The purpose of this review was to evaluate the studies reporting the association between animal feeding operations and measures of the health of individuals living near animal feeding operations but not actively engaged in livestock production in North America, the European Union, the United Kingdom, and Scandinavian countries. Based on the magnitude and the consistency of associations observed there was little compelling evidence for a consistent strong association between clinical measures of disease and proximity to AFOs. However, the body of work is small in this area and based on epidemiological studies which have greater potential for bias.
There was inconsistent evidence of a small increase in self-reported disease in people with allergies or familial history of allergies. The magnitude of associations for this subgroup of the population lay within 10% points of the null value (0.99 to 1.12) indicating a<10% increase in the prevalence of adverse health outcomes, with one exception, which reported an approximately 20% increase in prevalence of adverse outcomes. What was surprising about these associations was the lack of any indication of a dose response. Evidence of a dose response would have added weight to evidence of an association. For all of the associations evaluated, the explanatory variables were ordinal in nature, presumably designed to capture a dose response. The WHO Guidelines for Evaluation of Environmental Evidence suggest that the presence of a biological gradient is helpful in proposing a causal association for environmental health hazards 
There was evidence of a dose response for exposure variables that described aversion to odor; those individuals with the strongest aversion/detection to livestock odor were associated with the highest odds of self-reported wheeze. Using the odds ratio as the effect measure, the magnitude of the associations with odor were high, up to 300% increase in the odds of self reported outcomes in individuals who were strongly annoyed by odor. However, none of the clinical measures showed an association with measures of odor, which would have made the associations more compelling and demonstrated consistency of the association across various outcome measures. The location of the effect measure estimates and the width of the corresponding confidence intervals for clinical measure of disease showed little evidence of a consistent association, even a weak association, across the studies.
In an effort to understand how to establish causation claims when evaluating environmental causes, the report, “ Identifying the environmental causes of disease: how should we decide what to believe and when to take action,” published by The Academy of Medical Sciences, discussed several examples where non-experimental evidence has been used to evaluate environmental causes of disease 
. The report discussed examples where non-experimental evidence had led to relatively strong inferences, where non-experimental research had led to cases with probably valid causal inference, and where non-experimental research had led to probably misleading causal claims. Many conclusions and recommendations were included in the report, however relevant to this review was the observation that examples where non-experimental evidence had led to relatively strong inferences, shared several common features including a very large effect (such as lung cancer and smoking) or they applied to rare or unusual outcomes with distinctive features (neural tube defects and folate deficiency). Other characteristics were attention to alternative explanations and the availability of many studies conducted in multiple populations 
. Based on these observations, the body of evidence in this review is likely inadequate to evaluate causation because evidence is available from very few studies and the disease outcomes evaluated tend to be common non-specific outcomes, i.e., self reported wheeze.
A previous narrative review of the topic has suggested that “sufficient research supports actions to protect rural residents from the negative impacts of CAFOs on community health” and only mechanism research was warranted 
. However, the results of the current review do not strongly support this statement. The results of this review suggest that further research is warranted, particularly toward understanding proximity to animal agriculture, odor and mental health and the subgroup of people with self-reported allergies 
Several expert committee reports have provided guidelines on how to assess an association between an environmental exposure and disease occurrence 
. Both reports recommended that sources of bias be considered in primary research before concluding that causal associations exist. Based on our evaluation, we propose that the studies in this body of work could be viewed as two groups of work. The first group consisted of studies of greater use for establishing causation because of the design and execution of the study, of these there are currently too few, however they represent the majority of studies in this body of work (5 of 9). The second group consisted of studies that might be considered of less value for establishing causation and better for hypothesis generation because of the study design or execution.
It is imperative that future researchers evaluate the characteristics of the studies in the body of work and understand the limitations and strive to improve the designs used. Such an approach to future research will improve the evidentiary value of the work and its use for decision-making. Recommendations for design features that should be incorporated into future studies would include the use of quantifiable clinical outcomes and measures of exposure to AFOs, limits on the number of outcomes assessed or adjustment for multiple comparisons, inclusion of sample size justification and the null hypothesis to be tested, random selection of study participants, longitudinal study designs, appropriate evaluation of dose responses and the use of statistical methods that account for clustering when appropriate. Further, the combination of experimental and observational studies will likely be helpful in future causal discussions. Both study types should be included in future research as evidence from a mixture of well executed studies will be important for establishing if a causal association exists. This characteristic was a hallmark of prior examples where non-experimental evidence led to strong causal inference i.e. “In no instance, did one design provide the ‘clinching’ proof, but, in combination, they made causal inference a compelling probability“ 
Another recommendation is recognizing the hypothesis generating nature of some of the studies in the body of work. The concept that all research is not of equal evidentiary evidence value is not a new one and is the basis of the evidence pyramid 
. The area of environmental health assessment represents one of the areas where reliance of the epidemiological studies is often necessary; however even within epidemiological studies it is possible to assess internal validity. Included within this group of hypothesis generating studies are the ecological studies, which report associations between animal density and the occurrence of disease. Due to the potential for ecological fallacy, these studies should not be used for causal inference although some articles do seem to draw causal conclusions from the study results.
We encourage readers to evaluate the rationale for the discussion of biases within the studies as these represent a critical component – transparency – of the systematic review methodology. Finally, as systematic reviews place a heavy emphasis on transparency, it should be noted that several of the panel members have previously authored narrative reviews of this topic 
and two members of the review panel have previously received research funding for unrelated areas of swine health by the National Pork Board, which also funded this review. Four panel members have served as an advisory meeting members or as grant reviewers for the National Pork Board research program in the past 10 years.