To the Editors:
I read with interest the recent article by Gunen et al. 1, wherein the authors presented the hypothesis that nebulised budesonide might be an alternative to systemic corticosteroids in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). There are certain points which need discussing regarding their hypothesis of nebulised inhaled corticosteroids in COPD exacerbations.
First, exacerbations of COPD were considered to be a purely local disease: there is now enough evidence to support that COPD is, on the contrary, a systemic disease. Exacerbations of COPD are associated with increased levels of soluble markers of systemic inflammation in the serum 2, and the systemic inflammatory response at exacerbation is proportional to that occurring in the lower airway and is greater in the presence of a bacterial pathogen.
Secondly, the grading of the severity of acute COPD exacerbations is still a controversial issue and the inflammatory response may differ with the severity of exacerbation. In mild-to-moderate exacerbations there is an increase in neutrophils and eosinophils in sputum and the airway wall 3; while in severe exacerbations there is marked increase in neutrophils 4.
Thirdly, the precipitating cause for exacerbation was not taken into consideration, as patients with COPD exacerbations related to viral and bacterial origin have a significant eosinophilic response which may respond very well to inhaled corticosteroids 5. Neutrophilic inflammation is generally resistant to corticosteroids, whereas eosinophilic inflammation is suppressed. Corticosteroids decrease the survival of eosinophils in vitro, whereas they prolong the survival of neutrophils by inhibiting apoptosis 6.
Fourthly, it has been seen that ∼10% of the patients with stable obstructive disease have overlapping features of both asthma and COPD, and these patients may show a beneficial response to steroids 7. Even in asthma that is highly steroid responsive, high-dose inhaled steroids could not replace oral prednisolone in children with moderate-to-severe acute asthma 8.
Finally, the systemic absorption of such a high dose of inhaled corticosteroids should be kept in mind. Following nebulised administration of budesonide, ∼6% of the dose reaches the systemic circulation. Systemic absorption of the inhaled corticosteroids could have explained the beneficial effects of inhaled steroids noted in the study. Nebulised budesonide in a 1 mg (1,000 μg) dose produced anti-asthmatic and systemic effects equivalent to 35 mg and 7.6 mg of prednisone, respectively 9. Moreover, there is a ceiling of the beneficial effect of nebulised steroids beyond 1,600 μg·day−1.
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