DOES THE DISEASE STATE INFLUENCE THE RESPONSIVENESS OF HUMAN AIRWAYS STUDIED IN-VITRO

Human airway tissue has been used in vitro to study mechanisms of airw ay disease. However, there has never been a comprehensive study that h as looked at the influence of disease on the subsequent in vitro respo nsiveness of human airways. In this study, we obtained airway tissue f rom patients who were undergoing resection of the lung for carcinoma. We then compared the airway responsiveness in these tissues and in tis sues from patients who had undergone lung transplantation for alpha-1- antitrypsin deficiency, emphysema, or cystic fibrosis with the respons iveness 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 obt ained from all the sources studied. This was not true for acetylcholin e in that there were significantly lower responses in tissues from pat ients with alpha-1-antitrypsin deficiency (P = 0.02; n = 9) or from pa tients 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 def iciency group (P = 0.001; n = 10) and in specimens resected for carcin oma (P = 0.001; n = 6) than in the nondiseased group (n = 9). We concl ude that, apart from acetylcholine and carbachol, contractile and rela xant 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.