The adverse health effects of elevated exposures to PM10 (particulate matter collected through a size selective inlet with an efficiency of 50% for particles with an aerodynamic diameter of 10 μm) in relation to morbidity and mortality, especially in susceptible individuals, are now well recognised. PM10 consists of a variable cocktail of components differing in chemical composition and size. Epidemiological and toxicological data suggest that transition metals and ultrafine particles are both able to drive the cellular and molecular changes that underlie PM10-induced inflammation and so worsen disease status. Toxicological evidence also suggest roles for the biological components of PM10 including volatile organic compounds (VOC’s), allergens and bacterial-derived endotoxin. Many of these components, in particular transition metals, ultrafine particles, endotoxin and VOC’s induce a cellular oxidative stress which initiates an intracellular signaling cascade involving the activation of phosphatase and kinase enzymes as well as transcription factors such as nuclear factor kappa B. Activation of these signaling mechanisms results in an increase in the expression of pro-inflammatory mediators, and hence enhanced inflammation. Given that many of the components of PM10 stimulate similar or even identical intracellular signaling pathways, it is conceivable that this will result in synergistic or additive interactions so that the biological response induced by PM10 exposure is a response to the composition rather than the mass alone. A small number of studies suggest that synergistic interactions occur between ultrafine particles and transition metals, between particles and allergens, and between particles and VOC’s. Elucidation of the consequences of interaction between the components of PM10 in relation to their biological activity implies huge consequences for the methods used to monitor and to legislate pollution exposure in the future, and may drive a move from mass based measurements to composition.
seconds ; Transition Elements ; SIZES ; Drug Interactions ; Cellular biology

Objective: Chronic obstructive pulmonary disease (COPD) is associated with exacerbations and high risk of serious outcomes. Our goal was to determine the appropriateness of the emergency department (ED) management of COPD exacerbations. Methods: This observational cohort study incorporated a health records review and included COPD exacerbation cases seen at two large academic EDs. We included all patients with the primary diagnosis of COPD exacerbation. From the electronic medical record, demographic and clinical data were abstracted, and the Ottawa COPD Risk Score (OCRS) was calculated for each. Short-term serious outcomes included intensive care unit admission, intubation, myocardial infarction, noninvasive positive pressure ventilation (NIV), and death at 30 days. Cases were judged for appropriateness of treatment according to explicit indications and standards developed a priori. Results: We enrolled 500 cases with mean age of 71.9 years, 51.2% female patients, 50.2% admitted, and 4.4% death. The calculated OCRS score was >2 for 70.8% of patients. The treatments provided were inhaled β-agonists (82.6%), inhaled anticholinergics (76.6%), corticosteroids (75.2%), antibiotics (71.0%), oxygen (63.8%), NIV (8.8%), and intubation (0.6%). Overall, 50.0% of cases were judged to have had inadequate management due to missing treatments. Specifically, the proportion of missing treatments were inhaled β-agonist (17.0%), inhaled anticholinergic (22.6%), corticosteroids (24.4%), antibiotics (12.8%), and NIV (2.0%). Conclusion Adequate treatment of COPD exacerbation was lacking in 50.0% of patients in these two large academic EDs. Concerning were the number of patients not receiving corticosteroids or antibiotics. Implementation of explicit treatment standards should lead to improved patient care of this common and serious condition.

Objective: Chronic obstructive pulmonary disease (COPD) is associated with exacerbations and high risk of serious outcomes. Our goal was to determine the appropriateness of the emergency department (ED) management of COPD exacerbations. Methods: This observational cohort study incorporated a health records review and included COPD exacerbation cases seen at two large academic EDs. We included all patients with the primary diagnosis of COPD exacerbation. From the electronic medical record, demographic and clinical data were abstracted, and the Ottawa COPD Risk Score (OCRS) was calculated for each. Short-term serious outcomes included intensive care unit admission, intubation, myocardial infarction, noninvasive positive pressure ventilation (NIV), and death at 30 days. Cases were judged for appropriateness of treatment according to explicit indications and standards developed a priori. Results: We enrolled 500 cases with mean age of 71.9 years, 51.2% female patients, 50.2% admitted, and 4.4% death. The calculated OCRS score was >2 for 70.8% of patients. The treatments provided were inhaled β-agonists (82.6%), inhaled anticholinergics (76.6%), corticosteroids (75.2%), antibiotics (71.0%), oxygen (63.8%), NIV (8.8%), and intubation (0.6%). Overall, 50.0% of cases were judged to have had inadequate management due to missing treatments. Specifically, the proportion of missing treatments were inhaled β-agonist (17.0%), inhaled anticholinergic (22.6%), corticosteroids (24.4%), antibiotics (12.8%), and NIV (2.0%). Conclusion Adequate treatment of COPD exacerbation was lacking in 50.0% of patients in these two large academic EDs. Concerning were the number of patients not receiving corticosteroids or antibiotics. Implementation of explicit treatment standards should lead to improved patient care of this common and serious condition.

Objective: Chronic obstructive pulmonary disease (COPD) is associated with exacerbations and high risk of serious outcomes. Our goal was to determine the appropriateness of the emergency department (ED) management of COPD exacerbations. Methods: This observational cohort study incorporated a health records review and included COPD exacerbation cases seen at two large academic EDs. We included all patients with the primary diagnosis of COPD exacerbation. From the electronic medical record, demographic and clinical data were abstracted, and the Ottawa COPD Risk Score (OCRS) was calculated for each. Short-term serious outcomes included intensive care unit admission, intubation, myocardial infarction, noninvasive positive pressure ventilation (NIV), and death at 30 days. Cases were judged for appropriateness of treatment according to explicit indications and standards developed a priori. Results: We enrolled 500 cases with mean age of 71.9 years, 51.2% female patients, 50.2% admitted, and 4.4% death. The calculated OCRS score was >2 for 70.8% of patients. The treatments provided were inhaled β-agonists (82.6%), inhaled anticholinergics (76.6%), corticosteroids (75.2%), antibiotics (71.0%), oxygen (63.8%), NIV (8.8%), and intubation (0.6%). Overall, 50.0% of cases were judged to have had inadequate management due to missing treatments. Specifically, the proportion of missing treatments were inhaled β-agonist (17.0%), inhaled anticholinergic (22.6%), corticosteroids (24.4%), antibiotics (12.8%), and NIV (2.0%). Conclusion Adequate treatment of COPD exacerbation was lacking in 50.0% of patients in these two large academic EDs. Concerning were the number of patients not receiving corticosteroids or antibiotics. Implementation of explicit treatment standards should lead to improved patient care of this common and serious condition.

The adverse health effects of elevated exposures to PM(10) (particulate matter collected through a size selective inlet with an efficiency of 50% for particles with an aerodynamic diameter of 10 μm) in relation to morbidity and mortality, especially in susceptible individuals, are now well recognised. PM(10) consists of a variable cocktail of components differing in chemical composition and size. Epidemiological and toxicological data suggest that transition metals and ultrafine particles are both able to drive the cellular and molecular changes that underlie PM(10)-induced inflammation and so worsen disease status. Toxicological evidence also suggest roles for the biological components of PM(10) including volatile organic compounds (VOC's), allergens and bacterial-derived endotoxin. Many of these components, in particular transition metals, ultrafine particles, endotoxin and VOC's induce a cellular oxidative stress which initiates an intracellular signaling cascade involving the activation of phosphatase and kinase enzymes as well as transcription factors such as nuclear factor kappa B. Activation of these signaling mechanisms results in an increase in the expression of proinflammatory mediators, and hence enhanced inflammation. Given that many of the components of PM(10) stimulate similar or even identical intracellular signaling pathways, it is conceivable that this will result in synergistic or additive interactions so that the biological response induced by PM(10) exposure is a response to the composition rather than the mass alone. A small number of studies suggest that synergistic interactions occur between ultrafine particles and transition metals, between particles and allergens, and between particles and VOC's. Elucidation of the consequences of interaction between the components of PM(10) in relation to their biological activity implies huge consequences for the methods used to monitor and to legislate pollution exposure in the future, and may drive a move from mass based measurements to composition.