Pressure pulsations enhance penetration index in COPD

• Published in: Drug delivery and translational research Vol. 12; no. 6; pp. 1466 - 1474
• Main Authors: Gavriely, Noam, Volkov, Olga, Fink, Gershon, Shpirer, Isaac, Golan, Haim
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2022
• Subjects: Administration, Inhalation; Aerosols; Albuterol; Biomedical and Life Sciences; Biomedicine; Humans; Lung - diagnostic imaging; Nebulizers and Vaporizers; Original Article; Pharmaceutical Sciences/Technology; Pulmonary Disease, Chronic Obstructive - drug therapy; Small airways; Drug delivery; Terminal bronchioles; Penetration index; COPD; Pressure pulses
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-021-01027-z

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer (“NEB”) and with a combined Pulsehaler™/jet nebulizer (“PH + NEB”) treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, “PI”). There was a significant improvement in FEV 1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF 25–75 , FEV 1 %, FVC%, FEF 25 , FEF 50 , and FEF 75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF 25-75 (PH + NEB > NEB, p = 0.0176), FEF 75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved. Graphical abstract