Publications

BACKGROUND

Diverse environmental exposures, studied separately, have been linked to health outcomes in adult asthma, but integrated multi-factorial effects have not been modeled. We sought to evaluate the contribution of combined social and physical environmental exposures to adult asthma lung function and disease severity.

METHODS

Data on 176 subjects with asthma and/or rhinitis were collected via telephone interviews for sociodemographic factors and asthma severity (scored on a 0-28 point range). Dust, indoor air quality, antigen-specific IgE antibodies, and lung function (percent predicted FEV1) were assessed through home visits. Neighborhood socioeconomic status, proximity to traffic, land use, and ambient air quality data were linked to the individual-level data via residential geocoding. Multiple linear regression separately tested the explanatory power of five groups of environmental factors for the outcomes, percent predicted FEV1 and asthma severity. Final models retained all variables statistically associated (p < 0.20) with each of the two outcomes.

RESULTS

Mean FEV1 was 85.0 +/- 18.6%; mean asthma severity score was 6.9 +/- 5.6. Of 29 variables screened, 13 were retained in the final model of FEV1 (R2 = 0.30; p < 0.001) and 15 for severity (R2 = 0.16; p < 0.001), including factors from each of the five groups. Adding FEV1 as an independent variable to the severity model further increased its explanatory power (R2 = 0.25).

CONCLUSIONS

Multivariate models covering a range of individual and environmental factors explained nearly a third of FEV1 variability and, taking into account lung function, one quarter of variability in asthma severity. These data support an integrated approach to modeling adult asthma outcomes, including both the physical and the social environment.

The pathogenesis of human and simian immunodeficiency viruses is characterized by CD4(+) T cell depletion and chronic T cell activation, leading ultimately to AIDS. CD4(+) T helper (T(H)) cells provide protective immunity and immune regulation through different immune cell functional subsets, including T(H)1, T(H)2, T regulatory (T(reg)), and interleukin-17 (IL-17)-secreting T(H)17 cells. Because IL-17 can enhance host defenses against microbial agents, thus maintaining the integrity of the mucosal barrier, loss of T(H)17 cells may foster microbial translocation and sustained inflammation. Here, we study HIV-seropositive subjects and find that progressive disease is associated with the loss of T(H)17 cells and a reciprocal increase in the fraction of the immunosuppressive T(reg) cells both in peripheral blood and in rectosigmoid biopsies. The loss of T(H)17/T(reg) balance is associated with induction of indoleamine 2,3-dioxygenase 1 (IDO1) by myeloid antigen-presenting dendritic cells and with increased plasma concentration of microbial products. In vitro, the loss of T(H)17/T(reg) balance is mediated directly by the proximal tryptophan catabolite from IDO metabolism, 3-hydroxyanthranilic acid. We postulate that induction of IDO may represent a critical initiating event that results in inversion of the T(H)17/T(reg) balance and in the consequent maintenance of a chronic inflammatory state in progressive HIV disease.

BACKGROUND

Little is known about the frequency of significant hypoglycemic events in actual practice. Limited health literacy (HL) is common among patients with type 2 diabetes, may impede diabetes self-management, and thus HL could increase the risk of hypoglycemia.

OBJECTIVE

To determine the proportion of ambulatory, pharmacologically-treated patients with type 2 diabetes reporting > or =1 significant hypoglycemic events in the prior 12 months, and evaluate whether HL is associated with hypoglycemia.

RESEARCH DESIGN

Cross-sectional analysis in an observational cohort, the Diabetes Study of Northern California (DISTANCE).

SUBJECTS

The subjects comprised 14,357 adults with pharmacologically-treated, type 2 diabetes who are seen at Kaiser Permanente Northern California (KPNC), a non-profit, integrated health care delivery system.

MEASURES

Patient-reported frequency of significant hypoglycemia (losing consciousness or requiring outside assistance); patient-reported health literacy.

RESULTS

At least one significant hypoglycemic episode in the prior 12 months was reported by 11% of patients, with the highest risk for those on insulin (59%). Patients commonly reported limited health literacy: 53% reported problems learning about health, 40% needed help reading health materials, and 32% were not confident filling out medical forms by themselves. After adjustment, problems learning (OR 1.4, CI 1.1-1.7), needing help reading (OR 1.3, CI 1.1-1.6), and lack of confidence with forms (OR 1.3, CI 1.1-1.6) were independently associated with significant hypoglycemia.

CONCLUSIONS

Significant hypoglycemia was a frequent complication in this cohort of type 2 diabetes patients using anti-hyperglycemic therapies; those reporting limited HL were especially vulnerable. Efforts to reduce hypoglycemia and promote patient safety may require self-management support that is appropriate for those with limited HL, and consider more vigilant surveillance, conservative glycemic targets or avoidance of the most hypoglycemia-inducing medications.

BACKGROUND

Infantile hemangiomas are the most common benign tumors of infancy. Up to 38% of hemangiomas require treatment with systemic medications because of complications. Corticosteroids have been the mainstay for treating such hemangiomas. However, prospective studies evaluating their immunosuppressive effects in infants with hemangiomas are lacking.

OBSERVATIONS

Sixteen patients who presented to the Birthmark and Vascular Anomalies Center at the Children's Hospital of Wisconsin from November 1, 2006, through February 28, 2008, were enrolled in the study. A significant reduction in the numbers of all B- and T-lymphocyte subpopulations was observed after corticosteroid administration. CD19(+) B lymphocytes and CD4(+) T cells were significantly reduced by 8 weeks of corticosteroid therapy, whereas CD8(+) T cells were reduced at week 16 compared with baseline. Immune function was also affected because 13 and 5 patients had protective diphtheria titers and tetanus titers, respectively, 3 months after discontinuation of corticosteroid therapy compared with baseline.

CONCLUSIONS

These results demonstrate that corticosteroids measurably affect both lymphocyte cell numbers and function in this patient population. Prophylaxis with the combination of trimethoprim and sulfamethoxazole should be considered in infants treated with corticosteroids for infantile hemangiomas. We also recommend that tetanus and diphtheria antibodies be checked in patients who receive oral corticosteroids during the immunization period and that additional immunization be administered if the titers are not protective after corticosteroid therapy.