fluticasone and Contusions

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Contusions; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Substance Withdrawal Syndrome

Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.. 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.. All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.. Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Contusions; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Substance Withdrawal Syndrome

High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Biomarkers; Budesonide; Chronic Disease; Contusions; Creatinine; Female; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Quality of Life

Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Contusions; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Prospective Studies; Skin Diseases