Correspondence

Acute Exacerbations of Chronic Obstructive Pulmonary Disease

N Engl J Med 2002; 347:1533-1534November 7, 2002

Article

To the Editor:

In his Clinical Practice article (March 28 issue),1 Stoller states that the use of methylxanthines in patients with exacerbations of chronic obstructive pulmonary disease (COPD) remains “unclear.” My colleagues and I disagree. In a meta-analysis of randomized trials of methylxanthines, my team found no consistent benefit of methylxanthines for exacerbations of COPD and a clear increase in the risk of adverse effects.2 These findings concur with results of a systematic review of methylxanthines for exacerbations of asthma in adults.3

Stoller cites a large reduction in the rate of hospitalization among patients treated with aminophylline in one study of patients presenting to the emergency department with acute exacerbations of asthma or COPD. However, this reduction was not statistically significant among the patients with COPD4 and may have been offset by the trend toward increased rates of relapse among patients treated with methylxanthines and then sent home.2

Multiple international guidelines currently recommend methylxanthines for severe exacerbations. However, we agree with the American College of Physicians–American Society of Internal Medicine and the American College of Chest Physicians5 that current evidence does not support the use of methylxanthines for acute COPD. It strikes us that findings from systematic reviews should be applied in the development of guidelines, at the bedside, and in the case of COPD, in the search for new therapeutic agents. If methylxanthines are to play any part in the treatment of exacerbations of COPD, then new, more selective methylxanthines with fewer adverse effects will be required. As with other agents, randomized clinical trials will be necessary to evaluate any (probably small) clinical benefit in patients with exacerbations of COPD.

R. Graham Barr, M.D., M.P.H.
College of Physicians and Surgeons of Columbia University, New York, NY 10032
rgb9@columbia.edu

5 References

1. 1

   Stoller JK. Acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002;346:988-994
   Full Text | Web of Science | Medline

2. 2

   Barr RG, Rowe BH, Camargo CA Jr. Methyl-xanthines for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2001;1:CD002168-CD002168
   Medline

3. 3

   Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database Syst Rev 2000;4:CD002742-CD002742
   Medline

4. 4

   Wrenn K, Slovis CM, Murphy F, Greenberg RS. Aminophylline therapy for acute bronchospastic disease in the emergency room. Ann Intern Med 1991;115:241-247
   Web of Science | Medline

5. 5

   Bach PB, Brown C, Gelfand SE, McCrory DC. Management of exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence. Ann Intern Med 2001;134:600-620
   Web of Science | Medline

Author/Editor Response

Dr. Stoller replies:

To the Editor: Barr favors a stronger recommendation against the use of methylxanthines in patients with acute exacerbations of COPD. I completely agree that randomized, controlled trials and systematic reviews are the preferred basis for making clinical recommendations and would not want my statement that the “benefits of using a methylxanthine drug . . . remain unclear” to be misconstrued as a strong endorsement for using methylxanthines in this setting. Rather, my goal in citing the morsel of evidence from randomized trials supporting the use of a methylxanthine in managing acute exacerbations of COPD1 was to help explain why four of the five available guidelines (including that of the Global Initiative for Chronic Obstructive Lung Disease2) indicate that methylxanthines may be considered a “salvage” therapy in this setting.

I hope that in noting that I did not recommend methylxanthines for the patient described in the vignette in my article, Barr recognizes that my statement and his may differ more in tone and flavor than in substance.

James K. Stoller, M.D.
Cleveland Clinic Foundation, Cleveland, OH 44195
stollej@ccf.org

2 References

1. 1

   Wrenn K, Slovis CM, Murphy F, Greenberg RS. Aminophylline therapy for acute bronchospastic disease in the emergency room. Ann Intern Med 1991;115:241-247
   Web of Science | Medline

2. 2

   Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. 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;163:1256-1276
   Medline

Citing Articles (1)

Citing Articles

1. 1

   Kim Fromme, Harriet de Wit, Kent E. Hutchison, Lara Ray, William R. Corbin, Travis A.R. Cook, Tamara L. Wall, David Goldman. (2004) Biological and Behavioral Markers of Alcohol Sensitivity. Alcoholism: Clinical & Experimental Research 28:2, 247-256
   CrossRef