慢性支气管炎患者小气道的长期清除：实验和理论数据

Svartengren Magnus, Svartengren Katharina, Europe Eeva, Falk Rolf, Hofmann Werner, Sturm Robert, Philipson Klas, Camner Per

Division of Occupational Medicine, Department of Public Health Science, Karolinska Institutet, Stockholm, Sweden.

Exp Lung Res. 2004 Jul-Aug;30(5):333-53. doi: 10.1080/01902140490449436.

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.

对9名慢性支气管炎（CB）患者（年龄65±10岁，均值±标准差）的小气道长期清除情况（21天）进行了研究，并与15名年龄匹配的健康受试者（年龄67±7岁，均值±标准差）进行了比较。6名CB患者接受了两次研究。所有受试者均以极慢的吸入流速（0.05L/s）吸入用111In标记的单分散6微米聚四氟乙烯颗粒。采用这种吸入技术，颗粒主要沉积在小传导气道中。在吸入后0小时、24小时以及7天、14天和21天测量肺部留存情况。对于接受两次研究的CB患者，24小时时的肺部留存率（沉积百分比）具有高度可重复性，但与健康受试者的留存率无显著差异，此外，与气道阻力（Raw）和预测的FEV1%均无关。健康受试者和CB患者在24小时至21天期间均显示出显著的清除。CB患者的平均留存率更高（P<0.001），在7天、14天和21天时分别为24小时留存率的90%、89%、87%，而健康受试者在7天、14天和21天时的测量值分别为24小时留存率的80%、76%、71%。24小时后的清除情况（21天时的留存率）与预测的FEV1%显著相关，但与Raw无关。预测的FEV1%值降低与清除率较慢相关。进行了模型计算以估计肺内沉积模式。气道尺寸和不均匀通气的影响有限。然而，健康受试者和CB患者之间的差异有限。无法确定24小时后清除差异是区域沉积变化的影响，还是患病气道中小气道清除较慢的影响。这种使用极慢吸入流速靶向最小纤毛气道的技术为研究最小气道功能和药物递送提供了新的可能性，值得进一步研究。