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Caracas, Venezuela
Correspondence to: Fernan Caballero-Fonseca, MD, Immunology Department, Centro Médico-Docente La Trinidad, Caracas, Venezuela
To the Editor:
With growing concern, we read the report by Todd et al (October 2001 supplement)1 about clinically significant adrenal suppression related to the administration of inhaled corticosteroids. That article and others, such as the one by Zimmerman et al,2 have been linked to the use of the most potent of the inhaled corticosteroids, fluticasone, probably because of its well-known high lipophilicity, which confers a very high volume of distribution and a long plasmatic half-life.3 Another report4 described a 6-year-old girl with obvious features of hypercortisolism who experienced an acute adrenal insufficiency episode that had been induced by the administration of budesonide after her treatment had been switched from fluticasone.
Earlier, in 1993, we had reported5 on a patient with similar clinical features. This child had been treated with customary doses of beclomethasone without any warning or evidence of hypercortisolism. All these reports were largely ignored and were considered to be extremely rare situations.
A few years later, Carrel et al6 described the condition of a 3.5-year-old child who had been treated with a low dose of prednisone (2.5 mg every other day) and inhaled beclomethasone (255 µg/d) and who experienced an episode of severe hypoglycemia and cortisol deficiency that was virtually identical to that observed in our patient. At that time, this observation came to no surprise to us, since Tabachnik and Zadik7 also had reported severe adrenal suppression even at conventional steroid doses.
Recently, Lipworth8 has repeatedly elaborated on the issue of adrenal suppression by inhaled fluticasone and has raised concerns about the probable large volume of distribution of mometasone furoate, despite previous claims for its very low (ie, < 1%) systemic bioavailability.9
In view of these observations, we encourage physicians to be aware of the possibility of systemic effects of inhaled corticosteroids in some asthmatic patients and of its clinical relevance, as these rare but very real events may occur not only with fluticasone treatment but also with all inhaled steroids that are currently on the market.
References
Antrim Hospital, Antrim, Northern Ireland
Correspondence to: Geoffrey R.G. Todd, MD, Antrim Hospital, 45 Bush Rd, Antrim, Northern Ireland BT41 2RL
To the Editor:
We thank Doctors Caballero-Fonseca and Sanchez-Borges for their interest in our abstract (October 2001 supplement).1 We reported on a large case series of patients who had experienced acute adrenal crisis due to inhaled steroids, nearly all due to fluticasone (> 94%). Acute adrenal crisis was an extremely rare phenomenon before the introduction of fluticasone in the United Kingdom in 1994. We believe that our study highlighted important differences among the inhaled corticosteroid agents, and it specifically opposes the view that the most recently introduced inhaled steroid, fluticasone, has the best benefit/risk ratio.
However, we would like to emphasize that all the authors of our article are very enthusiastic prescribers of inhaled steroids as a first-line treatment for patients with all but the mildest forms of asthma. Inflammatory processes are absolutely fundamental to the pathogenesis of asthma, and inhaled steroids are by far the most effective drugs at reducing inflammation in asthma patients. They are also the most effective drugs at reducing the burden of asthma (ie, improving exercise tolerance, reducing days lost from school, preventing acute exacerbations, preventing hospital admissions, and decreasing the risk of death from asthma). In the vast majority of patients, the benefits greatly outweigh the risks. For example, in a long-term study (mean study duration, 9.92 years) of budesonide treatment (patient age range, 3 to 13 years) with a mean daily dose of 412 µg/d (dose range, 110 to 887 µg/d), there was no effect on final adult height and no evidence of any other significant side effects.2 This is most compelling and reassuring evidence of the long-term safety at least of this particular inhaled steroid in children.
We therefore believe in the early introduction of inhaled steroids in adequate dosages for the control of asthma, as is advised by all national and international guidelines, and that the safest amount of an inhaled steroid to administer to any child is the minimum amount required to control the asthma. Under these circumstances, the benefits of inhaled steroids greatly outweigh the morbidity and mortality associated with uncontrolled asthma. For example, it is important to remember that since the introduction of inhaled budesonide > 20 years ago, there have been > 10 billion patient-days of use of this drug, and reported serious side effects have been extremely rare. What other drug that we prescribe can claim such a safety record?
References
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