The effects of airway disease on the deposition of inhaled drugs

Abstract

Introduction: The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol deposition patterns has been the focus of intense research that combines the fields of physics, radiology, physiology, and biology.

Areas covered: The review covers the physics of aerosol transport in the lung, experimental, and in-silico modeling approaches to determine lung dose and aerosol deposition patterns, the effect of asthma, chronic obstructive pulmonary disease, and cystic fibrosis on aerosol deposition, and the clinical translation potential of determining aerosol deposition dose.

Expert opinion: Recent advances in in-silico modeling and lung imaging have enabled the development of realistic subject-specific aerosol deposition models, albeit mainly in health. Accurate modeling of lung disease still requires additional refinements in existing imaging and modeling approaches to better characterize disease heterogeneity in peripheral airways. Nevertheless, recent patient-centric innovation in inhaler device engineering and the incorporation of digital technology have led to more consistent lung deposition and improved targeting of the distal airways, which better serve the clinical needs of patients.

Keywords: Aerosol dosimetry; COPD; asthma; gamma scintigraphy; in-silico modeling.

Figure 1:

Planar 2D deposition scintigraphy images showing a deposited radiolabeled aerosol in the lungs of (A) an adult and (B) an 8-year-old child. Posterior images shown. (Unpublished data obtained from studies approved by the Institutional Review Board of the University of Pittsburgh. Informed consent was obtained from subject and/or parent).

Figure 2.

Multiscale model based on subject-specific anatomical (1) and physiological data. CT-based 3D/CFPD models of the large airways (2) are bidirectionally coupled with semi-individualized 1D functional MPPD aerosol transport models (3). Flow at each outlet of the 3D domain is determined based on lobar volume expansion measured on CT lung images obtained at two time points (4). Simulations are performed for subject-specific breathing patterns (5). Predictions (6) are then validated with subject and exposure-specific experimental data (7).