The Local Side Effects of Inhaled Corticosteroids: Current Understanding and Review of the Literature

doi:10.1378/chest.126.1.213

Chest

Volume 126, Issue 1, July 2004, Pages 213-219

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The frequent use of inhaled corticosteroids (ICSs), especially at higher doses, has been accompanied by concern about both systemic and local side effects. The systemic complications of ICSs have been extensively studied and are well-documented in the literature. There are comparatively few studies reporting on the local complications of ICSs. Compared with systemic side effects, the local side effects of ICSs are considered to constitute infrequent and minor problems. However, while not usually serious, these local side effects are of clinical importance. They may hamper compliance with therapy and the symptoms produced may mimic more sinister pathology. This review considers the prevalence of local side effects, their clinical features, the potential causes, the role of inhaler devices, and current measures that have been suggested to avoid the problem.

Section snippets

The Complications of ICSs

The frequent use of ICSs, especially at higher doses, has been accompanied by concern about both systemic side effects and local side effects. The systemic complications of ICSs have been extensively studied and are well-documented in the literature.^2,⁷ Systemic complications occur because up to 80% of the dose delivered by a conventional metered-dose inhaler (MDI) is swallowed.⁸ Systemic side effects are dose-dependent, and obvious differences exist between ICSs in their ability to cause

Prevalence

Reported prevalences vary significantly depending on the type of studies, length of observations, and methods for recording side effects (questionnaire or inspection). Many trials estimate these symptoms to occur in the region of 5 to 10% of the treated population, but no factual scientific evidence is given to corroborate these claims. Some studies quote figures of 55 to 58%,^16,¹⁸ but again these are largely symptom-based questionnaires. Dubus et al¹⁹ used both a questionnaire and a clinical

Etiology of Local Side Effects

Several studies have looked at local infective complications of steroid inhaler usage, such as oropharyngeal and laryngeal candidiasis^2,^7,¹⁷ (Fig 1), and dysphonic problems without candidiasis manifested as bowing of the vocal folds on phonation.¹⁸ To date, however, there have been no studies to evaluate the cause or nature of the inflammatory response at a local level (ie, pharyngeal and laryngeal) produced by the action of ICSs (Fig 2). Little is known about the very action that causes the

Clinical Features

There is a range of local side effects that includes perioral dermatitis,²⁰ tongue hypertrophy,²¹ oral and oropharyngeal candidiasis,^2,^7,¹⁷ pharyngeal inflammation, laryngeal disorders¹⁸ (Fig 3), cough during inhalation, and a sensation of thirst.¹⁹

Pharyngeal disease tends to present with pain, irritation, or soreness in the throat. The pain may be aggravated by swallowing (odynophagia), and, on occasions, patients may present with dysphagia. By far the most frequent local side effect is

Treatment of Local Side Effects

Without a specific diagnosis, it is difficult to comment on the most appropriate therapy to treat these problems. No study has been performed to evaluate the value of any specific treatment. Most patients are advised to rinse their mouths and oropharynx by gargling with water immediately after using the inhaler. Provision of a spacer device is an attempt to minimize laryngeal and pharyngeal deposition of the inhaled material. In one study,²⁴ this has been shown to be of some benefit, but, in

Type of Inhaler Device

An ideal inhaler device should deliver a predetermined dose of drug to the lungs, in an easy-to-use, reproducible, and cost-effective manner, with minimal deposition of drug in other sites.²² Both patient factors and the inhaler device itself can affect drug delivery. Age, physical disability, or cognitive disability may render a patient unable to use certain devices. Three main methods of dispersing medication into an aerosol will be described, as follows: pMDI; DPI; or nebulizer.²² A pMDI may

Conclusion

In order to establish more effective treatment of local side effects, they first need to be recognized. Local side effects are mostly minor and are of little consequence to the overall health of the patient. However, patients tend to be afraid of the side effects of ICSs, and local problems may have a deleterious effect on compliance. Some of the local side effects may be dose-dependent, and this emphasizes the need to find the lowest effective dose of an ICS. More importantly, however, the

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: N.J. Roland and R.K. Bhalla wrote the paper. R.K. Bhalla was investigating the clinical impact of this problem at the time of writing. J. Earis was supervising R.K. Bhalla in aspects of his research. N.J. Roland accepts full responsibility for the integrity of the article.

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Chest

ReviewsThe Local Side Effects of Inhaled Corticosteroids: Current Understanding and Review of the Literature

Section snippets

The Complications of ICSs

Prevalence

Etiology of Local Side Effects

Clinical Features

Treatment of Local Side Effects

Type of Inhaler Device

Conclusion

Am J Med

Respir Med

Biomed Pharmacother

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

Br J Dis Chest

Chest

Br J Dis Chest

Chest

J Allergy Clin Immunol

Chest

Int J Pharm

Glucocorticoid therapy for asthma: clinical pharmacology

J Allergy Clin Immunol

Effects of glucocorticoids on inflammatory cells relevant to their therapeutic applications in asthma

Am Rev Respir Dis

Effect of corticosteroids on airway hyper-responsiveness

Am Rev Respir Dis

Anti-inflammatory therapy for asthma

Annu Rev Med

Efficacy and safety of inhaled corticosteroids

Am J Respir Crit Care Med

The use of inhaled corticosteroids in adults with asthma

Drug Ther Bull

Effect of high-dose inhaled Budesonide on calcium and phosphate metabolism and the risk of osteoporosis

Am Rev Respir Dis

Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids

Thorax

Purpura and dermal thinning associated with high dose inhaled corticosteroids

BMJ

Easy bruising as a side effect of inhaled corticosteroids

Eur Respir J

Use of inhaled corticosteroids and the risk of cataracts

N Engl J Med

Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma

JAMA

Frequency of voice problems and cough in patients using pressurised aerosol steroid preparations

Eur Respir J

The effect of inhaled steroids on the upper respiratory tract

J Laryngol Otol

Dysphonia caused by inhaled steroids: recognition of a characteristic laryngeal abnormality

Thorax

Local side effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age and device

Allergy

Perioral dermatitis in children under steroid inhalation therapy

Ugeskr Laeger

Inhaler devices for asthma

Drug Ther Bull

Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year

Thorax

Reviews
The Local Side Effects of Inhaled Corticosteroids: Current Understanding and Review of the Literature