Chetta A, Zanini A, Foresi A, et al. Am J Respir Crit Care Med. 2003;167:751–757
Purpose of the Study.
To assess the effect of short-term treatment with high-dose (500 μg, twice daily) and low-dose (100 μg, twice daily) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling among asthmatic patients.
Thirty nonsmoking patients with mild/moderate asthma and baseline forced expiratory volume in 1 second values of ≥70% of predicted values. All patients had experienced no asthma attacks in the previous 2 months and controlled their symptoms with inhaled salbutamol only. Patients did not receive corticosteroids in the 6 months before the study and had not experienced any respiratory infections for 4 weeks before the investigation.
This was a double-blind, randomized, parallel-group study, with patients receiving FP at either 500 or 100 μg twice daily, with a spacer device. Treatments were administered for 6 weeks, and patients were assessed in the clinic on 5 separate days. Symptom diaries were maintained, spirometry and methacholine challenges were performed, and fiber-optic bronchoscopies were undertaken at specific time points during the investigation. Healthy volunteers underwent bronchoscopies for comparison.
Eighteen of 30 patients completed the study protocol, and adequate paired biopsy material for immunostaining was obtained for 16 patients, 8 in the group that received 500 μg of FP twice daily and 8 in the group that received 100 μg of FP twice daily. At baseline, patients with asthma differed significantly from the healthy volunteers with respect to the number of vessels and the vascular area. Among the asthmatic patients, the number of vessels was correlated with vascular area (P < .01) and the number of mast cells (P < .01). Bronchial responsiveness to methacholine, asthma symptom scores, and numbers of inflammatory cells decreased significantly after both low-and high-dose FP (P < .05); however, basement membrane thickness decreased only after high-dose FP (P < .05).
The results from this investigation demonstrated that, among patients with mild/moderate asthma, a high dose of inhaled FP, administered for 6 weeks, could significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.
The authors claim that this is the first published evidence that short-term treatment with high-dose FP significantly reduced the vascular component of airway remodeling among patients with mild/moderate asthma. The small number of subjects who completed the investigation and the short time of medication administration seem to limit the overall conclusions regarding the effects of high-dose FP on airway remodeling. These data could have significant clinical implications for the use of higher doses of inhaled corticosteroids in the ongoing treatment of patients with mild/moderate asthma, who might be receiving lower doses of these medications to control their disease.