bacteria have been isolated in the sputum of
COPD patients, such as Staphylococcus aureus
and enteric gram-negative pathogens, but these
organisms may represent the intrinsic microbiota
of COPD-diseased airways. Based on consistently
negative culture results, the lower airways have
long been considered sterile. In the last decade,
however, advanced DNA-based techniques have
demonstrated a complex microbial milieu in the
lower airways of normal patients.64 This microbiologic environment seems to certainly be associated with immunologic influences on airway
function. Much active research is aimed at defining
the microbiome of the lung in health and disease.
Early studies in this area have demonstrated that
the pathogenic makeup of the lower airways in
patients with COPD differs from that of individuals
without COPD and is not consistent across GOLD
stages.65 Particularly in severe disease, the airways
of COPD patients have a myriad of potential pathogens.66 Colonization of the airways may thus lead
to specific host-pathogen interactions that may
enable or predispose to exacerbations. Indeed,
various inflammatory markers, including TNF-α,
IL- 6, IL- 8 and neutrophil-derived cytokines, are
consistently elevated in COPD patients in a manner consistent with this hypothesis.67–69
The precise mechanism of how bacteria may
elicit a COPD exacerbation has only been partially
elucidated. When a patient acquires a new bac-
terial strain, pathogenic virulence combines with
the host lung’s defense mechanisms to affect a
change in airway and systemic inflammation. The
subsequent response can be strain-specific and
may lead to increased respiratory and systemic
symptoms, which develop into an exacerbation.
This mechanism is supported by evidence from
studies that show an increased risk of develop-
ing a COPD exacerbation after acquisition of a
new strain.70 Exposure to new bacterial strains can
generate a more intense neutrophilic inflammation
and increased inflammatory marker profile com-
pared to exposure to preexisting strains.71 Further
illustrating this concept, evidence suggests that
bacterial strains identified during COPD exacerba-
tions are more closely associated with pronounced
airway inflammation than those regarded as “air-
way colonizers.”72 One may conclude from this
evidence that different strains may lead to variable
host responses and that newer strain exposures
may have the most impact on airway function.
In a prospective, longitudinal cohort of COPD
patients, new strain acquisition (particularly with
H. influenzae, S. pneumoniae, M. catarrhalis, and
P. aeruginosa) was associated with both systemic
inflammation and an intense neutrophilic response
in the airway.71 Therefore, the microbial burden in
the lungs of patients with COPD likely represents a
complex immunologic environment whose balance
may underlie development of exacerbated disease.
Importantly, bacterial complications of COPD are
not limited to exacerbations of underlying airways
disease. COPD is a risk factor for the development
of pneumonia. Beyond the baseline increase in risk
of disease, many patients are treated with inhaled
corticosteroids, which have variably been associated with an increase in the risk of pneumonia.73,74
Therefore, patients with COPD who develop worsening cough and increasing dyspnea should be
closely evaluated for underlying pneumonia and
treated appropriately according to risk status and
local resistance patterns.
PATHOGENESIS
Regardless of the specific trigger, existing data
support the notion that exacerbations of COPD
are associated with increases in inflammation
