Angiotensin II antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice.

Based on current evidence, transforming growth factor (TGF)-beta plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that angiotensin II can serve as a stimulus for TGF-beta-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

Predictors of hospitalization in children with acute asthma.

OBJECTIVE: To identify predictors of long duration of bronchodilator therapy in children with acute asthma. STUDY DESIGN: An emergency department prospective cohort study of 278 children > or =12 months of age, with clinical and socioeconomic parameters collected at baseline and 4 hours after administration of corticosteroids. Patients were classified into short and long therapy groups, with interval from first albuterol dose to initiation of administration every 4 hours < or =12 or >12 hours, respectively. Predictors significant by univariate analysis were examined by multiple logistic regression. RESULTS: Five variables were associated with long therapy (n = 85) versus short therapy (n = 193): previous intensive care unit admission (odds ratio [OR] 7.2, 95% CI = 1.85, 27.7); baseline oxygen saturation < or =92% (OR 2.6, 95% CI = 0.89, 7.4), asthma score > or =6/9 (OR 2.9, 95% CI = 1.9, 4.37), oxygen saturation < or =92% (OR 6.6, 95% CI = 1.34, 32.0), and hourly albuterol dosing interval (OR 4.3, 95% CI = 0.82, 22.12) 4 hours after administration of corticosteroids. Probability of long therapy was 91.8% to 99% for > or =3 predictors, but only 40.6% to 61.8% for individual factors. CONCLUSION: A combination of 3 or more factors predicts long bronchodilator therapy and signals the need for hospitalization. Children with only one predictor can be safely treated in the emergency department or observation unit and reevaluated.