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The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. This was a case/control study of asthma among 324 pediatric participants. Subsequently, microarray genotype data became available, providing over 2 million variants, incidentally including some conferring risk for conditions for which the American College of Medical Genetics recommends return of results. The study investigators engaged in extensive consultation with the IRB, the tribal government, and local clinicians to better inform our approach. We were able to notify the two participants heterozygous for the one clinically actionable variant identified. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. While demanding considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants. [ABSTRACT FROM AUTHOR]

American Indian (AI)/Alaska Native children have increased asthma prevalence, morbidity, and mortality compared to non-Hispanic white children. Our study sought to examine environmental and socioeconomic factors of asthma among children in an AI community. This case-control study included children with physician-diagnosed asthma and age-matched controls, ages 6 through 17 years, in an AI community. Diagnosis and clinical characteristics were obtained from medical record review. Home visits included interviews regarding sociodemographic and household environmental exposures, physical exams, spirometry, and asthma control questionnaires (cases only). Among the 108 asthma cases and 215 controls, 64% had an annual household income of <$25,000. Children with asthma had significantly higher odds of living in a multi-unit dwelling (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2–4.4) or in residences with rodent or insect infestation (OR, 2.1; 95% CI, 1.1–3.8) and were less likely to live in homes with more than 8 occupants (OR, 0.5; 95% CI, 0.3–0.9). Also, there was a trend for lower caregiver education level, unmarried caregiver marital status, and annual household income level of <$25,000 in univariate analysis. However, after adjustment for socioeconomic status and household environmental factors, these estimates were not significant. Nearly half of cases had poorly controlled asthma and reported persistent cough, wheeze, and dyspnea, yet only 24% reported using a controller medication. In this low-income AI community, we identified several social and environmental determinants of asthma, which were mediated by socioeconomic status and other household environmental factors, suggesting a complex interplay between socioeconomic status and environmental exposures. Furthermore, many children with asthma reported poor asthma control. [ABSTRACT FROM AUTHOR]

Background: Asthma is recognized as intimately related to immunologic factors and inflammation, although there are likely multiple phenotypes and pathophysiologic pathways. Biomarkers of inflammation may shed light on causal factors and have potential clinical utility. Individual and population genetic factors are correlated with risk for asthma and improved understanding of these contributions could improve treatment and prevention of this serious condition.Methods: A population-based sample of 108 children with clinically defined asthma and 216 control children were recruited from a small community in the northern plains of the United States. A complete blood count, high sensitivity C-reactive protein, total IgE and specific antibodies to 5 common airborne antigens (CAA), in addition to basic demographic and anthropomorphic data were obtained. Logistic regression was primarily used to determine the association between these humoral factors and risk of asthma.Results: The body mass index (BMI) of those with asthma and their total leukocyte counts, percentage of eosinophils, and levels of total IgE were all greater than corresponding control values in univariate analysis. The presence of detectable, specific IgE antibodies to five common airborne antigens was more likely among cases compared with controls. In multivariate analysis, total IgE was independently associated with asthma; but not after inclusion of a cumulative measure of specific IgE sensitization.Conclusion: Many previously reported associations between anthropomorphic and immune factors and increased risk of asthma appear to be also present in this American Indian population. In this community, asthma is strongly associated with sensitization to CAA. [ABSTRACT FROM AUTHOR]