Progress in precision medicine in cystic fibrosis: a focus on CFTR modulator therapy.

The genetic multisystem condition cystic fibrosis (CF) has seen a paradigm shift in therapeutic approaches within the past decade. Since the first clinical descriptions in the 1930s, treatment advances had focused on the downstream consequences of a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel. The discovery of the gene that codes for CFTR and an understanding of the way in which different genetic mutations lead to disruption of normal CFTR function have led to the creation and subsequent licensing of drugs that target this process.

Revisiting a diagnosis of cystic fibrosis - Uncertainties and considerations.

There is now increased knowledge and experience of newborn screening around the world. There is also a better understanding of CF gene analysis, informed by international databases. This has resulted in a small number of children and adults having their diagnosis of CF reversed.

SARS-CoV-2 antibodies among people with cystic fibrosis prior to the vaccination campaign: A seroprevalence study in two specialized centres in Northern Italy.

The prevalence of anti-SARS-CoV-2 antibodies in people with cystic fibrosis (CF) is largely unknown. We carried out a cross-sectional study between March and June 2021 with the aim of estimating the seroprevalence of anti-SARS-CoV-2 antibodies in two CF centres in Northern Italy. Total serum anti-SARS-CoV-2 (spike) antibodies levels were measured and values ≥0.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.

Background: Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation.

Methods: We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK.

Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis.

Background: Defective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease.

Results: Here, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation.

Meteorological Factors Influence the Presence of Fungi in the Air; A 14-Month Surveillance Study at an Adult Cystic Fibrosis Center.

Background: Cystic fibrosis is an inherited disease that predisposes to progressive lung damage. Cystic fibrosis patients are particularly prone to developing pulmonary infections. Fungal species are commonly isolated in lower airway samples from patients with cystic fibrosis.

Fourier Transform Infrared Spectroscopy for Typing Burkholderia cenocepacia ET12 Isolates.

The IR Biotyper and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using ClinProTools software (MALDI-TOF MS-ClinProTools) are two novel typing methods that rely on the analysis of carbohydrate and peptide residues in intact bacterial cells. These two methods have shown promising results in the rapid and accurate typing of bacteria. In this study, we evaluated these novel typing methods in comparison with genotypic typing for cluster analysis of Burkholderia cenocepacia epidemic strain ET12, isolated from adult cystic fibrosis patients.

Delayed hepatic necrosis in a cystic fibrosis patient taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio).

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug.

Discovery of inhibition of and by the Brown Rot Basidiomycete Fungus, .

Antimicrobial resistance (AMR) has now emerged as a major global public health problem. Certain bacterial pathogens, particularly Gram negative organisms associated with patients with cystic fibrosis (CF), have become resistant to several classes of antibiotics resulting in pan-resistance, which creates a clinical treatment dilemma. This study wished to explore the production of antibacterial extracellular metabolites from plant pathogenic fungi.

Emerging Nonpulmonary Complications for Adults With Cystic Fibrosis: Adult Cystic Fibrosis Series.

Improved treatments for cystic fibrosis (CF)-related lung disease have resulted in increased longevity, but also increased prevalence and severity of extrapulmonary manifestations of CF, treatment-related complications, age-related conditions, and psychosocial effects of longstanding chronic disease. Likewise, the recognition of mild CF phenotypes has changed the landscape of CF disease. This review outlines our current understanding of the common extrapulmonary complications of CF, as well as the changing landscape and future directions of the extrapulmonary complications experienced by patients with CF.

Inflammation biomarkers in sputum for clinical trials in cystic fibrosis: current understanding and gaps in knowledge.

Rationale: Sputum biomarkers hold promise as a direct measure of inflammation within the cystic fibrosis (CF) lung, but variability in study design and sampling methodology have limited their use. A full evaluation of the reliability, validity and clinical relevance of individual biomarkers is required to optimise their use within CF clinical research.

Objectives: A biomarker Special Interest Working Group was established within the European Cystic Fibrosis Society-Clinical Trials Network Standardisation Committee, to perform a review of the evidence regarding sputum biomarkers in CF.

Use of anti-CMV immunoglobulins in lung transplant recipients: The French experience.

Rational: Pending the authorization of new anti-CMV drugs with fewer adverse effects, exploring the possibilities offered by CMV immunoglobulins (CMVIG) seems necessary. In France, access to CMVIG requires official authorization by the national Health authority and is restricted to second line rescue therapy for CMV infection/disease. The aim of this multicenter retrospective study is to describe the indications and clinical situations that justified its use in France.

Airway clearance and exercise for people with cystic fibrosis: Balancing longevity with life.

Airway clearance has been an integral part of cystic fibrosis (CF) care for almost as long as CF has been identified as a condition. From diagnosis as a neonate through to end-of-life care, airway clearance is an everyday aspect of life, adding a considerable treatment burden to the lives of people with CF. There are many different techniques used for airway clearance which have evolved over time with an aim to improve effectiveness, support adherence and, more recently, to consider the impact of burden.

Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial.

Introduction: Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months.

Outcomes of artery embolisation for cystic fibrosis patients with haemoptysis: a 20-year experience at a major Australian tertiary centre.

There are no published data on Australian adult cystic fibrosis (CF) patient outcomes post bronchial arterial embolisation (BAE). We report 20 years of experience of BAE at a major Australian tertiary adult CF centre, where 46 patients underwent 100 BAE during this period. Mortality rate was comparable to previous studies (4% per year) and most who died had repeat BAE requirements.

Anti-LPS IgA and IgG Can Inhibit Serum Killing of Pseudomonas aeruginosa in Patients with Cystic Fibrosis.

Pseudomonas aeruginosa is one of the principal pathogens implicated in respiratory infections of patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously, we demonstrated that impaired serum-mediated killing of P. aeruginosa was associated with increased severity of respiratory infections in patients with non-CF bronchiectasis.