Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

BACKGROUND: Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases. OBJECTIVE: We hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs. METHODS: We recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced. RESULTS: We show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis. CONCLUSIONS AND CLINICAL RELEVANCE: Collectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

Indoor air pollution and asthma. Results from a panel study.

Although there is abundant clinical evidence of asthmatic responses to indoor aeroallergens, the symptomatic impacts of other common indoor air pollutants from gas stoves, fireplaces, and environmental tobacco smoke have been less well characterized. These combustion sources produce a complex mixture of pollutants, many of which are respiratory irritants. We report here results of an analysis of associations between indoor pollution and several outcomes of respiratory morbidity in a population of adult asthmatics residing in the Denver, Colorado, metropolitan area. A panel of 164 asthmatics recorded in a daily diary the occurrence of several respiratory symptoms, nocturnal asthma, medication use, and restrictions in activity, as well as the use of gas stoves, wood stoves, or fireplaces, and exposure to environmental tobacco smoke. Multiple logistic regression analysis suggests that the indoor sources of combustion have a statistically significant association with exacerbations of asthma. For example, after correcting for repeated measures and autocorrelation, the reported use of a gas stove was associated with moderate or worse shortness of breath (OR, 1.60; 95% CI, 1.11-2.32), moderate or worse cough (OR, 1.71; 95% CI, 0.97-3.01), nocturnal asthma (OR, 1.01; 95% CI, 0.91-1.13), and restrictions in activity (OR, 1.47; 95% CI, 1.0-2.16). Among this panel of relatively moderate to severe asthmatics, the respiratory irritants produced by several domestic combustion sources were associated with increased morbidity.

Air pollution and respiratory morbidity among adults in southern California.

This paper reports the results of an investigation of the acute effects of air pollution in 321 nonsmoking adults residing in Southern California. Previous epidemiologic investigations of effects of acute exposure to ozone have focused on groups who may not be representative of the general public, such as asthmatics or student nurses. For this study, participants recorded the daily incidence of several respiratory symptoms over a 6-month period between 1978 and 1979. The authors examined the impact of ambient concentrations of ozone, particulate sulfates, and other air pollutants on the incidence of respiratory morbidity, measured as either upper or lower respiratory tract symptoms. Using a logistic regression model, the authors found a significant association between the incidence of lower respiratory tract symptoms and 1-hour daily maximum ozone levels (odds ratio (OR) = 1.22, 95% confidence interval (Cl) 1.11-1.34, for a 10 parts per hundred million (pphm) change), 7-hour average ozone levels (OR = 1.32, 95% Cl 1.14-1.52), and ambient sulfates (OR = 1.30, 95% Cl 1.09-1.54, for a 10-micrograms/m3 change), but no association was found with coefficient of haze, a more general measure of particulates. The existence of a gas stove in the home was also associated with lower respiratory tract symptoms (OR = 1.23, 95% Cl 1.03-1.47). The effects of ozone were greater in the subpopulation without a residential air conditioner. In addition, ozone appears to have had a greater effect among individuals with a preexisting respiratory infection.

Monoclonal antibodies as probes for unique antigens in secretory cells of mixed exocrine organs.

In the past, it has been difficult to identify the secretory product and control mechanisms associated with individual cell types making up mixed exocrine organs. This report establishes the feasibility of using immunological methods to characterize both the biochemical constituents and regulatory mechanisms associated with secretory cells in the trachea. Monoclonal antibodies directed against components of tracheal mucus were produced by immunizing mice with dialyzed, desiccated secretions harvested from tracheal organ culture. An immunofluorescence assay revealed that of the total 337 hybridomas screened, 100 produced antibodies recognizing goblet cell granules; 64, gland cell granules; and 3, antigen confined to the ciliated apical surface of the epithelium. The tracheal goblet cell antibody described in this report was strongly cross-reactive with intestinal goblet cells, as well as with a subpopulation of submandibular gland cells, but not with cells of Brunner's glands or the ciliated cell apical membrane. The serous cell antibody was not cross-reactive with goblet, Brunner's gland, or submandibular cells, or the ciliated cell apical membrane. The antibody directed against the apical membrane of ciliated cells did not cross-react with gland or goblet cells or the apical membrane of epithelial cells in the duodenum. Monoclonal antibodies, therefore, represent probes by which products unique to specific cells or parts of cells in the trachea can be distinguished. The antibodies, when used in enzyme immunoassays, can be used to quantitatively monitor secretion by individual cell types under a variety of physiological and pathological conditions. They also provide the means for purification and characterization of cell-specific products by immunoaffinity chromatography.

Nursing leadership in the critical care setting.

The challenge of a nursing leadership role within the critical care setting is most unique in that two competencies are required--clinical and administrative talents. The development of such leaders also presents a challenge to administrators of health care settings. With administrative support of the nurse who aspires to such a role, we will continue to provide the caliber of care required by acutely ill and injured patients. Based on a philosophy of management that promotes both clinical and administrative talents, this plan will not only best serve the patient population of acute/critical care units but will also help foster the professional commitment of nurse practitioners and encourage them to aspire to such roles.