Respiratory health risks from intensive livestock production, risk estimation and prevention
Omwonenden van veehouderijen hebben een verhoogd risico op longontsteking maar oorzaken zijn nog onbekend. In het voorgestelde onderzoek worden mogelijke oorzaken van longontsteking in een gebied met veel intensieve veehouderij onderzocht. Dit wordt gedaan door patiënten met longontstekingen in de buurt van veehouderijen en patiënten die verder weg wonen te vergelijken. Daarbij maken we gebruik van nieuwe (moleculaire) technieken waarmee blootstelling aan micro-organismen, stof en endotoxinen en het voorkomen van longontsteking in samenhang wordt onderzocht. Met dit onderzoek willen we uiteindelijk het risico op longontsteking verminderen, door wetenschappelijk inzicht te verkrijgen in de oorzaken en de mogelijkheden voor vermindering van die blootstelling te onderzoeken. Daarnaast kunnen met de verkregen inzichten gezondheidsrisico’s bij toekomstige uitbraken van door dieren veroorzaakte ziekten vroegtijdig worden ingeschat. Daarmee kunnen snel en effectief maatregelen worden genomen.
Samenvatting van de aanvraag
Exposures which originate from livestock farms have adverse health effects. Several distinct signals have been found recently: respiratory symptoms and medication use in chronic obstructive pulmonary disease (COPD) patients , airway obstruction and an elevated risk for pneumonia near poultry and goat farms, accompanied by a shift in the respiratory microbiome. The underlying causes have not been unraveled. In particular the pneumonia risk has considerable public health impact with a conservative estimate of more than 3000 cases annually in the Netherlands. We hypothesize that the excess pneumonia risk results from either inhalation of potentially farm-related pathogens, or, alternatively, from farm-related exposures that lead to changes in the composition and diversity of the upper respiratory tract microbiome and virome leading to excess pneumonia risk through dysbiosis We aim to: In this project we aim to: 1. Characterize the livestock farm metagenome (both the microbiome (bacterial genomes) and virome (viral plus bacteriophage genome)) and their relative concentration in a farm/environmental/human/patient sample) by fingerprinting in animal populations, in farm dust samples, and respiratory samples from persons exposed to livestock farm emissions. 2. Relate the farm animal and environmental metagenome to farm characteristics and management practices. 3. Study the etiology of pneumonia in humans living in intensive livestock farming areas by systematic assessment of known, and alternative causes, including known and uncommon pathogens, shifts in microbial community composition and indirect effects of dust resulting from microbial or viral toxins (such as, endotoxin),and/or irritant gas exposures with host-mediated effects. 4. Measure and model movement of microbes and viruses to exposed neighboring residents using existing emission models and refine these approaches by combining measurements and modeling. 5. Create regional maps that describe concentrations of selected relevant microbial pollutants to facilitate identification of high risk populations under normal operational circumstances and during animal disease outbreaks. These aims will be realized by conducting epidemiological case control studies in COPD and pneumonia cases in an area with intensive livestock farming. Differences in overall bacterial community composition and presence of specific viruses will be explored and compared between case and control groups to identify causal factors responsible for the excess pneumonia risk. The phageome will be explored as indicator of exposure at the population level to bacterial material from a specific farm. The high evolutionary rate of bacteriophages provide a useful, farm specific sequence signature. The unique farm signature will be compared with the phage signatures found in the environmental samples and attribution analysis will be performed by building so called Land Use Regression models for the phase signatures. These data allow us to define the quantitative flow of bacteria, phage, viruses and bacterial products from a specific farm to environmental sampling points that are localized in areas with residents under normal operational conditions and during outbreaks. The obtained information will be used in dispersion models to model environmental exposure for a whole region and relate environmental exposure to disease data from electronic medical records. The proposed study contributes to greater understanding of inter-relationships between the (farm-) environment, the airway microbiome and respiratory health effects by integrating geo-spatial and molecular epidemiological concepts. The study will contribute to science-based preventive strategies. Current practices to reduce health risks that originate from livestock-related emissions are based on monitoring of zoonoses and diminishing the likelihood of transmission. These preventive strategies have a limited scope and instead need to be based on population exposure reduction strategies, limiting exposure resulting from livestock farms and improve surveillance using novel molecular approaches. The studies in this proposal will be completed by experts in human, animal and environmental health. This creates opportunities to take a leading role in studying these health risks on a national and international level. We apply a “one health” approach, considering human, veterinary and environmental medicine and health as part of a single system and integrating molecular metagenomic analysis with analytical epidemiological approaches and human exposure modeling in an innovative way.