Presented by:
MaCie Rogers
Pharm.D Candidate 2013
• Accelerated loss of lung function and death are often
associated with acute exacerbations of Chronic Obstructive
Pulmonary Disease (COPD)
• An acute exacerbation of COPD is defined as “an increase in
dyspnea, cough, or sputum production warranting a change in
therapy.”
• Pulmonary hypertension is a major complication of COPD and
can predict the occurrence of an acute exacerbation
• Identifying patient’s at high risk of exacerbation would be
paramount to improving quality of life and preserving lung
function
• Computed tomography (CT) can be
used to measure the diameter of the
pulmonary artery and the ratio of
that diameter to the diameter of the
aorta (PA:A ratio)
• The authors of this study
hypothesized that a PA:A
ratio>1would be associated with a
history of severe exacerbations of
COPD and independently associated
with an increased risk of future
events
• A multi-center observational trial including current and former
smokers with COPD (the COPDGene Trial)
• Inclusion criteria: 45 to 80 years old, current or former smoker
with a history of 10 pack-years or more
• Total enrollment: 10,300 participants, 3464 with Global
Initiative for Chronic Obstructive Lung Disease (GOLD) stage II
to IV. Of these patients, 2985(86%) participated in a
longitudinal follow-up study to prospectively track clinical course
• 2005 participants from the ECLIPSE trial (a 3-year longitudinal
study with the objective to identify surrogate endpoints
associated with COPD exacerbations) were used as a
validation cohort
• Acute exacerbations were self-reported in both the COPDGene
and the ECLIPSE studies, defined and quantified by answers to
questions in a respiratory questionnaire
• Severe and Mild-to-moderate exacerbations were
differentiated by required hospital admission for treatment vs.
outpatient treatment with antibiotics or systemic glucocorticoids
• The occurrence and frequency of all exacerbations (mild-tomoderate and severe) were documented as secondary
endpoints
• More patients with PA:A ratio >1reported a severe
exacerbation in the year before enrollment. (53% vs. 13%;
Odds ratio, 7.44; 95% CI, 6.23 to 8.89; P<.001)
• The occurrence of severe exacerbations were also associated
with increased pulmonary artery diameter, increased
percentage of lung volume with emphysema on CT, and
increased gas trapping on CT
• Severe exacerbations were
shown to be independently
associated with younger
age, lower FEV1 scores,
higher SGRQ scores, and
PA:A ratio >1
• At enrollment (OR 4.78; 95%
CI, 3.43-6.65; P<0.001),
• During longitudinal follow-up
(OR 3.44; 95% CI, 2.784.25; P<0.001)
• Associations with age and
presence of GERD were no
longer significant during
follow-up
A PA:A ratio >1(as detected through CT) is associated with future
exacerbations of COPD, especially those requiring hospitalization
and therefore can be used to identify a subpopulation at high risk
for hospitalization
• Limitation: This is an observational study and therefore the
conclusion that PA:A ratio elevations cause acute exacerbations
of COPD cannot be definitively drawn.
• Strength: Agreement of findings with the external validation,
ECLIPSE trial, cohort significantly strengthen the results
• Wells MJ, Washko GR, MeiLan HK, et al. Pulmonary Arterial
Enlargement and Acute Exacerbations of COPD. N Eng J Med
2012;367(10); 913-921