Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD. A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case–control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23–1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs. Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk–benefit balance is crucial for the indication of ICSs.