Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes

This article is made available through the Brunel Open Access Publishing Fund and is distributed by the Creative Commons CC-BY 3.0 license, under which all are free to reuse or distribute the article under the condition that this original publication must be cited.Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.World Anti Doping Agenc

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Reduction of adhesion formation and promotion of wound healing after laminectomy by pharmacological inhibition of pro-inflammatory cytokines: an experimental study in the rat

In a previous experiment using TNF inhibition in the rat it was accidentally found that adhesion and scar formation was reduced compared to previous experience. Wound and bone healing also seemed enhanced. The present study was conducted to assess if this observation could be verified in a controlled setting using a standardized laminectomy in the rat. Five rats received doxycycline and five other rats received saline and served as control. Macroscopic blinded evaluation 1 week after the laminectomy revealed that adhesion and scar formation was less in doxycycline-treated animals than in control animals. Wound and bone healing was found to be better in doxycycline-treated animals. The mechanisms for the observed effects cannot be fully understood but the data indicate that further research may lead to opportunities to design pharmacological modalities to reduce adhesion and scar formation, maybe in combination with suitable barriers

Life cycle assessment in green chemistry: overview of key parameters and methodological concerns

Several articles within the area of green chemistry often promote new techniques or products as 'green' or 'more environmentally benign' than their conventional counterpart although these articles often do not quantitatively assess the environmental performance. In order to do this, life cycle assessment (LCA) is a valuable methodology. However, on the planning stage, a full-scale LCA is considered to be too time consuming and complicated. Two reasons for this have been recognised, the method is too comprehensive and it is hard to find inventory data. In this review, key parameters are presented with the purpose to reduce the time-consuming steps in LCA. In this review, several LCAs of so-called 'green chemicals' are analysed and key parameters and methodological concerns are identified. Further, some conclusions on the environmental performance of chemicals were drawn. For fossil-based platform chemicals several LCAs exists but for chemicals produced with industrial biotechnology or from renewable resources the number of LCAs is limited, with the exception of biofuels, for which a large number of studies are made. In the review, a significant difference in the environmental performance of bulk and fine chemicals was identified. The environmental performance of bulk chemicals are closely connected to the production of the raw material and thereby different land use aspects. Here, a lot can be learnt from biofuel LCAs. In many of the reviewed articles focusing on bulk chemicals a comparison regarding fossil and renewable raw material was done. In most of the comparisons the renewable alternative turned out to be more environmentally preferable, especially for the impact on GWP and energy use. However, some environmental concerns were identified as important to include to assess overall environmental concern, for example eutrophication and the use of land. To assess the environmental performance of green chemicals, quantitative methods are needed. For this purpose, both simple metrics and more comprehensive methods have been developed, one recognised method being LCA. However, this method is often too time consuming to be valuable in the process planning stage. This is partly due to a lack of available inventory data, but also because the method itself is too comprehensive. Here, key parameters for the environmental performance and methodological concerns were described to facilitate a faster and simpler use of LCA of green chemicals in the future