Potla Srinivasa, Smaldone Gerald C
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Stony Brook University Medical Center, Stony Brook, New York, USA.
J Aerosol Med Pulm Drug Deliv. 2024 Dec;37(6):338-345. doi: 10.1089/jamp.2024.0026. Epub 2024 Oct 22.
In normal subjects, during tidal breathing, aerosols deposit by settling in small airways. With obstructive lung disease (OLD), collapse of airways during expiration causes turbulence and increased deposition in central airways. High-flow nasal cannula (HFNC) therapy, washing out dead space, may affect deposition mechanisms and drug delivery. This study compared aerosol deposition and airway responsiveness in OLD after traditional and HFNC nebulization therapy. Twelve subjects with moderate to severe OLD participated in a two-day study. Spirometry was measured pre- and post-aerosol inhalation. On Day 1 (D1) subjects tidally inhaled radiolabeled albuterol (Tc DTPA) by mouth via AeroTech II, (Biodex. Shirley, NY). Day 2 (D2) inhalation was via HFNC using (InspiRx, Inc. Somerset, NJ). The HFNC system (60 L/m) was infused by syringe pump at 50 mL/h. D2 lung deposition was monitored in real time by gamma camera to match D1. Pre and post heart rate, O sat, and nasopharyngeal deposition (NP) were measured. Mechanistic contributions were modeled using multiple linear regression (MLR) of deposition rate (DR µg/m) as a function of breathing frequency, airway geometry (FEV), and parenchymal integrity (DLCO). Albuterol lung depositions were matched ( = 0.13) with D1 central/peripheral (sC/P) ratios 1.99 ± 0.98. Following HFNC, peripheral deposition increased (31% ± 33%, sC/P = 1.51 ± 0.43, = 0.01). D2/D1% change FVC increased by 16.1 ± 16.7% ( = 0.003). NP deposition averaged 333% of lung. Heart rate and O sat were unaffected ( = 0.31, = 0.63 respectively). DR analysis was markedly different between D1 ( = 0.82) and D2 ( = 0.12). In subjects with OLD, HFNC nebulization at 60 L/min was well tolerated and increased peripheral drug delivery. Spirometry significantly improved. Systemic effects were undetected indicating limited nasal absorption. MLR demonstrated that different mechanisms of deposition govern traditional vs HFNC aerosol delivery. Breath-enhanced nebulization via HFNC may provide controllable and effective aerosol therapy in OLD.
在正常受试者中，潮式呼吸时，气溶胶通过沉降在小气道中沉积。患有阻塞性肺病（OLD）时，呼气期间气道塌陷会导致湍流并增加在中央气道中的沉积。高流量鼻导管（HFNC）疗法可清除死腔，可能会影响沉积机制和药物递送。本研究比较了传统雾化疗法和HFNC雾化疗法后OLD患者的气溶胶沉积和气道反应性。12名中重度OLD患者参与了一项为期两天的研究。在吸入气溶胶前后测量肺活量。在第1天（D1），受试者通过AeroTech II（Biodex，纽约雪莉）经口潮式吸入放射性标记的沙丁胺醇（锝二乙三胺五乙酸）。第2天（D2）通过使用HFNC（InspiRx公司，新泽西州萨默塞特）进行吸入。HFNC系统（60 L/分钟）由注射泵以50 mL/小时的速度输注。通过γ相机实时监测D2的肺部沉积以与D1匹配。测量心率、血氧饱和度和鼻咽部沉积（NP）的前后值。使用沉积率（DR，μg/m）作为呼吸频率、气道几何形状（第一秒用力呼气容积）和实质完整性（一氧化碳弥散量）的函数的多元线性回归（MLR）对作用机制进行建模。沙丁胺醇肺部沉积与D1中央/外周（sC/P）比值1.99±0.98相匹配（P = 0.13）。HFNC治疗后，外周沉积增加（31%±33%，sC/P = 1.51±0.43，P = 0.01）。D2/D1用力肺活量（FVC）变化百分比增加了16.1±16.7%（P = 0.003）。NP沉积平均为肺部沉积的333%。心率和血氧饱和度未受影响（分别为P = 0.31，P = 0.63）。D1（P = 0.82）和D2（P = 0.12）的DR分析明显不同。在OLD患者中，60 L/分钟的HFNC雾化耐受性良好，并增加了外周药物递送。肺活量显著改善。未检测到全身效应，表明鼻腔吸收有限。MLR表明传统雾化与HFNC气溶胶递送的沉积机制不同。通过HFNC进行的呼吸增强雾化可能为OLD提供可控且有效的气溶胶治疗。
