Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice.

BACKGROUND: Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia. METHODS: C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured. RESULTS: Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model. CONCLUSIONS: Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.

Exercise electrocardiography.

Treadmill exercise electrocardiography is a test commonly employed to diagnose coronary artery disease and has powerful prognostic value. It is most accurate when the resting ECG is normal, and because of significant limitations in sensitivity and specificity, the test is most useful when the pretest probability of disease is in the intermediate range. The usual criterion for diagnosing myocardial ischemia is horizontal or downsloping ST-segment depression that measures > or = 1 mm (0.1 mv) 0.08 seconds after the J point, and the specificity of this finding is greatly enhanced by the patient's developing typical angina during the test. Sensitivity and/or specificity may be improved by modifications of the ECG-lead system, computer-assisted measurement of more complex exercise-test variables, using test scores that incorporate coronary risk factors, and by adding radionuclide or echocardiographic imaging modalities that assess myocardial perfusion and/or the metabolic or contractile consequence of myocardial ischemia, as well as the electrocardiographic and symptomatic ones.