Treatment of moderate persistent asthma in adolescents and adults
- Stephen Peters, MD, PhD, FACP, FCCP, FAAAAI, FCPP
Stephen Peters, MD, PhD, FACP, FCCP, FAAAAI, FCPP
- Professor of Medicine and Pediatrics
- Wake Forest University Health Sciences
- Jennifer W McCallister, MD, FACP, FCCP
Jennifer W McCallister, MD, FACP, FCCP
- Associate Professor of Clinical Internal Medicine
- The Ohio State University Wexner Medical Center
- Rodolfo Pascual, MD
Rodolfo Pascual, MD
- Associate Professor of Internal Medicine
- Wake Forest University Health Sciences
The principal goals of treatment of moderate persistent asthma are to minimize symptoms, normalize pulmonary function, prevent exacerbations, and improve health-related quality of life. A theoretical goal is to prevent the putative long-term consequences of airway inflammation, particularly airway remodeling and chronic persistent airway obstruction. (See "Pathogenesis of asthma".)
The standard pharmacologic approaches to moderate persistent asthma in adolescents (children over the age of 12 years) and adults will be reviewed here. This information is consistent with the “National Asthma Education and Prevention Program (NAEPP): Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma – Full Report 2007" . Similar guidelines have been published by the Global Initiative for Asthma (GINA) .
An overview of asthma management, including trigger control and the use of controller medications for asthma in children younger than 12 years of age, is presented separately. (See "An overview of asthma management" and "Trigger control to enhance asthma management" and "Asthma in children younger than 12 years: Treatment of persistent asthma with controller medications".)
●Daily symptoms of asthma
- National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051) www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on December 04, 2014).
- Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA). www.ginasthma.org (Accessed on January 30, 2015).
- Bateman ED, Boushey HA, Bousquet J, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004; 170:836.
- Drazen JM, Israel E, Boushey HA, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network. N Engl J Med 1996; 335:841.
- Chervinsky P, van As A, Bronsky EA, et al. Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group. J Allergy Clin Immunol 1994; 94:676.
- Haahtela T, Järvinen M, Kava T, et al. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med 1991; 325:388.
- Juniper EF, Kline PA, Vanzieleghem MA, et al. Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics. Eur Respir J 1990; 3:1122.
- Juniper EF, Kline PA, Vanzieleghem MA, et al. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis 1990; 142:832.
- Salmeron S, Guerin JC, Godard P, et al. High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study. Am Rev Respir Dis 1989; 140:167.
- Donahue JG, Weiss ST, Livingston JM, et al. Inhaled steroids and the risk of hospitalization for asthma. JAMA 1997; 277:887.
- Stempel DA, Meyer JW, Stanford RH, Yancey SW. One-year claims analysis comparing inhaled fluticasone propionate with zafirlukast for the treatment of asthma. J Allergy Clin Immunol 2001; 107:94.
- Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343:332.
- FDA Alert for healthcare professionals Salmeterol xinofoate inhaltion powder (marketed as Serevent Diskus). www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm.
- FDA Alert for healthcare professionals Fluticasone propionate and salmeterol inhalation powder (marketed as Advair Diskus). www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm.
- Lazarus SC, Boushey HA, Fahy JV, et al. Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001; 285:2583.
- Cates CJ, Cates MJ, Lasserson TJ. Regular treatment with formoterol for chronic asthma: serious adverse events. Cochrane Database Syst Rev 2008; :CD006923.
- A combination of fluticasone and salmeterol for asthma. In: The Medical Letter on drugs and therapeutics, 43, New Rochelle, NY 2000. p.31.
- Kavuru M, Melamed J, Gross G, et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2000; 105:1108.
- Markham A, Jarvis B. Inhaled salmeterol/fluticasone propionate combination: a review of its use in persistent asthma. Drugs 2000; 60:1207.
- Nathan RA, Nolte H, Pearlman DS, P04334 Study Investigators. Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids. Allergy Asthma Proc 2010; 31:269.
- Greening AP, Ind PW, 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.
- Woolcock A, Lundback B, Ringdal N, Jacques LA. 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.
- Pauwels RA, Löfdahl CG, Postma DS, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med 1997; 337:1405.
- Greenstone IR, Ni Chroinin MN, Masse V, et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database Syst Rev 2005; :CD005533.
- O'Byrne PM, Naya IP, Kallen A, et al. Increasing doses of inhaled corticosteroids compared to adding long-acting inhaled beta2-agonists in achieving asthma control. Chest 2008; 134:1192.
- Ni Chroinin M, Greenstone I, Lasserson TJ, Ducharme FM. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database Syst Rev 2009; :CD005307.
- Vaquerizo MJ, Casan P, Castillo J, et al. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma. Thorax 2003; 58:204.
- Price DB, Hernandez D, Magyar P, et al. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 2003; 58:211.
- Virchow JC Jr, Prasse A, Naya I, et al. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Am J Respir Crit Care Med 2000; 162:578.
- Israel E, Cohn J, Dubé L, Drazen JM. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group. JAMA 1996; 275:931.
- Joos S, Miksch A, Szecsenyi J, et al. Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax 2008; 63:453.
- Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med 2011; 364:1695.
- Tamaoki J, Kondo M, Sakai N, et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Am J Respir Crit Care Med 1997; 155:1235.
- Rivington RN, Boulet LP, Côté J, et al. Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on high-dose inhaled steroids. Am J Respir Crit Care Med 1995; 151:325.
- Evans DJ, Taylor DA, Zetterstrom O, et al. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med 1997; 337:1412.
- Fjellbirkeland L, Gulsvik A, Palmer JB. The efficacy and tolerability of inhaled salmeterol and individually dose-titrated, sustained-release theophylline in patients with reversible airways disease. Respir Med 1994; 88:599.
- Tee AK, Koh MS, Gibson PG, et al. Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev 2007; :CD001281.
- Davies B, Brooks G, Devoy M. The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies. Respir Med 1998; 92:256.
- Engel T, Dirksen A, Heinig JH, et al. Single-dose inhaled budesonide in subjects with chronic asthma. Allergy 1991; 46:547.
- Peters SP, Jones CA, Haselkorn T, et al. Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey. J Allergy Clin Immunol 2007; 119:1454.
- Chapman KR, Boulet LP, Rea RM, Franssen E. Suboptimal asthma control: prevalence, detection and consequences in general practice. Eur Respir J 2008; 31:320.
- Lazarus SC, Chinchilli VM, Rollings NJ, et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med 2007; 175:783.
- Pedersen SE, Bateman ED, Bousquet J, et al. Determinants of response to fluticasone propionate and salmeterol/fluticasone propionate combination in the Gaining Optimal Asthma controL study. J Allergy Clin Immunol 2007; 120:1036.
- American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009; 360:1487.
- Kiljander TO, Junghard O, Beckman O, Lind T. Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2010; 181:1042.
- Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev 2010; :CD005535.
- Brown RW, O'Brien CD, Martin UJ, et al. Long-term safety and asthma control measures with a budesonide/formoterol pressurized metered-dose inhaler in African American asthmatic patients: a randomized controlled trial. J Allergy Clin Immunol 2012; 130:362.
- Chauhan BF, Ducharme FM. Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev 2014; :CD003137.
- Busse WW, Shah SR, Somerville L, et al. Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients. J Allergy Clin Immunol 2008; 121:1407.
- Cates CJ, Lasserson TJ. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events. Cochrane Database Syst Rev 2010; :CD007694.
- Lasserson TJ, Ferrara G, Casali L. Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Cochrane Database Syst Rev 2011; :CD004106.
- Bernstein DI, Hébert J, Cheema A, et al. Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma. Allergy Asthma Clin Immunol 2011; 7:21.
- O'Byrne PM, Bisgaard H, Godard PP, et al. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med 2005; 171:129.
- Rabe KF, Atienza T, Magyar P, et al. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006; 368:744.
- Beasley R, Weatherall M, Shirtcliffe P, et al. Combination corticosteroid/β-agonist inhaler as reliever therapy: a solution for intermittent and mild asthma? J Allergy Clin Immunol 2014; 133:39.
- Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2013; :CD009019.
- Papi A, Marku B, Scichilone N, et al. Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial. Lancet Respir Med 2015; 3:109.
- Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev 2013; :CD007313.
- Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 2010; 363:1715.
- Paggiaro P, Halpin DM, Buhl R, et al. The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial. J Allergy Clin Immunol Pract 2016; 4:104.
- Beeh KM, Moroni-Zentgraf P, Ablinger O, et al. Tiotropium Respimat® in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma. Respir Res 2014; 15:61.
- Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ 2003; 327:891.
- Sadatsafavi M, Lynd L, Marra C, et al. Comparative outcomes of leukotriene receptor antagonists and long-acting β-agonists as add-on therapy in asthmatic patients: a population-based study. J Allergy Clin Immunol 2013; 132:63.
- Deykin A, Wechsler ME, Boushey HA, et al. Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma. Am J Respir Crit Care Med 2007; 175:228.
- Brozek JL, Kraft M, Krishnan JA, et al. Long-acting β2-agonist step-off in patients with controlled asthma. Arch Intern Med 2012; 172:1365.
- Hawkins G, McMahon AD, Twaddle S, et al. Stepping down inhaled corticosteroids in asthma: randomised controlled trial. BMJ 2003; 326:1115.
- Lemanske RF Jr, Sorkness CA, Mauger EA, et al. Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial. JAMA 2001; 285:2594.
- Peters SP. Safety of inhaled corticosteroids in the treatment of persistent asthma. J Natl Med Assoc 2006; 98:851.
- GENERAL PRINCIPLES
- Patient education
- Immunotherapy for allergic asthma
- SHORT-ACTING BETA AGONISTS
- INITIATING CONTROLLER THERAPY
- Preferred options
- - Medium-dose inhaled GCs
- - Low-dose inhaled GCs plus a LABA
- A course of oral GCs in addition
- Alternate options
- - Leukotriene-modifying agents
- - Theophylline
- ADJUSTING THERAPY
- Assessing control
- Increasing therapy
- - Medium-dose inhaled GCs plus a LABA
- - Medium-dose inhaled GCs plus tiotropium
- - Medium-dose inhaled GCs plus a leukotriene-modifying agent
- - Combining multiple therapies
- Decreasing therapy
- ACUTE EXACERBATIONS
- LONG-TERM MONITORING
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS