Decreased insulin dose-adjusted hemoglobin A1c in adults with cystic fibrosis-related diabetes treated with elexacaftor-tezacaftor-ivacaftor.

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) became available for adults with cystic fibrosis (CF) in 2019, but its impact on CF-related diabetes (CFRD) remains unclear.

Methods: A single-center retrospective cohort study was conducted among adults with CFRD to examine the change in insulin dose-adjusted Hemoglobin A1c (IDAA1c). Linear mixed effects model (LMEM) analysis was used to investigate the change in IDAA1c between baseline and 24 months of follow up, comparing an ETI-treated group to an unexposed group.

Population Pharmacokinetics of Elexacaftor, Tezacaftor and Ivacaftor in a Real-World Cohort of Adults with Cystic Fibrosis.

Background And Objectives: Elexacaftor-tezacaftor-ivacaftor (ETI), a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has become the therapeutic standard of care for most people with cystic fibrosis (pwCF). People with cystic fibrosis exhibit differences in CFTR genotypes and have important differences in phenotypic characteristics including age, body weight, pancreatic status, disease severity, and comorbidities. While these differences predict large interindividual variability (IIV) in ETI exposure, there is a unique dose regimen recommended for adults.

Reversal of cylindrical bronchial dilatations in a subset of adults with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

Background: This study sought to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations.

Methods: Chest computed tomography (CT) scans performed prior to and 12 months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatations (the latter served as controls, with three controls per case) were selected.

The French compassionate programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del variant.

Background: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (CF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for people with CF carrying one of 177 rare variants.

Methods: An observational study was conducted to evaluate the effectiveness of ETI in people with CF with advanced lung disease who were not eligible for ETI in Europe.

Acneiform Eruption Following Elexacaftor-Tezacaftor-Ivacaftor Treatment in Patients With Cystic Fibrosis.

Importance: A new treatment for cystic fibrosis combining 3 CFTR modulators-elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA)-has recently been approved for cystic fibrosis treatment. The cutaneous adverse effects following treatment with this combination are poorly described in the literature.

Objective: To describe the clinicopathological features and treatment response of ELX-TEZ-IVA-associated acneiform eruptions in patients with cystic fibrosis.

Otological Manifestations in Adults with Primary Ciliary Dyskinesia: A Controlled Radio-Clinical Study.

Primary ciliary dyskinesia (PCD) is a rare genetical disease characterized by an abnormal structure or function of the cilia, causing sinusitis, otitis, and bronchiectasis. Hearing loss affects 60% of PCD patients, but data are lacking concerning hearing and temporal bone imaging in adults. Our aim was to describe clinical and radiological ear disease in adults with genetically confirmed PCD.

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.

Diagnosis Yield and Safety of Surgical Biopsy in Interstitial Lung Diseases: A Prospective Study.

Background: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis.

"Il faut continuer à poser des questions" patient reported outcome measures in cystic fibrosis: An anthropological perspective.

Background: People with cystic fibrosis (pwCF) are central in the development of patient-led assessment tools. Qualitative analysis of a frequently used CF-specific patient-reported outcome measure (PROM) sought patient recommendations for development of a new quality of life (QoL) tool.

Methods: We performed an inventory of PROMs, symptom-report and QoL tools used in clinical trials within the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) and in routine clinical practice among Cystic Fibrosis Europe and ECFS members.

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia.

Background: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigating relationships have been unsuitable for rare diseases.

Methods: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD.

Standardised clinical data from patients with primary ciliary dyskinesia: FOLLOW-PCD.

Clinical data on primary ciliary dyskinesia (PCD) are limited, heterogeneous and mostly derived from retrospective chart reviews, leading to missing data and unreliable symptoms and results of physical examinations. We need standardised prospective data collection to study phenotypes, severity and prognosis and improve standards of care. A large, international and multidisciplinary group of PCD experts developed FOLLOW-PCD, a standardised clinical PCD form and patient questionnaire.

TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella.

Cilia and flagella are evolutionarily conserved organelles whose motility relies on the outer and inner dynein arm complexes (ODAs and IDAs). Defects in ODAs and IDAs result in primary ciliary dyskinesia (PCD), a disease characterized by recurrent airway infections and male infertility. PCD mutations in assembly factors have been shown to cause a combined ODA-IDA defect, affecting both cilia and flagella.

Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers.

Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed.

Critical Evaluation of Sinonasal Disease in 64 Adults with Primary Ciliary Dyskinesia.

To date, no study precisely described ear, nose and throat (ENT) disease in adults with primary ciliary dyskinesia (PCD) and its relationship with ciliary function/ultrastructure. A retrospective study of standardized ENT data (exam, audiogram, sinus Computed tomography (CT), and bacteriology) was conducted in 64 adults with confirmed PCD who were followed in two ENT reference centers. Rhinorrhoea and hearing loss were the main symptoms.

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia.

Background: The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD).

Methods: Adult (≥18 years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density.

A prospective analysis of unplanned patient-initiated contacts in an adult cystic fibrosis centre.

Background: Timely response should be provided when patients contact the cystic fibrosis (CF) centre in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults.

Methods: A two-stage prospective study was undertaken from 1 January to 31 December 2015 at Cochin Hospital, Paris (France).

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease.

Objective: To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting.

Methods: A multicentre observational study investigated adverse events, treatment discontinuation, FEV and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV below 40% predicted.

Results: Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment.

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

Background And Aims: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre.

Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia.

Introduction: Primary ciliary dyskinesia (PCD) is a genetic disease characterised by abnormalities in ciliary function, responsible for chronic pulmonary and sinonasal diseases. Adult clinical features and outcome are poorly described.

Objectives: To assess the clinical characteristics and disease progression in adults with PCD.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

Background/objectives: Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown.

Methods: Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded.

Renin-associated hypertension after bronchial artery embolization in cystic fibrosis.

Bronchial artery embolization is the recommended therapy for massive hemoptysis in patients with cystic fibrosis (CF). We report on two cases of multiple renal infarcts and renin-associated hypertension and hypokalemia occurring in CF adults after bronchial artery embolizations. These complications were presumably related to crossing of small calibrated microspheres through arteriovenous anastomoses.

Reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin.

Background: Azithromycin reduces exacerbations in cystic fibrosis (CF) patients. Our aim was to investigate its association with nontuberculous mycobacteria isolation and macrolide susceptibility.

Methods: From 2006 to 2010, all adult CF subjects at Cochin Hospital (Paris, France) harboring at least one positive NTM isolate were identified (Cases).