A Cochrane review [Abstract] 1 included 55 studies with a total of 16 154 subjects with stable chronic obstructive pulmonary disease (COPD). Long term use of ICS (> 6 months) did not consistently reduce the rate of decline in FEV1 (generic inverse variance analysis: MD 5.80 ml/year with ICS over placebo, 95% CI -0.28 to 11.88; 2 333 participants; pooled means analysis: 6.88 ml/year, 95% CI 1.80 to 11.96; 4 823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI 0.83 to 1.16; 8 390 participants). Long term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14; 2 586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08; 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2 507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46; 5 586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86; 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years.
Another Cochrane review [Abstract] 2 included 43 studies with a total of more than 30 000 subjects with COPD. There were 26 fluticasone studies (n = 21 247) and 17 budesonide studies (n = 10 150). Fluticasone increased non-fatal serious adverse pneumonia events (requiring hospital admission) (OR 1.78, 95% CI 1.50 to 2.12; 18 more per 1000 treated over 18 months). Budesonide also increased non-fatal serious adverse pneumonia events compared with placebo, but the effect was less precise and was based on shorter trials (OR 1.62, 95% CI 1.00 to 2.62; 6 more per 1000 treated over 9 months). No significant difference in overall mortality rates was observed between either of the inhaled steroids and the control interventions, and pneumonia-related deaths were too rare to permit conclusions to be drawn.
A meta-analysis 3 included 11 randomized controlled trials with a total of 14 426 participants. In trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths /4 636 patients in the treatment group, 148 deaths / 4 597 patients in the control group; RR 0.86; 95% 95% CI 0.68 to 1.09). ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases / 5 405 patients vs. 561 cases / 5 371 patients in the control group; RR 1.34; 95% CI 1.03 to 1.75).
A systematic review 4 including 9 RCTs with a total of 3 976 subjects was abstracted in DARE. The use of inhaled corticosteroids was associated with a 30% reduction in exacerbations (RR 0.70, 95% CI 0.58 to 0.84; 6 trials). Sensitivity analysis revealed no dose-response effect. If the patients received systematic steroids during the run-in phase, the difference between the groups was not significant (RR 0.77, 95% CI 0.56 to 1.09). There was no significant difference between groups in all-cause mortality (RR 0.84, 95% CI 0.60 to 1.18; 5 trials). Concerning FEV1 (9 trials), the results were variable. Only 2 trials found a statistically significant difference between the groups. Oropharyngeal candidiasis (RR 2.1, 95% CI 1.5 to 3.1) and skin bruising (RR 2.1, 95% CI 1.6 to 2.8) were more common in patients treated with corticosteroids.
A systematic review 5 including 6 studies with a total of 3 571 subjects was abstracted in DARE. Treatment with inhaled corticosteroids produced no statistically significant effect on decline in FEV1 over time: the WMD was -5.0 ml/year (95% CI -11.2 to +1.2; 6 RCTs).
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