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      Future perspectives of anticholinergics for the treatment of asthma in adults and children

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          Despite major advances in therapeutic interventions and the availability of detailed treatment guidelines, a high proportion of patients with symptomatic asthma remain uncontrolled. Asthma management is largely guided by the Global Initiative for Asthma (GINA) strategy and is based on a backbone of inhaled corticosteroid (ICS) therapy with the use of additional therapies to achieve disease control. Inhaled long-acting bronchodilators alone and in combination are the preferred add-on treatment options. Although long-acting muscarinic antagonists (LAMAs) are a relatively recent addition to disease management recommendations for asthma, tiotropium has been extensively studied in a large clinical trial program. In Europe and the United States, tiotropium is approved for patients aged ≥6 years and uncontrolled on medium- to high-dose ICS/long-acting β 2-agonists at GINA Steps 4 and 5 with a history of exacerbations. Evidence supports the efficacy of tiotropium Respimat ® in adults in terms of lung function and asthma control, with a safety profile comparable with that of placebo across a range of asthma severities. Similarly, clinical trials in patients aged 1–17 years have shown improvements in lung function and trends toward improved asthma control. Furthermore, its efficacy makes tiotropium relatively easy to incorporate into routine clinical practice, irrespective of allergic status and without the need for patient phenotyping. Tiotropium is a cost-effective treatment that may offer an important alternative to other, more expensive add-on therapies. This review discusses the potential future position of LAMAs in clinical practice by considering the continuously evolving evidence. Prominence is given to tiotropium, the only LAMA supported by a structured clinical trial program in asthma to date, while also considering other recommended treatment options for patients with uncontrolled asthma. The importance of effective patient/caregiver–clinician communication and shared decision-making in enhancing treatment adherence is also highlighted.

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          Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.

          For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.
            • Record: found
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            • Article: not found

            Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial.

            Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count.
              • Record: found
              • Abstract: found
              • Article: not found

              Low-dose inhaled corticosteroids and the prevention of death from asthma.

              Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                14 March 2019
                : 15
                : 473-485
                [1 ]Pulmonary Department, Johannes Gutenberg University Hospital Mainz, Mainz, Germany, roland.buhl@ 123456unimedizin-mainz.de
                [2 ]Children’s Center Bethel, Evangelic Hospital Bethel, Department of Pediatrics, Bielefeld, Germany
                [3 ]University Children’s Hospital, Allergy Center Ruhr, Ruhr University Bochum, Bochum, Germany
                Author notes
                Correspondence: Roland Buhl, Pulmonary Department, Johannes Gutenberg University Hospital Mainz, Langenbeckstraße 1, 55131 Mainz, Germany, Tel +49 613 117 7271, Email roland.buhl@ 123456unimedizin-mainz.de
                © 2019 Buhl and Hamelmann. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.



                pediatric asthma, adherence, asthma management, lama, tiotropium, anticholinergic, asthma


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