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

Sammanfattning: A large part of the population (at least 10%) suffers from asthma or chronic bronchitis. Knowledge ofdeposition and clearance of inhaled particles in the respiratory tract in this group of patients is essential forestimating environmental health hazards, as well as optimal effects of therapeutic aerosols. These patientsoften have variable or chronic airways obstruction, resulting in a different deposition pattern compared withhealthy 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 sometimessuboptimal. Mucociliary clearance is often impaired in these patients, as assessed from measurements inlarger airways, but very little is known about clearance in the smallest airways of the tracheobronchialregion.Aims: To investigate whether differences in the pharynx and larynx could explain the wide variation inmouth and throat deposition among asthmatics, and whether an added external resistance during inhalationwould influence this deposition by dilating the airways; to examine the relationship between lung functionand 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 includedin this study. Pharynx and larynx function was assessed by fiberoptic laryngoscopy. Mouth and throat, andregional lung deposition was estimated after inhalation of radiolabelled ("'In) test particles. Lung retentionwas measured for up to 72-96 h, using a profile scanner. Theoretical calculations for an extremely slowinhalation 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 pharyngealnarrowing during inhalation was related to high mouth and throat deposition, whereas a laryngeal narrowingseemed to be related to a decrease in peripheral lung deposition. At inhalation with increased externalresistance, a marked reduction in mouth and throat deposition (range 20-44%), with a corresponding increasein 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 airwaydimensions (larger airways mainly). Deposition data were well reproducible and agreed well with theoreticalcalculations and experimental data for healthy subjects. Clearance in small ciliated airways seemed to beincomplete, both in healthy subjects and patients with obstructive airway diseases with significant retentionsmeasured over 72 h, possibly about 40% of the particles assumed to be deposited in the tracheobronchialregion. In patients with bronchitis, we found a negative relationship between sputum volume and particleretention at the exposure supposed to reflect clearance mainly in small airways.Conclusions: Pharyngeal configuration affects deposition of particles in the mouth and throat. Addedexternal resistance improves regional deposition of aerosol particles in asthmatics with high mouth and throatdeposition. Overall tracheobronchial clearance (mucociliary clearance and cough) may be quite effective incentral airways in patients with bronchitis, probably due to a productive cough. Clearance in the bronchiolarregion, however, seemed to be incomplete in all individuals, probably due to ineffective mucociliarytransport and cough clearance in this region. However, in patients with bronchitis, an increased amount ofmucus seemed to improve clearance in these airways. Deposition may be increased in the small airways byinhaling aerosol particles extremely slowly, which points to a potentially useful approach of therapeuticimportance.Key words: bronchial asthma, chronic bronchitis, immotile-cilia syndrome, tracheobronchial clearance,mucus, cough, particle deposition, laryngoscopy, lung function ISBN 91-628-1822-8

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