Effects in man and rabbits of inhalation of cotton dust or extracts and purified endotoxins.

314-321. The incidence of byssinosis in workers in a cotton card-room, where the airborne concentration of bacterial endotoxins was 7·2 μg./m., was 32%; and 47% in a hemp card-room where the endotoxin concentration was 8·7 μg./m.; no cases were observed among workers exposed to only traces of endotoxins. The effect of the inhalation by aerosol of purified endotoxin on F.E.V. and F.V.C. was studied in normal subjects and in patients with chronic bronchitis. A significant reduction in F.E.V. lasting more than 6 hours was observed in two out of eight normal subjects, in one out of three subjects with chronic bronchitis inhaling 80 μg. endotoxin, and in one out of four subjects with chronic bronchitis inhaling 40 μg. endotoxin. These results show that the inhalation of bacterial endotoxin can produce, in some individuals, changes in F.E.V. similar to those experienced on Mondays by some card-room workers. A study of the mechanism of pathogenesis of inhaled bacterial endotoxins was carried out on rabbits subjected for 20 weeks to aerosols of purified endotoxin (20 μg./day) and cotton extract (2 mg./day). This treatment produced patterns of bronchitis: a increase in the respiratory tract fluid with increased protein content and characteristic histopathological changes. The bronchitis occurred after the appearance of cross-reacting circulating antibodies against endotoxin and cotton extract. These antibodies were detected with the haemagglutination tests after the first three weeks of treatment, and in subsequent weeks reached progressively higher titres, up to a maximum of 1:512. A challenging aerosol of 0·1 mg. endotoxin in two rabbits and 10 mg. cotton extract in another two of the rabbits treated as above produced a marked increase in pulmonary resistance lasting more than two hours. In control rabbits a challenging aerosol of 1 mg. endotoxin or 100 mg. cotton extract caused only a moderate increase in pulmonary resistance, which returned to normal in less than one hour. It may be concluded that the repeated inhalation of endotoxins induces in rabbits a state of hypersensitivity and at the same time the appearance of inflammatory reactions in the bronchi and alterations in the mechanical properties of the lung. These changes may be significant in the pathogenesis of byssinosis.