Journal of Cystic Fibrosis最新文献

Cystic fibrosis (CF) care has been revolutionized by CFTR modulators, particularly the triple combination elexacaftor/tezacaftor/ivacaftor (ETI). However, a subset of people with CF (pwCF) carrying ETI-unresponsive variants still lack effective therapies. A nextgeneration modulator combination, vanzacaftor/tezacaftor/deutivacaftor (VTD), shows promise in addressing this gap. Phase 3 trials report superior efficacy of VTD in reducing sweat chloride and suggest potential benefit for 31 CFTR variants previously deemed ETI-unresponsive based on limited in vitro data. Reassessment of these variants reveals that some demonstrate residual function or borderline ETI responsiveness, challenging their unresponsive classification. Differences in molecular interactions, particularly within NBD1 and modulator-binding sites, may account for variant-specific responses. Patient-derived intestinal organoid (PDIO) assays showed significant functional improvement with VTD, but not ETI, in 2 pwCF with G458V and G85R mutations, supporting the notion of distinct mechanisms of action. These findings underscore the need to refine CFTR variant classifications and highlight the limitations of current in vitro thresholds. While PDIOs offer physiologically relevant insights, clinical outcomes remain the ultimate determinant of therapeutic benefit. Broader access to raw data and individualized in vitro-clinical correlations are essential for informed therapeutic decisions. VTD offers new hope for pwCF with rare or previously unresponsive variants, reinforcing the importance of a personalized, datadriven approach to CF care.

Background: Financial challenges are common among people with cystic fibrosis (PwCF). We explored the financial and healthcare tradeoffs that PwCF and their care partners make to meet healthcare needs, and how these tradeoffs vary across people from different income levels.

Methods: Adults (≥18 years) with cystic fibrosis and parents/guardians/spouses of PwCF completed the Cystic fibrosis Outcomes, Social needs and Tradeoffs due to Coverage and Financial burden (COST-CF) survey between February and May 2024. We compared financial and healthcare tradeoffs and desired support over the prior 12 months across income groups, based on 2024 US Federal Poverty Level (FPL) guidelines.

Results: Sixty-seven percent of 936 respondents experienced one or more financial issues caused by CF medical bills, ranging from 80% among those with ≤500% FPL to 47% among those with >500% FPL. The most common included actions taken to manage finances (64%) (e.g., delay of major purchases), financial consequences (57%) (e.g., inability to accumulate savings), and challenges meeting expenses (31%). Fifty-five percent of 877 respondents reported using one or more strategies to save money on CF healthcare costs, ranging from 65% among people with ≤500% FPL to 39% among those with >500% FPL. While 45% reported proactive cost-reduction strategies (e.g., discussions to reduce costs of care; requesting lower cost medications), more than one-quarter reported delaying or skipping medications (29%) or care (25%).

Conclusions: PwCF and care partners face substantial financial burdens, with greater burdens among those with lower incomes. Many also report healthcare tradeoffs, which may impact long-term health outcomes.

Background: Telehealth has been widely incorporated into cystic fibrosis (CF) care in Australia and other countries, with a largely hybrid approach of multidisciplinary telehealth alongside traditional in-person care. While feasibility and acceptability of telehealth-based care has been established, the impact on CF-related health outcomes has not been comprehensively assessed.

Methods: Retrospective cohort study using national Australian Cystic Fibrosis Registry Data (ACFDR). Primary outcomes were change in percent predicted forced expiratory volume in one second (ppFEV₁) in adults and body mass index (BMI) z-score in children. Secondary outcomes included lung function, BMI, microbiology and hospital admissions. Telehealth use was stratified according to percentage of telehealth visits out of total CF clinic visits during the study period, examined as quartiles. Analyses were conducted using Analysis of Covariance (ANCOVA) and logistic regression, to isolate the effect of telehealth use quartile on outcomes after adjusting for confounders.

Results: Complete data from 1250 patients, (646 < 18 yr, 594 ≥ 18 yrs), were analysed. There was less decline in ppFEV₁ in adults (β = 6.06, p < 0.001), and lower detection of Pseudomonas aeruginosa in adults (OR = 0.419, p = 0.035) and children (OR = 0.182, p = 0.011) who received greater than 75% of visits via telehealth. However, high telehealth use was associated with reduced microbiological sampling. Telehealth was not associated with change in BMI or hospitalisations.

Conclusions: Population level data from the ACFDR demonstrates that higher telehealth usage was not associated with adverse health outcomes and was associated with a reduced decline in ppFEV₁ in adults.

Sputum analysis is the standard method for microbiological surveillance in cystic fibrosis (CF). However, CFTR modulator therapy has markedly reduced sputum production, creating an urgent need to evaluate alternative sampling strategies. Upper airway sampling has been proposed as a potential surrogate, but its ability to reflect the lower airway microbiota remains unclear. This study evaluated whether upper airway microbiota profiling can reliably represent the lower airway in adults with CF. In this prospective observational study, we compared the airway microbiota of 70 adults with CF and 10 healthy volunteers using oropharyngeal rinse (OPR) and sputum samples. Microbiota profiling was performed using 16S rRNA gene sequencing, with alpha- and beta-diversity, taxonomic composition, and divergence from healthy controls assessed for both sample types. The OPR and sputum microbiota of adults with CF were compositionally distinct, whereas healthy volunteers exhibited highly similar communities between sample types. Firmicutes dominated within OPR samples, while Proteobacteria, particularly Pseudomonas, predominated in sputum. Only 3 of 52 awCF who had Pseudomonas detected in sputum showed detectable, low-level OPR signals. Both sample types became increasingly dysbiotic with worsening lung function, reflecting greater deviation from healthy community structure. Although dysbiosis correlated across sample types, the divergence between upper and lower airways did not relate to lung function. These findings indicate that OPR sampling does not reliably identify key lower-airway pathogens. However, the association between OPR and lung function suggests that upper-airway sampling may reflect the degree of lower-airway dysbiosis, warranting further investigation.