Dual therapy strategies for COPD: the scientific rationale for LAMA + LABA.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide. Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations. Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation. Long-acting ß2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD. The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects. Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe. Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA. Several other agents are in the late stages of development, most of which offer once-daily dosing. The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations. These evolving treatments will provide new opportunities and challenges in the management of COPD.

Hydralazine treatment alters body composition in the rabbit model of obesity.

AIMS: While hydralazine is commonly used as monotherapy in animal studies, its potential side effects are seldom acknowledged. Purported side effects occur from sympathetic and renin-angiotensin system activation, and include tachycardia, oedema, and nausea. We hypothesized that these side effects would alter body composition by increasing body water and/or decreasing body fat. METHODS: Female New Zealand White rabbits were divided into lean and obese control and hydralazine-treated groups. Lean rabbits ate a maintenance diet for 12 weeks; obese rabbits ate an ad lib high fat diet. Hydralazine was administered at 6 and 10-14 mg kg(-1) day(-1) for lean and obese hydralazine groups, respectively. Body composition was determined using triplicate 2-3 g samples of whole body homogenate, and analysed using 2 x 2 ANOVA for diet vs. hydralazine effects. RESULTS: Hydralazine-treated animals had lower body fat (15.7 +/- 1.1 and 21.8 +/- 1.0%, respectively) and higher body water (59.8 +/- 0.8 and 55.4 +/- 0.6%, respectively) compared with controls. While obese controls were heavier than obese hydralazine-treated animals (5.12 +/- 0.09 vs. 4.73 +/- 0.11 kg, respectively) and had greater overall feed consumption (13.5 +/- 0.4 vs. 11.8 +/- 0.4 kg, respectively), a subsequent analysis using subsets that did not differ in body weight or feed consumption yielded the same conclusions. Plasma adrenaline and noradrenaline did not differ between control and hydralazine-treated groups. CONCLUSIONS: Use of hydralazine to control blood pressure alters body composition. Direct or indirect effects of hydralazine may impact physiological systems under study. Alterations in adipose tissue may be of particular concern because of its endocrine function.