Deposition-dependent normal ranges for radioaerosol assessment of lung mucus clearance

Deposition distribution variability strongly influences data from radioaerosol mucus clearance measurements. We investigated how one clearance measurement-the area under the 0-6 h tracheobronchial retention curve (AUC)-relates to three different indices characterizing initial particle distribution. These indices were a conventional penetration index (PI), retention at 24 h (R(24)) and an Airways Penetration Index (API). API is an estimate of an outer to inner zone ratio for "tracheobronchial" (short-term cleared) deposition. Data were analyzed from "control" tests on 35 normal nonsmoking volunteers (16 females, 19 males, age 18-72 years). The strongest clearance-deposition correlation (r = 0.84, p < 0.0001) was obtained with API, yielding a narrower normal range than those with PI or R(24). No influence of age was detected. Data from repeat tests on 17 subjects demonstrated AUC changes correlating closely with API changes (r = 0.92, p < 0.0001), confirming the potential value of API as a "predictor" of clearance changes resulting simply from a changed distribution of initial deposition along the tracheobronchial airway generations. Additional data from 19 "placebo" tests on normal subjects gave AUC values within or close to suggested normal confidence limits derived from the control subject plots of AUC against, respectively, PI, R(24), and API. Quantitative attention to the influence of depositionclearance relationships should help in analyzing data from studies where posttreatment aerosol distribution cannot be exactly matched to the pretreatment situation. Deposition-corrected clearance provides an approach to improved estimation of clearance "normality."