vx-770 and Pulmonary-Disease--Chronic-Obstructive

Topics: Aged; Aminophenols; Bronchitis, Chronic; Chloride Channel Agonists; Cystic Fibrosis Transmembrane Conductance Regulator; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Molecular Targeted Therapy; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Quinolones; Risk Assessment; Treatment Outcome

The drug combination elexacaftor-tezacaftor-ivacaftor (ETI) proved highly effective in the improvement of the respiratory symptoms, the percentage of predicted forced expiratory volume in 1 s (FEV1), and to reduce rates of pulmonary exacerbations in people with cystic fibrosis (CF) with at least one F508del mutation. The objectives of the study were to evaluate the impact of ETI on the daily treatment burden due to patient decision and the evolution of lung function parameters at 6 months of treatment in real life.. A single-center observational study was realized including adult patients starting ETI therapy from March 10, 2020 to April 5, 2022. Clinical characteristics were collected at initiation (T0) and at 6 months (T6) of treatment. Outcome measures included names and number of chronic daily medications, respectively lung function parameters: FEV1, forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), forced expiratory flow at 25-75% of FVC (FEF25-75), β-angle and FEF50/PEF ratio.. Sixty-five patients were included with a mean age of 29.4 ± 8.5 years old, 48% of them F508del homozygous previously treated by lumacaftor-ivacaftor. At T6, the median number of daily medications decreased from 13 [2-24] to 9 [1-19] (p < 0.001). All the studied functional respiratory parameters were improved: FEV1 +18%, FVC +14%, FEF25-75% + 18% (all p < 0.001), as well the airflow obstruction: FEV1/FVC +6%, FEF50/PEF by 0.1 ± 0.1 and β-angle by 10° ± 13° (all p ≤ 0.007).. ETI therapy can reduce the daily treatment burden in real-life at 6 months of treatment, increase a large number of lung function parameters and improve airflow obstruction.

Topics: Adult; Aminophenols; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Combinations; Humans; Lung; Mutation; Pulmonary Disease, Chronic Obstructive; Young Adult

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel are established as the primary causative factor in the devastating lung disease cystic fibrosis (CF). More recently, cigarette smoke exposure has been shown to be associated with dysfunctional airway epithelial ion transport, suggesting a role for CFTR in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, the identification and characterization of a high throughput screening hit

Topics: Administration, Oral; Aminopyridines; Animals; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Drug Evaluation, Preclinical; Gene Deletion; Half-Life; Humans; Protein Binding; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; Solubility; Structure-Activity Relationship