Publications

The airway is a primary portal of entry for noxious environmental stimuli that can trigger airway remodeling, which contributes significantly to airway obstruction in chronic obstructive pulmonary disease (COPD) and chronic asthma. Important pathologic components of airway remodeling include fibrosis and abnormal innate and adaptive immune responses. The positioning of fibroblasts in interstitial spaces suggests that they could participate in both fibrosis and chemokine regulation of the trafficking of immune cells such as dendritic cells, which are crucial antigen-presenting cells. However, physiological evidence for this dual role for fibroblasts is lacking. Here, in two physiologically relevant models - conditional deletion in mouse fibroblasts of the TGF-β-activating integrin αvβ8 and neutralization of αvβ8 in human COPD fibroblasts - we have elucidated a mechanism whereby lung fibroblast chemokine secretion directs dendritic cell trafficking, in a manner that is critically dependent on αvβ8-mediated activation of TGF-β by fibroblasts. Our data therefore indicate that fibroblasts have a crucial role in regulating both fibrotic and immune responses in the lung.

BACKGROUND

Pesticides are widely used in agriculture, and off-target pesticide drift exposes workers and the public to harmful chemicals.

OBJECTIVE

We estimated the incidence of acute illnesses from pesticide drift from outdoor agricultural applications and characterized drift exposure and illnesses.

METHODS

Data were obtained from the National Institute for Occupational Safety and Health's Sentinel Event Notification System for Occupational Risks-Pesticides program and the California Department of Pesticide Regulation. Drift included off-target movement of pesticide spray, volatiles, and contaminated dust. Acute illness cases were characterized by demographics, pesticide and application variables, health effects, and contributing factors.

RESULTS

From 1998 through 2006, we identified 2,945 cases associated with agricultural pesticide drift from 11 states. Our findings indicate that 47% were exposed at work, 92% experienced low-severity illness, and 14% were children (< 15 years). The annual incidence ranged from 1.39 to 5.32 per million persons over the 9-year period. The overall incidence (in million person-years) was 114.3 for agricultural workers, 0.79 for other workers, 1.56 for nonoccupational cases, and 42.2 for residents in five agriculture-intensive counties in California. Soil applications with fumigants were responsible for the largest percentage (45%) of cases. Aerial applications accounted for 24% of cases. Common factors contributing to drift cases included weather conditions, improper seal of the fumigation site, and applicator carelessness near nontarget areas.

CONCLUSIONS

Agricultural workers and residents in agricultural regions had the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard, causing large drift incidents. Our findings highlight areas where interventions to reduce off-target drift could be focused.

BACKGROUND

Studies of the retreatment with consensus interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.

AIMS

The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006.

RESULTS

A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P<0.0001). A 2-log10 or greater drop in HCV RNA after 24 weeks of PEG-IFN/RBV was a predictor of subsequent SVR to CIFN/RBV.

CONCLUSIONS

CIFN/RBV was used frequently in clinical practice for retreatment of PEG-IFN/RBV. In this setting, early treatment discontinuation was common. Overall SVR was low, although response was significantly better in prior PEG-IFN/RBV relapsers and those who had a 2-log(10) or greater decline than in nonresponders.