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354

R EVIEW SERIES

COPD exacerbations ? 3: Pathophysiology
D E O’Donnell, C M Parker
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Thorax 2006;61:354–361. doi: 10.1136/thx.2005.041830

Exacerbations of chronic obstructive pulmonary disease
(COPD) are associated with increased morbidity and
mortality.The effective management of COPD
exacerbations awaits a better understanding of the
underlying pathophysiological mechanisms that shape its
clinical expression. The clinical presentation of
exacerbations of COPD is highly variable and ranges from
episodic symptomatic deterioration that is poorly
responsive to usual treatment, to devastating life
threatening events. This underscores theheterogeneous
physiological mechanisms of this complex disease, as well
as the variation in response to the provoking stimulus. The
derangements in ventilatory mechanics, muscle function,
and gas exchange that characterise severe COPD
exacerbations with respiratory failure are now well
understood. Critical expiratory flow limitation and the
consequent dynamic lung hyperinflation appear to be theproximate deleterious events. Similar basic mechanisms
probably explain the clinical manifestations of less severe
exacerbations of COPD, but this needs further scientific
validation. In this review we summarise what we have
learned about the natural history of COPD exacerbations
from clinical studies that have incorporated physiological
measurements. We discuss the pathophysiology ofclinically stable COPD and examine the impact of acutely
increased expiratory flow limitation on the compromised
respiratory system. Finally, we review the chain of
physiological events that leads to acute ventilatory
insufficiency in severe exacerbations.
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T

See end of article for
authors’ affiliations.......................
Correspondence to:
Dr D E O’Donnell, Division
of Respiratory and Critical
Care Medicine, 102 Stuart
Street, Kingston, Ontario,
Canada K7L 2V6;
odonnell@post.queensu.ca
Received 22 August 2005
Accepted 8 January 2006
.......................

www.thoraxjnl.com

he progression of chronic obstructive pulmonary disease (COPD) is associated with
increasing frequency andseverity of exacerbations. COPD exacerbations are clearly linked to
impoverished health status and can be life
threatening, particularly in patients with
advanced disease.1 In some patients exacerbations result in prolonged activity limitation and
can quickly reverse the hard won benefits of
exercise training programmes. The clinical diagnosis of COPD exacerbations is currently made
on the basisof sustained worsening of the
common respiratory symptoms. For the purpose
of this review, we will use the simple pragmatic
definition of a COPD exacerbation recently
provided by the Canadian Thoracic Society: ‘‘a
sustained worsening of dyspnea, cough or sputum
production leading to an increase in the use of

maintenance medications and/or supplementation with
additional medications’’.2The clinical manifestations of COPD exacerbations are highly variable
and reflect broad heterogeneity in the underlying
pathophysiology of COPD as well as diversity in
the nature and effect of the inciting agent.
Expiratory flow limitation (EFL), as a consequence of airway inflammation, is the pathophysiological hallmark of COPD. Exacerbations
fundamentally reflect acute worsening of EFL,
andthere is evidence for both increased airway
inflammatory activity and worsening airway
obstruction as plausible explanations.3
It is reasonable to assume that worsening
airway inflammation is the primary inciting
event of COPD exacerbations and may be caused
by bacteria, viruses, or environmental pollutants,
including cigarette smoke. The mechanisms of
acute worsening of EFL in the...
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