Oral vs IV Corticosteroids for

In-hospital Treatment of COPD

Exacerbations
course of COPD is punctuated by
T heacuteclinical
exacerbations. These have been defined as
an event in the natural course of the disease
characterized by a change in the patients baseline
dyspnea, cough and/or sputum that is beyond normal
day-to-day variation, is acute in onset and may
warrant a change in regular medication . . .1 The
worsening symptoms are accompanied by variable
decrements in lung function and worsening health
status, with improvement in dyspnea and lung function generally within 1 to 2 weeks after initiation of
treatment.2 However, the decline in health status
may persist for months or even longer in cases of
frequently recurring exacerbations,3 and frequent
exacerbations may augment the accelerated rate of
lung function decline that characterizes disease
progression in COPD.4 While most patients with
an acute exacerbation of COPD (AECOPD) are
managed as outpatients, the treatment failure rate
(requirement for intensification of therapy, unscheduled office or emergency department visits
or hospitalization) is high, and epidemiologic studies5 indicate that 15 to 22% may require hospitalization.
Hospital admissions for AECOPD have increased
in recent years; in-hospital mortality rates of approximately 10% overall have been reported,6 while
much higher rates (approximately 25%) have been
observed in patients with acute ventilatory failure requiring admission to an ICU.7 Moreover, follow-up
studies6 have revealed a mortality rate of 33% within a
year of hospitalization for AECOPD. Besides its deleterious impact on the health and survival of individual
patients, hospitalization for AECOPD is an important
societal health issue, accounting for 70% of the $18
billion in direct health-care costs for COPD in the
United States.8
Because of the serious impact of acute exacerbations, a major goal of COPD management is their
prevention and treatment. Maintenance therapy
with inhaled bronchodilators with or without inhaled
corticosteroids has been shown to be beneficial
as preventive therapy for reducing the frequency
of exacerbations.9 Regarding the management of
AECOPD, current guidelines recommend an intensification of short-acting inhaled bronchodilator therapy, antibiotics (for patients with sputum
purulence or those requiring mechanical ventilation), a 7- to 10-day course of oral corticosteroids
(30 to 40 mg/d of prednisolone) for home management, and oral or IV corticosteroids for hospital
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treatment.1 The recommendation of systemic corticosteroid therapy is based on evidence from

well-designed randomized controlled clinical trials
that demonstrate such benefits as shortening of
recovery time, earlier improvement in lung function, decrease in the risk of early relapse, and
reduction in the length of hospital stay. For
hospital management, both IV and oral corticosteroids have been found to be effective,10,11 with no
evidence that prolonged extension of oral therapy
(8 weeks vs 2 weeks) is more efficacious.10 What is
still unclear, however, is whether any greater
efficacy ensues from the IV vs oral route of
administration, and from higher doses (eg, 125 mg
of methylprednisolone q6h IV for the first 3
hospital days)10 than lower ones (eg, 30 mg of
prednisone po qd),11 although higher doses have
been shown to increase the risk of side effects (eg,
hyperglycemia).10
In the current issue of CHEST (see page 1741),
de Jong and colleagues12 address the first of these
two questions. They hypothesized that oral prednisolone is not inferior to IV prednisolone when
administered in bioequivalent doses (60 mg) over
5 days to patients hospitalized for management of
a severe AECOPD, followed by a gradual tapering
regimen of oral prednisolone beginning with a
dose of 30 mg/d for a total 11-day course. The
authors found that the oral and IV routes resulted
in equivalent rates of treatment failure (the primary end point, defined as death, ICU admission,
rehospitalization for COPD, or the need to intensify pharmacotherapy). Secondary outcomes were
also equivalent, including improvement in FEV1
and quality of life from the day of hospital admission and length of hospital stay. A strength of the
study is its carefully controlled, double-blind, double-dummy experimental design with stratified
allocation to the treatment arms to achieve balance between the two groups on potentially influential baseline features, so that the results are
unlikely to be confounded by differences in disease severity, preadmission therapy, or prior exacerbation history. Other strengths are the inclusion
of patients who had failed outpatient treatment
with oral corticosteroids, thereby making the results relevant to real-world clinical scenarios, and
the completeness of the follow-up data for accurate capture of treatment failures following hospital discharge. A weakness of the study, however, is
the exclusion of patients with very severe exacerbations manifested by acute ventilatory failure or
with significant comorbidities, so that the results
cannot be extrapolated to these not uncommon
subsets of patients hospitalized with a COPD
exacerbation. A surprising finding is the relatively
Editorials

high treatment failure rate in both treatment

groups at 90 days (61.7% and 56.3%), which is
higher than the failure rate at a comparable time
period in the study of Nieweoehner et al (37%).10
A subanalysis suggests that differences between
the two studies in entry criteria (the latter study
excluded patients who had used systemic corticosteroids within the preceding 30 days) probably do
not explain this discrepancy. However, the lower
treatment failure rate in the study by Niewoehner
et al10 might be attributable to the much higher
3-day initial and 15-day cumulative doses of prednisolone administered in that study (total of 1,680
mg) compared to the doses used in the current
study over 11 days (405 mg). Future carefully
designed trials will need to address the impact of
different dosing regimens of systemic corticosteroids on outcomes in patients hospitalized with an
AECOPD. Nonetheless, since doses were equivalent between the two treatment arms in the study
of de Jong et al,12 their observations of similar
efficacy in a head-to-head equivalence trial of oral
vs IV corticosteroids provide convincing support
for the more convenient and less costly oral route
in the inpatient management of AECOPD whenever oral intake is feasible.
Donald P. Tashkin, MD, FCCP
Los Angeles, CA
Dr. Taskin is Professor of Medicine, David Geffen School of
Medicine at UCLA.
The author has no conflict of interest to disclose.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Donald P. Tashkin, MD, FCCP, Professor of
Medicine, David Geffen School of Medicine at UCLA, 10833 Le
Conte Ave, Los Angeles, CA 90095-1690; e-mail: dtashkin@
mednet.ucla.edu
DOI: 10.1378/chest.07-1622

References
1 Global initiative for chronic obstructive pulmonary disease.
Global strategy for the diagnosis, management and prevention of COPD 2006. Available at: www.goldcopd.org/
Guideline item. Accessed January 22, 2007
2 Parker CM, Voduc N, Aaron SC, et al. Physiological changes
during symptom recovery from moderate exacerbations of
COPD. Eur Respir J 2005; 26:376 378
3 Spencer S, Jones PW, GLOBE Study Group. Time course of
recovery of health status following an infective exacerbation
of chronic bronchitis. Thorax 2003; 58:589 593
4 Donaldson GC, Seemungal TA, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;
57:847 852
5 Celli BR, Barnes PJ. Exacerbations of chronic obstructive
pulmonary disease. Eur Respir J 2007; 29:1224 1238
6 Gunen H, Hacievliyagil SS, Kosar F, et al. Factors affecting
survival of hospitalized patients with COPD. Eur Respir J
2005; 26:234 241
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7 Ai-Ping C, Lee K-H, Lim T-K. In-hospital and 5-year mortality of patients treated in the ICU for acute exacerbation of
COPD: a retrospective study. Chest 2005; 128:518 524
8 Wouters EF. Economic analysis of the Confronting COPD
survey: an overview of results. Respir Med 2003; 97(Suppl
C):S3S14
9 Sin DD, McAlister FA, Man SFP, et al. Contemporary
management of chronic obstructive pulmonary disease: scientific review. JAMA 2003; 290:23012312
10 Niewoehner DE, Erbland MC, Deupree RH, et al. Effect
of systemic glucocorticoids on exacerbations of chronic
obstructive pulmonary disease. N Engl J Med 1999; 340:
19411947
11 Davies L, Angus RM, Calverley PMA. Oral corticosteroids in
patients admitted to hospital with exacerbations of chronic
obstructive pulmonary disease: a prospective randomized
controlled trial. Lancet 1999; 354:456 460
12 de Jong YP, Uil SM, Grotjohan HP, et al. Oral or intravenous
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17411747

Hypercapnic Obstructive Sleep

Apnea
An Underappreciated Marker of
Severity
during wakefulness is a marker of
H ypercapnia
disease severity in patients with sleep apnea.

These patients are often very obese, have long apnea

events with marked oxygen desaturation, evidence of
pulmonary hypertension, and right-heart failure.
Without appropriate treatment, such patients require frequent hospital admission1 and have alarming mortality rates.2 Fortunately, following the successful application of continuous positive airway
pressure (CPAP) or bilevel ventilation, daytime hypercapnia often improves3 and recurrent hospital
admission rates decrease.1
Unfortunately, clinicians may underestimate the
severity of illness of these patients and often miss
an opportunity to intervene. Presenting symptoms
are nonspecific and include fatigue, sleepiness,
subtle changes in mental status, and headaches.
Since there is often no increase in respiratory rate or
use of accessory muscles to breathe, their tenuous
status is not fully appreciated. Even the underlying
obstructive sleep apnea (OSA) as well as the
hypoventilation in these patients is often missed.
When oxyhemoglobin desaturation and right-heart
failure are detected, supplemental oxygen is often
provided without the knowledge of arterial blood
gas abnormalities. Therefore, these hypercapnic
patients often go unrecognized and undertreated
with high risk for recurrent hospitalization and
even early death.2
CHEST / 132 / 6 / DECEMBER, 2007

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