Health Evidence Bulletins - Wales
Team Leader: Dr Michael Burr Date of completion: 5/3/98

The contents of this bulletin are likely to be valid for approximately one year, by which time significantly new research evidence may become available

10. Chronic Bronchitis and Emphysema - Drug management

(Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation)

The Statements The Evidence
10a. British Guidelines for the management of chronic bronchitis and emphysema (chronic obstructive pulmonary disease) are availablei. i. The COPD Guidelines Group of the Standards of Care Committee of the British Thoracic Society. BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997; 52 suppl.5
(Type V evidence - expert opinion)
10b. Patients with severely hypoxaemic chronic obstructive pulmonary disease survive longer if given domiciliary oxygen for at least 15 hours per dayi.
(Health gain notation - 1 "beneficial")
Patients whose PaO2 exceeds 7.9 kilopascals (60 mm Hg) gain only small benefits (as measured by physiological function, exercise tests, and quality of life)ii.
i. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; i: 681-686
(Type II evidence - randomised controlled trial);
ii. McDonald CF, Blyth CM, Lazarus MD, Marschner I, Barter CE. Exertional oxygen of limited benefit in patients with chronic obstructive pulmonary disease and mild hypoxemia. American Journal of Respiratory and Critical Care Medicine 1995; 152: 1616-1619
(Type II evidence - randomised controlled trial)
10c. Inhaled bronchodilators are helpful for many patients. A combination of salbutamol and ipratropium is more effective on lung function than either drug alone, avoiding the risk of side effects consequent upon larger doses of either drugi. Salmeterol is also beneficial for the control of symptomsii.
(Health gain notation - 2 "likely to be beneficial")
i. COMBIVENT Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone: an 85-day multicenter trial. Chest 1994; 105: 1411-1419
(Type II evidence - randomised controlled trial);
ii. Ulrik CS. Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study. Thorax 1995; 50: 750-754
(Type II evidence - randomised controlled trial)
10d. Oral theophylline is helpful to some patients but not to others; since theophylline-response cannot be predicted, it should be tested on individual patients, preferably in n of 1 trialsi,ii. It is a useful addition to inhaled bronchodilator therapy in these patientsiii,iv.

(Health gain notation - 3 "trade-off between beneficial and adverse effects")

i. Kirsten, DK, Wegner RE, Jörres RA, Magnussen H. Effects of theophylline withdrawal in severe chronic obstructive pulmonary disease. Chest 1993; 104: 1101-1107 (Type II evidence - randomised controlled trial);
ii. Mahon J, Laupacis A, Donner A, Wood T. Randomised study of n of 1 trials versus standard practice. British Medical Journal 1996; 312: 1069-1074
(Type II evidence - randomised controlled trial);
iii. Karpel JP, Kotch A, Zinny M, Pesin J, Alleyne W. A comparison of inhaled ipratropium, oral theophylline plus inhaled b -agonist, and the combination of all three in patients with COPD. Chest 1994; 105: 1089-1094 (Type II evidence - randomised controlled trial);
iv. Fink G, Kaye C, Sulkes J, Gabbay U, Spitzer SA. Effect of theophylline on exercise performance in patients with severe chronic obstructive pulmonary disease. Thorax 1994; 49: 332-334
(Type II evidence - randomised controlled trial)


10e. The value of inhaled steroids for chronic obstructive pulmonary disease should become clear on the completion of large studies currently in progressi,ii; existing evidence about inhaled and oral steroids, based on lung function, exercise and other psychological tests, is equivocaliii,iv.

(Health gain notation - 4 "unknown")

i. Pauwels RA, Lofdahl C-G, Pride NB, Postma DS, Laitinen LA, Ohlsson SV. European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design. European Respiratory Journal 1992; 5: 1254-126
(Large randomised trial currently in progress);
ii. ISOLDE Trial
(Large randomised trial currently in progress - Contact Glaxo on 0181 422 3434);
iii. Lange P. Corticosteroids in obstructive lung disease. European Respiratory Review 1995; 5: 31, 333-338
(Type II evidence - summary of randomised controlled trials);
iv. Callahan CM, Dittus RS, Katz BP. Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease: a meta-analysis. Annals of Internal Medicine 1991; 114: 216-223
(Type I evidence - meta analysis)
10f. Antibiotics confer some benefit (improvements in symptoms, duration and lung function) in acute exacerbations of chronic obstructive pulmonary diseasei.
(Health gain notation - 1"beneficial")
i. Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis. Journal of the American Medical Association 1995; 273: 957-960
(Type I evidence - meta-analysis)
10g. There is uncertainty about the value of nebulizers; for most adult patients with severe disease nebulizers have no advantage over inhalers in terms of lung function and quality of lifei and may even be less effectiveii.

(Health gain notation - 5 "unlikely to be beneficial")

i. Hansen NCG, Evald T and Ibsen TB. Terbutaline inhalations by the Turbuhaler as replacement for domiciliary nebulizer therapy in severe chronic obstructive pulmonary disease. Respiratory Medicine 1994; 88: 267-271
(Type II evidence - randomised controlled trial);
ii. Hansen NCG, Andersen PB. Salbutamol powder inhaled from the Diskhaler compared to salbutamol as nebulizer solution in severe chronic airways obstruction. Respiratory Medicine 1995; 89: 175-179
(Type II evidence - randomised controlled trial)

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