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      Drug Design, Development and Therapy (submit here)

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      Early achievement and maintenance of stable asthma control using initially higher-dose inhaled corticosteroids as part of combination therapy: an open-label pilot study

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          Abstract

          Background

          Uncontrolled asthma is characterized by considerable variability. Well controlled asthma is associated with less unplanned use of health care resources and fewer acute exacerbations. In this study, we attempted to increase inhaled corticosteroid (ICS) doses initially in suboptimally controlled asthmatics, hypothesizing that early achievement of asthma control using this strategy would be associated positively with a higher level of stability.

          Methods

          This was a randomized, open-label, prospective study including patients with uncontrolled asthma who were randomized to receive higher-dose (HD) ICS in combination with a long-acting beta-agonist (LABA) for one month and then shifted to doses suggested in the practice guidelines (GD) or to receive GD therapy alone. Lung function, ie, forced expiratory volume in one second (FEV 1), peak expiratory flow, Asthma Control Test scores, and frequency of acute exacerbations, was followed up for one year.

          Results

          Seventy-six patients were treated with the HD strategy and 80 with the GD strategy. The increase in FEV 1 from baseline was greater in the HD group than in the GD group, especially during the first month of treatment (304 ± 49 mL versus 148 ± 39 mL, respectively, P = 0.01). Numbers of patients with completely or well controlled asthma were higher in the HD group than in the GD group (92.1% versus 81.1%, respectively, P = 0.03). Further, there was a significant difference between the groups with regard to frequency of acute exacerbations (9.2% in the HD group versus 21.3% in the GD group, P = 0.02); this effect was more pronounced for patients in the HD group with partially controlled or uncontrolled asthma.

          Conclusion

          Patients receiving HD therapy achieved asthma control more rapidly and maintained greater stability than those receiving GD therapy. This represents a novel strategy for gaining disease control in patients with uncontrolled asthma.

          Most cited references26

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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.
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            Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.

            The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
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              A 10 year asthma programme in Finland: major change for the better.

              A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society. The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched. The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were 218 million euro which had fallen to 213.5 million euro in 2003. Costs per patient per year have decreased 36% (from 1611 euro to 1031 euro). It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                17 June 2013
                : 7
                : 477-484
                Affiliations
                [1 ]Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
                [2 ]Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taipei, Taiwan
                [3 ]Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
                Author notes
                Correspondence: Hao-Chien Wang, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, Tel +88 62 2312 3456 ext 2905, Fax +88 62 2358 2867, Email haochienwang@ 123456gmail.com
                Article
                dddt-7-477
                10.2147/DDDT.S44231
                3692346
                23818758
                b15ff464-5f19-4f9b-84b0-3668009cca59
                © 2013 Cheng et al, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                asthma,treatment,inhaled corticosteroids,higher doses
                Pharmacology & Pharmaceutical medicine
                asthma, treatment, inhaled corticosteroids, higher doses

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