elevated markers of systemic inflammation, worse lung function, and more emphysema present on radiographic imaging
(23, 24).
AECOPD is associated with an increased systemic inflammatory state. It might be expected that during an AECOPD
vascular function would worsen and might be related to the
cardiac and prothrombotic events that have been described
in the clinical presentation of patients with AECOPD (4, 25).
We hypothesized that the acute inflammatory state induced
by AECOPD impairs vascular function measured by FMD
and NMD and improves following exacerbation resolution.
Some of this data was presented previously as an abstract
(26).
METHODS
Study patients
Patients were identified from those hospitalized for AECOPD, which was defined using previously published guidelines (27). Patients were 40– 80 years old and had ≥20 pack-year history of smoking. Patients were excluded if there was
pneumonia or pulmonary edema on chest radiograph, acute
coronary syndrome, or history of peripheral vascular disease
or aortic aneurysm. Healthy nonsmokers were studied to ensure that FMD could be performed reproducibly compared to
published normal control data, and were men and women age
40– 80, who did not have coronary artery disease, diabetes,
uncontrolled hypertension, COPD, lung cancer or interstitial
lung disease. The protocol (#4593) was approved by the Temple University Institutional Review Board. All patients provided written informed consent.
Study design
Figure 1 shows the study design and patient flow throughout the study. Patients under went bedside spirometry, history
and physical exam. All patients had FMD and NMD measured within 72 hours of hospitalization (FMD-1 and NMD-
1). Patients were asked to return for repeat measurement of
FMD and NMD (FMD-2 and NMD-2) 3 months following
hospitalization.
Flow-mediated dilation
FMD and NMD of the brachial artery were performed according to established guidelines and previously published
studies (28, 29). Prior to FMD or NMD patients fasted for
12 hours, and did not receive bronchodilators or venipuncture within 4 hours. Patients were asked to abstain from
smoking for 24 hours and all reported they had done so prior
to FMD and NMD. All vascular studies were performed in
a quiet room with the subject lying down. The nitroglycerin phase was omitted if the systolic blood pressure was
< 100 mmHg. FMD and NMD were calculated as the percent
change in brachial artery diameter from baseline to flow or
nitroglycerin mediated dilation.
Demographic data
Demographic data was collected from patient interview and
review of the medical record. Cardiovascular risk was calcu-
Figure 1. Study design: 19 patients were enrolled in the study at time
of AECOPD admission. All 19 had FMD but 1 patient was unable to
receive sublingual nitroglycerin secondary to systolic blood pressure
below 100 mmHg. Then, 11 patients did not return for repeat FMD
or NMD because 7 were lost to follow-up, 2 had repeat AECOPD,
1 was transplanted and 1 died. Eight of the remaining patients had
FMD. One patient was unable to have NMD at follow up due to systolic
blood pressure < 100 mm Hg. Definition of abbreviations: AECOPD
(acute exacerbation of COPD), FMD (Flow-mediated dilation), NMD
(Nitroglycerin-mediated dilation).
lated using the ATP (Adult Treatment Panel) III calculator
according to the Third Report of the National Cholesterol Education Program Expert Panel. Cardiomyopathy was defined
as left ventricular ejection fraction <50%, and hypercholesterolemia was defined as a total cholesterol >200 mg/dL. Hypertension, diabetes, and depression were self reported, and
the patient’s outpatient medication list was documented at
time of enrollment.
Spirometry
Spirometry performed by the patient within the previous year
following ATS guidelines (30) was used as baseline spirometry. Spirometry data are presented as percent predicted using
prediction equations from NHANES III (31).
Statistical methods
The t-test, paired t-test, and Pearson correlation were used
where appropriate. Univariate analysis was performed to
identify the factors influencing FMD or NMD. Small sample size prevented a multivariate analysis from being performed. A Wilcoxon signed rank test was used to compare
measurements of FMD and NMD at AECOPD and following resolution of AECOPD because the data was not normally
distributed.
RESULTS
Demographics
Nineteen patients (12 men and 7 women) age 61.1 ± 7.2
yrs, FEV1 26.1 ± 16% predicted, admitted for AECOPD had
FMD and NMD measured. Eight patients had measurements
