Standards for the care of people with cystic fibrosis (CF); Planning for a longer life.

This is the final of four papers updating standards for the care of people with CF. That this paper "Planning a longer life" was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy.

Use of elexacaftor/tezacaftor/ivacaftor leads to changes in detection frequencies of Staphylococcus aureus and Pseudomonas aeruginosa dependent on age and lung function in people with cystic fibrosis.

Objectives: The impressive improvements of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) function by elexacaftor/tezacaftor/ivacaftor (ETI) result in changes in the detection frequencies of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). We assessed determinants of the response to ETI with regards to SA and PA detection frequencies as documented in the German CF registry for people with CF (pwCF) ≥12 years.

Methods: We evaluated changes in the detection frequencies of SA and PA for 21 months before and after initiation of ETI and used different statistical tests to identify determinants of detection changes.

Epidemiological trends in nontuberculous mycobacterial infection among people with cystic fibrosis in Germany.

Objectives: People with cystic fibrosis (pwCF) are at risk for infection with nontuberculous mycobacteria (NTM). The epidemiology and screening practice of NTM among pwCF in Germany are largely unknown and require investigation.

Methods: We analyzed the data of the German Cystic Fibrosis Registry from 2016 to 2020 for NTM.

Complementary Dual Approach for In Silico Target Identification of Potential Pharmaceutical Compounds in Cystic Fibrosis.

Cystic fibrosis is a genetic disease caused by mutation of the CFTR gene, which encodes a chloride and bicarbonate transporter in epithelial cells. Due to the vast range of geno- and phenotypes, it is difficult to find causative treatments; however, small-molecule therapeutics have been clinically approved in the last decade. Still, the search for novel therapeutics is ongoing, and thousands of compounds are being tested in different assays, often leaving their mechanism of action unknown.

Integrating Text Mining into the Curation of Disease Maps.

An adequate visualization form is required to gain an overview and ultimately understand the complex and diverse biological mechanisms of diseases. Recently, disease maps have been introduced for this purpose. A disease map is defined as a systems biological map or model that combines metabolic, signaling, and physiological pathways to create a comprehensive overview of known disease mechanisms.

Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR.

Cystic fibrosis (CF) is a genetic disease caused by mutations in , which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body. Recently, some therapeutics became available that directly target dysfunctional CFTR, yet research for more effective substances is ongoing. The database CandActCFTR aims to provide detailed and comprehensive information on candidate therapeutics for the activation of CFTR-mediated ion conductance aiding systems-biology approaches to identify substances that will synergistically activate CFTR-mediated ion conductance based on published data.

CFTR Lifecycle Map-A Systems Medicine Model of CFTR Maturation to Predict Possible Active Compound Combinations.

Different causative therapeutics for CF patients have been developed. There are still no mutation-specific therapeutics for some patients, especially those with rare CFTR mutations. For this purpose, high-throughput screens have been performed which result in various candidate compounds, with mostly unclear modes of action.

CFTR: New insights into structure and function and implications for modulation by small molecules.

Structural biology and functional studies are a powerful combination to elucidate fundamental knowledge about the cystic fibrosis transmembrane conductance regulator (CFTR). Here, we discuss the latest findings, including how clinically-approved drugs restore function to mutant CFTR, leading to better clinical outcomes for people with cystic fibrosis (CF). Despite the prospect of regulatory approval of a CFTR-targeting therapy for most CF mutations, strenuous efforts are still needed to fully comprehend CFTR structure-and-function for the development of better drugs to enable people with CF to live full and active lives.