Effects of inhaled corticosteroids /long-acting agonists in a single inhaler versus inhaled corticosteroids alone on all-cause mortality, pneumonia, and fracture in chronic obstructive pulmonary disease: A nationwide cohort study 2002-2013.

BACKGROUND: Both inhaled corticosteroids (ICS) and long-acting ?-agonists (LABA) have been recommended for the treatment of severe/moderate chronic obstructive pulmonary disease (COPD), but mild COPD has not been frequently studied.

METHODS: We performed a prospective cohort study to compare the effect of inhaled corticosteroid (ICS) and ICS/long-acting ?-agonist (LABA) in a single inhaler on all-cause mortality and adverse events, such as pneumonia and fracture, in patients with newly diagnosed chronic obstructive pulmonary disease (COPD). We used representative nationwide cohort data from the Korean National Health Insurance claims database (2002-2013). Patients who were at least 40-years-old, newly diagnosed with COPD, and prescribed ICS or ICS/LABA in a single inhaler (N = 1995). To analyze the data, we utilized a Cox's proportional hazard regression.

RESULTS: Among the total of 1995 patients, 807 had severe COPD (FEV1  < 50%) and 1188 had mild/moderate COPD (FEV1  ? 50%). The cumulative incidence and 5-year cumulative incidence of all-cause mortality was 59.5% and 29.6% for ICS users, and 35.8% and 20.2% for single inhaler ICS/LABA users, respectively. The adjusted hazard ratio (HR) of all-cause mortality for new ICS/LABA users, compared with that in new ICS users, was 0.77 (95% CI: 0.62-0.95) for the total population. For the severe and non-severe COPD groups, the adjusted HRs of all-cause mortality for new ICS/LABA users were 1.07 (95% CI: 0.65-1.76) and 0.70 (95% CI: 0.55-0.89), respectively. There was no difference in the risk for the first hospitalization due to pneumonia between new ICS and ICS/LABA users among the total population (HR: 1.02; 95% CI: 0.79-1.34). The adjusted HR of the first hospitalization for fractures in new ICS/LABA users, compared with that in new ICS users, was 0.60 (95% CI: 0.39-0.92) for the total population.

CONCLUSIONS: Among newly diagnosed COPD patients and new users of ICS or ICS/LABA, use of ICS/LABA in a single inhaler was associated with lowered risk of all-cause mortality and delayed first hospitalization for fracture, as compared with use of ICS alone. However, there was no significant difference in terms of first hospitalization for pneumonia.