Journal of Cystic Fibrosis最新文献

Background: Despite high rates of anxiety and depression, research regarding the effect of psychological interventions on people with CF (pwCF) is limited. We evaluated the impact of UPLIFT (Using Practice and Learning to Increase Favorable Thoughts), a group telehealth intervention using mindfulness-based cognitive behavioral therapy (MBCT), on symptoms of anxiety and depression in pwCF.

Methods: This multicenter randomized trial compared changes in symptoms of anxiety and/or depression in adult pwCF who participated in the 8-week UPLIFT intervention to a treatment-as-usual (TAU) group. Follow up assessments occurred immediately after and 6- and 12-months post-intervention. Primary outcome measures were change in Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scores modeled in separate linear mixed-effects models.

Results: Sixty-six pwCF participated. At baseline, 43 (65.15%) had some minimal symptoms of depression (PHQ-9≥5) and 44 (66.67%) had some minimal symptoms of anxiety (GAD-7≥5). During the 12 month follow up period, the overall change in PHQ-9 was greater in the UPLIFT group compared to TAU (p = .049). Analysis of individual time points showed a statistically significant difference between groups in change from baseline immediately post-treatment (-2.321, SD 0.684 vs 0.362, SD 0.656, p = .005); differences persisted but were not statistically significant at 6 and 12 months. Similar trends for changes in GAD-7 were non-significant.

Conclusions: Participation in UPLIFT, a group telehealth intervention using MBCT, provides short-term improvement in symptoms of depression, as measured by changes in PHQ9. Improvement in symptoms of anxiety were suggested but could not be statistically confirmed.

Even as many outcomes for people living with cystic fibrosis (PLwCF) improve, individuals still experience extensive symptom burdens. From birth, many PLwCF experience both pain as a symptom of their CF disease and procedural pain, posing detriments to health, functioning, and quality of life. Despite its prevalence and impact, there is no CF-specific guidance for the assessment and management of pain. Similarly, no guidance exists regarding communication with PLwCF about their pain experiences or its impact on their lives. Therefore, the Cystic Fibrosis Foundation (CFF) assembled an expert panel of clinicians, researchers, PLwCF, and caregivers to develop consensus recommendations for pain management in CF. We utilized literature review and expert opinion to develop 13 recommendations addressing pain assessment, management, and communication. Recommendations are centered on guiding principles of utilizing a multimodal approach to pain management, offering age and developmentally appropriate assessment and interventions, concurrently treating underlying conditions causing, contributing to, and/or exacerbated by pain, considering societal stigma of the pain experience, particularly for minoritized and marginalized people, and sensitivity to issues of access and cost. These recommendations are intended to guide clinicians in managing pain and improving quality of life for PLwCF with pain at all stages of illness and development.

As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including elexacaftor/tezacaftor/ivacaftor (ETI) have become widely used in eligible patients with cystic fibrosis (CF), the use of these medications in pregnant people has become a critical area of investigation. Since these medications appear generally safe to both mother and fetus when taken by pregnant people with CF, interest has pivoted to the use of ETI in CF carrier mothers to decrease morbidity and mortality from meconium ileus (MI) in fetuses with cystic fibrosis. Here we discuss three infants at our institution with ultrasound findings of MI who were exposed to prenatal ETI through CF carrier mothers for the purposes of treating MI and lowering risk of intestinal complications from this severe manifestation of CF. These cases differ in the timing of ETI initiation, severity of outcome, and accessibility of this off-label medication use to families depending on their insurance. All infants and mothers tolerated the medication well without significant side effects. One infant had complete MI resolution, one had persistent MI at birth with easy clearance with minimally invasive therapies, and one had persistent MI requiring jejunostomy. The infant with the most severe outcome had the shortest duration of ETI exposure and may have been able to receive this medication sooner had a referral to a CF center been made. These cases highlight the potentially life-altering effects of prenatal ETI use and the need for awareness of this clinical situation among fetal care providers.

Background: The splice variant 3849+10kbC->T (c.3717+12191C>T) (3849 variant) is a residual function CFTR variant, characterized by insertion of an in-frame stop codon into most CFTR transcripts. Both ivacaftor (Iva) and tezacaftor/ivacaftor (Tez/Iva) have been approved for people with CF (pwCF) carrying the 3849 variant. In-vitro studies for elexacaftor/tezacaftor/ivacaftor (ETI) did not include the 3849 variant as responsive to ETI. We present the clinical effectiveness of ETI in pwCF homozygous for the 3849 variant or heterozygous for 3849 and class I variants previously treated with Iva or Tez/Iva.

Methods: We conducted a multi-center observational study of pwCF homozygous for the 3849 variant or heterozygous for 3849 and class I variants who were transitioned from Iva or Tez/Iva to ETI. We collected clinical data, including sweat chloride concentrations, pulmonary function tests, BMI and intravenous antibiotic treatments.

Results: We identified nine pwCF heterozygous for 3849 and class I variants and one pwCF homozygous for the 3849 variant. Prior to transitioning to ETI, nine pwCF were treated with Tez/Iva and one with Iva. Compared to baseline, median sweat chloride concentration declined from 48 to 35 mEq/L (p = 0.009). Median FEV₁ increased from 53 % to 65 % (p = 0.006). Pulmonary exacerbations requiring intravenous antibiotics declined from mean 1.4 to 0.6 in the twelve months before and after ETI.

Conclusions: We demonstrate the clinical effectiveness of ETI in pwCF carrying the 3849 variant, in excess of the response to Iva or Iva/Tez. Our results provide preliminary support for clinical use of ETI in pwCF carrying the 3849+10kbC->T variant.

Treatment-associated differences in Pseudomonas aeruginosa (Pa) density in sputum have been used as a response biomarker in clinical trials of cystic fibrosis (CF) therapies. Although most studies have included placebo-treated groups as comparators, variability of Pa density in untreated individuals has rarely been reported. We measured day-to-day differences in Pa density in 267 sputum sample pairs collected from 13 adults with CF during days in which no changes in antibiotic therapy occurred. Although the mean sputum Pa density change across all sample pairs was modest (-0.09 log₁₀ 16S rRNA gene copies/mL), variability in day-to-day changes were substantial (SD = 1.09) with one-quarter of sample pairs having >1 log₁₀ differences in Pa density; approximately 8 % of pairs had >2 log₁₀ differences in density. Day-to-day variability in Pa density differed substantially between study participants (p = .001). These results will support the design and interpretation of studies using sputum Pa density change as an efficacy biomarker.

Background: Cystic fibrosis (CF) is a chronic condition that requires complex and long-term treatments. While substantial research has explored treatment burden associated with CF; its impact remains complex to quantify. This review aims to identify the different methods used in the literature to measure treatment burden in people with CF (pwCF).

Method: Five databases were searched for interventional and observational studies that focused primarily on treatment burden. The studies were presented using narrative synthesis structured around the perspective of treatment burden (subjective vs. objective).

Results: This review synthesised 17 articles, which utilised subjective and objective measures separately or collectively. Twelve studies used subjective treatment burden measures (CF-specific and generic scales), while 14 studies used objective measures (treatment time, volume and complexity, and cost). Eight studies investigated treatment burden reported by proxy on behalf of children with CF. The most used measures were treatment time (9/17) and CF questionnaire-revised (CFQ-R) treatment burden subscale (6/17). Older age and lower lung function were associated with greater burden, treatment time, and complexity. Caregivers/parents reported worse treatment burden compared to children with CF (6-13 y/o) when completing the same measure.

Conclusion: No single measure used in the reviewed studies fully the multidimensional nature of treatment burden and summarised it in a single score. Given the rapidly evolving landscape of CF care a pragmatic approach to capture a broader array of treatment burden dimensions may be to routinely complement subjective measures with objective measures.

Background: Parents play a major role in shaping their children's physical activity (PA) behaviour. This study aimed to investigate the association between PA of youth with Cystic Fibrosis (YwCF) and their parents.

Methods: PA was measured by an ActiGraph GT3x-BT for seven consecutive days. Data were processed by GGIR and PA intensities were based on the age-specific Hildebrand equations. Moderate-to-vigorous PA was chosen as primary outcome.

Results: 26 YwCF-parent dyads participated. A significant positive association was found between parental PA behaviour and YwCF's PA behaviour for both moderate-to-vigorous PA and total PA (R² = 0.60; p = 0.001; R² = 0.64; p < 0.001). Furthermore, YwCF with less active parents perform 16 min/day less moderate-to-vigorous PA compared to YwCF with more active parents (p = 0.004).

Conclusion: Higher parental PA levels are strongly associated with higher YwCF's PA levels. This association needs to be confirmed in a larger cohort to explore whether parental behaviour is an effective strategy to improve YwCF's PA levels.

Background: This report summarizes the 2023 inaugural annual meeting of the Cystic Fibrosis Foundation's Prioritizing Research in Mental Health (PRIME) working group. This workshop focused on mental health and elexacaftor/tezacaftor/ivacaftor (ETI).

Methods: We reviewed existing literature and identified key gaps and study design considerations in preclinical work, pharmacokinetics/pharmacodynamics, mood/anxiety, quality of life/self-perception, neuropsychological symptoms, sleep, and symptom management.

Results: Limited studies have identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. Longitudinal human studies reporting mean changes generally show no change or improvement. However, case reports and single-center studies identify subgroups reporting new or worsening symptoms.

Conclusions: Future studies should focus on understanding the role of CFTR in the nervous system, defining ETI impacts in preclinical models, and mechanistic investigations. Innovative methods with larger samples and comprehensive assessments are needed to determine the incidence of new/worsening symptoms throughout the lifespan and effective management strategies.