Background Oral corticosteroid (OCS) use increases the risk of systemic adverse effects including osteoporosis, fractures, diabetes, ocular disorders and respiratory infections. We sought to understand if there is an increased risk of these adverse effects from inhaled corticosteroids (ICS) use in adults with asthma.

Methods MEDLINE and EMBASE databases were searched to identify studies measuring adverse effects with ICS use in asthma, with those investigating a majority population of COPD patients excluded. Studies were grouped by outcome: bone mineral density (BMD), respiratory infection (pneumonia, tuberculous or non-tuberculous mycobacterial infection), diabetes and ocular disorder (glaucoma or cataracts). Study information was extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomised controlled trials) and ROBINS-I tool (observational studies). A narrative synthesis was carried out due to the low number of studies with the same outcome measurement.

Results Thirteen studies met the inclusion criteria, two trials and eleven observational studies, all analysing the effects of ICS compared with non-ICS use for particular outcomes. Study outcomes by number of studies were: six BMD, six infection (four pneumonia, one tuberculous, one non-tuberculous mycobacterial), one ocular disorder (cataracts) and no diabetes. Studies addressing BMD were limited by study size, lack of generalisability, and short follow-up. BMD was measured from a range of bones via ultrasound or x-ray absorptiometry; most found a loss of BMD. Studies addressing infection suffered from lack of power, misclassification and selection bias; most studies found an increased risk of infection. Only one study assessed ocular disorders, they found an increased risk of cataracts. This study likely suffered from residual confounding. Most studies were unable to fully account for OCS exposure, total ICS exposure or difference between ICS drugs and their varying dosages.

Conclusion There is a paucity of studies assessing systemic adverse effects from ICS use in adults with asthma. Current evidence is limited by multiple biases and lack of generalisability but suggests an increased risk of BMD loss, respiratory infection and cataracts. Further studies are needed to fill this evidence gap, including identifying high risk patients, and quantifying dose-related or specific ICS-related effects.