Scheuch G, Kohlhäufl M, Möller W, Brand P, Meyer T, Häussinger K, Sommerer K, Heyder J
Clinical Cooperation Group Inflammatory Lung Diseases, Institute for Inhalation Biology, The Helmholtz Center Munich, Gauting, Germany.
Exp Lung Res. 2008 Nov;34(9):531-49. doi: 10.1080/01902140802341710.
The aim of this study was to determine particle clearance and retention from non-alveolated airways of 14 healthy subjects (HS), 10 subjects with asymptomatic bronchial hyperresponsiveness (BHR), and 23 patients with chronic obstructive pulmonary disease (COPD). Monodisperse iron oxide particles of 1.6 micro m geometric and 3.5 micro m aerodynamic diameter labeled with (99m)Tc were delivered to the airways by inspiration of small aerosol boli into shallow volumetric lung depths. In each subject the penetration front depth of the aerosol boli was adjusted to 55% of the Fowler dead space of the airways. Particle deposition was enhanced by about 7 seconds of breath-holding after bolus inhalation. Retention of the particles in the airways during the 48 hours after their administration was assessed by measuring the decline in lung activity with a sensitive gamma counter. Particle deposition was not significantly different among study groups. Twenty-four hour particle retention in the airways was not different among study groups. Sixty-one percent of the particles were retained at 24 hours in HS, 58% in BHR, and 64% in COPD. However, subjects with BHR showed accelerated mucociliary clearance compared to healthy subjects, whereas clearance was retarded in COPD patients. This long-term particle retention in the airways has to be taken into account in aerosol toxicology risk assessment and aerosol therapy dose evaluation.
本研究的目的是确定14名健康受试者(HS)、10名无症状支气管高反应性(BHR)受试者和23名慢性阻塞性肺疾病(COPD)患者的非肺泡气道中颗粒的清除和滞留情况。通过向浅容积肺深度吸入小剂量气溶胶团,将几何直径为1.6微米、空气动力学直径为3.5微米且标记有(99m)Tc的单分散氧化铁颗粒输送至气道。在每个受试者中,将气溶胶团的穿透前沿深度调整至气道福勒死腔的55%。在吸入团注后屏气约7秒可增强颗粒沉积。通过用灵敏的γ计数器测量肺部活性的下降来评估给药后48小时内颗粒在气道中的滞留情况。各研究组之间的颗粒沉积无显著差异。各研究组气道中24小时颗粒滞留情况无差异。24小时时,HS组61%的颗粒被滞留,BHR组为58%,COPD组为64%。然而,与健康受试者相比,BHR受试者的黏液纤毛清除加快,而COPD患者的清除则延迟。在气溶胶毒理学风险评估和气溶胶治疗剂量评估中,必须考虑颗粒在气道中的这种长期滞留情况。