Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study

Introduction: The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta2-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments. Methods: Adults with mild-to-moderatesevere persistent asthma were randomized to fluticasone/formoterol (100/10 or 250/10 μg twice daily [b.i.d.]) or fluticasone/salmeterol (100/50 or 250/50 μg b.i.d.) for 12 weeks. The onset of bronchodilation (the first post-dose time point at which the forced expiratory volume in 1 second [FEV1] was ≥12% greater than the pre-dose value), responder rates (the proportion of patients achieving bronchodilation), and changes in FEV1 were assessed at days 0 (baseline) and 84. Results: Fluticasone/formoterol (n = 101) provided more rapid onset of bronchodilation than fluticasone/salmeterol (n = 101) over the first 120 min post-dose on days 0 (hazard ratio [HR] = 1.47 [95% CI 1.05–2.05]) and 84 (HR = 1.77 [95% CI 1.14–2.73]). The odds of a patient achieving bronchodilation within 5 min of dosing were almost four-times higher with fluticasone/formoterol than with fluticasone/salmeterol on day 0 (odds ratio [OR] = 3.97 [95% CI 1.96–8.03]) and almost 10-times higher on day 84 (OR = 9.58 [95% CI 2.14–42.90]); the odds of achieving bronchodilation within 120 min post-dose were approximately twofold higher with fluticasone/formoterol on both days. The overall percentage increase in least-squares (LS) mean FEV1 during the 120-min post-dose period was significantly greater with fluticasone/formoterol than fluticasone/salmeterol on days 0 (LS mean treatment difference: 4.70% [95% CI 1.57–7.83]; P = 0.003) and 84 (2.79% [95% CI 0.65–4.93]; P = 0.011). Conclusion: These analyses showed that fluticasone/formoterol provided a faster onset of bronchodilation than fluticasone/salmeterol, which was maintained over 12 weeks of treatment. This benefit may facilitate treatment adherence among patients with asthma

Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

<p>Abstract</p> <p>Background</p> <p>The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear.</p> <p>Methods</p> <p>The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV₁95% of predicted) who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV₁) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg), formoterol (4.5 μg), salbutamol (2 × 100 μg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day.</p> <p>Results</p> <p>In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV₁within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV₁.</p> <p>Conclusions</p> <p>A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov number NCT00272753</p

A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV₁ profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting β₂-agonist, in patients with chronic obstructive pulmonary disease

Background: This randomised, double-blind, four-way, crossover, Phase II study compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative dosing frequencies of two total daily doses of olodaterol (5 and 10 mu g) in patients with chronic obstructive pulmonary disease (COPD). Methods: Patients received olodaterol 2 mu g twice daily (BID), 5 mu g BID, 5 mu g once daily (QD) and 10 mu g QD in a randomised sequence over 3-week treatment periods. Co-primary end points were FEV, area under the curve from 0 to 12 h (AUC(0-12)) and area under the curve from 12 to 24 h (AUC(12-24)) responses. Additional lung-function responses, pharmacokinetics and safety were assessed. Results: 47 patients were treated. All olodaterol doses provided significant increases in FEV, versus baseline (p < 0.001) and FEV, time profiles were nearly identical for olodaterol 5 and 10 mu g QD. Olodaterol 5 pg QD demonstrated improved FEV, AUC(0-12) and similar AUC(12-24) versus 2 mu g BID. Olodaterol 5 mu g QD showed slightly increased FEV, AUC(0-12) but lower AUC(12-24) compared to 5 mu g BID. Bronchodilation over 24 h was similar for olodaterol 5 pg QD and BID. All doses were well tolerated. Conclusions: Olodaterol 5 pg QD is efficacious in COPD, with a superior bronchodilatory profile compared to 2 mu g BID, which is close to the same total daily dose, and a similar degree of bronchodilation over 24 h compared with double the daily dose (administered as 10 pg QD or 5 mu g BID)

Tiotropium Respimat® add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics

BACKGROUND: Despite currently available therapies and detailed treatment guidelines, many patients with asthma remain symptomatic. Tiotropium delivered by the soft mist inhaler Respimat®, as add-on therapy to medium-dose inhaled corticosteroids (ICS), has been shown to improve lung function and asthma control in patients with symptomatic moderate asthma. OBJECTIVE: To determine whether the efficacy of tiotropium Respimat® in asthma differs by patients' study baseline characteristics. METHODS: Two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group studies (MezzoTinA-asthma®; NCT01172808 and NCT01172821) of once-daily tiotropium Respimat 5 μg and 2.5 μg add-on to ICS were conducted in patients with symptomatic asthma despite treatment with medium-dose ICS with or without additional controllers. Subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, risk of severe asthma exacerbation and Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by patients' baseline characteristics. RESULTS: In this analysis, 523 patients received placebo while 517 and 519 patients received the 5 μg and 2.5 μg dose of tiotropium Respimat, respectively. The magnitude of the improvements in lung function and asthma control, as well as the reduced risk of severe exacerbation with both doses of tiotropium Respimat versus placebo, was independent of a broad range of baseline characteristics. CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS is a beneficial treatment option for patients with asthma who remain symptomatic despite at least medium-dose ICS, regardless of baseline characteristics

Augmented reality—The way forward in patient education for intracranial aneurysms? A qualitative exploration of views, expectations and preferences of patients suffering from an unruptured intracranial aneurysm regarding augmented reality in patient education

Objectives: The goal of this project is to explore the views, expectations and preferences of patients with an unruptured intracranial aneurysm regarding the use of AR in patient education.Methods: To gain an in-depth understanding of the patients’ perspective, a face-to-face interview study was conducted using an interview protocol with a predefined topic list. All interviews were audio-recorded and transcribed verbatim afterwards. Transcripts were analyzed using thematic content analyses. Coding was performed using Atlas.ti software.Results: Seventeen interviews were conducted. The views, expectations and preferences of patients regarding patient education with AR could be subdivided into 15 categories, which could be grouped into 4 general themes: 1) experiences with current patient education, 2) expectations of AR in patient education, 3) opportunities and limitations of AR, and 4) out-of-hospital use of an AR application. Patients’ expectations were predominantly positive regarding improving patients’ understanding of their medical situation and doctor-patient communication.Discusssion: This study suggests that patients with unruptured intracranial aneurysms are open to receive patient education regarding their disease with AR. Patients expect that AR models can help patients with intra-cranial aneurysms better understand their disease, treatment options and risks. Additionally, patients expect AR could improve doctor-patient communication

New insights into the pathogenesis of severe corticosteroid-dependent asthma

Severe asthma is characterized by persistent T-cell activation, as demonstrated in both peripheral blood and bronchial mucosa. Endobronchial biopsy specimens of patients with severe, corticosteroid-dependent asthma revealed increased expression of CD25+ on mucosal T cells. Increased immunoreactivity, for IL-5 further supports the evidence that the inflammatory response is orchestrated by T-H2-type T cells. Peripheral blood eosinophils and total serum IgE levels were increased in the absence of allergen and despite optimal treatment. The chemokine IL-8 may also be an aggravating factor in severe asthma; as well as being a potent chemotactic and activating factor for neutrophils, it may also be chemoattractant for eosinophils. We have recently detected increased levels of free IL-8 in the peripheral blood of patients with chronic severe asthma but not in healthy control subjects or in patients with mild asthma, even after allergen challenge. In patients with severe asthma there may be an imbalance between IL-8 production and the blocking capacity of IL-S autoantibodies. Higher levels of IL-8 complexed to IgA autoantibody and increased numbers of activated T cells were also found in patients with unstable asthma compared with patients who had severe but stable disease. We conclude that IL-8 may provide an additional marker of asthma severity and corticosteroid responsiveness