Exposure to indoor biomass fuel pollutants and asthma prevalence in Southeastern Kentucky: results from the Burden of Lung Disease (BOLD) study.

BACKGROUND: Asthma is a chronic inflammatory respiratory disease, characterized by episodic and reversible airflow obstruction and airway hyperresponsiveness and is influenced by both genetic and environmental factors. METHODS: The Burden of Obstructive Lung Disease (BOLD) survey was used to determine the prevalence of self-reported asthma in a target population of 325,000 adults aged > or =40 in Southeastern Kentucky. Postbronchodilator spirometry was used to classify subjects based on lung function. Risk factors for asthma in this population, in particular indoor usage of biomass fuels, were evaluated. RESULTS: The overall study population was comprised of 508 individuals, with 15.5% reporting current asthma and 5.8% reporting former asthma. In this population, the following risk factors for asthma were identified: female sex, smoking, less than a high school education, increasing body mass index (BMI), and a history of cooking indoors with coal and wood. Cooking indoors with wood and coal for more than 6 months of one's life was shown to significantly increase the odds of reporting current asthma (odds ratio (OR) = 2.3, confidence interval (CI) 1.1, 5.0), whereas no effect was seen from a history of heating indoors with wood and coal (OR = 0.8, CI 0.4, 1.8). CONCLUSIONS: Current or former asthma was reported by 21.3% of the adult population. A history of using biomass fuels when cooking indoors significantly increased the risk of reporting current asthma in this population.

SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation.

Cytokine responses can be regulated by a family of proteins termed suppressors of cytokine signaling (SOCS) which can inhibit the JAK/STAT pathway in a classical negative-feedback manner. While the SOCS are thought to target signaling intermediates for degradation, relatively little is known about how their turnover is regulated. Unlike other SOCS family members, we find that SOCS2 can enhance interleukin-2 (IL-2)- and IL-3-induced STAT phosphorylation following and potentiate proliferation in response to cytokine stimulation. As a clear mechanism for these effects, we demonstrate that expression of SOCS2 results in marked proteasome-dependent reduction of SOCS3 and SOCS1 protein expression. Furthermore, we provide evidence that this degradation is dependent on the presence of an intact SOCS box and that the loss of SOCS3 is enhanced by coexpression of elongin B/C. This suggests that SOCS2 can bind to SOCS3 and elongin B/C to form an E3 ligase complex resulting in the degradation of SOCS3. Therefore, SOCS2 can enhance cytokine responses by accelerating proteasome-dependent turnover of SOCS3, suggesting a mechanism for the gigantism observed in SOCS2 transgenic mice.

Efficacy of NNRTI-based antiretroviral therapy initiated during acute HIV infection.

OBJECTIVE: Characterize responses to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral treatment (ART) initiated during acute HIV infection (AHI). DESIGN: This was a prospective, single-arm evaluation of once-daily, co-formulated emtricitabine/tenofovir/efavirenz initiated during AHI. METHODS: The primary endpoint is the proportion of responders with HIV RNA less than 200 copies/ml by week 24. We examined time to viral suppression and CD8 cell activation in relation to baseline participant characteristics. We compared time to viral suppression and viral dynamics using linear mixed-effects models between acutely infected participants and chronically infected controls. RESULTS: Between January 2005 and May 2009, 61 AHI participants were enrolled. Of participants whose enrollment date allowed 24 and 48 weeks of follow-up, 47 of 51 (92%) achieved viral suppression to less than 200 copies/ml by week 24, and 35 of 41 (85.4%) to less than 50 copies/ml by week 48. The median time from ART initiation to suppression below 50 copies/ml was 93 days (range 14-337). Higher HIV RNA levels at ART initiation (P = 0.02), but not time from estimated date of infection to ART initiation (P = 0.86), were associated with longer time to viral suppression. The median baseline frequency of activated CD8+CD38+HLA-DR+ T cells was 67% (range 40-95), and was not significantly associated with longer time to viral load suppression (P = 0.15). Viremia declined to less than 50 copies/ml more rapidly in AHI than chronically infected participants. Mixed-model analysis demonstrated similar phase I HIV RNA decay rates between acute and chronically infected participants, and more rapid viral decline in acutely infected participants in phase II. CONCLUSION: Once-daily emtricitabine/tenofovir/efavirenz initiated during AHI achieves rapid and sustained HIV suppression during this highly infectious period.