The effect of exhalation before the inhalation of dry powder aerosol drugs on the breathing parameters, emitted doses and aerosol size distributions

Árpád Farkas; Gábor Tomisa; Szilvia Kugler; Attila Nagy; Attila Vaskó; Erika Kis; Georgina Szénási; Gabriella Gálffy; Alpár Horváth

doi:10.1016/j.ijpx.2023.100167

The effect of exhalation before the inhalation of dry powder aerosol drugs on the breathing parameters, emitted doses and aerosol size distributions

Int J Pharm X. 2023 Feb 4:5:100167. doi: 10.1016/j.ijpx.2023.100167. eCollection 2023 Dec.

Authors

Árpád Farkas¹, Gábor Tomisa², Szilvia Kugler¹, Attila Nagy³, Attila Vaskó⁴, Erika Kis⁵, Georgina Szénási², Gabriella Gálffy⁶, Alpár Horváth²

Affiliations

¹ Centre for Energy Research, Konkoly Thege M. út 29-33, 1121 Budapest, Hungary.
² Chiesi Hungary Kft., Dunavirág utca 2, 1138 Budapest, Hungary.
³ Wigner Research Centre for Physics, Konkoly Thege M. út 29-33, 1121 Budapest, Hungary.
⁴ Pulmonology Clinic, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
⁵ Babes-Bolyai University, Hungarian Department of Biology and Ecology, Cluj-Napoca, Romania.
⁶ County Institute of Pulmonology, Department of Pulmonology, Munkácsy M. u. 70, 2045 Törökbálint, Hungary.

Abstract

Airway deposition of aerosol drugs is highly dependent on the breathing manoeuvre of the patients. Though incorrect exhalation before the inhalation of the drug is one of the most common mistakes, its effect on the rest of the manoeuvre and on the airway deposition distribution of aerosol drugs is not explored in the open literature. The aim of the present work was to conduct inhalation experiments using six dry powder inhalers in order to quantify the effect of the degree of lung emptying on the inhalation time, inhaled volume and peak inhalation flow. Another goal of the research was to determine the effect of the exhalation on the aerodynamic properties of the drugs emitted by the same inhalers. According to the measurements, deep exhalation before drug inhalation increased the volume of the inhaled air and the average and maximum values of the inhalation flow rate, but the extent of the increase was patient and inhaler specific. For different inhalers, the mean value of the relative increase in peak inhalation flow due to forceful exhalation was between 15.3 and 38.4% (min: Easyhaler®, max: Breezhaler®), compared to the case of normal (tidal) exhalation before the drug inhalation. The relative increase in the inhaled volume was between 36.4 and 57.1% (min: NEXThaler®, max: Turbuhaler®). By the same token, forceful exhalation resulted in higher emitted doses and smaller emitted particles, depending on the individual breathing ability of the patient, the inhalation device and the drug metered in it. The relative increase in the emitted dose varied between 0.2 and 8.0% (min: Foster® NEXThaler®, max: Bufomix® Easyhaler®), while the relative enhancement of fine particle dose ranged between 1.9 and 30.8% (min: Foster® NEXThaler®, max: Symbicort® Turbuhaler®), depending on the inhaler. All these effects and parameter values point toward higher airway doses due to forceful exhalation before the inhalation of the drug. At the same time, the present findings highlight the necessity of proper patient education on the importance of lung emptying, but also the importance of patient-specific inhaler-drug pair choice in the future.

Keywords: AF, aerosolized fraction; Aerosol drug delivery; BMI, body mass index; Breathing parameters; CAD, computer aided design; COPD, chronic obstructive pulmonary disease; CT, computed tomography; DPI, dry powder inhaler; Dry powder inhalers; ED, emitted dose; FEV1, expiratory volume at the end of the first second of forced exhalation; FPF, fine particle fraction; FVC, forced vital capacity; GSD, geometric standard deviation; ICS, inhalation cortico-steroid; IV, inhaled volume; IVC, inspiratory vital capacity; IVdev, inhaled volume through an inhalation device; Inhalation therapy; LABA, long-acting beta-agonist; Lung emptying; MMAD, mass median aerodynamic diameter; PEF, peak expiratory flow; PIF, peak inhalation flow; PIFdev, peak inhalation flow through an inhalation device; PIL, patient information leaflet; Q, mean inhalation flow rate; Qdev, mean inhalation flow rate through an inhalation device; SPC, summary of product characteristics; tin, inhalation time; tin-dev, inhalation time through an inhalation device.