Regional Deposition of Coarse Particles and Ventilation Distribution in Healthy Subjects and Patients with Cystic Fibrosis

Abstract

The efficacy of inhaled pharmaceuticals depends, in part, on their site of respiratory deposition. Markedly nonuniform ventilation distribution may occur in persons with obstructive airways diseases and may affect particle deposition. We studied the relationship between regional deposition (RDep) and regional ventilation (RVent) in a group of 12 cystic fibrosis (CF) patients with mild to moderate airway obstruction (63 +/- 8% predicted FEV1) and 11 healthy nonsmoking volunteers (104 +/- 13% predicted FEV1) using planar scintigraphic methods. RDep was assessed from initial deposition and 24-h retention images for monodisperse technetium-99m-labeled iron oxide particles (5-microm MMAD). Regional volumes and RVent were assessed from xenon-133 equilibrium and washout, respectively. Six regions of interest per lung were established by dividing each lung into thirds by height and approximately half by width. The two lower regions of the left lung were not analyzed due to activity in the stomach. Remaining regions were categorized as central (two interior-most regions) and peripheral (eight exterior regions). RDep and RVent were computed for the eight peripheral regions. Tracheobronchial (TB) deposition was estimated for each of the peripheral regions as the difference between initial activity and decay-corrected 24-h retention or parenchymal deposition. RDep was computed as the fraction of material within a region normalized to regional volume. RVent for each region was determined by normalizing the xenon washout rate for that region by the total washout rate for the eight peripheral regions. Significant linear associations were found between RDep and RVent in both the healthy subjects and CF patients. In healthy subjects, RDep in the TB airways was positively associated with RVent (p = 0.03). In CF patients, RDep in the TB airways was negatively associated with RVent (p = 0.04) and RDep in the parenchyma was positively associated with RVent (p < 0.001). The initial pattern of RDep in the lung was not significantly associated with RVent in either group. These data suggest that significant coarse particle deposition may occur in the TB airways of poorly ventilated lung regions in CF patients, whereas, particle deposition in the TB airways of the healthy subjects follows ventilation.

What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study

“…For example in the presence of constricted or obstructed airways can be expected to interfere with the relationship between ventilation and deposition. A narrow airway (such as in cystic fibrosis (18) or asthma (10) ) both collects aerosol particles and reduces ventilation of subtended regions of the lung. Indeed, no relationship between ventilation and deposition could be found in 10 subjects with HIV infections using a 2D gammascintigraphy.…”

Human inhalation exposure to iron oxide particles

“…In addition to smokers, the lung function of cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), emphysema, bronchial hyper-responsiveness (BHR), sarcoidosis (SAR), idiopathic pulmonary fibrosis (IPF), chronic obstructive bronchitis (COB), and primary cilia dyskinesia (PCD) patients were also studied with iron oxide particles [50][51][52][53][54][55][56]. The primary objective of the studies by Brown, Meyer and Scheuch was to determine the influence of controlled breathing on particle deposition in order to optimize the delivery of therapeutic aerosols in lung disease patients.…”

Respiratory System Deposition with a Novel Aerosol Delivery System in Spontaneously Breathing Healthy Adults

“…In order to minimize radiation exposure, a pre-inhalation xenon scan was not done, and the regions of interest were obtained from the first image, when the lungs had the highest number of counts, and which offers the clearest definition of the lung borders 14 (Fig. 2).…”