Sweat chloride and lung function responses to elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with two versus one responsive CFTR variants: an analysis of two real-world observational studies.

Background: Among people with cystic fibrosis, sweat chloride and lung function response to elexacaftor-tezacaftor-ivacaftor (ETI) is variable. We hypothesised that the presence of two versus one ETI-responsive CFTR variant could predict response variability.

Methods: In this analysis of two real-world observational studies, data from a French national cohort of adults (aged ≥18 years) with cystic fibrosis and at least one F508del variant treated with ETI and the French compassionate programme for ETI in people (aged ≥6 years) with cystic fibrosis without F508del were used to examine sweat chloride concentrations (SCCs) after ETI initiation, and the absolute change in SCC and percentage of predicted forced expiratory volume in 1 s (ppFEV) following ETI initiation.

Change in the 6-min walk test among 71 patients with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has led to substantial improvements in the clinical outcome of people with cystic fibrosis (pwCF). However, its effects on exercise capacity remain uncertain.

Methods: This retrospective cohort study included 71 pwCF who started ETI between March 2020 and September 2022.

Beyond the Lung. Impact of Elexacaftor/Tezacaftor/Ivacaftor on Sinonasal Disease in Children With Cystic Fibrosis.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) therapy that improves pulmonary function and chronic rhinosinusitis (CRS) in cystic fibrosis (CF) adults with at least one copy of the F508del CFTR mutation. The purpose of this study is to evaluate the impact of ETI on CRS symptoms in children and adolescents with CF.

Methods: The MODUL-CF observational study is a multicenter prospective cohort study enrolling CF children with at least 1 F508del mutation in France.

Impact of elexacaftor/tezacaftor/ivacaftor on glucose tolerance in adolescents with cystic fibrosis.

Background: Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI impact on glucose tolerance remains controversial.

Methods: All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible.

The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study.

Background: Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted.

Physical activity promotion in French cystic fibrosis centers: capitalizing on experience.

Background: Physical activity (PA) provides physical and psychosocial benefits for people with cystic fibrosis (pwCF). However, practice levels remain below recommendations and strategies for promoting PA in specialist centers need to be better identified. The socio-ecological model of health emphasizes the central role of policies and environment in influencing individuals' health behaviors.

Theratyping cystic fibrosis patients to guide elexacaftor/tezacaftor/ivacaftor out-of-label prescription.

Background: Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator () gene. Considering that pwCF carrying rare variants may benefit from ETI, including variants already validated by the US Food and Drug Administration (FDA), a compassionate use programme was launched in France. PwCF were invited to undergo a nasal brushing to investigate whether the pharmacological rescue of CFTR activity by ETI in human nasal epithelial cell (HNEC) cultures was predictive of the clinical response.

Screening strategies for glucose tolerance abnormalities and diabetes in people with cystic fibrosis.

The increase in life expectancy of patients with cystic fibrosis has come with new comorbidities, particularly diabetes. The gradual development of glucose tolerance abnormalities means that 30 to 40% of adults will be diabetic. Cystic fibrosis-related diabetes is a major challenge in the care of these patients because it is a morbidity and mortality factor at all stages of the disease.

Randomized controlled trial of home-based vs. hospital-based pulmonary rehabilitation in post COVID-19 patients.

Background: Between 30% and 60% of people who have been infected with COVID-19 still had symptoms 3 months after the start of the disease. Prescribing a pulmonary rehabilitation program in rehabilitation facilities for post COVID-19 patients could help alleviate the symptoms. However, rehabilitation facilities known to provide good quality care to COVID-19 patients and all other patients, could become saturated by the rise in cases.

Clinical practice versus guidelines for the screening of cystic fibrosis-related diabetes: A French survey from the 47 centers.

This study aimed to analyze clinical practices concerning cystic fibrosis-related diabetes (CFRD) screening in France. A web-based questionnaire was distributed between December 1, 2020 and January 31, 2021 among 47 cystic fibrosis centers including pediatric, adult, and mixed units. In accordance with guidelines, 92.

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis.

Background: Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.

Methods: Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease.

Perceptions of barriers to and facilitators of physical activity in adults with cystic fibrosis.

Background: Physical activity (PA) is a proven therapeutic tool to increase the quality of life and life expectancy in people with cystic fibrosis (pwCF). Despite this, the PA level of pwCF is lower than recommended.

Objectives: This study was conducted to identify the barriers to and facilitators of PA in adults with CF with heterogeneous severity.

Using chest computed tomography and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis.

Objectives: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). The aim of this study was to assess lung structural changes after 1 year of lumacaftor-ivacaftor treatment and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.

Methods: Adolescents and adults with CF from a French multicentre real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pre-therapeutic and follow-up chest computed tomography (CT) scans available.

Development and validation of the Cystic Fibrosis Decisional Balance for Physical Activity scale (CF-DB-PA).

Background: People with cystic fibrosis (pwCF) derive several physiological and psychological benefits from regular physical activity (PA), but the practice is lower than recommended. Knowledge about the facilitators of and barriers to PA at the individual level is important to act positively on PA behaviors. This study validated the Cystic Fibrosis Decisional Balance for Physical Activity scale (CF-DB-PA) for adults with CF.

Rapid Improvement after Starting Elexacaftor-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease.

Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV (ppFEV) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted.

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function.

Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV.

Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV<40 or ppFEV≥90 in comparison with those with ppFEV [40-90[.

Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis.

Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes.

Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis.

Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation. To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting. The study was conducted in the 47 CF reference centers in France.

Overall and differentiated sensory responses to cardiopulmonary exercise test in patients with cystic fibrosis: kinetics and ability to predict peak oxygen uptake.

Purpose: We evaluated the validity of predicting peak oxygen uptake ([Formula: see text]O) from submaximal ratings of perceived exertion (RPE) during incremental cardiopulmonary exercise test (CPET) in patients with cystic fibrosis (CF) and compared the predictive accuracy between overall and differentiated RPE scores.

Methods: Thirty-five adults with CF (FEV = 58 ± 23%) performed a CPET on cycle ergometer with gas exchange measurements. Leg, chest and overall RPE were collected every minute throughout the test.

Eosinophilic granulomatosis with polyangiitis in children: Data from the French RespiRare® cohort.

Objectives: To describe the characteristics of pediatric cases of eosinophilic granulomatosis with polyangiitis (EGPA), a systemic necrotizing vasculitis rarely diagnosed in children, retrieved from the French Reference Center for rare pediatric lung diseases and compared with adult cases included in the French Vasculitis Study Group cohort.

Methods: We collected information on pediatric EGPA disease presentation, management, and outcome. Cases met the Lanham criteria and/or American College of Rheumatology classification criteria.

Retrospective observational study of French patients with cystic fibrosis and a Gly551Asp-CFTR mutation after 1 and 2years of treatment with ivacaftor in a real-world setting.

Background: Ivacaftor has been shown to improve lung function and body weight in patients with CF and a gating mutation. Real-world evaluation is warranted to examine its safety and effectiveness over the long term.

Methods: A retrospective observational multicentre study collected clinical data in the year before and the 2years after ivacaftor initiation in patients with CF and a Gly551Asp-CFTR mutation.

DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis.

Background: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients.

The 1-Minute Sit-to-Stand Test in Adults With Cystic Fibrosis: Correlations With Cardiopulmonary Exercise Test, 6-Minute Walk Test, and Quadriceps Strength.

Background: Exercise testing is part of the regular assessment of patients with cystic fibrosis (CF). We aimed to evaluate (1) the convergent validity of the 1-min sit-to-stand (STS) test in CF by investigating its relationships with peak oxygen uptake (peak V̇ ), quadriceps strength, and quality of life and (2) to compare these associations with those of the 6-min walk test (6MWT).

Methods: Twenty-five adults with CF (FEV = 59 ± 24%) performed the STS test, the 6MWT, quadriceps strength assessment, and cardiopulmonary exercise test (CPET).