Permeability of the Bronchial Mucosa to99mTc-DTPA in Asthma

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Abstract
Previous investigators, using 99mTc-DTPA aerosol as a marker to assess epithelial permeability in asthma, did not find an increased permeability in this group. However, they either failed to deliver the aerosol to the optimal site (bronchial mucosa, not alveoli) or failed to account for mucociliary clearance in analyzing their results. We studied 10 asthamtics and eight age-matched control subjects using a dosimeter (Spira-Elektra 2) and a carefully controlled breathing pattern to deliver aerosol to the subjects'' airways. Two aerosols were delivered on separate days in each patient; 99mTc-DTPA aerosol, and 99mTc-HSA (human serum albumin), using similar breathing patterns to ensure reproducibility of the deposition pattern with the two aerosols. From measurements of retention versus time over a 1-h period, rate constants Ktot and Km were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modeling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. There was no significant difference between Ktot in normal subjects and asthmatics; however, because of the slower mucociliary clearance in the asthmatic group, and the relative importance of mucociliary clearance in determining the washout of 99mTc-DTAP aerosol, there was a significant difference in airway permeability between the normal subjects and the asthmatics (t1/2 = 296 min .+-. 141 SD and 126 min .+-. 58, p < 0.01, in normal subjects and asthmatics, respectively). Thus, we have shown that this index of airway permeability was increased in asthmatics, supporting the theory that inflammation of the airway epithelium plays a role in the pathogenesis of asthma. Furthermore, this test may be used as a tool to assess pharmacologic treatment of this disorder.