Inhaled corticosteroids (ICSs) are recommended for treatment of persistent asthma. Several ICSs are available and delivered by a variety of devices. After the banning of chlorofluorocarbon (CFC), a formulation of hydrofluoroalkane (HFA)-flunisolide marketed with an in-built spacer has been developed, complying with the request of efficacy and safety for children and adults. It delivers an aerosol with mass median aerodynamic diameter smaller than that of the CFC-formulation (1.2 vs 3.8 m). The extrafine aerosol and the add-on spacer are peculiarities of HFA-flunisolide with respect to the traditional ICSs, assuring larger lung deposition, lower oro-pharyngeal dose and targeting small airways. HFA-flunisolide with the spacer is effective at one-third the dose of CFC-flunisolide delivered without spacer. HFA-flunisolide may be considered an effective alternative to currently available ICSs for asthma management of adult and pediatric patients 6 years of age and older.

Feline bronchial disease is commonly treated with oral glucocorticoids (OGC), which might be contraindicated in cats with certain infectious, endocrine, renal, or cardiac diseases. Inhalant GC (IGC) maximize local efficacy and minimize systemic bioavailability. We evaluated systemic endocrine and immune effects of IGC (flunisolide, 250 microg/puff q12h) versus OGC (prednisone, 10 mg/d PO) and placebo. Six healthy cats received each drug for 2 weeks followed by a 1-month washout. Testing included determination of single early morning cortisol concentration, results of ACTH stimulation, the urine cortisol-to-creatinine ratio (UC: Cr), lymphocyte phenotype, lymphocyte blastogenesis, serum total IgA and IgM concentrations, and cytokine profiles. Significant differences between treatments were not apparent for serum immunoglobulin concentrations, or expression (mRNA) for the cytokines, interleukin (IL-) 2, IL-4, and IL-10, or gamma interferon. Single early morning cortisol concentration was lower for IGC (0.68 - 0.74 microg/dL), compared with that associated with placebo (2.82 +/- 1.94 microg/dL; P = .033). The ACTH-stimulated peak cortisol concentrations were lower after treatment in cats receiving IGC (before, 8.5 +/- 50.2 microg/dL; after, 2.9 +/- 3.3 microg/dL, P = .0004), but not OGC (before, 8.0 +/- 6.1 microg/dL; after, 6.0 +/- 4.5 microg/dL, P = .07). Similarly, UC: Cr (0.8 +/- 0.8) before IGC was lower than the value (5.02 +/- 3.62; P = .019) after IGC. Compared with placebo, cats given OGC, but not IGC, had significantly lower total percentages of T and B cells. Lymphocyte proliferation was decreased in cats receiving OGC, but not IGC, in comparison with placebo (6.9 +/- 3.3; 24.0 +/- 6.5; 18.8 +/- 14.0, respectively). Significantly more IL-10 mRNA transcription was detected in cats administered OGC or IGC, compared with placebo. Although IGC suppress the hypothalamic-pituitary-adrenocortical axis, IGC had minimal effects on the systemic adaptive immune system.

Our research evaluates the efficacy of the inalation therapy by mineral sulphureous water in patients suffering from cronic bronchopneumopathy.

A multicenter, randomized, open-label, crossover study with two 4-week evaluation periods compared patient preference and ease of teaching correct inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers (pMDIs). Patients 18 to 65 years of age with stable, mild to moderate asthma, who required or were eligible for inhaled corticosteroid therapy, were randomized to treatment sequences consisting of 4-week evaluation periods with Pulmicort Turbuhaler (budesonide inhalation powder) two puffs (400 microg) bid and one of three inhaled corticosteroids via pMDI: Aerobid-M (flunisolide) four puffs (1 mg) bid, Flovent (fluticasone propionate) two puffs (440 microg) bid, or Vanceril Double Strength (beclomethasone dipropionate) five puffs (420 microg) bid. Patients indicated device preference at study end and completed the Patient Device Experience Assessment (PDEA) questionnaire after each evaluation period. Ease of teaching, time required to master use of the device, percentage of patients demonstrating mastery on the first attempt, and the number of attempts required to demonstrate mastery were assessed. Despite previous use of pMDIs by most patients, Pulmicort Turbuhaler was significantly preferred (p < 0.001) and required significantly less time to master than pMDIs (p < 0.001). Median times to device mastery were 3.67 min for Pulmicort Turbuhaler versus 5.33 min for pMDIs. Patients rated Pulmicort Turbuhaler significantly better than pMDIs on PDEA ease of use (p = 0.0005) and overall satisfaction (p < 0.0001) single-item scales and all four multi-item scales (pharyngeal symptoms, oral sensation, operational use, and inhaler attributes; p < 0.05). Overall, patients preferred Pulmicort Turbuhaler over pMDIs and required less time to be taught how to correctly use Turbuhaler trade mark.

Despite advancements in treatment, the incidence of asthma, asthma-related deaths and hospitalizations for asthma have increased significantly during the past decade. Although asthma mortality may now be decreasing, reasons for the worsening of morbidity and mortality in asthma remain unclear. These unexpected changes in asthma severity have sparked renewed interest in research into the pathogenesis and treatment of the condition. Beta(2)-Adrenergic agonists are the most commonly used class of drugs for the treatment of asthma. Recent concerns about safety issues for beta-agonists caused reevaluation of prescribing practices, and using them on an as-needed basis is now more frequently accepted and recommended. In acute asthma, a beta(2)-adrenergic agonist is still the medication of choice. Long-acting salmeterol and formoterol, administered only twice daily, can decrease symptoms of asthma during day and nighttime. On the other hand, the role of tolerance to their bronchodilator and bronchoprotective effects is still to be determined in the treatment of asthma. Theophylline, whose use has been limited by the potential for serious toxicity, may regain an important position in asthma treatment with the development of the knowledge about its antiinflammatory actions. Dosing theophylline on a time- related basis also improves the risk/benefit ratio and makes it a useful drug for nocturnal asthma. Ipratropium bromide, an anticholinergic drug, still awaits a defined role in the treatment of asthma. Studies on its use for acute asthma have not achieved consensus and, for nocturnal asthma, the short duration of effect limits the benefits. Corticosteroids, including inhaled steroids, have measurable effects on symptoms, lung function, bronchial responsiveness and inflammation associated with asthma. Side effects of chronic use limit systemic, but not inhaled administration. Newer preparations, like budesonide, flunisolide and fluticasone, decrease the incidence of possible side effects related to inhaled steroids by having better ratio of topical to systemic potency. Daily doses up to 1600 micro g of beclomethasone (or equivalent) are considered safe and higher doses should be reserved for patients with moderate to severe asthma. Although future trials are necessary to clarify many issues related to dosing of inhaled steroids, chronotherapy studies have shown that single administration between 3 and 5:30 p.m. may be as effective as 4 times a day dosing.

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an accepted indicator of potential side effects from inhaled corticosteroids. Although cortisol monitoring is frequently used to detect changes in HPA axis activity, the optimal method for identifying the subset of asthma patients on inhaled steroids who experience severe cortisol suppression of potential clinical significance has not been established. The objective of this study was to compare several methods for assessing HPA axis activity in asthma patients taking inhaled corticosteroids. After screening, 153 patients with mild to moderate asthma were randomly assigned to receive inhaled fluticasone propionate (110, 220, 330, or 440 microg bid), flunisolide (500 microg or 1000 microg bid), or one of two control regimens (prednisone or placebo) for 21 days. Salivary (8 a.m.) and urinary (24-h) cortisol determinations were compared against 22-hour area under the serum cortisol concentration-time curve (AUC0-22 h) measured at baseline and on day 21. Comparisons were also made against 8 a.m. serum cortisol. A significant positive correlation was found between AUC0-22 h of serum cortisol and 8 a.m. serum cortisol level (r = 0.5140; p = 0.0001). The AUC0-22 h of serum cortisol was weakly correlated with 24-hour urinary cortisol levels, both corrected (r = 0.4388; p = 0.0001) and uncorrected (r = 0.3511; p = 0.0001) for creatinine excretion. The 8 a.m. salivary cortisol level correlated positively with the 8 a.m. serum cortisol level (r = 0.5460; p = 0.0001). Salivary cortisol was both sensitive and specific for the detection of a 50% decline in AUC0-22 h of serum cortisol. Cortisol reductions of this magnitude have been observed following repeated use of inhaled steroids. Because it is noninvasive, salivary cortisol measurement offers distinct advantages as a screening method for detecting pronounced HPA axis suppression in asthma patients receiving corticosteroid therapy.

Different glucocorticoids have been compared with respect to the inhibition of corticotropin-releasing factor (CRF)-mediated adrenocorticotropin (ACTH) secretion from pituitary fragments of the rat. The influence of time of exposure to glucocorticoids and glucocorticoid concentration has been investigated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was measured by a chemiluminescence immunoassay. ACTH secretion was monitored over three days. Inhibition of CRF-stimulated ACTH secretion by glucocorticoids was quantified by the area under the curve of CRF-stimulated ACTH secretion over baseline. Concentrations needed to inhibit ACTH secretion decreased with the receptor affinities of the glucocorticoids as follows: fluticasone propionate; receptor affinity 1800, concentration 10(-8) M; budesonide, 935 and 3-2.5 x 10(-8) M; flunisolide, 478 and 5 x 10(-7) M; prednisolone, 10 and 10(-6) M. CRF-stimulated secretion was inhibited by glucocorticoids after incubation for 1 min at concentrations between 10(-8) and 10(-6) M. The same absolute quantity of the glucocorticoids produced no inhibition when incubation was prolonged to 50 min or when a lower concentration was used. Immediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of glucocorticoids by prolonging drug release.

This study tested the effectiveness of flunisolide in the treatment of children with seasonal allergic rhinitis. Thirty-five children between the ages of 5 and 14 years used an intransal preparation of either flunisolide (200 micrograms/day) or placebo for a 6-week double-blind parallel trial consisting of a 2-week baseline phase and a 4-week treatment phase, conducted during a period of 'high' pollen counts in Adelaide, South Australia. Flunisolide was effective in reducing four symptoms of hay fever: sneezing, stuffy nose, runny nose and eye itch. Sixty-four percent of the flunisolide-treated group and 33% of the placebo-treated group noted substantial or total control of their hay fever symptoms (P < 0.05). The effect of the intranasal administration of flunisolide on the pituitary-adrenal axis was monitored by performing plasma cortisol measurements (a.m. and p.m.) and 24-hr urinary free cortisol excretion studies for each patient. The data confirmed that 200 micrograms/day intranasal flunisolide does not suppress the pituitary-adrenal-axis in this young patient population.

Flunisolide nasal spray was compared to its propylene and polyethylene glycol vehicle in a randomized double-blind study of 20 adult patients with perennial rhinitis. After a two-week baseline period patients received either active flunisolide 50 microgram q.i.d. or placebo for four weeks. Laboratory studies included serum 8 a.m. cortisols, nasal air-flow measurements and nasal smears for eosinophils and fungi. Patients kept daily symptom diaries. There was no difference between active and placebo groups for sneezing, runny nose or nose blowing. Although post-nasal drip showed the greatest improvement in the active group, there was a trend for improvement in both groups. By the second week the percentage of eosinophils on nasal smear significantly decreased in both groups. Nasal air-flow measurements also showed improvement in both active and placebo groups. There was no change in serum cortisol levels compared to baseline. Side effects were similar in both active and placebo groups. Although no positive fungal cultures were obtained during the double-blind study. Candida was cultured during the long-term program in one patient.