Harshness and unpredictability: Childhood environmental links with immune and asthma outcomes.

The environment has pervasive impacts on human development, and two key environmental conditions - harshness and unpredictability - are proposed to be instrumental in tuning development. This study examined (1) how harsh and unpredictable environments related to immune and clinical outcomes in the context of childhood asthma, and (2) whether there were independent associations of harshness and unpredictability with these outcomes. Participants were 290 youth physician-diagnosed with asthma. Harshness was assessed with youth-reported exposure to violence and neighborhood-level murder rate. Unpredictability was assessed with parent reports of family structural changes. Youth also completed measures of asthma control as well as asthma quality of life and provided blood samples to assess immune profiles, including in vitro cytokine responses to challenge and sensitivity to inhibitory signals from glucocorticoids. Results indicated that harshness was associated with more pronounced pro-inflammatory cytokine production following challenge and less sensitivity to the inhibitory properties of glucocorticoids. Furthermore, youth exposed to harsher environments reported less asthma control and poorer quality of life. All associations with harshness persisted when controlling for unpredictability. No associations between unpredictability and outcomes were found. These findings suggest that relative to unpredictability, harshness may be a more consistent correlate of asthma-relevant immune and clinical outcomes.