[Show abstract][Hide abstract] ABSTRACT: Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome-proliferator-activated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle matrix production and migration. PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPRE-luciferase reporter plasmid. We observed that human airway smooth muscle cells express α, β, and γ PPAR. A 6-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist indicating endogenous PPAR activity. The PPAR-ligands ciglitazone, 15d-PGJ2, and WY-14643 decreased migration towards PDGF. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through COX-2 induction and PGE2 production that increased c-AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells. We conclude that PPAR-ligands decrease human airway smooth muscle migration and matrix production and are therefore potentially useful to modulate airway remodelling.
Preview · Article · May 2012 · European Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: The ability to assess the inflammatory status of a patient's airway using a noninvasive method is the ideal situation for clinicians. Owing in part to the relationship between the levels of exhaled nitric oxide to inflammation and the ease of the technique, the measurement of the fraction of exhaled nitric oxide (F(E)NO) has achieved considerable attention, particularly with respect to asthma. A multitude of studies have shown that when measured in exhaled air, this unique molecule has the potential to have both diagnostic and therapeutic roles in the clinical setting for many pulmonary diseases. The incorporation of F(E)NO into asthma management and treatment algorithms may help shed further insight on the current control and future risk of patients. Research is ongoing to determine the biology and the benefits of the use of F(E)NO in respiratory conditions in addition to asthma. This review will briefly outline the pathophysiology of nitric oxide, the measurement of F(E)NO and the potential clinical uses of F(E)NO in asthma and a number of other respiratory diseases. Despite its promise, until further research is conducted, the use of F(E)NO cannot be recommended for routine clinical management of respiratory diseases at present, but should be considered as an adjuvant to help guide therapy in certain patients with asthma and in those with eosinophilic bronchitis.
No preview · Article · Feb 2012 · Expert Review of Respiratory Medicine
[Show abstract][Hide abstract] ABSTRACT: The present case series describes four patients with asthma, airway hyperresponsiveness and neutrophilic bronchitis who harboured abnormal cystic fibrosis transmembrance conductance regulator (CFTR) gene mutations. It serves both to alert clinicians to consider CFTR-related disease in both young and elderly patients with persistent neutrophilic bronchitis, and to highlight the potential utility of future genetic testing for CFTR abnormalities in patients with asthma and recurrent bronchitis or pansinusitis, and the role of nebulized hypertonic saline as a therapeutic option in these patients.
Full-text · Article · Jan 2012 · Canadian respiratory journal: journal of the Canadian Thoracic Society