Publications

By convention, airborne particles ≤0.1 μm (100 nm) are defined as ultrafine particles (UFPs). UFPs can comprise a large number of particles in particulate matter with aerodynamic diameters ≤2.5 μm (PM). Despite the documented respiratory health effects of PM and concerns that UFPs might be more toxic than larger particular matter, the effects of UFPs on the respiratory system are not well-described. Even less is known about the respiratory health effects of UFPs among particularly vulnerable populations including children. We reviewed studies examining respiratory health effects of UFPs in children and identified 12 relevant articles. Most (8/12) studies measured UFP exposure using central ambient monitors, and we found substantial heterogeneity in UFP definitions and study designs. No long-term studies were identified. In single pollutant models, UFPs were associated with incident wheezing, current asthma, lower spirometric values, and asthma-related emergency department visits among children. Also, higher exhaled nitric oxide levels were positively correlated with UFP dose among children with asthma or allergy to house dust mites in 1 study. Multivariate models accounting for potential co-pollutant confounding yielded no statistically significant results. Although evidence for a relationship between UFPs and children's respiratory is accumulating, the literature remains inconclusive. Interpretation of existing data is constrained by study heterogeneity, limited accounting for UFP spatial variation, and lack of significant findings from multi-pollutant models.

BACKGROUND AND OBJECTIVES

Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation.

RESULTS

The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology.

CONCLUSIONS

APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.