Comparison of Clearance of Particles Inhaled With Bolus and Extremely Slow Inhalation Techniques

Patients with hereditary a 1 -proteinase inhibitor (a 1 -PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, a 1 -PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug.In order to optimise this treatment approach, lung deposition of inhaled radiolabelled a 1 -PI (Prolastin1) was studied using four different commercial inhalation devices (PARI-LC Star1, HaloLite1, and AKITA1 system in combination with LC Star1 and Sidestream1) in six patients with a 1 -PI deficiency and mild-to-severe chronic obstructive pulmonary disease.The time required to deposit 50 mg of the Prolastin1 (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled a1-PI. This time was shortest for the AKITA1 system (18-24 min) and significantly higher for the PARI-LC Star1 (44 min) and the HaloLite1 (100 min).The higher efficiency of drug delivery using the AKITA1 system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.

Section: Discussionmentioning

confidence: 99%

Peripheral deposition of α₁‐protease inhibitor using commercial inhalation devices

Brand¹,

Beckmann²,

Enriquez³

et al. 2003

“…Both the healthy subjects and the CF patients were exposed using the same equipment for particles production procedure and inhalation. Identical inhalation pattern was used and radioactivity was measured in the lung with the same detectors throughout the study in both groups [5,20,21]. The average anthropomorphic and lung function data (mean¡SD) of the healthy subjects are given in table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Any particles remaining in the lung after 24 h represent alveolar deposition [1,2]. However, previous studies of healthy subjects using a shallow bolus technique as well as studies using extremely slow inhalation flow (0.05 L?s -1 ) and 6 mm particles, resulting in particles deposited in the small airways, show that a considerable fraction of particles may be retained after 24 h [3][4][5] These studies provide evidence that the rapid clearance phase in the tracheobronchial region is followed by a second, slower clearance phase, though still more rapid than alveolar clearance. This intermediate clearance phase, proposed to represent clearance of particles deposited in the bronchiolar region, has been included in the revised dosimetric model for the human respiratory tract, adopted by the International Commission on Radiological Protection (ICRP) [6].…”

mentioning

confidence: 99%

Long-term clearance from small airways in patients with cystic fibrosis

Lindström

Camner²,

Falk³

et al. 2005

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways.Radiolabelled Teflon particles (6 mm) were inhaled with an extremely slow inhalation flow, 0.05 L?s -1 . Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects.The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12)(13)(14)(15)(16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase.The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

“…Immediately after inhalation, and 24 h later, radioactivity was measured using two 127651-mm NaI detectors fitted with collimators [21][22][23][24][25][26]. The c-spectra from each detector were acquired separately.…”

Section: Measurement Of Radioactivitymentioning

confidence: 99%

Long-term clearance from small airways decreases with age

Svartengren

Falk²,

Philipson³

2005

128

The prevalence of respiratory symptoms increases with age. Age has been found to be negatively associated with large airway clearance. The small airways region is considered important for development of airway disease.Clearance after the first 24 h was studied in 46 healthy subjects with a wide age distribution, (mean 42, range 19–81 yrs). All subjects inhaled monodisperse 6 μm Teflon particles labelled with111In, with an extremely slow inhalation flow (0.05 L·s−1). The particles were mainly deposited in the small conducting airways. Lung retention was measured at 0 and 24 h, and at 7, 14 and 21 days after inhalation.Significant relationships were found for the individual 24 h “large” airway clearance in per cent of initial lung deposition with age, forced expiratory volume in one second and forced vital capacity. Age was negatively associated with “small” airway clearance after 24 h as estimated at 2, 7, 14 and 21 days. Using stepwise linear regression only age remained significantly associated to clearance.In conclusion, small airway clearance over 21 days was found to decrease with age. This might be one factor associated with the high prevalence of respiratory symptoms associated among the elderly.