Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma

Abstract

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.

The role of nebulised budesonide in the treatment of exacerbations of COPD

“…Since their topical anti-inflammatory activity is high, they are safely used as a substitute for inhaled corticosteroids in patients with stable COPD and bronchial asthma, where necessary. However, there are only a few studies in the literature related to their use in the management of exacerbations of bronchial asthma and COPD [9][10][11][12][13][14]. The total daily dosages used in the relevant studies ranged 1-8 mg, differing according to the methodology and the patient groups used in the studies.…”

Relative lung delivery of fluticasone propionate via large volume spacer or nebuliser in healthy volunteers

“…In a study with more severe prednisolone-dependent asthmatics, serum cortisol levels were in the normal range after 3 months of treatment with nebulised FP in a dose of 0.5 mg or 2 mg twice daily, and its use facilitated oral steroid tapering [2]. Single-and chronic-dosing studies with nebulised budesonide in healthy and asthmatic subjects have shown no detectable systemic bioactivity in a dose of 4 mg/day on serum cortisol, osteocalcin or eosinophils [8,9].…”

“…There is, however, only limited evidence supporting nebulised delivery of FP in this patient group [2]. Furthermore, no controlled studies exist comparing delivery of FP via spacer or nebuliser in patients with severe asthma.…”

Children with Difficult Asthma: A Practical Approach

“…No study of nebulized budesonide has been carried out in steroid-dependent older children, but an open study in 42 adults who were given 2 mg/day found that 55% were able to reduce their oral steroid intake by a mean of 59% (63). A recent trial of nebulized fluticasone in oral steroid-dependent adult asthmatics showed a small reduction in mean daily prednisolone dosage, using a dose of fluticasone of 4 mg/day ORDER REPRINTS Children with Difficult Asthma 197 (64). In using a nebulizer, it is best to use a mouthpiece, but if a mask is needed, it should be tight fitting, and children should be advised to wash their faces and rinse their mouths afterward.…”