Background-Endothelin (ET)-1 is a bronchoconstrictor peptide produced in th
e airways. It has been implicated in the pathogenesis of asthma and virally
mediated airway inflammation and may play a role in exacerbations of chron
ic obstructive pulmonary disease (COPD).
Methods-Seventy one patients with COPD were followed prospectively and samp
led for plasma and sputum ET-1 levels when stable and during an exacerbatio
n. Sputum was also examined for cytokines, human rhinovirus, and Chlamydia
pneumoniae.
Results-Plasma ET-1 levels were available for 67 patients with stable COPD
(mean (SD) 0.58 (0.31) pg/ml); 28 pairs of stable-exacerbation plasma sampl
es had a mean stable ET-1 level of 0.54 (0.30) pg/ml rising to 0.67 (0.35)
pg/ml at exacerbation (mean difference 0.13, 95% confidence interval (CI) 0
.04 to 0.21, p = 0.004). Plasma ET-1 levels in the 67 patients with stable
COPD were inversely correlated with baseline forced expiratory volume in on
e second (FEV1; r = -0.29, p = 0.022) and forced vital capacity (FVC; r = -
0.38, p = 0.002). The change in plasma ET-1 levels during an exacerbation c
orrelated with the change in oxygen saturation (Sao(2); r = -0.41, p = 0.03
6). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 le
vels were 5.37 (0.97-21.95) pg/ml rising to 34.68 (13.77-51.95) pg/ml durin
g an exacerbation (mean difference 25.14, 95% CI 3.77 to 46.51, p = 0.028).
This increase in sputum ET-1 levels correlated with the increase in plasma
ET-1 levels (r = 0.917, p = 0.001) and sputum interleukin (IL)-6 levels (r
= 0.718, p = 0.013).
Conclusions-Sputum levels of ET-1 rise in COPD patients during an exacerbat
ion and this is reflected by a smaller rise in plasma ET-1 levels. ET-1 may
have a role in mediating airway inflammatory changes during exacerbations
of COPD.