Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate.

Aim: Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%.

A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma.

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo.

Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma.

Background: There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with moderate persistent asthma.

Objective: We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life.

Methods: Fourteen patients with moderate persistent asthma (mean FEV(1), 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol.

Reproducibility of response to nasal lysine-aspirin challenge in patients with aspirin-induced asthma.

Background: Peak nasal inspiratory flow (PNIF) and acoustic rhinometry objectively measure the effects of nasal provocation testing. Although the latter is conventionally used in nasal lysine-aspirin challenge, use of the former in aspirin-induced asthma (AIA) has never been evaluated.

Objective: To evaluate the reproducibility of PNIF and acoustic rhinometry following nasal lysine-aspirin challenge in AIA.

Effects of butterbur treatment in intermittent allergic rhinitis: a placebo-controlled evaluation.

Background: Butterbur (Petasites hybridus) contains the active ingredient petasin, which exhibits antileukotriene and antihistamine activity. Previous studies of intermittent allergic rhinitis (IAR) have demonstrated a comparable response to butterbur compared with a histamine H1-receptor antagonist on the 36-Item Short-Form Health Survey quality-of-life score. However, there has been no placebo-controlled study of the effects of butterbur use on objective and subjective outcomes in IAR.

Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma.

Aims: There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-moderate persistent asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life.

Methods: Nineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion.

Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate.

Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%).

Repeated dosing effects of mediator antagonists in inhaled corticosteroid-treated atopic asthmatic patients.

Background: The anti-inflammatory effects of repeated dosing with mediator antagonists as add-on therapy to that with inhaled corticosteroids (ICSs) in patients with asthma remain to be fully established.

Objective: We elected to evaluate the effects of repeated dosing with fexofenadine (FEX) and montelukast (ML) at clinically recommended doses in ICS-treated asthmatic patients using adenosine monophosphate (AMP) bronchial challenge as the primary outcome.

Methods: Eighteen atopic asthmatic patients receiving a mean (+/- SEM) dose of 631 +/- 104 micro g daily of ICSs, which remained unchanged throughout the entire study, were randomized in double-blind, cross-over fashion to receive FEX, 180 mg, ML, 10 mg, or placebo (PL) for 1 week.

The effects of histamine and leukotriene receptor antagonism on nasal mannitol challenge in allergic rhinitis.

Aims: It is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus.

Methods: A double-blind, randomized, placebo-controlled, crossover design was employed. Nine patients with allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg, montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal peak inspiratory flow recordings over 60 min.

Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma.

We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 microg/SM 50 microg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each.