Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease
M Roland, A Bhowmik, R J Sapsford, T A R Seemungal, D J Jeffries, T D Warner, J A Wedzicha
Academic Respiratory
Medicine and The William Harvey Research Institute, St Bartholomew's
and Royal London School of Medicine and Dentistry, London EC1A
7BE, UK
Correspondence to: Professor J A Wedzicha J.A.Wedzicha{at}mds.qmw.ac.uk
Received 4 May 2000; Returned to authors 19 July 2000; Revised version received 31 July 2000; Accepted for publication 25 September 2000
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 (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 correlated with the
change in oxygen saturation (SaO2; 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.
Keywords: endothelin-1; chronic obstructive pulmonary disease; inflammation; cytokines; sputum
© 2001 by Thorax
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