Models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major global health problem and is predicted to become the third most common cause of death by 2020. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition, and therefore there is a need to understand the pathophysiological mechanisms that could lead to new therapeutic strategies. The development of experimental models will help to dissect these mechanisms at the cellular and molecular level. COPD is a disease characterized by progressive airflow obstruction of the peripheral airways, associated with lung inflammation, emphysema and mucus hypersecretion. Different approaches to mimic COPD have been developed but are limited in comparison to models of allergic asthma. COPD models usually do not mimic the major features of human COPD and are commonly based on the induction of COPD-like lesions in the lungs and airways using noxious inhalants such as tobacco smoke, nitrogen dioxide, or sulfur dioxide. Depending on the duration and intensity of exposure, these noxious stimuli induce signs of chronic inflammation and airway remodelling. Emphysema can be achieved by combining such exposure with instillation of tissue-degrading enzymes. Other approaches are based on genetically-targeted mice which develop COPD-like lesions with emphysema, and such mice provide deep insights into pathophysiological mechanisms. Future approaches should aim to mimic irreversible airflow obstruction, associated with cough and sputum production, with the possibility of inducing exacerbations

Effects of diet and exercise interventions on diabetes risk factors in adults without diabetes: meta-analyses of controlled trials

BACKGROUND AND AIMS: Fasting insulin (FI), fasting glucose (FG), systolic blood pressure (SBP), high density lipoproteins (HDL), triacylglycerides (TAG), and body mass index (BMI) are well-known risk factors for type 2 diabetes. Reliable estimates of lifestyle intervention effects on these factors allow diabetes risk to be predicted accurately. The present meta-analyses were conducted to quantitatively summarize effects of diet and exercise intervention programs on FI, FG, SBP, HDL, TAG and BMI in adults without diabetes. MATERIALS AND METHODS: MEDLINE and EMBASE were searched to find studies involving diet plus exercise interventions. Studies were required to use adults not diagnosed with type 2 diabetes, involve both dietary and exercise counseling, and include changes in diabetes risk factors as outcome measures. Data from 18, 24, 23, 30, 29 and 29 studies were used for the analyses of FI, FG, SBP, HDL, TAG and BMI, respectively. About 60% of the studies included exclusively overweight or obese adults. Mean age and BMI of participants at baseline were 48 years and 30.1 kg/m(2). Heterogeneity of intervention effects was first estimated using random-effect models and explained further with mixed-effects models. RESULTS: Adults receiving diet and exercise education for approximately one year experienced significant (P <0.001) reductions in FI (-2.56 ± 0.58 mU/L), FG (-0.18 ± 0.04 mmol/L), SBP (-2.77 ± 0.56 mm Hg), TAG (-0.258 ± 0.037 mmol/L) and BMI (-1.61 ± 0.13 kg/m(2)). These risk factor changes were related to a mean calorie intake reduction of 273 kcal/d, a mean total fat intake reduction of 6.3%, and 40 minutes of moderate intensity aerobic exercise four times a week. Lifestyle intervention did not have an impact on HDL. More than 99% of total variability in the intervention effects was due to heterogeneity. Variability in calorie and fat intake restrictions, exercise type and duration, length of the intervention period, and the presence or absence of glucose, insulin, or lipid abnormalities explained 23-63% of the heterogeneity. CONCLUSIONS: Calorie and total fat intake restrictions coupled with moderate intensity aerobic exercises significantly improved diabetes risk factors in healthy normoglycemic adults although normoglycemic adults with glucose, insulin, and lipid abnormalities appear to benefit more