Inhaled glucocorticoids placebo

The long-term effects of budesonide on adrenal function have been assessed in 63 asthmatic children using budesonide 400 micrograms/day, nedocromil 16 mg/day, or placebo over 3 years (74). There were no differences in serum cortisol concentrations after ACTH stimulation between the three treatment groups, regardless of the time after ACTH administration or months of follow-up. Cumulative inhaled glucocorticoid exposure did not affect the serum cortisol response to ACTH or urinary free cortisol excretion at 3 years. 

The efficacy of clodronate in treating glucocorticoid-induced bone loss in asthmatic subjects has been evaluated in a double-blind study in 74 adults (41 women and 33 men, mean age 57 years) with a long history (mean 8.1 years) of oral and inhaled glucocorticoid use, randomized to clodronate 800,1600, or 2400 mg/day or placebo (130). There was no increase in bone mineral density with placebo or clodronate 800 mg/day, but a significant dose-related increase with clodronate 1600 and 2400 mg/day. The most common adverse effect was gastric irritation in the patients who took the highest dose of clodronate. 

The equivalence of inhaled glucocorticoids based on equipotent (cortisol suppression) effects has been studied by the Asthma Clinical Research Network (ACRN). Six different inhaled glucocorticoids and matched placebos (beclomethasone chlorofluorocarbon, budesonide dry powder inhaler, fluticasone dry powder inhaler, fluticasone chlorofluorocarbon metered-dose inhaler, flunisolide chlorofluorocarbon, and triamcinolone chlorofluorocarbon) were compared by measuring their systemic effects (18). 

In a double-blind, randomized pilot study of the efficacy and adverse effects of inhaled fluticasone in 25 newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome, the infants were randomized to receive inhaled fluticasone 1000 micrograms/day or placebo (47). The hypothalamic-pituitary-adrenal axis was assessed by the response to corticotropin-releasing factor. AU basal and post-stimulation plasma corticotropin and serum cortisol concentrations were significantly less with inhaled fluticasone than placebo. Cumulative high-dose inhaled glucocorticoids caused moderately severe suppression of both the pituitary and the adrenal glands. This systemic activity is probably associated with pulmonary vascular absorption that avoids hepatic first-pass metabolism. 

Salmeterol 50 micrograms plus fluticasone 500 micrograms bd delivered via a combination inhaler (plus a placebo inhaler) have been compared with the same drug regimen dehvered by separate inhalers in a randomized, double-bhnd trial over 28 weeks in 503 asthmatic patients aheady taking inhaled glucocorticoids (17). 

The risk of pneumonia in patients with asthma using inhaled glucocorticoids has been evaluated in a meta-analysis of trials of budesonide in asthma [6 ]. The primary data set consisted of 26 double-blind, placebo-controlled trials that lasted at least 3 months (n = 9067 for budesonide and 5926 for the comparator) sponsored by AstraZeneca. In a secondary data set 60 double-blind trials that lasted at least 3 months, but lacked placebo control were evaluated (n = 33496 for budesonide and 2773 for fluticasone propionate). In the primary data set, the occurrence of pneumonia-related adverse events was 0.5% (10/1000 patient-years) for... 

In a follow-up study of 232 patients from the Childhood Asthma Management Program (CAMP), a randomized, placebo-controlled comparison of budesonide and nedocromil, long-term use of inhaled glucocorticoids in the recommended dose ranges, in combination with occasional bursts of prednisone, was not associated with an increased risk of cataracts, with a median follow-up of 12 years [8 ]. 

In a systematic review comparing LABAs and placebo and LABAs + inhaled glucocorticoids and inhaled glucocorticoids alone for at least 12 weeks (n - 36 588), LABAs were associated with an increase in catastrophic... 

In a pooled analysis of two identical multicenter randomized placebo-controlled trials, roflumilast ( = 1537) and placebo ( = 1534) were compared in patients with severe COPD with a chronic bronchitis phenotype and at least one exacerbation requiring glucocorticoids treatment in the previous year [113 ]. Inhaled glucocorticoids, tiotropium, and theophylline were not allowed. Treatment with roflumilast increased the pre-bronchodilator FEVj and reduced the rate of exacerbations. However, adverse events were more common in the intervention group (67% versus 62%), and withdrawal secondary to these effects including headaches, nausea, and diarrhea,... 

Contact allergy to glucocorticoids is not rare in patients with atopic dermatitis. In patients with known contact allergy to budesonide, allergic skin reactions can also occur when inhaled forms of the drug are used, as shown by a randomized, double-bhnd, placebo-controlled study in 15 non-asthmatic patients with budesonide hypersensitivity on patch testing (101). In four of seven patients who used inhaled budesonide, there was reactivation of the 6-week-old patch test sites and they had new distant skin lesions. No flare-up reactions were observed in the other 11 patients (three had used inhaled budesonide and eight placebo for 1 week). None of the patients developed respiratory symptoms spirometry and peak expiratory flow rates remained normal. 

The results from a subset of patients evaluated in a phase HI clinical study in adults with moderate-to-severe asthma provided further evidence of a positive trend to a biological effect (Table 2) (35). In 513 patients evaluated, the circulating eosinophil counts were reduced in patients treated with omalizumab, and fewer patients had abnormally elevated eosinophil counts. These positive trends were also evident during the second phase of the study at a time when patients had reduced their dose of inhaled corticosteroid (ICS) under cover of omalizumab treatment (overall results showed a median percent reduction in ICS dose of 75% vs. 50% on placebo, and 40% of omalizumab-treated patients vs. 19% of placebo patients withdrew from glucocorticoid treatment completely, both p < 0.001) (36). 

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