Global Initiative for Chronic Obstructive Lung Disease - GOLD

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Some pathological abnormalities, such as inflammation of
the submucosal glands and hyperplasia of goblet cells,
may contribute to chronic sputum production, although
these pathological abnormalities are not present in all
patients with this symptom.
Dyspnea, an abnormal awareness of the act of breathing,
usually reflects an imbalance between the neural drive to
the respiratory muscles and the effectiveness of the
resulting ventilation. Different individuals use different
words to describe the feeling of breathlessness, which is
also influenced by other factors such as mood. In COPD
patients, dyspnea is mainly the result of impaired lung
mechanics (increased airways resistance, decreased
elastic recoil). It is only present on vigorous exercise in
the early stages of disease but may be present at rest as
the mechanical impairment becomes severe.
PATHOLOGY AND
PATHOPHYSIOLOGY OF
EXACERBATIONS
The progressive course of COPD is complicated by
exacerbations that have many causes and occur with
increasing frequency as the disease progresses.
Pathology
Distinguishing the pathology of these acute events from
that of the underlying disease is difficult because patients
experiencing an exacerbation are usually too ill to study.
The limited evidence available suggests that mild COPD
exacerbations are associated with increases of both
neutrophils and eosinophils in sputum and biopsies, while
severe COPD exacerbations are associated with an
increase in sputum neutrophils and eosinophils 18,19 . At
least in sputum, the changes in inflammatory cells during
exacerbations of COPD are the same as those observed
during exacerbations of asthma 115-119 . So far no study has
been conducted examining the pathological abnormalities
associated with fatal exacerbations of COPD, which can be
considered the extreme end of the spectrum of severity.
Pathophysiology
Expiratory airflow is almost unchanged during mild
exacerbations 18 , and only slightly reduced during severe
exacerbations 120,121 . Although the pathophysiology of
exacerbations is not fully understood, the primary
physiological change in severe exacerbations is a further
worsening of gas exchange, primarily produced by
increased V A /Q inequality. As V A /Q relationships worsen,
increased work of the respiratory muscles results in
greater oxygen consumption, decreased mixed venous
oxygen tension, and further amplification of gas
exchange abnormalities 120 . Worsening of V A /Q relationships
has several causes in exacerbations. Airway
inflammation and edema, mucus hypersecretion, and
bronchoconstriction may contribute to changes in the
distribution of ventilation, while hypoxic constriction of
pulmonary arterioles may modify the distribution of
perfusion. Additional contributors to worsening gas
exchange in exacerbations include abnormal patterns of
breathing and fatigue of the respiratory muscles. These
can cause further deterioration in blood gases and
worsening of respiratory acidosis, leading to severe
respiratory failure and death 120-123 . Alveolar hypoventilation
also contributes to hypoxemia, hypercapnia, and
respiratory acidosis. In turn, hypoxemia and respiratory
acidosis promote pulmonary vasoconstriction, which
increases pulmonary artery pressures and imposes an
added load on the right ventricle.
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