Weighted Mean FEV1 Research Articles

The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma

GSK256066 is a selective phosphodiesterase 4 inhibitor that can be given by inhalation, minimising the potential for side effects. We evaluated the effects of GSK256066 on airway responses to allergen challenge in mild asthmatics.MethodsIn a randomised, double blind, cross-over study, 24 steroid naive atopic asthmatics with both early (EAR) and late (LAR) responses to inhaled allergen received inhaled GSK256066 87.5 mcg once per day and placebo for 7 days, followed by allergen challenge. Methacholine reactivity was measured 24 h post-allergen. Plasma pharmacokinetics were measured. The primary endpoint was the effect on LAR.ResultsGSK256066 significantly reduced the LAR, attenuating the fall in minimum and weighted mean FEV1 by 26.2% (p = 0.007) and 34.3% (p = 0.005) respectively compared to placebo. GSK256066 significantly reduced the EAR, inhibiting the fall in minimum and weighted mean FEV1 by 40.9% (p = 0.014) and 57.2% (p = 0.014) respectively compared to placebo. There was no effect on pre-allergen FEV1 or methacholine reactivity post allergen. GSK256066 was well tolerated, with low systemic exposure; plasma levels were not measurable after 4 hours in the majority of subjects.ConclusionsGSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma.Trial RegistrationThis study is registered on clinicaltrials.gov NCT00380354

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD

The objectives of this study were to determine the effect of single and repeat dosing with oral ondansetron, a 5-HT3-specific receptor blocker, on the degree and duration of bronchodilation induced by inhaled ipratropium bromide in patients with COPD. Five clinics and university medical centers in four countries participated in the study; 47 patients with COPD were randomized to treatment; 44 completed all treatments. Patients had a baseline (pre-bronchodilator) FEV1>1 L and post-bronchodilator (200 mcg salbutamol) FEV1<90% of predicted, with FEV1 reversibility (to 80 mcg inhaled ipratropium bromide and 400 mcg salbutamol) of at least 12% or 200 mL over baseline. The study was divided into two parts. In Part A, each patient received in a random order, four-way crossover manner, single doses of ondansetron placebo (oral) plus ipratropium bromide placebo (inhaled), ondansetron placebo plus ipratropium bromide 40 mcg inhaled via MDI, ondansetron 24 mg oral plus ipratropium bromide placebo and ondansetron 24 mg plus ipratropium bromide 40 mcg. In Part B, each patient received in a random order, two-way crossover manner, ipratropium bromide 40 mcg tid via MDI plus ondansetron 8 mg oral, qid, for 2 days; on day 3 patients received a single dose of ipratropium bromide 40 mcg plus 8 mg oral ondansetron. Alternatively, patients received ipratropium bromide via MDI and oral ondansetron placebo, as described above. Statistically significant differences in weighted mean FEV1 (0–6 h), peak FEV1 and FEV1 determined 6 h post-dose were noted comparing ipratropium bromide to placebo. Similar positive results were observed for sGaw and FVC. Addition of ondansetron to ipratropium bromide did not significantly modify values obtained with ipratropium alone. Ipratropium bromide induced a marked bronchodilation, compared to placebo. Addition of ondansetron (single or repeated doses) did not significantly increase the degree or duration of bronchodilation induced by ipratropium alone. sGaw was consistently more sensitive than FEV1 in measuring extent and duration of bronchodilation.

The Spacehaler ™ for delivery of salbutamol: a comparison with the standard metered-dose inhaler plus Volumatic ™ spacer device

The Spacehaler ™ is a new, compact, pressurized aerosol device that uses the same canister as a conventional metered-dose inhaler (MDI). Its design, however, reduces the velocity of the aerosol cloud that emerges from the inhaler, thereby reducing the amount of the non-respirable fraction of the drug delivered to the patient. Large volume spacers achieve a similar effect, but they are bulky and therefore inconvenient to use and carry around. This study compared the bronchodilator effect of 200 μg salbutamol delivered by the Spacehaler ™ to that of an MDI used with a Volumatic ™ spacer (MDI plus spacer) in patients with reversible obstructive airways disease. Twenty-five patients with asthma, having a forced expiratory volume in 1 s (FEV 1) between 50 and 90% predicted and a reversibility of ≥15% to 200 μg salbutamol given by the conventional (standard) MDI entered the study. On two separate study days, they inhaled 200 μg salbutamol either via the Spacehaler ™ or the MDI plus spacer. To maintain blinding, they received placebo on both study days via the alternate device. Their FEV 1, forced vital capacity (FVC) and peak expiratory flow (PEF) were measured before and at regular intervals for 6 h after inhalation. Assessment of equivalence between the two devices was based on whether the 90% confidence interval for the difference between the weighted mean FEV 1 was within ±0·251. Patient preference was assessed by a questionnaire at the end of the second study day. Twenty-four patients completed the study. Both devices produced a significant improvement in FEV 1 ( P<0·02). The upper and lower 90% confidence limits for the difference in weighted mean FEV 1 between the devices was ±0·041, and the 99% confidence limits were +0·061 and −0·071. The weighted means for FVC and PEF, and the duration of effect and peak responses for FEV 1, FVC and PEF also showed no difference between the two devices. Patients found no difficulty in using the Spacehaler ™, and 20 out of 24 patients (83·3%) preferred it to the MDI plus spacer. The bronchodilator effect of 200 μg salbutamol administered by a Spacehaler ™ was equivalent to that produced by an MDI plus spacer in this group of patients with reversible airways obstruction. The majority of patients preferred it to a large volume spacer.