Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease.
BACKGROUND
Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways. It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease (COPD).


METHODS
Seventy one patients with COPD were followed prospectively and sampled for plasma and sputum ET-1 levels when stable and during an exacerbation. 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 samples 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 one second (FEV(1); 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 correlated with the change in oxygen saturation (SaO(2); r = -0.41, p = 0.036). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 levels were 5.37 (0.97-21.95) pg/ml rising to 34.68 (13.77-51.95) pg/ml during 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 exacerbation 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.
Roland
M
M
Academic Respiratory Medicine and The William Harvey Research Institute, St Bartholomew's and Royal London School of Medicine and Dentistry, London EC1A 7BE, UK.
Bhowmik
A
A
Sapsford
R J
RJ
Seemungal
T A
TA
Jeffries
D J
DJ
Warner
T D
TD
Wedzicha
J A
JA
D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D016001:Confidence Intervals; D016207:Cytokines / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000503:physiopathology*; D011446:Prospective Studies; D012229:Rhinovirus / Q000302:isolation & purification; D013183:Sputum / Q000737:chemistry* / Q000382:microbiology; D014797:Vital Capacity / Q000502:physiology
D015415:Biomarkers; D016207:Cytokines; D019332:Endothelin-1