Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis

BackgroundRecent studies have suggested a possible association between respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to ascertain the risk of upper respiratory tract infection (URTI) with long-term inhaled corticosteroid use among patients with asthma.MethodsThrough a comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google Scholar from inception to May 2018, we included randomized controlled trials of any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse event. We conducted meta-analyses by the Peto approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI.ResultsSeventeen trials (15,336 subjects) were included. Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08-1.42; I-2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03; I-2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I-2 = 25%; p = 0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto OR, 1.18; 95% CI 1.02-1.38; p = 0.03; heterogeneity: I-2 = 21%) but not budesonide, low-dose fluticasone treatment was associated with a significantly higher risk of URTI but not high dose.ConclusionsThis study raises safety concerns about the risk of URTI associated with ICS use in patients with asthma, but it should be further investigated.