Pressure pulsations enhance penetration index in COPD

Drug Deliv Transl Res. 2022 Jun;12(6):1466-1474. doi: 10.1007/s13346-021-01027-z. Epub 2021 Jul 28.


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 FEV1 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, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (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.

Keywords: COPD; Drug delivery; Penetration index; Pressure pulses; Small airways; Terminal bronchioles.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Albuterol
  • Humans
  • Lung / diagnostic imaging
  • Nebulizers and Vaporizers*
  • Pulmonary Disease, Chronic Obstructive* / drug therapy


  • Aerosols
  • Albuterol