Dual Pathway Clearance of99mTc-DTPA from the Bronchial Mucosa

Abstract

Many studies have reported clearance rates of 99mTc-DTPA from the alveolar epithelial surface, but few have measured clearance of this solute from the bronchial mucosa. Those that have attempted such measurements have discounted the possibility that 99mTc-DTPA may be removed from the bronchial airways by mucocilliary transport as well as by absorption through the epithelium. This study was designed to better approximate the rate of 99mTc-DTPA absorption across the bronchial epithelium by correcting the measurements of total 99mTc-DTPA clearance for mucus transport. On two separate study days, each normal, nonsmoking subject (n = 8) breathed an aqueous aerosol (2.0 .mu.m MMAD, .sigma.g = 2.0) containing 99mTc bound to DTPA or human serum albumin (HSA) (a relatively nonpermeable solute that is cleared only by mucus transport over the period of measured clearance) while seated in front of a gamma camera. Breathing pattern was standarized to produce a similar central deposition of particles on both study days. From measurements of retention versus time over a 1-h period, exponential 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. Results showed that mucus clearance (Km) accounted for two thirds of the total rate of 99mTc-DTPA clearance (Ktot) (mean Ktot = 0.00985, Km = 0.00968, and Kp = 0.00287/min). The mean half-time (T1/2) of bronchial permeability derived from Kp was 296 .+-. 141 min. In five of the subjects, we also measured alveolar clearance of 99mTc-DTPA by depositing the aerosol in the peripheral airways. The rate of alveolar permeability in these subjects (mean T1/2 = 107 min) was three times the rate of their bronchial absorption (mean T1/2 = 316 min). Measurements of this index of bronchial permeability may prove to be useful in the study of inflammatory airway diseases such as asthma or in characterizing airway damage from environmental pollutants.