ABSTRACT
It is now widely accepted that chronic obstructive pulmonary disease (COPD) is
an inflammatory disease in which there is luminal, bronchial wall, and interstitial
inflammatory cell activity (1-4) and resultant tissue damage (5). There is accumula-
ting evidence that acute exacerbations of COPD (AECOPD) are associated with
an increase in this inflammation and damage and that this is related predominantly
to neutrophilic inflammation, although there may be subsets of patients with a
bronchial eosinophilia (6-8). There is also evidence of increased oxidative stress
during exacerbations (9,10). The problem in reviewing the literature is the general
lack of information on the nature of the exacerbations described. The definitions of
AECOPD have often been somewhat vague but have included an increase in
symptoms for 2 or more days (11). The so-called ‘‘Anthonisen criteria’’ (12) of
major symptoms (increased dyspnea, sputum volume, and sputum production) and
minor symptoms (including sore throat, nasal discharge, fever, wheeze, and cough)
have often been employed (5,11). It is clear, however, that corticosteroids (12,13),
antibiotics (14,15) and antioxidants (16,17) may all have beneficial effects on some
exacerbations. This suggests that inflammation, bacteria, and oxidative stress all play
a role. An ideal biomarker would detect all such episodes or be specific to one
subtype. At present, few authors have attempted to characterize the nature of their
exacerbations in detail, which makes interpretation of the role of biomarkers often
II. The Ideal Biomarker
The characteristics of an ideal biomarker include a molecule for which there is a
relatively noninvasive test that may be performed even in patients with severe
disease and one that can be undertaken repeatedly in the same individual (i.e., there
should be good subject acceptability). The test should be specific for the process
being assessed, have good reproducibility, and be sensitive to small and early
changes in disease status, ideally in a linear fashion. Prospective studies of the levels
of the parameter in the stable state and during the prodrome, onset, and resolution of
different types of exacerbation should be available. The ideal biomarker would be
easy and cheap to measure and sufficiently stable to allow measurement after a
period of sample storage. The laboratory assays should have been well validated in
appropriate specimens, including spiking experiments where appropriate (18).
Ultimately a suitable biomarker could be used to identify impending exacerbations
in prospective studies of COPD. It could also be used to facilitate early therapeutic
intervention in the clinical setting and hence to avoid full-blown exacerbations and
their economic impact (19) and personal consequences (20). It must be appreciated
that many studies of AECOPD have involved incompletely characterized patients
and=or different subsets of the COPD superfamily (19). Furthermore, different definitions of exacerbation have been employed (8,11,21,22) and it is therefore
critical to define both the population of patients and the type of exacerbation to
which a particular potential biomarker may be applicable. Changes in airway
inflammatory cell numbers (in particular, neutrophils and eosinophils) occur during
AECOPD and may provide useful markers of exacerbation in sputum and broncho-
scopic specimens as well as influencing treatment. These changes have been
described in detail elsewhere in this text and are not discussed further here.
