corticoid trong copd

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new england journal

of

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editorials

Systemic Corticosteroids for Acute Exacerbations
of Chronic Obstructive Pulmonary Disease

Richard S. Irwin, M.D., and J. Mark Madison, M.D.

Chronic obstructive pulmonary disease (COPD) is a
common disease that affects up to 24 million people
in the United States and leads to substantial disabil-
ity and death.

1

Patients with COPD have about three
acute exacerbations of their disease per year,

2

many
of which result in unscheduled visits to a physician
or emergency department and to hospitalization.
Although it is currently the fourth leading cause of
death in the United States

1

and the sixth world-
wide,

3

COPD is predicted to be the third leading
cause of death and fifth leading cause of disability in
the world by 2020.

3

Although there is no universally accepted defini-
tion of COPD

4

or an acute exacerbation of COPD,

5

because experts have promulgated criteria that vary
in some respects, most current definitions contain
the same key elements.

4

The definition of the Glob-
al Initiative for Chronic Obstructive Lung Disease

6

has gained widespread acceptance: “COPD is a dis-
ease state characterized by airflow limitation that is
not fully reversible. The airflow obstruction is usu-
ally both progressive and associated with an abnor-
mal inflammatory response of the lungs to noxious
particles or gases.” This definition specifies that
poorly reversible airflow limitation due to other ob-
structive airway diseases (e.g., bronchiectasis, cyst-
ic fibrosis, or asthma) is not included unless these
diseases coexist with COPD.

4,6

An acute respiratory deterioration in a patient

with COPD can be due to many conditions, such as
pneumonia, congestive heart failure, pneumotho-
rax, and venous thromboembolism, but they are not
generally considered acute exacerbations of COPD
itself. Many have defined an acute exacerbation of
COPD as a subjective increase, from base line, in
some combination of dyspnea, sputum purulence,
and sputum volume owing to acute tracheobronchi-
tis,

5,7

which has an infectious cause approximately
80 percent of the time and occurs in a patient with
established COPD. An important element of this
definition is that causes of respiratory deterioration
other than acute tracheobronchitis are excluded.

5

It is not clear why this definition has not been uni-
versally accepted, because it is the one that has been
used most consistently in rigorous double-blind,
randomized, placebo-controlled trials assessing
therapies for an acute deterioration in respiratory
status in patients with COPD.

8-11

Recent randomized, double-blind, placebo-con-

trolled trials or meta-analyses of such trials have fi-
nally provided clinicians with high-quality evidence
that patients with an acute exacerbation of COPD
can benefit from multiple therapies,

12

including
systemic corticosteroids.

10,12

For patients with at
least moderate COPD at base line (as defined by a
forced expiratory volume in one second [FEV

1

] of
less than 0.8 liter or a ratio of FEV

1

to forced vital ca-
pacity of less than 50 percent), short-term systemic
corticosteroids, in combination with other effective
therapies,

12

have provided relatively small but clin-
ically significant improvements in the duration of
hospitalization, lung function, and the incidence of
treatment failure; the results have been observed in
specific groups of inpatients (those with hypercap-
nia and those without hypercapnia who are breath-
ing spontaneously) and outpatients.

10

The results of the study by Aaron et al.

11

in this
issue of the

Journal

lend further support to the short-
term use of systemic corticosteroids for acute exac-
erbations of COPD and fill a gap in information re-
garding the role of systemic corticosteroids after
discharge from the emergency department. As com-
pared with placebo, a 40-mg dose of oral prednisone
once daily for 10 days, given in combination with
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oral antibiotics and inhaled bronchodilators, de-
creased the rate of clinical relapse (defined as an un-
scheduled visit to a physician, a return to the emer-
gency department, or worsening dyspnea) within
the next 30 days (relapse rate, 27 percent, vs. 43
percent in the placebo group; P=0.05) and, after
10 days of therapy, improved FEV

1

(mean increase
from base line, 34 percent vs. 15 percent; P=0.007)
and dyspnea (P=0.04).

Although we know which patients with an exac-
erbation of COPD are likely to benefit from systemic
corticosteroids and in which settings, the optimal
dose and need for tapering, route of administration,
and length of treatment are uncertain. The most re-
cent data

10,11

support the use of a short course of
no more than 10 to 15 days. Improved clinical out-
comes have been achieved with dosages ranging
from 30 mg of oral prednisolone daily or 40 mg of
oral prednisone daily in outpatient and emergency
department settings to 125 mg of intravenous meth-
ylprednisolone every six hours for three days, fol-
lowed by 60 mg of oral prednisone daily for four
days and then by a gradual tapering of the dose to
zero on day 15, in hospitalized patients.

10

Oral corticosteroids are often prescribed for pa-
tients with stable COPD to prevent acute exacerba-
tions and improve lung function and reduce symp-
toms. However, the benefits of this strategy have
been studied in patients with stable COPD of at least
moderate severity and have been found to be mar-
ginal at best. In a meta-analysis of 10 trials, patients
with stable COPD who were receiving oral cortico-

steroids had a clinically meaningful improvement in
FEV

1

only 10 percent more often than did similar
patients who were receiving placebo.

13

Moreover,
in a double-blind, randomized, placebo-controlled
trial involving 38 patients, the discontinuation of
long-term treatment with oral prednisone did not
lead to a significant increase in exacerbations of
COPD over a six-month period.

14

In summary, evidence from rigorously designed
trials has helped to clarify the role of systemic cor-
ticosteroids in treating and preventing acute exac-
erbations of COPD. First, systemic corticosteroids
have an established role in the treatment of specific
groups of patients who have acute exacerbations of
COPD. Even though it is still not clear how their
beneficial effects are achieved,

15

short courses of
systemic corticosteroids in patients with at least
moderately severe COPD, in combination with other
effective therapies, can significantly improve clini-
cal outcomes in outpatient and inpatient settings
and after discharge from the emergency depart-
ment. On the other hand, the role of systemic corti-
costeroids in treating acute exacerbations of COPD
in patients who are receiving mechanical ventilation
has yet to be rigorously studied. Second, although
systemic corticosteroids are often prescribed for pa-
tients with stable COPD to prevent acute exacerba-
tions, the evidence does not support the routine use
of this practice. Although it is not the focus of this
editorial, the fact that the role of inhaled, as opposed
to systemic, corticosteroids in preventing acute ex-
acerbations of COPD continues to be intensely in-
vestigated is important.

16-18

We encourage readers
to monitor this literature closely.
Although the benefits of short-term therapy with
systemic corticosteroids during acute exacerbations
of COPD are real and important, they are of moder-
ate magnitude and are not the answer to controlling
or reversing the epidemic of COPD. In addition, be-
cause patients with COPD are at increased risk for
drug-related side effects, it is important to inform

them of the potential side effects (as well as bene-
fits) of corticosteroids, to monitor patients for side
effects, and to intervene to minimize such effects
whenever possible.

19

From the Division of Pulmonary, Allergy, and Critical Care Medi-
cine, University of Massachusetts Medical School, Worcester.

1.

Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC.
Chronic obstructive pulmonary disease surveillance — United States,
1971–2000. MMWR CDC Surveill Summ 2002;51:(SS-6):1-16.

2.

Seemungal TAR, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ,
Wedzicha JA. Effect of exacerbation on quality of life in patients with
chronic obstructive pulmonary disease. Am J Respir Crit Care Med
1998;157:1418-22.

3.

Murray CJ, Lopez AD. Alternative projections of mortality and
disability by cause 1990-2020: Global Burden of Disease Study. Lan-
cet 1997;349:1498-504.

4.

Snider GL. Nosology for our day: its application to chronic ob-
structive pulmonary disease. Am J Respir Crit Care Med 2003;167:
678-83.

5.

Madison JM, Irwin RS. Chronic obstructive pulmonary disease.
Lancet 1998;352:467-73.

6.

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 Initia-
tive for Chronic Obstructive Lung Disease (GOLD) Workshop sum-
mary. Am J Respir Crit Care Med 2001;163:1256-76.

7.

Sethi S. Infectious etiology of acute exacerbations of chronic
bronchitis. Chest 2000;117:Suppl 2:380S-385S.

8.

Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic
obstructive pulmonary disease exacerbations: a meta-analysis. JAMA
1995;273:957-60.

9.

McCrory DC, Brown C, Gelfand SE, Bach PB. Management of
acute exacerbations of COPD: a summary and appraisal of pub-
lished evidence. Chest 2001;119:1190-209.

10.

Singh JM, Palda VA, Stanbrook MB, Chapman KR. Corticoster-
oid therapy for patients with acute exacerbation of chronic obstruc-
tive pulmonary disease: a systematic review. Arch Intern Med 2002;
162:2527-36.

11.

Aaron SD, Vandemheen KL, Hebert P, et al. Outpatient oral
Copyright © 2003 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org on November 29, 2004 . This article is being provided free of charge for use in Viet Nam.

n engl j med

348;26

www.nejm.org june

26, 2003

editorials

2681

prednisone after emergency treatment of chronic obstructive pul-
monary disease. N Engl J Med 2003;348:2618-25.

12.

Snow V, Lascher S, Mottur-Pilson C. The evidence base for man-
agement of acute exacerbations of COPD: clinical practice guide-
line. Chest 2001;119:1185-9.

13.

Callahan CM, Dittus RS, Katz BP. Oral corticosteroid therapy for
patients with stable chronic obstructive pulmonary disease: a meta-
analysis. Ann Intern Med 1991;114:216-23.

14.

Rice KL, Rubins JB, Lebahn F, et al. Withdrawal of chronic sys-
temic corticosteroids in patients with COPD: a randomized trial. Am
J Respir Crit Care Med 2000;162:174-8.

15.

Brightling CE, Monteiro W, Ward R, et al. Sputum eosinophilia
and short-term response to prednisone in chronic obstructive pulmo-
nary disease: a randomised controlled trial. Lancet 2000;356:1480-5.

16.

Alsaeedi A, Sin DD, McAlister FA. The effects of inhaled cortico-

steroids in chronic obstructive pulmonary disease: a systematic
review of randomized placebo-controlled trials. Am J Med 2002;
113:59-65.

17.

Van der Valk P, Monninkoff E, van der Palen 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;166:1358-63.

18.

Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and
fluticasone in the treatment of chronic obstructive pulmonary dis-
ease: a randomised controlled trial. Lancet 2003;361:449-56.

19.

McEvoy CE, Niewoehner DE. Adverse effects of corticosteroid
therapy for COPD: a critical review. Chest 1997;111:732-43.

Copyright © 2003 Massachusetts Medical Society.

Improving the Quality of Care — Can We Practice
What We Preach?

Earl P. Steinberg, M.D., M.P.P.

It has been 30 years since Wennberg and Gittelsohn

published their landmark article demonstrating
substantial variation among different geographic
areas in the provision of medical services.

1

Since
then, investigators have found variation in the de-
livery of virtually every aspect of health care that has
been examined. From the perspective of the quality
of care, the variation that is the greatest cause for
concern is that between actual practice and evi-
dence-based “best practice.”
Over the past 30 years, progress has been made
in several areas that are vital to quality improvement.
Practice guidelines have become more rigorously
evidence-based and are now packaged in ways that
make it easier to put them into practice. Tremen-
dous progress has been made in the development of
valid, reliable, and practical measures of the quality
of care

2

that are now applied in managed care

3

and
fee-for-service settings.

4

There are many indications
of an increased focus on quality, and we have made
great progress in our understanding of factors that
contribute to substandard quality

2

and of interven-
tions that do (and those that do not) improve the
quality of care.

2,5,6

In this issue of the

Journal,

McGlynn and col-
leagues

7

report the results of a large national study
of the content of care provided to adults between
1996 and 1998. Although the “headline” finding of
the study is that adults received 55 percent of rec-
ommended care according to 439 process-of-care

measures, the most enlightening findings are those
in the measure-specific results. The biggest limita-
tion of the study derives from the likelihood that
documentation was poor in the charts that were
used to determine what care patients had received.
Because of this limitation, along with the focus on
compliance with multiple recommendations for the
management of a given clinical condition rather
than on how well the condition was controlled, it
would not be appropriate to interpret the findings
of this study as showing that a typical adult in the
United States has a 50–50 chance of receiving ade-
quate care of a particular clinical condition. None-
theless, the study adds detailed information to a
substantial body of research that shows that the
quality of the care delivered in the United States is
considerably lower than it should be.

8

What will it take to do better? Four actions are
likely to have the greatest effect. First, quality of
care should be measured and reported routinely at
both the national and provider-specific (e.g., hos-
pital and physician) levels. In September 2003, the
Agency for Healthcare Research and Quality will
publish the first annual National Healthcare Qual-
ity Report, which will include 150 measures. A sep-
arate effort is needed, however, to report on the
quality of care delivered by individual facilities and

physicians. Such an effort would benefit from the
involvement of professional societies in measure-
ment and quality-improvement activities.

9

Both
types of activities are consistent with the missions
of professional societies. Examples of such leader-
ship, as well as the benefits of it, can be observed in
the Dialysis Outcomes Quality Initiative of the Na-
tional Kidney Foundation,

10

the End-Stage Renal
Disease (ESRD) Clinical Performance Measures
Project,

11

and the Guidelines Applied in Practice
Initiative of the American College of Cardiology.

12
Copyright © 2003 Massachusetts Medical Society. All rights reserved.
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