Bacterial infection is the most common cause of the adult respiratory distress syndrome which, in turn is associated with endothelial capillary permeability and alveolar oedema. Previously, we have demonstrated the direct cytotoxicity of the bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells. The purpose of this study was to investigate the effect of Exo A and LPS on pulmonary epithelial cells in vitro. We also tested the protective effect of dibutyryl cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity. In cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as measured by 51Cr release from these cells. LPS did not injure RAEC's. Pretreatment of RAEC with db-cAMP (1 mM) attenuated Exo A induced cytotoxicity. We conclude that (1) Exo A directly injures epithelial lung cells and may contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar epithelial cells in this model are resistant to LPS induced injury.

OBJECTIVE To define the basis for the conflicting reports on the prognosis of lung cancer in young adults. DESIGN Retrospective review of lung cancer patients between 1977 and 1988. SETTING Medical centers in Chicago (Northwestern Memorial Hospital), northern Israel (Rambam Medical Center), and northern Italy (S. Anna and U. of Pavia Hospitals). PATIENTS Patients were < or = 45 years of age with a diagnosis of primary lung cancer identified from tumor registry records, pathology reports, and hospital charts, plus a sample of patients > 45 years of age. MEASUREMENTS AND MAIN RESULTS In Chicago, younger patients had a higher incidence of chest pain, fever, and neurologic symptoms at presentation than the older patients, and fewer were asymptomatic. They also had more lower lobe lesions on chest roentgenogram, a higher incidence of adenocarcinoma, more advanced disease, an increased likelihood of receiving chemotherapy, and reduced survival (p < 0.03). The poorer prognosis was due to more advanced disease at presentation. In Israel, younger patients more frequently presented with stage I disease than the older patients and they had a higher incidence of adenocarcinoma, an increased likelihood of receiving treatment especially surgery, and better survival (p < 0.02). There were no differences between the two age groups for symptoms, symptom duration, and chest roentgenogram findings. Compared with the younger patients in Chicago and Israel, those from northern Italy had more squamous cell cancers and fewer adenocarcinomas, more commonly presented with stage I or II disease, received radiation therapy less frequently, and were given supportive care more often. Survival was low and comparable to that reported from Chicago. CONCLUSION Differences exist in the clinical characteristics, pathologic findings, and prognosis of younger and older patients with lung cancer from the same region and of younger patients from different regions. The difference in prognosis is related in part to the stage of disease at presentation and the ability to undergo resectional surgery.