Review: inhaled corticosteroids increase risk of oral candidiasis, dysphonia, and pharyngitis in persistent asthma
Q Do inhaled corticosteroids increase risk of oral candidiasis, dysphonia, and pharyngitis in patients with persistent asthma?
Medline (January 1966 to June 2004) and EMBASE/Excerpta Medica (January 1974 to June 2004).
Study selection and assessment:
randomised, placebo controlled trials (RCTs) that evaluated oral inhaled corticosteroids (low dose <400 μg/d, medium dose 401–499 μg/d, or high dose ⩾1000 μg/d) alone or in combination in adults and adolescents with persistent asthma and reported incidence of oral candidiasis, dysphonia, or pharyngitis. Studies of patients who had chronic obstructive pulmonary disease were excluded. 23 RCTs met the selection criteria. The inhaled corticosteroids evaluated were fluticasone propionate (19 arms; 13 dry powder inhaler [DPI], 6 metered dose inhaler [MDI]), triamcinolone acetonide (8 arms; all MDI), budesonide (10 arms; 8 DPI, 2 MDI), beclomethasone dipropionate (11 arms; all MDI), and mometasone furoate (11 arms; 8 DPI, 3 MDI). Quality assessment of individual trials was based on randomisation; double blinding; clear definition of study objectives, treatments, and diagnostic criteria; and allocation concealment according to the Cochrane grading system. 6 RCTs had adequate concealment.
incidence of oral candidiasis, dysphonia, or pharyngitis.
Meta-analysis showed that all doses of inhaled corticosteroids, regardless of the delivery device used, led to a higher risk of oral candidiasis (20 RCTs; odds ratio [OR] 3.6, p⩽0.001), dysphonia (15 RCTs; OR 5.2, p⩽0.001), and pharyngitis (16 RCTs; OR 2.2, p⩽0.001) than placebo. Fluticasone propionate had the highest risk of oral candidiasis (8 RCTs; OR 5.4, p<0.001), and budesonide had the highest risk of dysphonia (1 RCT; OR 11.5, p = 0.02) and pharyngitis (2 RCTs; OR 5.1, p = 0.04). Dosage. The effect of inhaled corticosteroids was greater at high doses for oral candidiasis (8 RCTs; OR 4.3, p<0.001), dysphonia (7 RCTs; OR 11.3, p<0.001), and pharyngitis (6 RCTs; OR 2.2, p = 0.01). Delivery device. The effect of inhaled corticosteroids was greater with delivery by MDI for oral candidiasis (7 RCTs; OR 5.4) and dysphonia (6 RCTs; OR 5.7); effects of inhaled corticosteroids delivered by MDI or DPI were similar for pharyngitis (MDI = 7 RCTs, OR 1.8; DPI = 9 RCTs, OR 2.0). P values were not provided for these comparisons.
Overall, inhaled corticosteroids increase risk of oral candidiasis, dysphonia, and pharyngitis in patients with persistent asthma. High doses increase risk of oral candidiasis, dysphonia, and pharyngitis. Delivery by metered dose inhaler increases risk of oral candidiasis and dysphonia.
- Lisa Cicutto, RN, PhD, ACNP
- National Jewish Medical and Research Center, Denver, Colorado, USA University of Toronto, Toronto, Ontario, Canada
More than 50% of patients experience oropharyngeal adverse events (OAEs) with inhaled corticosteroid use.1 Cough is also an associated adverse event,1 but the meta-analysis by Rachelefsky et al did not include this as an outcome. Other limitations of the review include capturing only studies up to 2004 and not evaluating nebulisers or newer inhaled corticosteroids (eg, ciclesonid).
Use of inhaled corticosteroids is complicated by several interrelated factors: drug, dose, device, carrier (no carrier v lactose), and propellant (chlorofluorocarbon or hydrofluoroalkane). The review attempts to draw conclusions about these by comparing effects across RCTs in which various combinations of drug, dose, device, carrier, and propellant are compared with placebo rather than evaluating RCTs in which these factors were randomised. The conclusions must therefore be viewed as tentative. Not all device types—DPI or MDI—are equivalent (eg, particle size may vary). The review suggested that hydrofluoroalkane devices posed fewer risks of OAEs than chlorofluorocarbon devices. Perhaps this will reduce the prevalence of OAEs. However, some countries have yet to adopt the Montreal Accord agreement banning chlorofluorocarbon containing devices.
OAEs can be costly for patients and for society. Patients who rely on their voice for employment (eg, teachers, singers, sales people) are most affected by dysphonia and may face difficult clinical decisions: controlling their asthma or impairing their ability to work. OAEs may cause patients to take a “medication holiday” or lead to informed non-compliance, resulting in reduced dosages of the most effective class of anti-asthma medication used to control the underlying inflammatory component of asthma. OAEs can also lead to more frequent healthcare visits to diagnose problems (side effects) and identify solutions.
Strategies commonly used for reducing OAEs, such as using spacers for MDIs and mouth rinsing after use of inhaled corticosteroids, reduce oropharyngeal deposition, but further investigation is needed to determine whether this leads to fewer OAEs. When faced with this clinical dilemma, it is best to work with patients to identify the combination that is most advantageous—that is, the right inhaled corticosteroid, right dose, right device, and the use of potentially preventive strategies. This requires nurses to be involved in helping patients to determine which approach is best for them so that the benefits of using inhaled corticosteroids outweigh the costs.
For correspondence: Dr G S Rachelefsky, Allergy Research Foundation Inc, Los Angeles, CA, USA.
Sources of funding: Sanofi-Aventis US and ALTANA Pharma US.