Systemic steroid therapy for pneumonic chronic obstructive pulmonary disease exacerbation: A retrospective cohort study.

The effectiveness of systemic steroid therapy on mortality in patients with pneumonic chronic obstructive pulmonary disease (COPD) exacerbation is unclear. We evaluated the association between systemic steroid therapy and 30-day mortality after adjusting for known confounders, using data from the Health, Clinic, and Education Information Evaluation Institute in Japan, which longitudinally followed up patients in the same hospital. We selected patients aged ≥40 years admitted for pneumonic COPD exacerbation. The exclusion criteria were censoring within 24 h, comorbidity with other respiratory diseases, and daily steroid use. Systemic steroid therapy was defined as oral/parenteral steroid therapy initiated within two days of admission. The primary outcome was the 30-day mortality rate. To account for known confounders, each patient was assigned an inverse probability of treatment weighting. The outcome was evaluated using logistic regression. Among 3,662 patients showing pneumonic COPD exacerbation, 30-day mortality in the steroid therapy and non-steroid therapy groups was 27.6% (169/612) and 21.9% (668/3,050), respectively. Systemic steroid therapy indicated a slightly higher estimated probability of 30-day mortality (difference in the estimated probabilities, 2.65%; 95% confidence interval, -1.23 to 6.54%, p-value = 0.181). Systemic steroid therapy within two days of admission was associated with higher 30-day mortality rates in pneumonic COPD exacerbation. Further validation studies based on chart reviews will be needed to cope with residual confounders

Mechanisms of atrial fibrillation:Lessons from animal models

Studies in animal models have provided extremely important insights about atrial fibrillation (AF). The classic mechanisms that still form the framework for our understanding of AF (focal activity, single-circuit or "mother wave" reentry, and multiple circuit reentry) were established based on animal studies almost 100 years ago. The past 10 years have witnessed a tremendous acceleration of animal work in this area, including the development of a range of AF models in clinically relevant pathological substrates (eg, atrial tachycardia remodeling, congestive heart failure, pericarditis, ischemic heart disease, mitral valve disease, volume overload states, respiratory failure) and the establishment of an increasing number of genetically defined transgenic mouse models. This article reviews the contribution of animal models to our knowledge about AF mechanisms and to clinical management, dealing with such issues as the theory of reentry; the specific applications of various animal models and their contribution to our understanding of electrophysiologic, ionic, and molecular mechanisms; the role of the autonomic nervous system and regional factors; and the development of novel therapeutic approaches. The complementary nature of animal research and clinical investigation is emphasized and the clinical relevance of findings in experimental models is highlighted

Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs

Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by atrial tachycardia-induced remodeling in dogs. Methods and results: Dogs were subjected to atrial tachypacing at 400 bpm in the absence and presence of treatment with prednisone (15 or 50 mg/day) or ibuprofen (anti-inflammatory) or cyclosporine-A (calcineurin inhibitor). Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. A final open-chest study was performed on day 8. Serum G reactive protein was measured by ELISA and nitric oxide synthase by Western blotting. The mean duration of induced atrial fibrillation was markedly increased by tachypacing alone, from 26 +/- 8 to 962 +/- 317 s (p <0.0 1), and the atrial effective refractory period was decreased from 117 +/- 4 to 73 +/- 7 ms (p <0.001; cycle-length 300 ms). Tachypacing-induced effective refractory period shortening and atrial fibrillation promotion were unaffected by ibuprofen or cyclosporine-A; however, both doses of prednisone suppressed tachypacing-remodeling effects (atrial fibrillation duration to 96 60 s and 28 +/- 11 s at higher and lower doses, respectively; effective refractory period to 101 +/- 6 ms for higher-dose and 105 +/- 3 ms for lower-dose group). In addition, prednisone (but not ibuprofen or cyclosporine) significantly decreased C-reactive protein concentrations and attenuated the increase in endothelial nitric oxide synthase expression caused by atrial tachypacing. Conclusions: Prednisone prevents the electrophysiological and atrial fibrillation-promoting effects of atrial tachycardia-remodeling, possibly by an anti-inflammatory action, whereas the less potent anti-inflammatory ibuprofen and the calcineurin inhibitor cyclosporine-A are without effect. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Direct acyclic graph.

In our statistical analysis models, the following confounders were adjusted: age (≥70 years old), body mass index (25), presence of the previous admission due to pneumonia or COPD exacerbation within 90 days before the index date, the activity of daily living on admission (Barthel index: 0 to 300/μL), and blood urea nitrogen (≥7 mmol/L), and use of broad-spectrum antibiotics. (PNG)</p

Subcategories of systemic steroid therapy.

The effectiveness of systemic steroid therapy on mortality in patients with pneumonic chronic obstructive pulmonary disease (COPD) exacerbation is unclear. We evaluated the association between systemic steroid therapy and 30-day mortality after adjusting for known confounders, using data from the Health, Clinic, and Education Information Evaluation Institute in Japan, which longitudinally followed up patients in the same hospital. We selected patients aged ≥40 years admitted for pneumonic COPD exacerbation. The exclusion criteria were censoring within 24 h, comorbidity with other respiratory diseases, and daily steroid use. Systemic steroid therapy was defined as oral/parenteral steroid therapy initiated within two days of admission. The primary outcome was the 30-day mortality rate. To account for known confounders, each patient was assigned an inverse probability of treatment weighting. The outcome was evaluated using logistic regression. Among 3,662 patients showing pneumonic COPD exacerbation, 30-day mortality in the steroid therapy and non-steroid therapy groups was 27.6% (169/612) and 21.9% (668/3,050), respectively. Systemic steroid therapy indicated a slightly higher estimated probability of 30-day mortality (difference in the estimated probabilities, 2.65%; 95% confidence interval, -1.23 to 6.54%, p-value = 0.181). Systemic steroid therapy within two days of admission was associated with higher 30-day mortality rates in pneumonic COPD exacerbation. Further validation studies based on chart reviews will be needed to cope with residual confounders.</div