O'BYRNE, PM, M. DOLOVICH, R. DIRKS, RS ROBERTS, AND MT NEWHOUSE. Lung epithehal permeability: reZation to nonspecific airway responsiveness. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 57 (1): 77-84, 1984.-Lung epithelial permeability was measured in five normal, five asthmatic, and five smoking subjects by quantifying removal from the lung and accumulation in the blood of an inhaled radiolabeled lowmolecular-weight substance, technetium-99m-labeled diethyleneaminepentaacetate(ggmTc-DTPA). Measurements on 2 control days were highly reproducible. Nonspecific bronchial responsiveness to histamine was determined in all subjects on a 3rd day, and the results were expressed as the provocation concentration producing a fall in forced expiratory volume in 1 s of 20%(PC,, histamine). Lung epithelial permeability was similar for the normal and asthmatic subjects. However, smokers had greatly increased permeability when compared with the other two groups. The responsiveness to histamine was increased in the asthmatics but within the normal range for normal subjects and smokers. No relationship was established between increased epithelial permeability and increased responsiveness to histamine. Results indicate that increased permeability of the epithelial lining of the bronchi is not a dominant factor in the increased nonspecific responsiveness to histamine observed in asthma. half-micron aerosol; histamine; asthma; smoking

THE PERMEABILITY of the lung epithelium in both animals and humans has been measured by use of either high-or low-molecular-weight solutes instilled or inhaled into the airway surface, with the rate of transfer of the tracer substance from the airway lumen into the blood providing an index of the permeability integrity of the epithelium (l-3, 13, 27, 32). Hyperpermeability of the mucosa to horseradish peroxidase (HRP, mol wt 40,000) has been shown to occur in guinea pigs after inhalation of histamine or methachol ine (3). Us ing Ascaris-sensitive rhesus monkeys Boucher et al.(2) showed that the increased bronchial responsiveness to histamine observed after allergen challenge was associated with a parallel increase in the permeability of the airways as indicated by increased