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Globally, almost 3 billion people rely on biomass (wood, charcoal, crop residues, and dung) and coal as their primary source of domestic energy. Exposure to indoor air pollution (IAP) from the combustion of solid fuels is an important cause of morbidity and mortality in developing countries. In this paper, we review the current knowledge on the relationship between IAP exposure and disease and on interventions for reducing exposure and disease. We take an environmental health perspective and consider the details of both exposure and health effects that are needed for successful intervention strategies. We also identify knowledge gaps and detailed research questions that are essential in successful design and dissemination of preventive measures and policies. In addition to specific research recommendations, we conclude that given the interaction of housing, household energy, and day-to-day household activities in determining exposure to indoor smoke, research and development of effective interventions can benefit tremendously from integration of methods and analysis tools from a range of disciplines in the physical, social, and health sciences.