No abstract

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity.We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients.Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage.AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

No abstract

AbstractAimsSuccessful management of IPF will likely require multi-drug therapy as its pathogenesis is thought to be both driven by both pro-inflammatory and pro-fibrotic pathways. We hypothesized that the available anti-fibrotic agents, pirfenidone and nintedanib, may exhibit synergy in suppressing lung fibroblast extracellular matrix protein generation when administered in combination with other orally active agents.Materials and MethodsA fibroblastic cell line (AKR-2B) was stimulated with TGF-β1 and used to screen a library of over 1500 FDA approved drugs. Extracellular matrix protein generation was assessed via fibronectin ELISA assay and maintenance of cell viability confirmed with XTT assay.ResultsThe screening revealed sixty-two drugs from the repurposed drug-screening library that were shown to significantly suppress fibronectin expression and not result in cell death. Specifically drugs within the category of NSAIDs, steroids, azole antifungal agents, and antipyrine were associated with significant suppression of fibronectin on ELISA analysis. Surprisingly, we observed anti-fibrotic activity across a number of the azole antifungal compounds. We next assessed whether combination of azoles would exhibit synergy when combined with current anti-fibrotic therapies in the stimulated fibroblasts. As proof of concept, we demonstrated in vitro synergy between oxiconazole and nintedanib in suppressing fibroblast generation of extracellular matrix fibronectin.ConclusionsThese results suggest an approach to identify potential combinations of therapy that may improve patient outcomes by reducing cost and potential toxicities during treatment.

No abstract