Deposition and clearance of inhaled particles in patients with obstructive airway diseases

Abstract

A large part of the population (at least 10%) suffers from asthma or chronic bronchitis. Knowledge of deposition and clearance of inhaled particles in the respiratory tract in this group of patients is essential for estimating environmental health hazards, as well as optimal effects of therapeutic aerosols. These patients often have variable or chronic airways obstruction, resulting in a different deposition pattern compared with healthy subjects, with an increased deposition in the tracheobronchial region in the patients. Furthermore, it has been shown that there are wide variations (10-fold) in mouth and throat deposition among asthmatics, implying that the dose of a therapeutic aerosol in the lungs is difficult to predict, and is sometimes suboptimal. Mucociliary clearance is often impaired in these patients, as assessed from measurements in larger airways, but very little is known about clearance in the smallest airways of the tracheobronchial region.

Aims: To investigate whether differences in the pharynx and larynx could explain the wide variation in mouth and throat deposition among asthmatics, and whether an added external resistance during inhalation would influence this deposition by dilating the airways; to examine the relationship between lung function and regional lung deposition in patients with obstructive airway diseases; to study deposition and clearance -particularly in small ciliated airways - in the same group, with respect to the efficacy of cough.

Patients and methods: Patients with asthma, chronic bronchitis and immotile-cilia syndrome were included in this study. Pharynx and larynx function was assessed by fiberoptic laryngoscopy. Mouth and throat, and regional lung deposition was estimated after inhalation of radiolabelled ("'In) test particles. Lung retention was measured for up to 72-96 h, using a profile scanner. Theoretical calculations for an extremely slow inhalation flow (0.05 I/s) suggest particle deposition mainly in the bronchiolar region, whereas a normal flow(0.51/s) increases deposition mainly in the central airways.

Results: In patients with asthma, mouth and throat deposition varied between 9 and 76%. A pharyngeal narrowing during inhalation was related to high mouth and throat deposition, whereas a laryngeal narrowing seemed to be related to a decrease in peripheral lung deposition. At inhalation with increased external resistance, a marked reduction in mouth and throat deposition (range 20-44%), with a corresponding increase in lung deposition, was observed in the subjects with initially high mouth and throat deposition (> 30%). In patients with bronchitis, differences in regional lung deposition were related to variations in airway dimensions (larger airways mainly). Deposition data were well reproducible and agreed well with theoretical calculations and experimental data for healthy subjects. Clearance in small ciliated airways seemed to be incomplete, both in healthy subjects and patients with obstructive airway diseases with significant retentions measured over 72 h, possibly about 40% of the particles assumed to be deposited in the tracheobronchial region. In patients with bronchitis, we found a negative relationship between sputum volume and particle retention at the exposure supposed to reflect clearance mainly in small airways.

Conclusions: Pharyngeal configuration affects deposition of particles in the mouth and throat. Added external resistance improves regional deposition of aerosol particles in asthmatics with high mouth and throat deposition. Overall tracheobronchial clearance (mucociliary clearance and cough) may be quite effective in central airways in patients with bronchitis, probably due to a productive cough. Clearance in the bronchiolar region, however, seemed to be incomplete in all individuals, probably due to ineffective mucociliary transport and cough clearance in this region. However, in patients with bronchitis, an increased amount of mucus seemed to improve clearance in these airways. Deposition may be increased in the small airways by inhaling aerosol particles extremely slowly, which points to a potentially useful approach of therapeutic importance.