Incidence of oral thrush in patients with COPD prescribed inhaled corticosteroids: Effect of drug, dose, and device

Respir Med. 2016 Nov;120:54-63. doi: 10.1016/j.rmed.2016.09.015. Epub 2016 Sep 22.


Background and aims: Little information is available on real-life occurrence of oral thrush in COPD patients treated with ICS. We investigated oral thrush incidence in COPD patients prescribed FDC ICS/LABA therapies and assessed whether it is modulated by the ICS type, dose, and delivery device.

Methods: We conducted a historical, observational, matched cohort study (one baseline year before and one outcome year after initiation of therapy) using data from the UK Optimum Patient Care Research Database. We assessed oral thrush incidence in patients initiating long-acting bronchodilators or FDC ICS/LABA therapy. We then compared different combination therapies (budesonide/formoterol fumarate dihydrate [BUD/FOR] and fluticasone propionate/salmeterol xinafoate [FP/SAL]) and devices (DPI and pMDI).

Results: Patients prescribed FDC ICS/LABA had significantly greater odds of experiencing oral thrush than those prescribed long-acting bronchodilators alone (adjusted OR 2.18 [95% CI 1.84-2.59]). Significantly fewer patients prescribed BUD/FOR DPI developed oral thrush compared with FP/SAL DPI (OR 0.77 [0.63-0.94]) when allowing for differences in prescribed doses between the drugs. A significantly smaller proportion of patients developed oral thrush in the FP/SAL pMDI arm than in the FP/SAL DPI arm (OR 0.67 [0.55-0.82]). Additionally, in the FP/SAL cohort (both DPI and pMDI), increased risk of oral thrush was significantly associated with high ICS daily dose (OR 1.97 [1.22-3.17] vs low daily dose).

Conclusions: ICS use increases oral thrush incidence in COPD and this effect is dose-dependent for FP/SAL therapies. Of the therapies assessed, FP/SAL pMDI and BUD/FOR DPI may be more protective against oral thrush.

Keywords: Chronic obstructive pulmonary disease; Dry powder inhaler; Inhaled corticosteroid; Oral candidiasis; Pressurised metered-dose inhaler; Spacer.

Publication types

  • Observational Study

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects*
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / adverse effects*
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Aged
  • Candida albicans / drug effects
  • Candidiasis, Oral / chemically induced*
  • Candidiasis, Oral / epidemiology
  • Cohort Studies
  • Drug Combinations
  • Dry Powder Inhalers / adverse effects
  • Dry Powder Inhalers / standards
  • Female
  • Humans
  • Incidence*
  • Male
  • Metered Dose Inhalers / adverse effects
  • Metered Dose Inhalers / standards
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / adverse effects*
  • Muscarinic Antagonists / therapeutic use
  • Outcome Assessment, Health Care
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • United Kingdom / epidemiology


  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Drug Combinations
  • Muscarinic Antagonists