Clinical course of mild-to-moderate idiopathic pulmonary fibrosis during therapy with pirfenidone: Results of the non-interventional study AERplus.

Introduction: Pirfenidone was the first anti-fibrotic drug approved in Europe in 2011 for the treatment of mild-to-moderate idiopathic pulmonary fibrosis.

Objectives: To investigate the clinical course of mild-to-moderate idiopathic pulmonary fibrosis in pirfenidone-treated patients in a real-world setting.

Methods: The non-interventional study was conducted at 18 sites in Germany from 6/2014-12/2016.

Short-term safety results from compassionate use of risdiplam in patients with spinal muscular atrophy in Germany.

Background: The oral, selective SMN2-splicing modifier risdiplam obtained European approval in March 2021 for the treatment of patients ≥ 2 months old with a clinical diagnosis of 5q-associated spinal muscular atrophy (SMA) 1/2/3 or with 1-4 SMN2 gene copies. For the preceding 12 months, this compassionate use program (CUP) made risdiplam available to patients with SMA1/2 in Germany who could not receive any approved SMA therapy.

Patients And Methods: Patients with SMA1/2, aged ≥ 2 months at enrollment, could be included if they were not eligible for, no longer responsive to, or not able to tolerate nusinersen or not able to receive onasemnogene abeparvovec.

IL-13 Impairs Tight Junctions in Airway Epithelia.

Interleukin-13 (IL-13) drives symptoms in asthma with high levels of T-helper type 2 cells (T2-cells). Since tight junctions (TJ) constitute the epithelial diffusion barrier, we investigated the effect of IL-13 on TJ in human tracheal epithelial cells. We observed that IL-13 increases paracellular permeability, changes claudin expression pattern and induces intracellular aggregation of the TJ proteins zonlua occludens protein 1, as well as claudins.

Inflammation-induced upregulation of P2X expression augments mucin secretion in airway epithelia.

Mucus clearance provides an essential innate defense mechanism to keep the airways and lungs free of particles and pathogens. Baseline and stimulated mucin secretion from secretory airway epithelial cells need to be tightly regulated to prevent mucus hypersecretion and mucus plugging of the airways. It is well established that extracellular ATP is a potent stimulus for regulated mucus secretion.

Vesicular control of fusion pore expansion.

Exocytic post-fusion events play an important role determining the composition and quantity of cellular secretion. In particular, Ca(2+)-dependent regulation of fusion pore dilation/closure is a key regulator for fine-tuning vesicle content secretion. This requires a tight temporal and spatial integration of vesicle fusion with the PM, Ca(2+) signals and translation of the Ca(2+) signal into fusion pore dilation via auxiliary factors.

Synaptotagmin-7 links fusion-activated Ca²⁺ entry and fusion pore dilation.

Ca(2+)-dependent regulation of fusion pore dilation and closure is a key mechanism determining the output of cellular secretion. We have recently described 'fusion-activated' Ca(2+) entry (FACE) following exocytosis of lamellar bodies in alveolar type II cells. FACE regulates fusion pore expansion and facilitates secretion.