Abstract
Chronic obstructive pulmonary disease (COPD) is a major problem in the elderly population, with approximately 10% of the population affected. Since COPD is an inflammatory disorder of the pulmonary system, corticosteroids might be expected to improve clinical outcomes of the disease.
Data from large, well designed randomised clinical trials in which approximately one third of patients were ≥65 years of age indicate that inhaled corticosteroids do not modify the natural history of COPD, as measured by the rate of decline in forced expiratory volume in 1 second (FEV1). However, these same studies also suggest that corticosteroids reduce the frequency of clinical exacerbations by nearly a third (compared with placebo). This beneficial effect is particularly pronounced among those with an FEV1 less than 50% of the predicted value. Withdrawal of inhaled corticosteroids, on the other hand, leads to increased symptoms and elevates the risk of exacerbations by 50% above baseline levels. Patients’ health-related quality of life is also improved by the use of inhaled corticosteroids.
It is clear that inhaled corticosteroids elevate the risk of thrush, dysphonia and skin bruising by 2-fold compared with placebo. In addition, the sum of evidence suggests a modest deleterious effect for inhaled corticosteroids on bone mineral density, especially for formulations that have an increased rate of systemic absorption. However, the clinical evidence of this observation is uncertain. The effect of inhaled corticosteroids on fracture risk is controversial with some observational studies suggesting a possible association. Whether inhaled corticosteroids increase the risk of ophthalmic complications (cataracts and glaucoma) is also uncertain.
In conclusion, the current evidence indicates that inhaled corticosteroid therapy produces short- and long-term clinical benefits in COPD patients with moderate-to-severe disease and should be used as adjunctive therapy for elderly patients with COPD who experience frequent exacerbations or have moderately reduced lung function.
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References
Hurd S. The impact of COPD on lung health worldwide: epidemiology and incidence. Chest 2000; 117Suppl. 2: 1–4
NHLBI morbidity and mortality chartbook, 1998 [online]. Available from URL: http://www.nhlbi.nih.gov/resources/docs/cht-book.htm [Accessed 2003 Aug 1]
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997; 349: 1498–504
Michaud CM, Murray CJ, Bloom BR. Burden of disease: implications for future research. JAMA 2001; 285: 535–9
Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001; 163: 1256–76
Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance: United States, 1971–2000. MMWR Surveill Summ 2002; 2; 51: 1–16
MacNee W, Calverley PM. Chronic obstructive pulmonary disease: management of COPD. Thorax 2003; 58: 261–5
Calverley PM. Inhaled corticosteroids are beneficial in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 341–2
Barnes PJ. Inhaled corticosteroids are not beneficial in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 342–4
Alsaeedi A, Sin DD, McAlister FA. The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials. Am J Med 2002; 113: 59–65
The Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000; 343: 1902–9
Bourbeau J, Rouleau MY, Boucher S. Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease. Thorax 1998; 53: 477–82
Weir DC, Bale GA, Bright P, et al. A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease. Clin Exp Allergy 1999; 29Suppl. 2: 125–8
Calverley P, Pauwels R, Vestbo J, et al. TRial of Inhaled STeroids ANd long-acting beta2 agonists study group: combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003 Feb 8; 361: 449–56
Vestbo J, Sorensen T, Lange P, et al. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999; 353: 1819–23
Burge PS, Calverley PM, Jones PW, et al. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate-to-severechronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000; 320: 1297–303
Paggiaro PL, Dahle R, Bakran I, et al. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease: International COPD Study Group. Lancet 1998; 351: 773–80
Yildiz F, Kaur AC, Ilgazli A, et al. Inhaled corticosteroids may reduce neutrophilic inflammation in patients with stable chronic obstructive pulmonary disease. Respiration 2000; 67: 71–6
Spitzer WO, Suissa S, Ernst P, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med 1992; 326: 501–6
Suissa S, Hemmelgarn B, Biais L, et al. Bronchodilators and acute cardiac death. Am J Respir Crit Care Med 1996; 154: 1598–602
Anthonisen NR, Connett JE, Enright PL, et al. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 2002; 166: 333–9
Ries AL, Kaplan RM, Limberg TM, et al. Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary disease. Ann Intern Med 1995; 122: 823–32
Griffiths TL, Burr ML, Campbell IA, et al. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial. Lancet 2000; 355: 362–8
Ries AL, Kaplan RM, Myers R, et al. Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial. Am J Respir Crit Care Med 2003; 167: 880–8
Medical Research Council Working Party Report. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; I: 681–5
Barnes PJ. Mechanisms in COPD: differences from asthma. Chest 2000; 117Suppl. 2: 10–4
Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl 2001; 34: 50–9
Hattotuwa KL, Gizycki MJ, Ansari TW, et al. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002; 165: 1592–6
Pesci A, Rossi GA, Bertorelli G, et al. Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis. Am J Respir Crit Care Med 1994; 149: 1311–6
Pesci A, Balbi B, Majori M, et al. Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease. Eur Respir J 1998; 12: 380–6
Balzano G, Stefanelli F, Iorio C, et al. Eosinophilic inflammation in stable chronic obstructive pulmonary disease: relationship with neutrophils and airway function. Am J Respir Crit Care Med 1999; 160: 1486–92
Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med 1997; 155: 449–53
Rutgers SR, Postma DS, ten Hacken NH, et al. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax 2000; 55: 12–8
Peleman RA, Rytila PH, Kips JC, et al. The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J 1999; 13: 839–43
Chanez P, Vignola AM, O’Shaugnessy T, et al. Corticosteroid reversibility in COPD is related to features of asthma. Am J Respir Crit Care Med 1997; 155: 1529–34
Brightling CE, Monteiro W, Ward R, et al. Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2000; 356: 1480–5
Confalonieri M, Mainardi E, Della Porta R, et al. Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease. Thorax 1998; 53: 583–5
Culpitt SV, Maziak W, Loukidis S, et al. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: 1635–9
Cox G, Whitehead L, Dolovich M, et al. A randomized controlled trial on the effect of inhaled corticosteroids on airways inflammation in adult cigarette smokers. Chest 1999; 115: 1271–7
McFadden Jr ER, Gilbert IA. Asthma. N Engl J Med 1992; 327: 1928–37
Polosa R, Rorke S, Holgate ST. Evolving concepts on the value of adenosine hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Thorax 2002; 57: 649–54
Kanner RE, Connett JE, Altose MD, et al. Gender difference in airway hyperresponsiveness in smokers with mild COPD. The Lung Health Study. Am J Respir Crit Care Med 1994; 150: 956–61
Vestbo J, Prescott E. Update on the “Dutch hypothesis” for chronic respiratory disease. Thorax 1998; 53Suppl. 2: 15–9
Tashkin DP, Altose MD, Connett JE, et al. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group. Am J Respir Crit Care Med 1996; 153: 1802–11
Rijcken B, Weiss ST. Longitudinal analyses of airway responsiveness and pulmonary function decline. Am J Respir Crit Care Med 1996; 154 (6 Pt 2): S246–9
Xu X, Rijcken B, Schouten JP, et al. Airways responsiveness and development and remission of chronic respiratory symptoms in adults. Lancet 1997; 350: 1431–4
Hospers JJ, Postma DS, Rijcken B, et al. Histamine airway hyper-responsiveness and mortality from chronic obstructive pulmonary disease: a cohort study. Lancet 2000; 356: 1313–7
Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med 1999; 340: 1941–7
Bullard MJ, Liaw SJ, Tsai YH, et al. Early corticosteroid use in acute exacerbations of chronic airflow obstruction. Am J Emerg Med 1996; 14: 139–43
Emerman CL, Connors AF, Lukens TW, et al. A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD. Chest 1989; 95: 563–7
Albert RK, Martin TR, Lewis SW. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med 1980; 92: 753–8
Sayiner A, Aytemur ZA, Cirit M, et al. Systemic glucocorti-coids in severe exacerbations of COPD. Chest 2001; 119: 726–30
Thompson WH, Nielson CP, Carvalho P, et al. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med 1996; 154: 407–12
Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999; 354: 456–60
Barnes PJ. Inhaled glucocorticoids for asthma. N Engl J Med 1995; 332: 868–75
Dompeling E, van Schayck CP, van Grunsven PM, et al. Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids: a 4-year prospective study. Ann Intern Med 1993; 118: 770–8
Kerstjens HA, Brand PL, Hughes MD, et al. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease: Dutch Chronic Non-Specific Lung Disease Study Group. N Engl J Med 1992; 327: 1413–9
van Schayck CP, Dompeling E, Rutten MP, et al. The influence of an inhaled steroid on quality of life in patients with asthma or COPD. Chest 1995; 107: 1199–205
Sin DD, Tu JV. Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 580–4
Soriano JB, Kiri V, Maier WC, et al. Inhaled corticosteroids with/without long-acting beta agonists reduce the risk of rehospitalization or deaths in COPD patients. Eur Respir J 2002; 20: 819–25
Sin DD, Man SFP. Inhaled corticosteroids and survival in COPD: does the dose matter? Eur Respir J 2003; 21: 260–7
Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med 1999; 340: 1948–53
Spencer S, Calverley PM, Sherwood Burge P, et al. Inhaled steroids in obstructive lung disease health status deterioration in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163: 122–8
Guyatt GH, Naylor CD, Juniper E, et al. Users’ guides to the medical literature: XII. how to use articles about health-related quality of life: Evidence-Based Medicine Working Group. JAMA 1997; 277: 1232–7
van der Valk P, Monninkhof E, van der Palen J, et al. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am J Respir Crit Care Med 2002; 166: 1358–63
Jones PW, Willits LR, Burge PS, et al. Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur Respir J 2003; 21: 68–73
Jarad NA, Wedzicha JA, Burge PS, et al. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease: ISOLDE Study Group. Respir Med 1999; 93: 161–6
O’Brien A, Russo-Magno P, Karki A, et al. Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction. Am J Respir Crit Care Med 2001; 164: 365–71
Sin DD, Man JP, Man SF. The risk of osteoporosis in caucasian men and women with obstructive airways disease. Am J Med 2003; 114: 10–4
Wong CA, Walsh LJ, Smith CJ, et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 2000; 355: 1399–403
Israel E, Banerjee TR, Fitzmaurice GM, et al. Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med 2001; 345: 941–7
Johnell O, Pauwels R, Lofdahl CG, et al. Bone mineral density in patients with chronic obstructive pulmonary disease treated with budesonide Turbuhaler. Eur Respir J 2002; 19: 1058–63
Martin RJ, Szefler SJ, Chinchilli VM, et al. Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med 2002; 165: 1377–83
Hubbard RB, Smith CJ, Smeeth L, et al. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002; 166: 1563–6
van Staa TP, Leufkens HG, Cooper C. Use of inhaled corticosteroids and risk of fractures. J Bone Miner Res 2001; 16: 581–8
Lau E, Mamdani M, Tu K. Inhaled or systemic corticosteroids and the risk of hospitalization for hip fracture among elderly women. Am J Med 2003; 114: 142–5
Jones A, Fay JK, Burr M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2002: CD003537
Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997; 337: 8–14
Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA 1998; 280: 539–43
Abuekteish F, Kirkpatrick JN, Russell G. Posterior subcapsular cataract and inhaled corticosteroid therapy. Thorax 1995; 50: 674–6
Simons FE, Persaud MP, Gillespie CA, et al. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids. Lancet 1993; 342: 776–8
Agertoft L, Larsen FE, Pedersen S. Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide. Eur Respir J 1998; 12: 130–5
Delcourt C, Cristol JP, Tessier F, et al. Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liees a l’Age. Am J Epidemiol 2000; 151: 497–504
Garbe E, LeLorier J, Boivin JF, et al. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA 1997; 277: 722–7
Mitchell P, Cumming RG, Mackey DA. Inhaled corticosteroids, family history, and risk of glaucoma. Ophthalmology 1999; 106: 2301–6
Malo JL, Cartier A, Ghezzo H, et al. Skin bruising, adrenal function and markers of bone metabolism in asthmatics using inhaled beclomethasone and fluticasone. Eur Respir J 1999; 13: 993–8
Passalacqua G, Albano M, Canonica GW, et al. Inhaled and nasal corticosteroids: safety aspects. Allergy 2000; 55: 16–33
Williams AJ, Baghat MS, Stableforth DE, et al. Dysphonia caused by inhaled steroids: recognition of a characteristic laryngeal abnormality. Thorax 1983; 38: 813–21
Brocklebank D, Wright J, Cates C. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma. BMJ 2001; 323: 896–900
Sorkness CA, LaForce C, Storms W, et al. Effects of the inhaled corticosteroids fluticasone propionate, triamcinolone acetonide, and flunisolide and oral prednisone on the hypothalamic-pituitary-adrenal axis in adult patients with asthma. Clin Ther 1999; 21: 353–67
Ringdal N, Lundback B, Alton M, et al. Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients. Respir Med 2000; 94: 482–9
Casale TB, Nelson HS, Stricker WE, et al. Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients. Ann Allergy Asthma Immunol 2001; 87: 379–85
Brus R. Effects of high-dose inhaled corticosteroids on plasma cortisol concentrations in healthy adults. Arch Intern Med 1999; 159: 1903–8
Acknowledgements
Dr Sin is supported by a New Investigator Award from the Canadian Institutes of Health Research and a Population Health Investigator Award from the Alberta Heritage Foundation for Medical Research.
Both Dr Sin and Dr Man have received honoraria for speaking engagements and have received research funding from GlaxoSmithKline & AstraZeneca.
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Sin, D.D., Man, S.F.P. Inhaled Corticosteroids in the Long-Term Management of Patients with Chronic Obstructive Pulmonary Disease. Drugs Aging 20, 867–880 (2003). https://doi.org/10.2165/00002512-200320120-00001
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DOI: https://doi.org/10.2165/00002512-200320120-00001