Articulo Interesante

REVIEW ARTICLE

Macrolide therapy for the prevention of acute
exacerbations in chronic obstructive pulmonary
disease
Manoj J. Mammen, Sanjay Sethi
University at Buffalo, State University of New York at Buffalo, Buffalo, New York, United States

KEy WoRds

AbsTRACT

antibiotic prophylaxis,
chronic obstructive
pulmonary disease,
exacerbation,
macrolide

Acute exacerbations are amajor contributor to health care costs and a leading cause of death in patients
with chronic obstructive pulmonary disease (COPD). A reduction in acute exacerbations of COPD (AECOPD)
would lead to significant improvements in patient well‑being and survival. Bacterial and viral infections
cause a majority of AECOPD episodes; however, with the exception of influenza and pneumococcal
vaccines,preventative therapies for exacerbations do not directly address these infectious causes of
AECOPD. Antibiotics were shown to have marginal benefit in preventing AECOPD several decades ago;
however, since then, pathogens and antibiotics have changed substantially. Macrolides display immuno‑
modulatory and anti‑inflammatory effects in addition to their direct antibacterial effect. Several studieshave examined macrolides in AECOPD prevention, with a recent landmark study by Albert et al. clearly
demonstrating the efficacy of azithromycin in preventing AECOPD. Unfortunately, the rate of isolation
of macrolide‑resistant pathogens does increase with such treatment. Macrolides could also suppress
bacterial colonization and thus decrease airway inflammation, thereby interrupting the viciouscycle of
inflammation and infection in COPD. COPD patients with two or more exacerbations a year in spite of
appropriate standard therapy are potential candidates for this therapeutic approach. However, optimal
duration and dosing of macrolide prophylaxis for AECOPD remains uncertain.

Introduction Chronic obstructive pulmonary dis‑

Correspondence to:
Sanjay Sethi, MD, FACP Professor
,of Medicine, Pulmonary/Critical Care/
Sleep Medicine, University at Buffalo,
State University of New York, Buffalo,
NY, USA, phone: +1‑716‑862‑7875,
fax: +1‑716‑862‑6526,
e‑mail: ssethi@buffalo.edu
Received: January 2, 2012.
Accepted: January 3, 2012.
Conflict of interest: none declared.
Pol Arch Med Wewn. 2011;
122 (1‑2): 54‑59
Copyright by Medycyna Praktyczna,
Kraków 2012

ease(COPD) is the 5th leading cause of death in
the United States (US) and is projected to increase
to the 3rd leading cause of death by the end of
the decade.1,2 Worldwide, COPD is the 4th lead‑
ing cause of death and nearly 25% of adults old‑
er than 40 years of age have COPD.3 COPD has
a projected 2010 direct cost of $29 billion and in‑
direct cost of $20 billion in the US alone.1 The Eu‑ropean Union spends 38 billion Euros in direct
costs for COPD. Undoubtedly, COPD is a major
global health care problem.
Contributing substantially to the morbidity
and mortality in patients with COPD are episodes
of increased respiratory and systemic symptoms
characterized as acute exacerbations (AECOPD).
Patients with frequent AECOPD have faster lung
function decline, prolonged time torecovery, and
increased incidence of depression, anxiety, and

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POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ

a poorer quality of life.4‑8 More than 30% of pa‑
tients discharged from an emergency room vis‑
it due to AECOPD will have recurrent symptoms
within 14 days and eventually 17% will require
hospitalization.9,10 Patients requiring 3 or more
hospitalizations in a year due to AECOPD have
asignificantly reduced 5‑year survival.11 Because
many exacerbations need additional medical care,
they are responsible for the consumption of sub‑
stantial health care resources. For instance, in
the US, exacerbations account for 16 million of‑
fice visits and over 500,000 hospitalizations per
year.12 It has been estimated that AECOPD man‑
agement is responsible for up to 50% of the over‑...