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

Introduction: 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. Methods: 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 (^99mTc DTPA) by mouth via AeroTech II, (Biodex. Shirley, NY). Day 2 (D2) inhalation was via HFNC using i-AIRE (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, O₂ 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 (FEV₁), and parenchymal integrity (DLCO). Results: Albuterol lung depositions were matched (p = 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, p = 0.01). D2/D1% change FVC increased by 16.1 ± 16.7% (p = 0.003). NP deposition averaged 333% of lung. Heart rate and O₂ sat were unaffected (p = 0.31, p = 0.63 respectively). DR analysis was markedly different between D1 (R² = 0.82) and D2 (R² = 0.12). Conclusion: 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.