Detection and follow-up of chronic obstructive pulmonary disease (COPD) and risk factors in the Southern Cone of Latin America. the pulmonary risk in South America (PRISA) study

<p>Abstract</p> <p>Background</p> <p>The World Health Organization has estimated that by 2030, chronic obstructive pulmonary disease will be the third leading cause of death worldwide. Most knowledge of chronic obstructive pulmonary disease is based on studies performed in Europe or North America and little is known about the prevalence, patient characteristics and change in lung function over time in patients in developing countries, such as those of Latin America. This lack of knowledge is in sharp contrast to the high levels of tobacco consumption and exposure to biomass fuels exhibited in Latin America, both major risk factors for the development of chronic obstructive pulmonary disease. Studies have also demonstrated that most Latin American physicians frequently do not follow international chronic obstructive pulmonary disease diagnostic and treatment guidelines. The PRISA Study will expand the current knowledge regarding chronic obstructive pulmonary disease and risk factors in Argentina, Chile and Uruguay to inform policy makers and health professionals on the best policies and practices to address this condition.</p> <p>Methods/Design</p> <p>PRISA is an observational, prospective cohort study with at least four years of follow-up. In the first year, PRISA has employed a randomized three-staged stratified cluster sampling strategy to identify 6,000 subjects from Marcos Paz and Bariloche, Argentina, Temuco, Chile, and Canelones, Uruguay. Information, such as comorbidities, socioeconomic status and tobacco and biomass exposure, will be collected and spirometry, anthropometric measurements, blood sampling and electrocardiogram will be performed. In year four, subjects will have repeat measurements taken.</p> <p>Discussion</p> <p>There is no longitudinal data on chronic obstructive pulmonary disease incidence and risk factors in the southern cone of Latin America, therefore this population-based prospective cohort study will fill knowledge gaps in the prevalence and incidence of chronic obstructive pulmonary disease, patient characteristics and changes in lung function over time as well as quality of life and health care resource utilization. Information gathered during the PRISA Study will inform public health interventions and prevention practices to reduce risk of COPD in the region.</p

Clinical and Experimental Human Sleep-Wake Pharmacogenetics

Sleep and wakefulness are highly complex processes that are elegantly orchestrated by fine-tuned neurochemical changes among neuronal and non-neuronal ensembles, nuclei, and networks of the brain. Important neurotransmitters and neuromodulators regulating the circadian and homeostatic facets of sleep-wake physiology include melatonin, γ-aminobutyric acid, hypocretin, histamine, norepinephrine, serotonin, dopamine, and adenosine. Dysregulation of these neurochemical systems may cause sleep-wake disorders, which are commonly classified into insomnia disorder, parasomnias, circadian rhythm sleep-wake disorders, central disorders of hypersomnolence, sleep-related movement disorders, and sleep-related breathing disorders. Sleep-wake disorders can have far-reaching consequences on physical, mental, and social well-being and health and, thus, need be treated with effective and rational therapies. Apart from behavioral (e.g., cognitive behavioral therapy for insomnia), physiological (e.g., chronotherapy with bright light), and mechanical (e.g., continuous positive airway pressure treatment of obstructive sleep apnea) interventions, pharmacological treatments often are the first-line clinical option to improve disturbed sleep and wake states. Nevertheless, not all patients respond to pharmacotherapy in uniform and beneficial fashion, partly due to genetic differences. The improved understanding of the neurochemical mechanisms regulating sleep and wakefulness and the mode of action of sleep-wake therapeutics has provided a conceptual framework, to search for functional genetic variants modifying individual drug response phenotypes. This article will summarize the currently known genetic polymorphisms that modulate drug sensitivity and exposure, to partly determine individual responses to sleep-wake pharmacotherapy. In addition, a pharmacogenetic strategy will be outlined how based upon classical and opto-/chemogenetic strategies in animals, as well as human genetic associations, circuit mechanisms regulating sleep-wake functions in humans can be identified. As such, experimental human sleep-wake pharmacogenetics forms a bridge spanning basic research and clinical medicine and constitutes an essential step for the search and development of novel sleep-wake targets and therapeutics