Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.

This article has been cited by other articles:

				R. D. Gray, G. MacGregor, D. Noble, M. Imrie, M. Dewar, A. C. Boyd, J. A. Innes, D. J. Porteous, and A. P. Greening Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 444 - 452. [Abstract] [Full Text] [PDF]

				D. Stolz, M. Christ-Crain, N. G. Morgenthaler, D. Miedinger, J. Leuppi, C. Muller, R. Bingisser, J. Struck, B. Muller, and M. Tamm Plasma Pro-Adrenomedullin But Not Plasma Pro-Endothelin Predicts Survival in Exacerbations of COPD Chest, August 1, 2008; 134(2): 263 - 272. [Abstract] [Full Text] [PDF]

				P. J. Barnes, B. Chowdhury, S. A. Kharitonov, H. Magnussen, C. P. Page, D. Postma, and M. Saetta Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 6 - 14. [Abstract] [Full Text] [PDF]

				A. Papi, F. Luppi, F. Franco, and L. M. Fabbri Pathophysiology of Exacerbations of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2006; 3(3): 245 - 251. [Abstract] [Full Text] [PDF]

				P. Mallia and S. L. Johnston Mechanisms and Experimental Models of Chronic Obstructive Pulmonary Disease Exacerbations Proceedings of the ATS, November 1, 2005; 2(4): 361 - 366. [Abstract] [Full Text] [PDF]

				A M Sutcliffe and A J Knox Muscling into cystic fibrosis airways Thorax, March 1, 2005; 60(3): 181 - 182. [Full Text] [PDF]

				P. J. Barnes Mediators of Chronic Obstructive Pulmonary Disease Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548. [Abstract] [Full Text] [PDF]

				A J White, S Gompertz, and R A Stockley Chronic obstructive pulmonary disease * 6: The aetiology of exacerbations of chronic obstructive pulmonary disease Thorax, January 1, 2003; 58(1): 73 - 80. [Abstract] [Full Text] [PDF]

				M Roland, A Bhowmik, R J Sapsford, T A R Seemungal, D J Jeffries, T D Warner, and J A Wedzicha Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease Thorax, January 1, 2001; 56(1): 30 - 35. [Abstract] [Full Text]

				A. Hill, S. Gompertz, and R. Stockley Factors influencing airway inflammation in chronic obstructive pulmonary disease Thorax, November 1, 2000; 55(11): 970 - 977. [Full Text]