pulmicort and Adrenal-Gland-Diseases

Inhaled corticosteroid (ICS) therapy is central to the long-term management of asthma and is extensively used in the management of chronic obstructive pulmonary disease (COPD). While administration via inhalation limits systemic exposure compared with oral or injected corticosteroids and, therefore, the risk of systemic corticosteroid-related adverse effects, concerns over the long-term safety of ICS persist. The assessment of the long-term effects of ICS therapy requires considerable research effort over years or even decades. Surrogate markers/predictors for clinical endpoints such as adrenal crisis, reduced final height and fractures have been identified for use in relatively short-term studies. However, the predictive value of such markers remains questionable.Inhaled budesonide has been available since the early 1980s and there is a considerable evidence base investigating the safety of this agent. To assess the long-term safety of inhaled budesonide therapy in terms of the actual incidence of the clinical endpoints adrenal crisis/insufficiency, reduced final height, fractures and pregnancy complications, we undertook a review of the scientific literature. The external databases BIOSIS, Cochrane Central Register of Controlled Trials, Current Contents, EMBASE, International Pharmaceutical Abstracts and MEDLINE were searched, in addition to AstraZeneca's internal product literature database Planet, up to 29 February 2008. Only original articles of epidemiological studies, national surveys, clinical trials and case reports concerning inhaled budesonide were included.Eight surveys of adrenal crisis were found. The only survey with specified criteria for diagnosis involved 2912 paediatricians and endocrinologists and revealed 33 patients with adrenal crisis associated with ICS therapy; only one patient used budesonide (in co-treatment with fluticasone propionate). In addition, 14 case reports of adrenal crisis in budesonide-treated patients were found. In only two of these, budesonide was used at recommended doses and in the absence of interacting medication.Three retrospective studies and one prospective study assessing final height were found. None of them showed any reduced final height in patients receiving inhaled budesonide during childhood or adolescence.Seventeen epidemiological studies investigating the risk of fractures were found. When adjusting for confounding factors, they did not provide any unequivocal data for an increased fracture risk wi

Topics: Administration, Inhalation; Adrenal Gland Diseases; Adult; Asthma; Body Height; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Female; Fractures, Bone; Humans; Pregnancy; Young Adult

The systemic and topical antiinflammatory activities of budesonide (B) were studied in rats and mice and compared with those of commercially available steroids. Betamethasone 17-valerate (BV) was used as the main reference compound, and fluosinolone acetonide (FA), hydrocortisone 17-butyrate (HB) and hydrocortisone 21-acetate (HA) were also used. B given systemically had stronger antiinflammatory effect than BV on carrageenin edema, cotton pellet granuloma, adjuvant arthritis, croton oil edema, PCA reaction, Arthus reaction, contact hypersensitivity and histamine or serotonin skin reaction. The potency of antiinflammatory activity of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was in the order of FA, B, BV, HB and HA. B given locally also produced stronger antiinflammatory effects than BV on carrageenin edema, cotton pellet granuloma, croton oil edema and contact hypersensitivity. The order of potency of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was the same as by systemic application. In general, the ratio of the dose required to cause atrophy of the thymus and adrenals to the dose required to produce the antiinflammatory effect was the greatest with B by both systemic and local application. The results suggest that B has a stronger antiinflammatory activity with fewer systemic side effects than conventional steroid compounds.

Topics: Adrenal Gland Diseases; Animals; Anti-Inflammatory Agents; Budesonide; Dermatitis; Dermatitis, Contact; Drug Evaluation, Preclinical; Lymphatic Diseases; Mice; Mice, Inbred ICR; Pregnenediones; Rats; Rats, Inbred Strains; Thymus Gland