with predominantly mild CF lung disease.

Methods: In this prospective observational study, we included pwCF aged 12-20 years with at least one F508del mutation, who collected oropharyngeal swabs before and after initiation of ETI therapy twice per week to biweekly over three months. We performed whole metagenome shotgun sequencing, followed by host DNA filtering and taxonomic profiling. We used linear and additive mixed effects models adjusted for known confounders and corrected for multiple testing to study longitudinal development of the microbiome. We analyzed bacterial diversity, abundance, and strain-level phylogeny.

Results: We analyzed the metagenomic data of 297 swabs of 20 pwCF. Microbiome composition changed after initiation of ETI therapy. We observed a slight diversification of the microbiome over time (Inv Simpson, Coef 0.085, 95 %CI 0.003, 0.17, p = 0.04). Strain-level analysis and clustering showed that strain retention of the most frequent bacterial species is predominant even during ETI therapy.

Conclusions: During three months of ETI therapy, commensal bacteria increased, which may help to prevent overgrowth of bacterial pathogens.