title: Airway endothelin levels in asthma: influence of endobronchial allergen challenge and maintenance corticosteroid therapy.
abstract: Endothelins (ETs) are 21 amino acid peptides which, in addition to their other properties, are potent bronchoconstrictors. Whilst there is evidence of the involvement of ET in the pathophysiology of chronic asthma, its contribution to the acute allergic response is undefined. To examine this, we have undertaken segmental bronchoprovocation with allergen and saline at separate sites in six atopic asthmatics receiving treatment with bronchodilators only and six atopic asthmatics additionally receiving treatment with inhaled corticosteroids. Each challenged segment was lavaged 10 min after bronchoprovocation and concentrations of immunoreactive ET were measured in bronchoalveolar lavage fluid. In the non-steroid-treated subjects, there were significantly lower ET levels at the allergen-challenged sites compared to the saline-challenged sites (p<0.05). In the steroid-treated subjects, on the other hand, there was no significant difference between the two sites. Levels of ET at the saline-challenged sites were significantly lower in the steroid-treated subjects compared to the non-steroid-treated subjects (p<0.04). These findings do not support the hypothesis that allergen exposure in asthma results in immediate release of endothelin. However, release at later time-points and a role for endothelin in late-phase bronchoconstriction are not excluded.
authors.affiliation: University Medicine, Southampton General Hospital, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Redington
authors.forename: D R
authors.initials: DR
authors.lastname: Springall
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: J
authors.initials: J
authors.lastname: Madden
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.forename: A J
authors.initials: AJ
authors.lastname: Frew
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: P H
authors.initials: PH
authors.lastname: Howarth
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002452:Cell Count; D016232:Endothelins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D011863:Radioimmunoassay; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D000485:Allergens; D001993:Bronchodilator Agents; D016232:Endothelins; D012965:Sodium Chloride; D006632:Histamine