Impact of inhaled corticosteroid-induced oropharyngeal adverse events: results from a meta-analysis

Ann Allergy Asthma Immunol. 2007 Mar;98(3):225-38. doi: 10.1016/S1081-1206(10)60711-9.


Background: Oropharyngeal adverse events associated with inhaled corticosteroid (ICS) use can affect adherence; however, these effects have been studied less extensively than those that occur systemically.

Objective: To calculate the risk of ICS-induced oral candidiasis, dysphonia, and pharyngitis among currently available therapies and to determine related effects of dose and device.

Methods: A computerized search in MEDLINE (January 1966 to June 2004) and EMBASE (January 1974 to June 2004) was conducted using indexed MedDRA terms for oropharyngeal adverse events. Odds ratios (ORs) were used to determine the rate of ICS-induced adverse events based on dose and device.

Results: A total of 23 studies (59 drug arms) were evaluated. Incidence of oral candidiasis (P < or = .001), dysphonia (P < or = .001), and pharyngitis (P < or = .023) increased significantly with dose vs placebo at all dose levels and combined, regardless of device. Overall, the ICS metered-dose inhaler (MDI) device (hydrofluoroalkane formulation, 4 arms; chlorofluorocarbon formulation, 26 arms) was associated with a 5-fold greater risk of oral candidiasis vs MDI placebo (OR, 5.40). In contrast, the ICS dry-powder inhaler (DPI) device had a 3-fold greater risk for oral candidiasis vs DPI placebo (OR, 3.24). A similar trend was observed with regard to dysphonia (ICS MDI: OR, 5.68; ICS DPI: OR, 3.74; both vs. placebo). Both ICS MDI and DPI were associated with an approximately 2-fold greater risk of pharyngitis compared with placebo.

Conclusions: Currently available inhaled corticosteroids canbe associated with oropharyngeal adverse events. Such events may be reduced by postdose mouth rinsing or use of a spacer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Candidiasis, Oral / chemically induced
  • Candidiasis, Oral / etiology
  • Double-Blind Method
  • Humans
  • Metered Dose Inhalers / adverse effects
  • Oropharynx / drug effects*
  • Pharyngitis / chemically induced
  • Pharyngitis / etiology
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Voice Disorders / chemically induced
  • Voice Disorders / etiology


  • Adrenal Cortex Hormones