Correspondence
In summary, our patients were in an advanced stage of their
disease and had associated pulmonary hypertension, which was
in general terms proportionate to the disease severity. At
present, pulmonary hypertension in these patients should not
be treated with specific therapy (2, 3).
Author Disclosure: I.B. has received lecture fees from GlaxoSmithKline (GSK) and
Bayer (both up to $1,000). J.A.B. has received consultancy fees from Praxis (up to
$1,000); he has received advisory board fees from GSK ($1,001–$5,000), and
Bayer-Schering (up to $1,000); he has received lecture fees from Actelion ($1,001–
$5,000), GSK ($1,001–$5,000), Pfizer (up to $1,000), and Bayer-Schering (up to
$1,000); he has received industry sponsored grants from Pfizer ($10,001–$50,000),
Bayer-Schering ($5,001–$10,000), and GSK ($10,001–$50,000).
ISABEL BLANCO, M.D.
JOAN ALBERT BARBERÀ, M.D., PH.D.
University of Barcelona
Barcelona, Spain
References
1. Blanco I, Gimeno E, Munoz PA, Pizarro S, Rodriguez-Roisin R, Roca J,
Barberà JA. Hemodynamic and gas exchange effects of sildenafil in
patients with COPD and pulmonary hypertension. Am J Respir Crit
Care Med 2010;181:270–278.
2. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barberà JA,
Beghetti M, Corris P, Gaine S, Gibbs JS, et al. Guidelines for the
diagnosis and treatment of pulmonary hypertension. Eur Respir J
2009;34:1219–1263.
3. Humbert M, Simonneau G. Vasodilators in patients with chronic ob-
structive pulmonary disease and pulmonary hypertension: not ready
for prime time! Am J Respir Crit Care Med 2010;181:202–203.
4. Casas A, Vilaró J, Rabinovich R, Mayer A, Barberà JA, Rodriguez-
Roisin R, Roca J. Encouraged 6-min walking test indicates maximum
sustainable exercise in COPD patients. Chest 2005;128:55–61.
5. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M,
Nakanishi N, Miyatake K. Clinical correlates and prognostic signifi-
cance of six-minute walk test in patients with primary pulmonary
hypertension: comparison with cardiopulmonary exercise testing. Am J
Respir Crit Care Med 2000;161:487–492.
Criteria for Antibiotic Therapy in Acute Exacerbations
of COPD
To the Editor:
With great interest we have read the article of Dr. Daniels and
colleagues (1), who, by means of a randomized placebo-controlled
trial, have investigated the use of antibiotics (AB) on top of
systemic corticosteroids in the treatment of hospitalized acute
chronic obstructive pulmonary disease (COPD) exacerbations.
Their primary outcome, clinical success on Day 30, was not
statistically different between the placebo and doxycycline
group, but the authors provided evidence that AB added
limited benefit to short-term clinical efficacy. More interesting
to us, however, is their finding that C-reactive protein (CRP),
with cut-offs of 50 mg/L, may identify exacerbations that do not
require AB.
For many years guidelines (2) have recommended the use of
AB for COPD exacerbations based on Anthonisen criteria (AC),
which comprise three patient- reported items: increased dyspnea,
increased sputum volume, and increased sputum purulence (3, 4).
Although useful by its simplicity, a proper prospective validation
is still missing and many situations occur in which clinicians have
to base their decision for AB on other, more objective criteria
such as severity of presentation, underlying disease, fever, chest
X-ray, and CRP.
In a prospectively collected database of patients hospitalized
for an acute COPD exacerbation between 2001 and 2005 at our
ward, we investigated which criteria were used for AB pre-
1207
scription. Of the 340 patients initially enrolled, 101 were excluded
from analysis because of a different final diagnosis (pneumonia,
heart failure, asthma, pulmonary embolism) or limited follow-up.
In the remaining 236 subjects, logistic regression demonstrated
that AC (odds ratio [OR], 3.77; confidence interval [CI], 1.65–
8.64), CRP (OR, 1.05; CI, 1.01–1.09) and temperature (OR, 2.36;
CI, 1.05–5.32) were independent determinants for AB prescrip-
tion, whereas severity of disease or presentation were not.
Interestingly and in contrast to guidelines, 38 patients (16%)
with at least two positive AC but with low CRP and no fever at
admission did not receive AB. When comparing them to the
group that received AB, mean length of hospitalization was
statistically significantly reduced (2 d, P , 0.01) in the non-AB
group, whereas time to next exacerbation and 3- year survival
were not affected.
Although our retrospective analysis does not validate the use
of CRP and temperature in the decision tree for AB, we believe
that more objective criteria and biomarkers (CRP, procalcitonin,
serum amyloid) should be integrated in the guidelines for AB
treatment of acute exacerbations (5, 6). The study of Dr. Daniels
indirectly supports this point of view. Identifying subgroups of
exacerbations in which AB have no benefit may eventually
reduce AB consumption and treatment costs.
Author Disclosure: S.P.-B. does not have a financial relationship with a commercial
entity that has an interest in the subject of this manuscript. A.F. does not have
a financial relationship with a commercial entity that has an interest in the subject
of this manuscript. M.D. has received consultancy fees from Dompe; he has
received advisory board fees from Boehringer, GlaxoSmithKline, and Nycomed
(each for $5,001–$10,000); he has received lecture fees from Pfizer ($5,001–
$10,000); he has received industry-sponsored grants from AstraZeneca ($5,001–
$10,000). W.J. has no financial relationship with a commercial entity that has an
interest in the subject of this manuscript.
SYLVIA PÉREZ-BOGERD, M.D.
ANTOINE FREMAULT, M.D.
MARC DECRAMER, M.D., PH.D.
WIM JANSSENS, M.D., PH.D.
University Hospital Leuven
Leuven, Belgium
References
1. Daniels JMA, Snijders D, deGraaf CS, Vlaspolder F, Jansen MH,
Boersma WG. Antibiotics in addition to systemic corticosteroids for
acute exacerbations of chronic obstructive pulmonary disease. Am J
Respir Crit Care Med 2010;181:150–157.
2. The Global Initiative for Obstructive Lung Disease home page (accessed
January 18, 2010). Available from: http://www.goldcopd.com.
3. Sethi S, Murphy TF. Infection in the pathogenesis and course of COPD.
N Engl J Med 2008;359:2355–2365.
4. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK,
Nelson NA. Antibiotic therapy in exacerbations of COPD. Ann Intern
Med 1987;106:196–204.
5. Bozinovski S, Hutchinson A, Thompson M, Macgregor L, Black J,
Giannakis E, Karlsson AS, Silvestrini R, Smallwood D, Vlahos R,
et al. Serum amyloid A is a biomarker of acute exacerbations of
COPD. Am J Respir Crit Care Med 2008;177:269–278.
6. Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C,
Huber P, Muller B, Tamm M. Antibiotic treatment of exacerbations
of COPD: a randomized, controlled trial comparing procalcitonin-
guidance with standard therapy. Chest 2007;13:9–19.
From the Authors:
We are most grateful to Drs. Pérez-Bogerd, Fremault,
Decramer, and Janssens for their interest in our article (1).
We agree that more objective criteria and markers should be
incorporated in therapeutic decision making in acute exacerba-
tion of chronic obstructive pulmonary disease (AECOPD),
especially when it comes to antibiotic therapy. It seems justified