232 research outputs found
Cyclosporine treatment of acquired hemophilia due to factor VIII antibodies
Acquired hemophilia, caused by autoantibodies against coagulation factor VIII, is usually treated with steroids, cyclophosphamide, intravenous gammaglobulins and sporadically other drugs. We describe the case of a patient in whom the common therapeutic choice was unsuccessful, but cyclosporine proved to be effective
The once-daily fixed-dose combination of olodaterol and tiotropium in the management of COPD : current evidence and future prospects
Long-acting bronchodilators are the cornerstone of pharmacologic treatment of chronic obstructive pulmonary disease (COPD). Spiolto (R) or Stiolto (R) is a fixed-dose combination (FDC) containing two long-acting bronchodilators, the long-acting muscarinic receptor antagonist tiotropium (TIO) and the long-acting beta 2-adrenoceptor agonist olodaterol (OLO), formulated in the Respimat (R) Soft Mist (TM) inhaler. A total of 13 large, multicentre studies of up to 52 weeks' duration have documented its efficacy in more than 15,000 patients with COPD. TIO/OLO 5/5 mu g FDC significantly increases pulmonary function compared with placebo and its respective constituent mono-components TIO 5 mu g and OLO 5 mu g. TIO/OLO 5/5 mu g also results in statistically and clinically significant improvements in patient-reported outcomes, such as dyspnoea, use of rescue medication, and health status. Addition of OLO 5 mu g to TIO 5 mu g reduces the rate of moderate-to-severe exacerbations by approximately 10%. Compared with placebo and TIO 5 mu g, TIO/OLO 5/5 mu g significantly improves exercise capacity (e.g. endurance time) and physical activity, the latter increase being reached by a unique combination behavioural modification intervention, dual bronchodilatation and exercise training. Overall, the likelihood for patients to experience a clinically significant benefit is higher with TIO/OLO 5/5 mu g than with its constituent mono-components, which usually yield smaller improvements which do not always reach statistical significance, compared with baseline or placebo. This supports the early introduction of TIO/OLO 5/5 mu g in the management of patients with symptomatic COPD
Efficacy of tiotropium-olodaterol fixed-dose combination in COPD
Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting beta(2)-agonist (LABA), commercialized under the name of Spiolto or Stiolto. The efficacy of tiotropium-olodaterol 5-5 mu g once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration. Tiotropium-olodaterol 5-5 mu g not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance. Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life. Differences between tiotropium-olodaterol 5-5 mu g and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID. However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life. Moreover, tiotropium-olodaterol 5-5 mu g was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function. Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers. Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy
Variability in lung deposition of inhaled drug, within and between asthmatic patients, with a pMDI and a dry powder inhaler, Turbuhaler (R)
Effect of switching from ECSC to GLI spirometric reference values on gold classification of severity of airflow obstruction
The 24 hour lung function time profile of olodaterol once daily versus placebo and tiotropium in patients with moderate to very severe chronic obstructive pulmonary disease
Background: Olodaterol is a once-daily long-acting β2-agonist being investigated for the treatment of chronic obstructive pulmonary disease, with ≥ 24 hour bronchodilator activity.
Methods: Two replicate, randomized, double-blind, four-way crossover (6-week treatment periods), active (tiotropium 18 μg via HandiHaler®)- and placebo-controlled trials were conducted to evaluate the 24 hour forced expiratory volume in 1 second (FEV1) profile of olodaterol (5 and 10 μg) once daily (via Respimat®). Patients continued with inhaled corticosteroids and xanthines. Spirometry was performed at baseline and over the entire 24 hour post-dose period at week 6 of each treatment phase. Co-primary end points were change from study baseline (response) in FEV1 area under the curve from 0–12 hours (AUC0–12) and FEV1 AUC from 12–24 hours (AUC12–24); key secondary end point was FEV1 AUC from 0–24 hours response.
Results: In study 1222.39, there was a significant difference from placebo in FEV1 AUC0–12 and AUC12–24 responses (P<0.0001) with olodaterol 5 μg (0.185 and 0.131 L) and 10 μg (0.207 and 0.178 L) at 6 weeks; similar results were observed for tiotropium (0.173 and 0.123 L). In study 1222.40, responses were 0.197 and 0.153 L with olodaterol 5 μg, 0.221 and 0.170 L with 10 μg, and 0.221 and 0.164 L with tiotropium versus placebo (P<0.0001). Incidence of adverse events was comparable across treatments.
Conclusions: These data confirm the 24 hour lung-function efficacy profile of once-daily olodaterol, with FEV1 responses comparable to tiotropium
Evidence for exercise training in autonomic function modulation in patients with chronic obstructive pulmonary disease (COPD) : a systematic review
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The lung function profile of once-daily tiotropium and olodaterol via Respimat® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler® (ENERGITO® study)
Background: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting beta(2)-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.
Objective: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.
Methods: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 mu g and 2.5/5 mu g) via Respimat (R) and twice-daily salmeterol + fluticasone propionate (50/500 mu g and 50/250 mu g) via Accuhaler (R) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC(0-12)) relative to the baseline after 6 weeks.
Results: Tiotropium + olodaterol 5/5 mu g and 2.5/5 mu g demonstrated statistically significant improvements in FEV1 AUC(0-12) compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 mu g and 2.5/5 mu g, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 mu g and 50/250 mu g, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC(0-24)).
Conclusion: Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD
Prevalence and clinical correlates of patient-reported autonomic symptoms among subjects with COPD
Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation
Central hypoventilation in adult patients is a rare life-threatening condition characterised by the loss of automatic breathing, more pronounced during sleep. In most cases, it is secondary to a brainstem lesion or to a primary pulmonary, cardiac or neuromuscular disease. More rarely, it can be a manifestation of congenital central hypoventilation syndrome (CCHS). We here describe a 25-year-old woman with severe central hypoventilation triggered by analgesics. Genetic analysis confirmed the diagnosis of adult-onset CCHS caused by a heterozygous de novo poly-alanine repeat expansion of the PHOX2B gene. She was treated with nocturnal non-invasive ventilation. We reviewed the literature and found 21 genetically confirmed adult-onset CCHS cases. Because of the risk of deleterious respiratory complications, adult-onset CCHS is an important differential diagnosis in patients with central hypoventilation
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