6,963 publications from this institution
The philosophical aspects of applying the principles of biomimicry are explored in a case study of structural design. Integrating structural engineering with services engineering can be regarded, to some extent, as taking principles from biological systems and applying them to large-scale conceptual design. The end-product discussed herein a so-called load-bearing duct, a functional naturally ventilated multi-storey office building that takes the applied loading efficiently both structurally and cost-effectively giving it the potential to be sustainable throughout its design life.
Peter Barnes first started his career in respiratory research in the late 1970s following studies at the Universities of Oxford and Cambridge. He is currently Professor of Thoracic Medicine at the National Heart and Lung Institute, Head of Respiratory Medicine at Imperial College and Honorary Consultant Physician at the Royal Brompton Hospital. He speaks to Future Medicinal Chemistry about the molecular mechanisms currently under investigation by his group, and discusses his views on the latest therapeutic breakthroughs and the future of respiratory research.
Background: Inhaled corticosteroids are recommended for COPD patients with FEV 1 ≤ 50% predicted, experiencing ≥2 exacerbations in 12 months. However, post-hoc analysis of the TORCH study revealed an increased risk of pneumonia of 50% in patients taking inhaled fluticasone propionate (FP) (ERJ 2009;34:641). This contrasts with a meta-analysis of patients taking budesonide (BUD) where there was no increased risk of pneumonia (Lancet 2009;374:712). The reason for this discrepancy is unclear, however, we hypothesise that the particulate nature of FP, due to high lipophilicity and low water solubility, leads to its uptake by phagocytes resulting in impaired function. Methods: Neutrophils and monocytes were isolated from the blood of COPD patients (n=10). Monocyte-derived macrophages (MDM) were generated from monocytes by 12d culture in media containing GM-CSF. All cells were incubated with steroid for 1h prior to phagocytosis assays with fluorescently-labelled polystyrene beads, Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP). Results: BUD (1μM) increased MDM phagocytosis of beads by 17% (p -10 -10 -6 M) significantly (p Conclusions: FP did not reduce phagocytic function of either MDM or neutrophils. BUD improved neutrophil phagocytosis of HI, which may explain differences in pneumonia incidence between FP and BUD in COPD patients.
Inhaled furosemide prevents bronchoconstriction induced by nebulized distilled water, exercise, and antigen challenge. We examined the effect of furosemide on cough induced by low chloride content solutions and by capsaicin in double-blind, placebo-controlled studies. A group of eight nonsmoking normal subjects was given furosemide (3.75 mg/ml inhaled for 8 min) and placebo (saline) immediately before consecutive 1-min inhalations of four isosmolar solutions with decreasing chloride content every 5 min from an ultrasonic nebulizer. Decreasing concentrations of chloride induced dose-related coughing, which was inhibited by furosemide. Thus, chloride-free solution induced 13.1 ± 1.6 coughs after placebo and 8.4 ± 1.9 coughs after furosemide (p < 0.005). In a separate study, six of the same normal subjects were given inhaled furosemide or placebo before inhaling one breath of capsaicin solution given in three consecutive increasing concentrations. Capsaicin induced dose-related coughing, which was not inhibited by furosemide. Thus, after placebo the highest concentration of capsaicin induced 20.8 ± 1.8 coughs and after furosemide, 21.5 ± 2.7 coughs. We conclude that furosemide may act by inhibiting the cough reflex indirectly, perhaps by changing local chloride ions within the vicinity of epithelial cough receptors.
Keywords:: asthmaCOPDcorticosteroidindacaterollong-acting β2-agonistlong-acting muscarinic antagonisttiotropium