Endothelin-1 in stable bronchiectasis

Abstract

Endothelin (ET)-1 has been suggested to promote neutrophil adhesion to endothelium, migration to inflamed areas, and release of elastase. ET-1 might therefore play a role in the pathogenesis of bronchiectasis, a chronic inflammatory and infective airway disease which is still poorly understood.Thirty five patients with stable bronchiectasis (20 females, mean age SD 49.1 15.0 yrs) and 18 control subjects (8 females, 49.4 11.3 yrs) were recruited prospectively. The ET-1 levels in serum and sputum were measured by commercially available enzyme linked immunosorbent assay (ELISA) kits.Patients with Pseudomonas aeruginosa in their sputum had a significantly higher serum level of ET-1 (median 25.8, interquartile range 13±43.9 pg . mL -1 ) than patients without P. aeruginosa (0, 0±10.5 pg . mL -1 ; p=0.0004) and healthy control subjects (4.6, 0±16.3 pg . mL -1 ; p=0.002). However, patients with and without P. aeruginosa infection had no significant difference in sputum ET-1 level (p=0.15). There was no correlation between serum or sputum ET-1 levels with the serum and sputum levels of the interleukin (IL)-1b, IL-8 and tumour necrosis factor (TNF)-a; the number of bronchiectasis lung lobes; and spirometry. Serum ET-1 level correlated with 24 h sputum volume for the bronchiectasis patients (r=0.51, p=0.002).The results, therefore, suggest a significant pathogenic role for endothelin-1 among Pseudomonas aeruginosa-infected patients with bronchiectasis. Further studies should be performed to evaluate the clinico-pathological correlation and expression of endothelin-1 in bronchiectasis.

Role of endothelin-1 in lung disease

“…Sputum ET-1 levels are increased in patients with cystic fibrosis [59], and sputum ET-1 correlated with Pseduomonas infection in noncystic fibrosis related bronchiectasis [70]. …”

Does airway colonization cause systemic inflammation in bronchiectasis?

“…Previous studies have shown the presence of intense inflammatory activity characterized by neutrophils, T-cells and interleukin (IL)-8 positive cells and elevated levels of IL-6, IL-8, tumour necrosis factor (TNF)-α, leukotriene B4, endothelin 1, elestase in sputum and bronchoalveolar lavage samples of bronchiectasis patients (7)(8)(9)(10)(11)(12). Recent evidence suggests the presence of systemic inflammation in chronic inflammatory airway diseases.…”

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

“…Macrophages contribute to neutrophil influx into the airways via the production of TNF-a [75] and endothelin (ET)-1 [113]. They also function as regulatory cells, releasing a number of inflammatory mediators, including TNF-a, IL-8, other CXC chemokines, monocyte chemotactic peptide 1, LTB 4 , ROS and a number of elastolytic enzymes [95,114,115].…”

“…Human airway epithelial cells produce ET-1, which promotes neutrophil adhesion to endothelial cells, migration to areas of inflammation and the release of elastase in vitro [113].…”