Clinical review
Clinical evidenceStable chronic obstructive pulmonary disease
Huib A M Kerstjens Department of Pulmonary Diseases, University
Hospital Groningen, PO Box 30 001, 9700 RB Groningen, Netherlands
h.a.m.kerstjens{at}int.azg.nl
This review is taken from Issue 1 of Clinical
Evidence, a new information resource for clinicians published by
BMJ Publishing Group. The compendium will be updated and expanded every
six months. Future issues of Clinical Evidence will cover
respiratory stimulants, DNAse,
1 antitrypsin
augmentation, and vaccination against influenza and
streptococcus.
Key messages
smoking cessation and long
term treatment with oxygen (in people with hypoxaemia)have been found
to alter the long term course of chronic obstructive pulmonary disease
2
agonists, and oral steroids; the effects of anticholinergic drugs and
2 agonists are not seen in all people with chronic
obstructive pulmonary disease, and the two agents combined are slightly
more effective than either alone.2 agonists, oral
corticosteroids, and antibiotics have not yet been evaluated for their
long term effects.but there is some evidence from RCTs that
maintenance treatment with inhaled corticosteroids may improve lung
function.
 |
Background |
|---|
Top
Background
Methods
2 agonists|
Interventions in stable chronic
obstructive pulmonary disease
|
| |
Methods |
|---|
This review deals only with maintenance treatment in stable chronic obstructive pulmonary disease, and not with treatment of acute exacerbations. A Clinical Evidence search was performed in July 1998. Where we found no systematic reviews, we searched for RCTs. Because we were interested in maintenance treatment, we did not include single dose or single day cumulative dose response trials.
|
Question: What are the short and long term effects of maintenance treatment in stable chronic obstructive pulmonary disease? |
| |
Option: Inhaled anticholinergic drugs |
|---|
Trials using a range of methods found that anticholinergic drugs achieve short term bronchodilation and relieve symptoms in people with chronic obstructive pulmonary disease. One large randomised controlled trial (RCT) found no evidence that maintenance treatment with inhaled anticholinergic drugs improved long term prognosis.
Benefits
We found no systematic review of the benefits of treatment with
inhaled anticholinergic drugs.
Harms
In the lung health study, serious adverse effects (cardiac
symptoms, hypertension, skin rashes, and urinary retention) occurred in
1.2% of patients receiving ipratropium bromide and 0.8% receiving
placebo.8 Dry mouth was the most common mild adverse
effect. One RCT in 233 people with asthma or chronic obstructive
pulmonary disease found that continuous treatment, as opposed to
treatment as needed, with bronchodilators (both ipratropium bromide and
fenoterol) resulted in faster decline in lung function.16
This finding has not been replicated by others, including the much
larger lung health study.8
Comment
Over a five year period, there was no evidence that patients
developed tachyphylaxis to the bronchodilating effect of ipratropium
bromide.8
| |
Option: Inhaled  2 agonists |
|---|
RCTs found that short acting and long acting inhaled
2 agonists achieve short term bronchodilation and
relieve symptoms in many people with chronic obstructive pulmonary
disease. The effects of maintenance treatment with 2
agonists on progression of the disease have not yet been adequately evaluated.
Benefits
We found no systematic review.
2 agonists in people with chronic
obstructive pulmonary disease. In general these reported improved
symptoms. About half of the trials that looked at exercise capacity
found improvements. 2 Agonists achieved variable degrees
of bronchodilation in the smaller and shorter studies. One RCT in 985 people with severe disease found a significant increase in lung
function in up to half of patients.17 The new long acting
inhaled 2 agonists have been tested in single dose and
short term studies. These suggest that their maximum effectiveness is
comparable to short acting 2 agonists, but with longer
duration.
18 19
At least three RCTs of salmeterol have
found significant improvements in symptoms and quality of life compared
with placebo, even in the presence of only modest or no change in lung
function.20-22
Maintenance treatment: We found no RCTs looking at reduction
of decline in lung function with inhaled 2 agonists
versus placebo.
Harms
In people with asthma, 2 agonists have been linked
to increased risk of death,23 worsened asthma control, and
deterioration in lung function. Similar data are not available for
chronic obstructive pulmonary disease. One RCT in 223 people with
asthma or chronic obstructive pulmonary disease found that continuous
treatment, as opposed to treatment as needed, with bronchodilators
(ipratropium bromide as well as fenoterol) resulted in faster decline
in lung function.16 We found no other studies of
2 agonists in chronic obstructive pulmonary disease
addressing this possibility. There are no systematic data on frequency
of adverse effects of 2 agonists in chronic obstructive
pulmonary disease. The most common immediate adverse effect is tremor,
which is usually worse in the first few days of treatment. High doses of 2 agonists can cause a fall in plasma potassium,
dysrhythmias, and reduced arterial oxygen tension.24
Comment
Long term placebo controlled RCTs of 2 agonists are
difficult to perform because of clinicians' firmly held belief in the
short term benefits of 2 agonists.
| |
Option: 2 agonists plus anticholinergic drugs |
|---|
RCTs found that combining a 2 agonist with an
anticholinergic drug provided small additional bronchodilation compared
with either drug alone.
Benefits
We found no systematic review of the benefits of 2
agonists plus anticholinergic drugs. We found three large RCTs (n=534,
195, and 652) comparing the addition of ipratropium to standard dose
inhaled 2 agonists for about 90 days in people with
stable chronic obstructive pulmonary disease.25-27 All
three found significant improvements in FEV1 of about 25%
with the combination compared with either drug alone.
Harms
There were no significant increases in adverse effects.
| |
Option: 2 agonists versus anticholinergics |
|---|
One systematic review of RCTs has found greater bronchodilator
response with anticholinergic agents than 2 agonists in
people with chronic obstructive pulmonary disease.
Benefits
Short term treatment: Several RCTs have compared ipratropium bromide versus a 2 agonist. They used a
range of methodologies and have not been systematically reviewed.
2 agonists for 90 days.28 Lung function
measurements were performed after bronchodilators were withheld for at
least 12 hours. The mean improvement in FEV1 was
significantly greater with ipratropium bromide than with the
2 agonists (28 ml increase v 1 ml decrease, P<0.05). A residual effect of the anticholinergic cannot be fully ruled out; this limits the interpretation of a favourable effect of
anticholinergics on decline in lung function compared with 2 agonists.
Harms
The adverse effects of 2 agonists (tremor and
dysrhythmias) are more frequent than those of anticholinergics.
Comment
It has been suggested that older people experience greater
bronchodilator response with anticholinergics than with 2 agonists, but this has not yet been adequately investigated.
| |
Option: Theophyllines |
|---|
We found limited evidence from small RCTs for at most a small bronchodilatory effect of theophyllines in people with chronic obstructive pulmonary disease. Adverse effects are common.
Benefits
We found no systematic review of the benefits of theophyllines in
chronic obstructive pulmonary disease.
Harms
The therapeutic range for theophyllines is small. Blood
concentrations of 15-20 mg/l are required for optimal effects. Adverse
effects include nausea, diarrhoea, headache, irritability, seizures,
and cardiac arrhythmias. These occur at highly variable blood
concentrations and, in many people, within the therapeutic range. Dose
must be adjusted individually according to smoking habits, infection,
and other treatments.
Comment
Non-bronchodilator effects of theophylline have been investigated
in laboratory settings, including effects on respiratory muscles and
improved right ventricular function. Their clinical significance has
not been established. Anti-inflammatory effects have been claimed in
asthma, especially at lower dosages, but have not been tested for in
chronic obstructive pulmonary disease.
| |
Option: Systemic corticosteroids |
|---|
One systematic review of short term RCTs has found significant bronchodilatory effect compared with placebo in people with chronic obstructive pulmonary disease. Long term effects on lung function have not been investigated in an RCT, and these would have to be weighed against potentially serious adverse effects.
Benefits
Short term treatment: We found one systematic review
published in 1991, which identified 15 RCTs of oral steroids in stable
chronic obstructive pulmonary disease.30 Duration of
treatment was generally 2-4 weeks. Meta-analysis of data from the 10 RCTs that met all inclusion criteria found that improvement of 20% or
more in baseline FEV1 occurred significantly more
often with oral corticosteroids than placebo (weighted mean difference in effect size 10%, 95% confidence interval 2% to 18%). When the other five RCTs were included, the difference in effect size was 11%
(4% to 18%).
Harms
Many reviews have elaborated on the considerable potential harms
of systemic corticosteroids. Perhaps the most important in this patient
population are osteoporosis and induction of overt diabetes.
Comment
If longer term (>2-4 weeks) use of oral steroids in chronic
obstructive pulmonary disease should be found to be useful, this would
have to be weighed against substantial adverse effects. Moreover, it
would be mandatory to compare the benefits and harms of these agents
with the benefits and harms of inhaled steroids.
| |
Inhaled corticosteroids |
|---|
Short term studies have found no evidence of effects of inhaled steroids. The few fully published long term studies found a small beneficial effect on lung function.
Benefits
Short term treatment: We found no systematic review. We
found a systematic review containing 13 placebo controlled RCTs.31 Nine were short term (10 days to 10 weeks), and
ranged in patient numbers from 10 to 127. All but one of these short term studies showed no significant benefit in change of
FEV1 from use of inhaled steroids in chronic
obstructive pulmonary disease. None of the studies measuring airway
hyperresponsiveness to histamine documented a change.
6
to 84 ml/year, P=0.095), or in the frequency of exacerbations. A
multicentre study, published since the search date for the systematic
review, evaluated six months' treatment with fluticasone in 281 people
with chronic obstructive pulmonary disease.33 This
found a significant reduction in moderate and severe (but not mild)
exacerbations, and a small but significant improvement in lung function
and six minute walking distance.
Harms
We found no good RCTs providing data on adverse effects of
prolonged inhaled steroids in chronic obstructive pulmonary disease,
and interpretation of available studies is hampered by concomitant use
of short bursts of oral steroids. Extrapolation from studies in people
with asthma is of limited value as patients with chronic obstructive
pulmonary disease are generally at higher risk for osteoporosis because
of age, menopausal status, inactivity, and cigarette
smoking.34
Comment
Three large, two to three year European multicentre RCTs of
inhaled steroids in chronic obstructive pulmonary disease (with about
300, 750, and 950 patients) have recently been completed, and full
results, including valuable information on adverse effects, should be
available soon (RA Pauwels, PS Burge, J Vestbo, personal communications). A large North American RCT is also under way (AS
Buist, personal communication).
| |
Option: Inhaled versus oral steroids |
|---|
We found limited evidence from RCTs that oral prednisolone is more effective than inhaled beclomethasone in people with mild to moderate chronic obstructive pulmonary disease.
Benefits
We found no systematic review.
Harms
None of the RCTs reported adverse effects.
Comment
The smallest RCT recruited only people known to be responsive to
oral steroids and did not report the severity of chronic obstructive
pulmonary disease.36 The other two RCTs included people
with chronic obstructive pulmonary disease of more than five years'
duration and FEV1 <70%
predicted.
35 37
All studies excluded people with evidence
of reversible airflow obstruction.
| |
Option: Mucolytic drugs |
|---|
One systematic review of RCTs has found that mucolytics have a modest beneficial effect on frequency and duration of exacerbations compared with placebo. The evidence also suggests a modest adverse effect on lung function.
Benefits
Maintenance treatment: We found one systematic review
updated in 1998, which identified 15 double blind placebo controlled
RCTs.38 Mucolytics significantly reduced the number of
exacerbations (weighted mean difference compared with placebo 0.105
exacerbations per month; 0.11 to 0.10, P<0.001) and days of
disability (weighted mean difference 0.664 days per month; 0.689
to 0.640). There was no significant difference in the number of days
patients were taking antibiotics per month (weighted mean difference
compared with placebo 0.677 days per month; 0.710 to 0.644). Most
of the trials were in people with mild disease. The two trials in
people with severe disease (FEV1 <50%) found greater reductions in frequency of exacerbation (weighted mean difference compared with placebo 0.142, 95% confidence interval not
given). There was no significant difference between N-acetylcysteine and other mucolytics as a group.
Harms
The review found a small but significant reduction in lung
function compared with placebo (weighted mean difference in
FEV1 compared with mucolytics 0.057 l;
0.039 to 0.075 l, and in forced vital capacity 0.04 l;
0.017 to 0.063 l).38 The review did not include a
separate analysis of the effect of N-acetylcysteine alone on decline in
lung function. There was no difference between mucolytics and placebo
in the total number of adverse events.38 Adverse effects
of N-acetylcysteine consist mainly of mild gastrointestinal complaints.
Comment
There was considerable heterogeneity between the RCTs, and it was
not possible to include symptom scores in the meta-analysis as these
were not reported in a sufficiently coherent fashion. The theoretical
antioxidant effect of N-acetylcysteine in slowing the decline in lung
function has not been proved. It is currently the subject of a large
European multicentre study (PNR Dekhuijzen, personal communication).
| |
Option: Antibiotics |
|---|
The effects of antibiotics in maintenance treatment of stable chronic obstructive pulmonary disease have not been evaluated in RCTs.
Benefits
Maintenance treatment: We found one systematic review
published in 1995, which identified no RCTs of the use of antibiotics
as maintenance treatment in stable chronic obstructive pulmonary
disease.39
Harms
The adverse effects of antibiotics vary greatly between agents and individuals.
| |
Option: Long term oxygen treatment |
|---|
We found limited evidence from one RCT that long term oxygen treatment improves survival in people with chronic obstructive pulmonary disease and hypoxaemia. Continuous treatment is more effective than nocturnal treatment.
Benefits
We found no systematic review. We found two RCTs on the effects of
long term domiciliary oxygen.
40 41
Harms
No adverse effects of long term oxygen have been reported.
Administration is cumbersome and expensive.
Comment
None.
| |
Footnotes |
|---|
Competing interests: HAMK has received funding from Astra, the manufacturer of budesonide, terbutaline, formoterol; Glaxo Wellcome, the manufacturer of beclomethasone, salbutamol, salmeterol; and Boehringer Ingelheim, the manufacturer of fenoterol and ipratropium bromide.
|
| |
References |
|---|
| 1. | Kerstjens HAM, Brand PLP, Postma DS. Risk factors for accelerated decline among patients with chronic obstructive pulmonary disease [review]. Am J Respir Crit Care Med 1996; 154: S266-S272. |
| 2. | American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease: ATS statement. Am J Respir Crit Care Med 1995; 152: S77-120. |
| 3. |
Whittemore AS, Perlin SA, DiCiccio Y.
Chronic obstructive pulmonary disease in lifelong nonsmokers: results from NHANES.
Am J Public Health
1995;
85:
702-706 |
| 4. |
Brunekreef B, Fischer P, Remijn B, van der Lende R, Schouten JP, Quanjer PH.
Indoor air pollution and its effects on pulmonary function of adult non-smoking women: III. Passive smoking and pulmonary function.
Int J Epidemiol
1985;
14:
227-230 |
| 5. | Rijcken B, Weiss ST. Longitudinal analyses of airway responsiveness and pulmonary function decline. Am J Respir Crit Care Med 1996; 154: S246-S249. |
| 6. | Dockery DW, Brunekreef B. Longitudinal studies of air pollution effects on lung function. Am J Respir Crit Care Med 1996; 154: S250-S256. |
| 7. | O'Connor GT, Sparrow D, Weiss ST. The role of allergy and non-specific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease: state of the art. Am Rev Respir Dis 1989; 140: 225-252[Medline]. |
| 8. | Anthonisen NR, Connett JE, Kiley JP, Altose MB, Failey WC, Buist AS, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA 1994; 272: 1497-1505[Abstract]. |
| 9. | Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD): a consensus statement of the European Respiratory Society. Eur Respir J 1995; 8: 1398-1420[Medline]. |
| 10. | Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987; 42: 773-778[Abstract]. |
| 11. | Jones PW, Quirk FH, Baveystock CM, 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[Medline]. |
| 12. | Braun SR, McKenzie WN, Copeland W, Kingman L, Ellersieck M, Knight GJ. A comparison of the effect of ipratropium bromide and albuterol in the treatment of chronic obstructive airway disease. Arch Intern Med 1989; 149: 544-547[Abstract]. |
| 13. | Higgins BG, Powell RM, Cooper S, Tattersfield AE. Effect of salbutamol and ipratropium bromide on airway calibre and bronchial reactivity in asthma and chronic bronchitis. Eur Respir J 1991; 4: 415-420[Abstract]. |
| 14. |
Ikeda A, Nishimura K, Koyama H, Izumi T.
Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.
Chest
1995;
107:
401-405 |
| 15. | Ikeda A, Nishimura K, Koyama H, Izumi T. Comparative dose-response study of three anticholinergic agents and fenoterol using a metered dose inhaler in patients with chronic obstructive pulmonary disease. Thorax 1995; 50: 62-66[Abstract]. |
| 16. | Van Schayck CP, Dompeling E, van Herwaarden CLA, Folgering H, Verbeek AL, van der Hoogen HJ, et al. Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomised controlled study. BMJ 1991; 303: 1426-1431. |
| 17. | Anthonisen NR, Wright EC, IPPB Trial Group. Bronchodilator response in chronic obstructive pulmonary disease. Am Rev Respir Dis 1986; 133: 814-819[Medline]. |
| 18. | Grove A, Lipworth BJ, Reid P, Smith RP, Ranage L, Ingram CG, et al. Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease. Thorax 1996; 51: 689-693[Abstract]. |
| 19. | Matera MG, Cazzola M, Vinciguerra A, Di Perna F, Calderaro F, Caputi M, et al. A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease. Pulm Pharmacol 1995; 8: 267-271[Medline]. |
| 20. | Boyd G, Morice AH, Pounsford JC, Siebert M, Peslis N, Crawford C. An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD). Eur Respir J 1997; 10: 815-821[Abstract]. |
| 21. | Jones PW, Bosh TK. Quality of life changes in COPD patients treated with salmeterol. Am J Respir Crit Care Med 1997; 155: 1283-1289[Abstract]. |
| 22. | 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[Abstract]. |
| 23. | Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, et al. The use of beta agonists and the risk of death and near death from asthma. N Engl J Med 1992; 326: 501-506[Abstract]. |
| 24. | Hall IP, Tattersfield AE. Beta-agonists. In: Clark TJH, Godfrey S, Lee TH, eds. Asthma. 3rd ed. London: Chapman and Hall Medical, 1992:341-365. |
| 25. | Combivent Inhalation Aerosol Study Group. In chronic obstructive pul-monary disease, a combination of ipratropium and albuterol is more effective than either agent alone: an 85-day multicenter trial. Chest 1994; 5: 1411-1419. |
| 26. | Levin DC, Little KS, Laughlin KR, Galbraith JM, Gustman PM, Murphy D, et al. Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease. Am J Med 1996; 100: 40-8S. |
| 27. |
Combivent Inhalation Solution Study Group.
Routine nebulized ipratropium and albuterol together are better than either alone in COPD.
Chest
1997;
112:
1514-1521 |
| 28. |
Rennard SI, Serby CW, Ghafouri M, Johnson PA, Friedman M.
Extended therapy with ipratropium is associated with improved lung function in patients with COPD: a retrospective analysis of data from seven clinical trials.
Chest
1996;
110:
62-70 |
| 29. | Calverley PMA. Symptomatic bronchodilator treatment. In: Calverley PMA, Pride N, eds. Chronic obstructive pulmonary disease. London: Chapman and Hall, 1995:419-446. |
| 30. | Callahan CM, Dittus RS, Katz BP. Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease: a meta-analysis. Ann Intern Med 1991; 114: 216-223. |
| 31. |
Barnes PJ, Pedersen S, Busse WW.
Efficacy and safety of inhaled corticosteroids: new developments.
Am J Respir Crit Care Med
1998;
157:
S1-53 |
| 32. |
Van Grunsven PM, van Schayck CP, Derenne JP, Kerstjens HA, Renkema TE, Postma DS, et al.
Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.
Thorax
1999;
54:
7-14 |
| 33. | Paggiaro PL, Dahle R, Bakran I, Frith L, Hollingworth K, Efthimou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. Lancet 1998; 351: 773-780[Medline]. |
| 34. |
McEvoy CE, Niewoehner DE.
Adverse effects of corticosteroid therapy for COPD: a critical review.
Chest
1997;
111:
732-743 |
| 35. | Robertson AS, Gove RI, Wieland GA, Burge PS. A double-blind comparison of oral prednisolone 40 mg/day with inhaled belomethasone dipropionate 1500 mg/day in patients with adult onset chronic obstructive airways disease. Eur J Respir Dis 1986; 69(suppl 146): 565-569. |
| 36. | Shim CS, Williams MH. Aerosol beclomethasone in patients with steroid-responsive chronic obstructive pulmonary disease. Am J Med 1985; 78: 655-658[Medline]. |
| 37. | Weir DC, Gove RI, Robertson AS, Burge PS. Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate. Thorax 1990; 45: 112-117[Abstract]. |
| 38. | Poole PJ, Black PN. Do mucolytics reduce the frequency of exacerbations in chronic bronchitis? In: Cochrane Collaboration ed. The Cochrane Library. Issue 4. Oxford: Update Software , 1998. |
| 39. | Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis. JAMA 1995; 273: 957-960[Abstract]. |
| 40. | 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. |
| 41. | Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980; 93: 391-398. |
© BMJ 1999
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
Related Article
- Stable chronic obstructive pulmonary disease
- M C Steiner, S Singh, M D L Morgan, Phillippa Poole, Peter Black, and Huib A M Kerstjens
BMJ 2000 320: 312.[Extract] [Full Text]
This article has been cited by other articles:
-
Peterson, G. M, Boyles, P. J, Bleasel, M. D, Vial, J. H
(2003). Ipratropium Treatment of Acute Airways Disease. The Annals of Pharmacotherapy
37: 339-344
[Abstract] [Full text] -
Lipworth, B. J.
(2001). Optimizing Bronchodilator Therapy for COPD. Chest
119: 1628-1630
[Full text] -
Beauchesne, M.-F.
(2001). Management of Chronic Obstructive Pulmonary Disease: A Review. Journal of Pharmacy Practice
14: 126-142
[Abstract] -
Tung, A.
(2000). Perioperative Ventilation of the Vascular Surgery Patient. SEMIN CARDIOTHORAC VASC ANESTH
4: 265-274
[Abstract] -
Steiner, M C, Singh, S, Morgan, M D L, Poole, P., Black, P., Kerstjens, H. A M
(2000). Stable chronic obstructive pulmonary disease. BMJ
320: 312-312
[Full text]
Rapid Responses:
Read all Rapid Responses
- Correction-Mucolytics and Lung Function
- Phillippa Poole, et al.
bmj.com, 31 Aug 1999 [Full text] - Incomplete Evidence Based Reviews may Condemn by Omission
- M C Steiner
bmj.com, 5 Oct 1999 [Full text] - A pressing need for the development of new therapies in COPD
- S K Agarwal
bmj.com, 28 May 2000 [Full text]
This article
-
Extract
- Respond to this article
- Read responses to this article
- Alert me when this article is cited
- Alert me when responses are posted
- Alert me when a correction is posted
- View citation map
Services
- Email this article to a friend
- Find similar articles in BMJ
- Find similar articles in PubMed
- Add article to my folders
- Download to citation manager
- Request Permissions
Citing Articles
Google Scholar
PubMed
Related content
Bookmark with
What's new
Latest blogs
Services
Tools
Online poll
Resources
Rapid responses for this article
Most read last week
Print issues
