Bronchial Smooth Muscle Cells of Asthmatics Promote Angiogenesis through Elevated Secretion of CXC-Chemokines (ENA-78, GRO-alpha, and IL-8)

<p>Background: Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors.</p><p>Objective: To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors.</p><p>Methods: Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay.</p><p>Results: Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p <0.001). Levels of ENA-78, GRO-alpha and IL-8 were significantly elevated in CM of BSMC from asthma patients (p <0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 (CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC.</p><p>Conclusions: BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-alpha and IL-8) produced by BSMC. Implications: CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients. Counteracting the CXCR2-mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma.</p>

Pilot randomised controlled trial of face-down posturing following phacovitrectomy for macular hole

BACKGROUND: To gather information on the effect of postoperative face-down posturing following combined phacoemulsification and vitrectomy for macular hole surgery in order to assist in the design of a larger definitive study. METHODS: Thirty phakic patients with stage II–IV full-thickness macular hole had combined phacoemulsification and pars plana vitrectomy with internal limiting membrane peel and 14% perfluoropropane (C(3)F(8)) gas. At the conclusion of surgery, patients were randomised either to face-down posture or to no posture, for 10 days. The primary outcome was macular hole closure. RESULTS: The macular hole was successfully closed in 93.8% of the face-down posture group and in all of the no-posture group. Mean visual improvement was 0.63 (SD=0.21) logMAR units in the face-down group and 0.53 (SD=0.22) in the no posture patients. CONCLUSION: Following combined phacoemulsification and vitrectomy, postoperative face-down posturing appears to make little difference to the final anatomical or visual outcome. If we assume a success rate of 95% in the posturing arm, and that there is no difference between posturing and non-posturing, then 798 patients would be required to be 90% sure that the 95% confidence interval will exclude a difference of more than 5%