High-Flow Nasal Aerosol Therapy: Regional Aerosol Deposition and Airway Responsiveness

Background: 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 mechanisms of particle deposition. This study compared aerosol deposition and responsiveness in OLD after traditional and HFNC therapy. Methods: Twelve subjects with moderate to severe OLD were enrolled for a two-day study. Spirometry was measured pre- and post-aerosol inhalation. On Day 1 (D1) subjects tidally inhaled radiolabeled albuterol (99mTc DTPA) via AeroTech II, (Biodex, Shirley, NY). Day 2 (D2) inhalation was via HFNC using i-AIRE (InspiRx, Somerset, NJ). The HFNC system (60 L/min) 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 pulse, O2 sat, and nasopharyngeal deposition (NP) were measured. Mechanistic contributions were modeled using multiple linear regression (MLR) of deposition rate (DR µg/min) as a function of breathing frequency, airway geometry (FEV1) and parenchymal integrity (DLCO). Results: Figure 1 illustrates the change in deposition from D1 to D2 in a single patient. Albuterol lung depositions were matched (P = .13) with D1 central/peripheral (sC/P) ratios 1.99 ± 0.98 (Figure 2 left). Following HFNC, peripheral deposition increased (31% ± 33%, sC/P = 1.51 ± 0.43, P = .01). D2/D1 % change FVC increased by 16.1 ± 16.7% (P = .003)(Figure 2 right). NP deposition averaged 332.6% of lung. Pulse and O2 sat were unaffected (P = .31, P = .63 respectively). DR analysis was markedly different between D1 (R2 = 0.829) and D2 (R2 = 0.071). Conclusions: HFNC nebulization at 60 L/min was well tolerated and practical. HFNC increased peripheral drug delivery in subjects with OLD with improvements in spirometry. Systemic effects were undetected indicating limited nasal absorption. MVA indicated different mechanisms of deposition govern traditional vs HFNC aerosol delivery. Breath-enhanced nebulization with HFNC may provide controllable and effective aerosol therapy in OLD.