Abstract
The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function.Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 μm geometric and 6.2 μm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49 % (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret24 with slow inhalation flow was 73.9 ± 1.9 % compared to 68.9 ± 7.5 % with normal inhalation flow in the three PCD subjects exposed twice. During day 7–21 the three PCD subjects exposed twice cleared 9 % with normal flow, probably representing predominantly alveolar clearance, compared to 19 % with slow inhalation flow, probably representing mainly small airway clearance.This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.
Highlights
Inhaled insoluble particles deposited in the lung are cleared by various clearance mechanisms depending on the site of deposition
Deposition The calculated regional deposition in different airway generations with the extremely slow inhalation flow, according to the theoretical model, showed that the main fraction was deposited in the small airways, i.e the bronchiolar region
Slow airway clearance Both in the primary ciliary dyskinesia (PCD) subjects and in the healthy controls there was significant difference in retention between each time point indicating a significant measured clearance continuing in the small airways in both groups
Summary
Inhaled insoluble particles deposited in the lung are cleared by various clearance mechanisms depending on the site of deposition. Respiratory Research 2006, 7:79 http://respiratory-research.com/content/7/1/79 are eliminated within 24 h by the mucociliary clearance mechanism, and it has long been assumed that any particles remaining in the lung at 24 h represent alveolar clearance [1,2] This is probably due to the deposition pattern of particles inhaled with normal inhalation flow which give a limited deposition in the small airways. Previous studies in healthy subjects using a shallow bolus technique as well as studies using extremely slow inhalation flow (0.05 L/s) and 6 μm particles, resulting in particles deposited in the small airways, show that a considerable fraction of particles may be retained after 24 h [3,4,5] This slow clearance phase, probably representing the small airways, continues and is shown to be faster than the alveolar clearance but much slower than clearance from the large airways. The slow clearance phase has been included in the revised dosimetric model for the human respiratory tract adopted by the ICRP [6], representing clearance of particles deposited in the bronchiolar region
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