Does the disease state influence the responsiveness of human airways studied in vitro?

Abstract

Human airway tissue has been used in vitro to study mechanisms of airway disease. However, there has never been a comprehensive study that has looked at the influence of disease on the subsequent in vitro responsiveness of human airways. In this study, we obtained airway tissue from patients who were undergoing resection of the lung for carcinoma. We then compared the airway responsiveness in these tissues and in tissues from patients who had undergone lung transplantation for alpha-1-antitrypsin deficiency, emphysema, or cystic fibrosis with the responsiveness in tissues obtained from donor lungs, i.e., nondiseased. When the relationships between concentration and response were compared, we found that for histamine, electrical field stimulation, levcromakalim, and isoproterenol similar responses could be expected in tissues obtained from all the sources studied. This was not true for acetylcholine in that there were significantly lower responses in tissues from patients with alpha-1-antitrypsin deficiency (P = 0.02; n = 9) or from patients having a lung resected for carcinoma (P = 0.01; n = 6) compared with that of the nondiseased group (n = 6). Similarly, for carbachol, the responses were significantly lower in the alpha-1-antitrypsin deficiency group (P = 0.001; n = 10) and in specimens resected for carcinoma (P = 0.001; n = 6) than in the nondiseased group (n = 9). We conclude that, apart from acetylcholine and carbachol, contractile and relaxant agonists give similar responses when used in human airway tissues from various sources. Our results highlight the importance of stating the source of tissue when human airways are to be studied.