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• W1978582522 abstract "The variability in symptom control is a challenging feature of asthma that necessitates careful monitoring and the need to step up and step down individualized therapeutic regimens over time. This stepwise concept in asthma therapy can be considered in at least 3 contexts. For lack of control that is persistent over long periods of time, an increase in the overall medication or a step-up long-term strategy is indicated. A second approach, the step-up short-term strategy, can be used during a temporary loss of acceptable control, such as at the onset of a viral respiratory tract illness. In these cases a step-up in therapy is usually terminated in 3 to 10 days once asthma control has been satisfactorily achieved. Finally, for treating symptoms related to the variability of asthma on a day-to-day basis, inhaled corticosteroids used concomitantly with a β-agonist have been evaluated, although this treatment is not currently approved in the United States. We will term this particular intervention a step-up intermittent strategy. Here we summarize the existing data regarding these 3 approaches to step up care and step down management, as well as to identify areas where more comparative studies are necessary to provide further guidance to clinicians regarding proper step-up and step-down strategies in the care of asthma. The variability in symptom control is a challenging feature of asthma that necessitates careful monitoring and the need to step up and step down individualized therapeutic regimens over time. This stepwise concept in asthma therapy can be considered in at least 3 contexts. For lack of control that is persistent over long periods of time, an increase in the overall medication or a step-up long-term strategy is indicated. A second approach, the step-up short-term strategy, can be used during a temporary loss of acceptable control, such as at the onset of a viral respiratory tract illness. In these cases a step-up in therapy is usually terminated in 3 to 10 days once asthma control has been satisfactorily achieved. Finally, for treating symptoms related to the variability of asthma on a day-to-day basis, inhaled corticosteroids used concomitantly with a β-agonist have been evaluated, although this treatment is not currently approved in the United States. We will term this particular intervention a step-up intermittent strategy. Here we summarize the existing data regarding these 3 approaches to step up care and step down management, as well as to identify areas where more comparative studies are necessary to provide further guidance to clinicians regarding proper step-up and step-down strategies in the care of asthma. Information for Category 1 CME CreditCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted.Date of Original Release: November 2011. Credit may be obtained for these courses until October 31, 2013.Copyright Statement: Copyright © 2011-2013. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Alex Thomas, MD, Robert F. Lemanske, Jr, MD, and Daniel J. Jackson, MDActivity Objectives1.To describe the evidence underlying strategies for stepping up asthma management.2.To describe the evidence underlying strategies for stepping down asthma management.3.To define asthma responsiveness.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: R. F. Lemanske, Jr, has served as a speaker for Merck, Doembecher Children's Hospital, Washington University, the Medicus Group, the Park Nicolet Institute, the American College of Allergy, Asthma & Immunology, the LA Allergy Society, the Michigan Allergy/Asthma Society, the Medical College of Wisconsin, the Fund for Medical Research and Education (Detroit), the Children's Hospital of Minnesota, the Toronto Allergy Society, the American Academy of Allergy, Asthma & Immunology, Beaumont Hospital (Detroit), the University of Illinois, the Canadian Society of Allergy and Clinical Immunology, New York Presbyterian, Med Media Educational Group, Onpointe Medical Communication, the Medical University of South Carolina, Health Matters Communication, Bishop McCann, Donohue, Purohit, Miller, the Center for Health Care Education, the University of California (San Francisco), the American Thoracic Society, the University of Iowa, Indiana University, the American Lung Association of the Upper Midwest, Vanderbilt University, Rochester Children's Hospital, the Colorado Allergy Society, and the Pennsylvania Allergy Society; has served as a consultant and speaker for AstraZeneca; has served as a consultant for Map Pharmaceuticals, Gray Consulting, Smith Research, the Merck Childhood Asthma Network, Novartis, Quintiles/Innovax, RC Horowitz & Co, International Meetings and Science, Scienomics, Scientific Therapeutics, Gray Consulting, Cognimed, SA Boney and Associates, and GlaxoSmithKline; is the author of Up-to-Date; and is a textbook editor for Elsevier, Inc. D. J. Jackson has received research support from Pharmaxis, the National Institutes of Health, and the American Academy of Allergy, Asthma & Immunology. A. Thomas has declared that he has no conflict of interest. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org. The accompanying tests may only be submitted online at www.jacionline.org. Fax or other copies will not be accepted. Date of Original Release: November 2011. Credit may be obtained for these courses until October 31, 2013. Copyright Statement: Copyright © 2011-2013. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates these educational activities for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Alex Thomas, MD, Robert F. Lemanske, Jr, MD, and Daniel J. Jackson, MD Activity Objectives1.To describe the evidence underlying strategies for stepping up asthma management.2.To describe the evidence underlying strategies for stepping down asthma management.3.To define asthma responsiveness. Recognition of Commercial Support: This CME activity has not received external commercial support. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: R. F. Lemanske, Jr, has served as a speaker for Merck, Doembecher Children's Hospital, Washington University, the Medicus Group, the Park Nicolet Institute, the American College of Allergy, Asthma & Immunology, the LA Allergy Society, the Michigan Allergy/Asthma Society, the Medical College of Wisconsin, the Fund for Medical Research and Education (Detroit), the Children's Hospital of Minnesota, the Toronto Allergy Society, the American Academy of Allergy, Asthma & Immunology, Beaumont Hospital (Detroit), the University of Illinois, the Canadian Society of Allergy and Clinical Immunology, New York Presbyterian, Med Media Educational Group, Onpointe Medical Communication, the Medical University of South Carolina, Health Matters Communication, Bishop McCann, Donohue, Purohit, Miller, the Center for Health Care Education, the University of California (San Francisco), the American Thoracic Society, the University of Iowa, Indiana University, the American Lung Association of the Upper Midwest, Vanderbilt University, Rochester Children's Hospital, the Colorado Allergy Society, and the Pennsylvania Allergy Society; has served as a consultant and speaker for AstraZeneca; has served as a consultant for Map Pharmaceuticals, Gray Consulting, Smith Research, the Merck Childhood Asthma Network, Novartis, Quintiles/Innovax, RC Horowitz & Co, International Meetings and Science, Scienomics, Scientific Therapeutics, Gray Consulting, Cognimed, SA Boney and Associates, and GlaxoSmithKline; is the author of Up-to-Date; and is a textbook editor for Elsevier, Inc. D. J. Jackson has received research support from Pharmaxis, the National Institutes of Health, and the American Academy of Allergy, Asthma & Immunology. A. Thomas has declared that he has no conflict of interest. Asthma is characterized by chronic airway inflammation, variable airflow obstruction, airway hyperresponsiveness, and recurrent symptoms.1EPRExpert Panel Report: guidelines for the diagnosis and management of asthma (EPR 1991). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda1991Google Scholar The variability in symptom control is a particularly challenging feature of asthma that necessitates careful monitoring and the need to step up and step down individualized therapeutic regimens over time. To provide guidance to clinicians regarding proper step-up and step-down strategies, both national (National Asthma Education and Prevention Program that has published 3 Expert Panel Reports [EPRs]) and international (Global Initiative for Asthma [GINA]) panels have continued to convene to review evidence and provide structured recommendations based on both the published literature and expert opinion when scientific and clinical data have been lacking.1EPRExpert Panel Report: guidelines for the diagnosis and management of asthma (EPR 1991). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda1991Google Scholar, 2EPR-2Expert Panel Report 2: guidelines for the diagnosis and management of asthma (EPR-2 1997). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda1997Google Scholar, 3EPR Update 2002Expert Panel Report: guidelines for the diagnosis and management of asthma. Update on selected topics 2002 (EPR-update 2002). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2003Google Scholar, 4Global Initiative for Asthma (GINA)Pocket guide for asthma management and prevention. National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda1998Google Scholar Crucial for the appropriate management of asthma are consistent measures to assess disease progression and response to therapy. As described in the EPR-3 report, the effective assessment and monitoring of asthmatic patients are closely linked to the concepts of severity, control, and responsiveness to treatment.5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google Scholar Asthma severity is defined as the intrinsic intensity of the disease process. Severity is measured most easily and directly in a patient not receiving long-term controller therapy. Asthma control is defined as the degree to which the manifestations of asthma (symptoms, functional impairments, and risks of untoward events) are minimized and the goals of therapy are met. Responsiveness to therapy is the ease with which asthma control is achieved by therapy. Both asthma severity and control are evaluated by using the domains of current impairment and future risk. Impairment is the frequency and intensity of symptoms and functional limitations the patient is experiencing or has recently experienced. Risk is the likelihood of asthma exacerbations, progressive decrease in lung function (or, for children, reduced lung growth), and/or risk of adverse effects from medication. In terms of the assessment of current impairment, both the frequency and intensity of symptoms are measured. This can be assessed by further delineating asthma symptoms, such as the frequency of nighttime awakenings, the need for a short-acting β-agonist (SABA) for the quick relief of symptoms, the number of work or school days missed, the effect on activities of daily living, and quality-of-life assessments. Validated questionnaires, such as the Asthma Control Test,6Nathan R.A. Sorkness C.A. Kosinski M. Schatz M. Li J.T. Marcus P. et al.Development of the Asthma Control Test: a survey for assessing asthma control.J Allergy Clin Immunol. 2004; 113: 59-65Abstract Full Text Full Text PDF PubMed Scopus (1931) Google Scholar the Childhood Asthma Control Test,7Liu A.H. Zeiger R. Sorkness C. Mahr T. Ostrom N. Burgess S. et al.Development and cross-sectional validation of the Childhood Asthma Control Test.J Allergy Clin Immunol. 2007; 119: 817-825Abstract Full Text Full Text PDF PubMed Scopus (632) Google Scholar the Asthma Control Questionnaire,8Juniper E.F. O’Byrne P.M. Guyatt G.H. Ferrie P.J. King D.R. Development and validation of a questionnaire to measure asthma control.Eur Respir J. 1999; 14: 902-907Crossref PubMed Scopus (1734) Google Scholar the Asthma Therapy Assessment Questionnaire control index,9Vollmer W.M. Markson L.E. O’Connor E. Sanocki L.L. Fitterman L. Berger M. et al.Association of asthma control with health care utilization and quality of life.Am J Respir Crit Care Med. 1999; 160: 1647-1652Crossref PubMed Scopus (316) Google Scholar and others have been used more frequently in recent years to help standardize the quantification of impairment. In addition to patient-reported symptoms, spirometry as a means to measure lung function can aid in classifying both severity and control.10Fuhlbrigge A.L. Weiss S.T. Kuntz K.M. Paltiel A.D. Forced expiratory volume in 1 second percentage improves the classification of severity among children with asthma.Pediatrics. 2006; 118: e347-e355Crossref PubMed Scopus (74) Google Scholar The EPR-3 emphasizes the importance of periodic assessments at 1- to 6-month intervals to assess asthma control. The goal of asthma therapy is to maintain long-term control by using the smallest amount of medication possible. Responsiveness to treatment is variable between patients, and follow-up assessments are critical to determine whether the goals of therapy are being met.5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google Scholar It is during these interval assessments that one must determine whether the goals of therapy are being met and decide whether the dose, number of medications, and/or frequency of administration should be increased, if necessary, and decreased when possible. In patients naive to asthma therapy, the initial step in choosing a therapeutic regimen is based on defining asthma severity (Fig 1). Patients with intermittent asthma are placed in the first of the 6 steps of the EPR-3 guideline–defined stepwise approach for managing asthma: as-needed use of SABAs (Fig 2). Should SABA use exceed 2 days per week, this would increase the patient’s severity level to persistent asthma, and a step-up would be recommended. Two exceptions to this guideline are exercised-induced bronchospasm and viral respiratory tract infections. For virus-induced exacerbations occurring more than every 6 weeks, a step-up (step 2) in therapy is recommended.5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google ScholarFig 2Stepwise approach for managing asthma. Initial step in therapy determined by asthma severity. Adjustment in therapy must take into account control and other patient characteristics such as risk. PRN, As needed.Adapted from the EPR-3.5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT) For patients whose symptoms are not controlled by step 1 intermittent SABA therapy (eg, daytime symptoms >2 days per week, nighttime symptoms >2 days per month, worsening lung function, and >2 exacerbation per year), step 2 care should also be initiated. Inhaled corticosteroids (ICSs) are the preferred treatment for step 2 therapy across ages. Once the initial step of care is chosen, the patient should be re-evaluated periodically to determine whether his or her asthma control is satisfactory. If the current step of care is not controlling the patient’s asthma based on the criteria defined in the EPR-3 guidelines (Fig 3), a step-up in care is initiated. Conversely, if the step of care has produced adequate control for prolonged periods of time, consideration should be given to step-down therapy based on the EPR-3 guideline recommendations.5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google Scholar The concept of step-up and step-down management in asthma therapy can be considered in at least 3 contexts (Fig 4). First, if lack of control is persistent over long periods of time (eg, 2-3 weeks or longer), an increase in the overall medication regimen will be prescribed by moving up 1 or 2 steps, as defined in the EPR-3 or GINA asthma guideline recommendations.4Global Initiative for Asthma (GINA)Pocket guide for asthma management and prevention. National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda1998Google Scholar, 5EPR-3Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program, Bethesda2007Google Scholar We will term this particular intervention the step-up long-term (SLT) strategy. This step-up in overall therapy is usually continued for 3 to 6 months to evaluate the ability and consistency of the new regimen to maintain adequate asthma control. At this point, consideration could be given to stepping down 1 absolute level with the stipulation that re-evaluation should occur within the next 1 to 2 months to determine the consistency of control that this step-down regimen is able to maintain over time. A second approach to step-up therapy might occur in relationship to an anticipated brief loss of control (days), such as at the onset of a viral respiratory tract illness11Gern J.E. Busse W.W. Relationship of viral infections to wheezing illnesses and asthma.Nat Rev Immunol. 2002; 2: 132-138Crossref PubMed Scopus (109) Google Scholar or as a consequence of an acute short-term exposure (eg, a furred pet) that has been known to induce a temporary loss of acceptable asthma control.12Van Metre Jr., T.E. Marsh D.G. Adkinson Jr., N.F. Fish J.E. Kagey-Sobotka A. Norman P.S. et al.Dos of cat (Felis domesticus) allergen 1 (Fel d 1) that induces asthma.J Allergy Clin Immunol. 1986; 78: 62-75Abstract Full Text PDF PubMed Scopus (85) Google Scholar In most cases this will entail a step-up in therapy consisting of more frequent short-acting β-agonist (SABA) use and, potentially, an increase from baseline in the dose of ICS aimed at preventing a more significant exacerbation requiring oral corticosteroid treatment. This step-up in therapy is usually terminated in 3 to 10 days once asthma control has been satisfactorily achieved; at this point, a step-down to the baseline medication regimen is instituted. For the purposes of this review, we will term this particular intervention the step-up short-term (SST) strategy. Finally, for treating symptoms related to the variability of asthma on a day-to-day basis, an ICS used concomitantly with a SABA or a long-acting β-agonist (LABA) has been evaluated. Although this type of therapy has been studied in clinical trials and approved for use in many parts of the world, it is currently not approved in the United States. We will term this particular intervention the step-up intermittent (SUI) strategy. Interestingly, this approach has been used in both step-up (using LABAs and SABAs)13Fitzgerald J.M. Boulet L.P. Follows R.M. The CONCEPT trial: a 1-year, multicenter, randomized, double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide in adults with persistent asthma.Clin Ther. 2005; 27: 393-406Abstract Full Text PDF PubMed Scopus (78) Google Scholar and step-down (using SABA)14Papi A. Canonica G.W. Maestrelli P. Paggiaro P. Olivieri D. Pozzi E. et al.Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma.N Engl J Med. 2007; 356: 2040-2052Crossref PubMed Scopus (277) Google Scholar, 15Martinez F.D. Chinchilli V.M. Morgan W.J. Boehmer S.J. Lemanske R.F. Mauger D.T. et al.Use of beclomethasone diproprionate as a rescue treatment for children with mild persistent asthma (TREXA): a randomized, double-blind, placebo-controlled trial.Lancet. 2011; 377: 650-657Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar treatment approaches. The SLT strategy was initially evaluated in moving from step 2 to step 3 care in adult patients whose asthma was not well controlled with low doses of ICSs. Studies by both Greening et al16Greening A.P. Ind P.W. Northfield M. Shaw G. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group.Lancet. 1994; 344: 219-224Abstract PubMed Scopus (935) Google Scholar and Woolcock et al17Woolcock A. Lundback B. Ringdal N. Jacques L.A. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids.Am J Respir Crit Care Med. 1996; 153: 1481-1488Crossref PubMed Scopus (682) Google Scholar using the SLT approach demonstrated that, in patients who symptoms are not well controlled on a low dose of ICSs, the addition of a LABA was superior to increasing the dose of ICS for many outcome measures in the impairment domain. These observations were subsequently extended to the risk domain in the Formoterol and Corticosteroid Establishing Therapy study.18Pauwels R.A. Lofdahl C.G. Postma D.S. Tattersfield A.E. O’Byrne P. Barnes P.J. et al.Effect of inhaled formoterol and budesonide on exacerbations of asthma.N Engl J Med. 1997; 337: 1405-1411Crossref PubMed Scopus (1515) Google Scholar This study evaluated the effect of adding a LABA to a fixed ICS dose, quadrupling the dose of ICS, or both on reducing asthma exacerbations. For 1 year, patients were treated twice daily with 100 μg of budesonide, 100 μg of budesonide and 12 μg of formoterol, 400 μg of budesonide, or 400 μg of budesonide and 12 μg of formoterol. With the addition of a LABA to a lower dose of ICS, severe exacerbations were reduced by 26%, and mild exacerbations were reduced by 40% when compared with lower-dose ICSs alone. The higher dose of ICS alone reduced the rates of severe exacerbations by 49% and mild exacerbations by 37%. When a LABA was added to the higher dose of ICS, severe exacerbations were reduced by 63%, and mild exacerbations were reduced by 62%. Both lung function and asthma symptoms improved with both higher ICS doses and formoterol, although the greatest improvements were achieved with formoterol. The issue of which SLT intervention leads to better overall asthma control when choosing between more ICS versus adding a LABA was comprehensively studied by Batemen et al19Bateman E.D. Boushey H.A. Bousquet J. Busse W.W. Clark T.J. Pauwels R.A. et al.Can guideline-defined asthma control be achieved? The gaining optimal asthma control study.Am J Respir Crit Care Med. 2004; 170: 836-844Crossref PubMed Scopus (1459) Google Scholar in the Gaining Optimal Asthma Control (GOAL) study. This randomized, double-blind, parallel-group study assessed the ability of predefined stepwise adjustments of fluticasone/salmeterol or fluticasone alone to achieve 2 predefined measures of asthma control. The definitions of control included composite measures of peak expiratory flow (PEF), rescue medication use, daytime and nighttime symptoms, exacerbations, emergency department visits, and other adverse events based on the GINA or National Institutes of Health (NIH) guidelines.4Global Initiative for Asthma (GINA)Pocket guide for asthma management and prevention. National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda1998Google Scholar Unlike previous studies of controller therapy that focused on improvements with fixed doses of medications, the GOAL study allowed for dose escalation in a stepwise approach to achieve more comprehensive and sustained control. Phase I of the study was the dose-escalation phase. During this time, treatment was stepped up every 12 weeks until asthma was totally controlled or until the medication reached 500 μg of fluticasone twice daily or 500/50 μg of fluticasone/salmeterol twice daily. Once asthma control was totally achieved or after 12 weeks of maximal medication dosing, the patients were advanced to phase II, the constant phase. During this double-blind treatment period, patients continued to take the same dose of controller medication for 1 year. Of note, in an effort to determine whether there were incremental effects over time of continuing to take these medications, there was no step-down treatment plan during this phase. Although the majority of patients achieved well-controlled or totally controlled asthma in this study, approximately 9% of patients in the fluticasone-only group and 5% of patients in the fluticasone/salmeterol group did not achieve well-controlled asthma in phase I or phase II, requiring escalation to the maximum treatment phase or oral corticosteroids and 500/50 μg of fluticasone/salmeterol. Nevertheless, the GOAL study provided strong evidence that patients with uncontrolled asthma from a varied range of severity were able to achieve and sustain guideline-defined control. It also demonstrated that stepping up therapy to achieve guideline-defined control, even in patients who did not achieve the most stringent definitions of “total control,” still resulted in significant improvements in health status and rates of exacerbation. Bateman et al19Bateman E.D. Boushey H.A. Bousquet J. Busse W.W. Clark T.J. Pauwels R.A. et al.Can guideline-defined asthma control be achieved? The gaining optimal asthma control study.Am J Respir Crit Care Med. 2004; 170: 836-844Crossref PubMed Scopus (1459) Google Scholar did emphasize that many risks of sustained treatment might take years to become clinically significant, and further research into step-down therapy once control was achieved was indicated. Regardless, the possibility of achieving guideline-based total control through medication escalation provided solid evidence for a stepwise approach to asthma management. A recent study completed by the Childhood Asthma Research and Education network has provided evidence to guide SLT in children whose symptoms are uncontrolled on low doses of ICSs and who require step 3 care. The Best Add-on Therapy Giving Effective Responses trial was a double-blind, 3-treatment, crossover trial in children aged 6 to 17 years with asthma uncontrolled by 100 μg of twice-daily fluticasone.20Lemanske R.F." @default.
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• W1978582522 title "Approaches to stepping up and stepping down care in asthmatic patients" @default.
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