Mortality glucocorticoids, inhaled

Mortality associated with glucocorticoid has been retrospectively studied in 556 patients with chronic obstructive pulmonary disease admitted to a rehabilitation center (353). Median survival was 38 months and 280 patients died during follow-up. On multivariate analysis, oral glucocorticoid use at a prednisone equivalent of 10 mg/day without inhaled glucocorticoid was associated with an increased risk of death (RR = 2.34 95% Cl = 1.24, 4.44), and 15 mg/day increased the risk further (RR = 4.03 95% Cl = 1.99, 8.15). The risk of death was not increased in those using 5 mg/day or when patients used any oral dose in combination with inhaled glucocorticoids. 

In an updated meta-analysis of 24 longterm randomized controlled trials involving 23096 participants there was a significantly increased risk of pneumonia with the use of inhaled glucocorticoids in COPD (RR = 1.6 95% Cl=1.4, 1.8) [1 ]. The increased risk of pneumonia was not accompanied by a corresponding increase in mortality. Elderly people and those with more severe disease and reduced lung function had the highest risk. 

In a study, from the same cohort, of the association of prior outpatient inhaled glucocorticoid therapy with mortality in 6353 patients with COPD who were hospitalized because of pneumonia, and of whom 38% were taking inhaled glucocorticoids, overall mortality was 9% at 30 days and 16% at 90 days [3 ]. In regression analyses, outpatient inhaled glucocorticoid therapy was associated with a lower mortality at both 30 days (OR = 0.8 95% Cl =0.7, 0.8) and 90 days (OR = 0.80 95% Cl=0.75, 0.86). 

A later prospective study of 490 patients with COPD who were admitted to hospital with radiologically confirmed community-acquired pneumonia, and of whom 77% were using inhaled glucocorticoids, has provided contradictory evidence [4 ]. There were no differences in any of the pneumonia severity markers between users of inhaled glucocorticoid and non-users. Multivariate analysis, after adjustment for COPD severity and pneumonia severity, showed that inhaled use of glucocorticoids was not independently associated with 30-day mortality (OR=1.7 95% CI=0.75, 3.9), 6-month mortality (OR = 1.6 95% Cl=0.82, 3.2), requirement for mechanical ventilation and/ or inotropic support (OR = 0.73 95%... 

In a meta-analysis of the effect of at least 12 weeks of treatment with a LABA on asthma-related and total morbidity and mortality in patients who were concomitantly using inhaled glucocorticoids (n = 29 401 patients over 8200 patient-years) there were 14 deaths in those using a LABA and eight in controls there were three asthma-related deaths and two asthma-related non-fatal intubations, all in those using a LABA (n - 15 710) [36 ]. The OR for total mortality was 1.26 (Cl = 0.58,2.74). Asthma-related deaths and intubations were few and there was insufficient power to draw conclusions about the effect of LABAs on these outcomes. 

In summary, salmeterol monotherapy in asthma increases the risk of asthma mortality, and this risk is reduced by concomitant use of an inhaled glucocorticoid. There is no evidence that combination salmeterol -b fluticasone in adults is associated with increased risks of serious adverse events or asthma mortality, although the latter conclusion is limited by low statistical power in the available studies. There may be an increased risk of non-fatal serious adverse events in children using salmeterol. 

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