Long-term clearance from small airways in patients with chronic bronchitis: experimental and theoretical data

Long-term clearance (21 days) from small airways was studied in 9 patients with chronic bronchitis (CB), 65 +/- 10 (mean +/- SD) years, and was compared to 15 age-matched healthy subjects of 67 +/- 7 (mean +/- SD) years. Six of the CB patients were studied twice. All subjects inhaled monodisperse 6 microm Teflon particles labelled with 111In with an extremely slow inhalation flow, 0.05 L/s. With this inhalation technique, particles are deposited mainly in the small conducting airways. Lung retention was measured at 0 and 24 hours, and at 7, 14, and 21 days after inhalation. Lung retention at 24 hours (% of deposition) was highly reproducible for the CB patients, studied twice, but it was not significantly different from that found for healthy subjects and, furthermore, not related to airway resistance (Raw), nor FEV1% predicted. Both healthy subjects and CB patients showed significant clearance in the period between 24 hours and day 21. The mean retention were higher (P<.001) in CB patients, 90%, 89%, 87% of 24 hours retention at 7, 14, and 21 days, compared to 80%, 76%, 71% of 24 hours retention at 7, 14, and 21 days measurements for healthy subjects. Clearance after 24 hours (retention at 21 days) was significantly related to FEV1% predicted, but not Raw. Reduced FEV1% predicted values was associated with slower clearance rates. Model calculations were performed to estimate intrapulmonary deposition patterns. A limited effect was shown for airway dimension and uneven ventilation. The differences between healthy and CB patients were, however, limited. It is not possible to conclude whether the difference in clearance after 24 hours is an effect of change in regional deposition, or slower small airway clearance in diseased airways. This technique to target the smallest ciliated airways, using an extremely slow inhalation flow, provides new possibilities to investigate smallest airway function and drug delivery that merits further investigations.