The Role of Corticosteroids in Chronic Obstructive Pulmonary Disease

ABSTRACT

Oral corticosteroids are powerful relatively nonspecific antiinflammatory agents with a range of well-characterized side effects. There is good evidence to show that they accelerate the rate of resolution of exacerbations of COPD and relapse is less likely if patients receive these drugs. Maintenance therapy with oral preparations is associated with worse mortality and skeletal muscle myopathy is a particular problem.

Corticosteroids have little effect on biopsy proven inflammation or its surrogates in COPD and did not change the rate of decline of FEV₁ over a range of spirometric disease severity in a number of trials each lasting 3 years. However, meta-analysis of the data suggests that a small effect (up to 10ml /year) might be present. There is more consistent evidence for an effect on postbronchodilator FEV₁ with both fluticasone propionate and budesonide. In patients with a postbronchodilator FEV₁ < 50% predicted where self-reported exacerbations become more common, inhaled corticosteroids can reduce the number of attacks. This effect is the major factor accounting for the reduction in deterioration in health status seen in patients who receive inhaled corticosteroids. Inhaled corticosteroids are much safer than oral therapy, although they do have a predictably higher incidence of candidiasis and hoarseness of the voice. Skin bruising is seen in patients with better lung function who use these drugs. Triamcinolone use is associated with reduction in bone density but this was not seen with budesonide. Combining an inhaled corticosteroid and a long-acting beta-agonist in the same inhaler increases the efficacy of the latte drug in COPD patients, with a significantly larger improvement in FEV₁, a larger reduction in reported breathlessness, and a reduction in exacerbation numbers in those with severe disease where beta-agonists appear to be less effective. Inhaled corticosteroids are not suitable for monotherapy in COPD but can be helpfully combined with an inhaled bronchodilator in patients with symptomatic disease.

KEYWORDS

Chronic obstructive pulmonary disease - corticosteroid - exacerbation - lung function

REFERENCES

• 1 Pauwels R A, Buist A S, Calverley P MA, Jenkins C R, Hurd S S. Global strategy for the diagnosis,management and prevention of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  163 1256-1276
• 2 Hogg J C, Chu F, Utokaparch S et al.. The nature of small-airway obstruction in chronic obstructive pulmonary disease.  N Engl J Med. 2004;  350 2645-2653
• 3 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 1902-1909
• 4 Davies L, Angus R M, Calverley P MA. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.  Lancet. 1999;  354 456-460
• 5 Wilson A M, Clark D J, McFarlane L, Lipworth B J. Adrenal suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers.  Eur J Clin Pharmacol. 1997;  53 33-37
• 6 Kim C S, Kang T C. Comparative measurement of lung deposition of inhaled fine particles in normal subjects and patients with obstructive airway disease.  Am J Respir Crit Care Med. 1997;  155 899-905
• 7 Nelson H S, Busse W W, DeBoisblanc B P et al.. Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.  J Allergy Clin Immunol. 1999;  103 267-275
• 8 Burge P S, Calverley P M, Jones P W, Spencer S, Anderson J A, Maslen T K. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.  BMJ. 2000;  320 1297-1303
• 9 Decramer M, Gosselink R, Troosters T, Verschueren M, Evers G. Muscle weakness is related to utilization of health care resources in COPD patients.  Eur Respir J. 1997;  10 417-423
• 10 Schols A M, Wesseling G, Kester A D et al.. Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids.  Eur Respir J. 2001;  17 337-342
• 11 Mahler D A, Wire P, Horstman D et al.. Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2002;  166 1084-1091
• 12 Hanania N A, Darken P, Horstman D et al.. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD.  Chest. 2003;  124 834-843
• 13 Szafranski W, Cukier A, Ramirez A et al.. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.  Eur Respir J. 2003;  21 74-81
• 14 Calverley P M, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease.  Eur Respir J. 2003;  22 912-919
• 15 Barnes P J, Ito K, Adcock I M. Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase.  Lancet. 2004;  363 731-733
• 16 Keatings V M, Collins P D, Scott D M, Barnes P J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.  Am J Respir Crit Care Med. 1996;  153 530-534
• 17 Culpitt S V, Rogers D F, Shah P et al.. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2003;  167 24-31
• 18 Llewellyn-Jones C G, Harris T AJ, Stockley R A. Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema.  Am J Respir Crit Care Med. 1996;  153 616-621
• 19 Sin D D, Lacy P, York E, Man S F. Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2004;  , (e-pub)
• 20 Davies L, Nisar M, Pearson M G, Costello R W, Earis J E, Calverley P MA. Oral corticosteroid trials in the management of stable chronic obstructive pulmonary disease.  QJM. 1999;  92 395-400
• 21 Brand P L, Quanjer P H, Postma D S et al.. Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.  Thorax. 1992;  47 429-436
• 22 Calverley P M, Burge P S, Spencer S, Anderson J A, Jones P W. Bronchodilator reversibility testing in chronic obstructive pulmonary disease.  Thorax. 2003;  58 659-664
• 23 Burge P S, Calverley P M, Jones P W, Spencer S, Anderson J A. Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study.  Thorax. 2003;  58 654-658
• 24 National Institute for Clinical Excellence . Chronic obstructive pulmonary disease; national clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care.  Thorax. 2004;  59(suppl 1) 1-232
• 25 Nisar M, Earis J E, Pearson M G, Calverley P M. Acute bronchodilator trials in chronic obstructive pulmonary disease.  Am Rev Respir Dis. 1992;  146 555-559
• 26 Albert R K, Martin T R, Lewis S W. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency.  Ann Intern Med. 1980;  92 753-758
• 27 Thompson W H, Nielson C P, Carvalho P, Charan N B, Crowley J J. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation.  Am J Respir Crit Care Med. 1996;  154 407-412
• 28 Niewoehner D E, Erbland M L, Deupree R H et al.. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease.  N Engl J Med. 1999;  340 1941-1947
• 29 Niewoehner D E, Collins D, Erbland M L. Relation of FEV(1) to clinical outcomes during exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.  Am J Respir Crit Care Med. 2000;  161 1201-1205
• 30 Aaron S D, Vandemheen K L, Hebert P et al.. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.  N Engl J Med. 2003;  348 2618-2625
• 31 Maltais F, Ostinelli J, Bourbeau J et al.. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.  Am J Respir Crit Care Med. 2002;  165 698-703
• 32 Sayiner A, Aytemur Z A, Cirit M, Unsal I. Systemic glucocorticoids in severe exacerbations of COPD.  Chest. 2001;  119 726-730
• 33 Renkema T E, Schouten J P, Koeter G H, Postma D S. Effects of long-term treatment with corticosteroids in COPD.  Chest. 1996;  109 1156-1162
• 34 Paggiaro P L, Dahle R, Bakran I, Frith L, Hollingworth K, Efthimiou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group [published erratum appears in Lancet 1998 Jun 27;351:1968].  Lancet. 1998;  351 773-780
• 35 Bourbeau J, Rouleau M Y, Boucher S. Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.  Thorax. 1998;  53 477-482
• 36 Wempe J B, Postma D S, Breederveld N, Kort E, van der Mark T W, Koeter G H. Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease.  Thorax. 1992;  47 616-621
• 37 Dompeling E, Van Schayck C P, Van Grunsven P M 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;  118 770-778
• 38 Hansen E F, Phanareth K, Laursen L C, Kok-Jensen A, Dirksen A. Reversible and irreversible airflow obstruction as predictor of overall mortality in asthma and chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1999;  159 1267-1271
• 39 Vestbo J, Sorensen T, Lange P, Brix A, Torre P, Viskum. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.  Lancet. 1999;  353 1819-1823
• 40 Pauwels R A, Lofdahl C-G, Laitinen L A et al.. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking.  N Engl J Med. 1999;  340 1948-1953
• 41 Calverley P M, Spencer S, Willits L, Burge P S, Jones P W. Withdrawal from treatment as an outcome in the ISOLDE study of COPD.  Chest. 2003;  124 1350-1356
• 42 Alsaeedi A, Sin D D, McAlister F A. 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
• 43 Sutherland E R, Allmers H, Ayas N T, Venn A J, Martin R J. Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis.  Thorax. 2003;  58 937-941
• 44 Calverley P, Pauwels R, Vestbo J et al.. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.  Lancet. 2003;  361 449-456
• 45 Jones P W, Quirk F H, Baveystock C M, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire.  Am Rev Respir Dis. 1992;  145 1321-1327
• 46 Vincken W, Van Noord J A, Greefhorst A P et al.. Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium.  Eur Respir J. 2002;  19 209-216
• 47 Spencer S, Calverley P MA, Burge P S, Jones P W. Health status deterioration in patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  163 122-128
• 48 van der V, Monninkhof E, van der P J, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study.  Am J Respir Crit Care Med. 2002;  166 1358-1363
• 49 Mahler D A, Wire P, Horstman D et al.. Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2002;  166 1084-1091
• 50 Pauwels R, Calverley P, Buist A S et al.. COPD exacerbations: the importance of a standard definition.  Respir Med. 2004;  98 99-107
• 51 Rodriguez-Roisin R. Toward a consensus definition for COPD exacerbations.  Chest. 2000;  117 398S-401S
• 52 Jones P W, Willits L R, Burge P S, Calverley P M. Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease.  Eur Respir J. 2003;  21 68-73
• 53 Spencer S, Calverley P M, Burge P S, Jones P W. Impact of preventing exacerbations on deterioration of health status in COPD.  Eur Respir J. 2004;  23 698-702
• 54 Global Initiative for Chronic Obstructive Lung Disease .Global strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. NIH Publication No 2701, 1-100. 2001, updated July 2004. Bethesda, MD; National Heart Blood and Lung Institute 2004
• 55 Celli B R, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.  Eur Respir J. 2004;  23 932-946
• 56 Sin D D, Tu J V. Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2001;  164 580-584
• 57 Suissa S. Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies.  Am J Respir Crit Care Med. 2003;  168 49-53
• 58 Soriano J B, Vestbo J, Pride N B, Kiri V, Maden C, Maier W C. Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice.  Eur Respir J. 2002;  20 819-825
• 59 Vestbo J. TORCH Study Group The TORCH (TOwards a Revolution in COPD Health) Survival Study protocol.  Eur Respir J. 2004;  24 206-210