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A comparison of techniques to assess regional deposition of aerosol particles in individuals with compromised lung function.

Specific information regarding regional deposition of aerosol particles is essential for minimizing health risks due to environmental or occupational aerosol particle exposures, and for effective inhalation therapy.  To date, only a few methods are available to generate this type of information.  The gamma imaging technique, which is the clinical standard, provides a rough qualitative estimation of the particle fraction deposited in the thoracic and extra thoracic regions but cannot differentiate between alveolar and bronchial regions with respect to particle deposition.  A comparison of two other techniques that provide quantitative analysis, the Clearance Derived Regional Deposition (CRD) technique and the new Single Breath Regional Deposition (SBRD) technique are the subject of this review.

The CRD technique can assess regional deposition quantitatively.  For this technique, bronchial deposition is derived form the particle fraction cleared via mucociliary transport during the first 24 hours after inhalation (fast cleared fraction), whereas alveolar deposition is proportional to the particle fraction still in the lungs after 24 hours (slow cleared fraction). However, this method is time consuming and requires the use of radioactive labeled aerosols.  This hinders its application for clinical routine.  Furthermore, this method assumes that all particles in the bronchial tree are cleared quickly whereas particles in the alveolar region are retained in the lung for longer periods.  Research has demonstrated that this is not always true and that bronchial deposition is a function of the geometric particle size.  These authors corrected for this overestimation. 

A new technique has recently been proposed, called the Single Breath Regional Deposition (SBRD).  This technique quantifies intrapulmonary distribution of particles deposited in the lungs using monodisperse inert and non-radioactive aerosols by measuring particle number concentrations of inhaled and exhaled test particles.  This measurement allows the quantification of particle deposition as a function of the volumetric lung depth. The authors used a fast mass spectrometer that measures the concentrations of various gases (respiratory and non respiratory) within the respired air as a function of the respired air volume to calculate dead space.  When the individual functional dead space of the lung is known, the fraction of particles deposited proximal and peripheral to the dead space can be calculated.  This represents deposition in the conducting airways and in the alveolar space, respectively.  This method was originally developed for aerosol boluses and has been generalized for single breath inhalations.   

These authors investigated the use of this SBRD test in patients with compromised lung function since these tests are purported to be influenced by lung disease. The results were compared to those values obtained by the CRD method, which has been validated for use in patients with COPD.  A comparison of the CRD and SBRD methods have been previously done in healthy subjects and the results showed good agreement.   Furthermore, prior studies between healthy and Chronic Obstructive Pulmonary Disease (COPD) patients, revealed that after 24 hours, the results were identical using the CRD method.  Therefore, it was concluded that CRD was a valid test in persons with COPD.  Thus, the CRD method has been tested in both healthy subjects and those with compromised lung function.  To date, the SBRD technique has only been performed in healthy subjects.  

Brand et al. measured the deposition of monodisperse test particles with aerodynamic diameters of 2,3, and 4 um (di-2-ethylhexylsebacate droplets) in 12 patients (8 males & 4 females) with homozygote alpha-1 antitrypsin deficiency and symptoms of moderate to severe chronic obstructive pulmonary disease.  

Notwithstanding a slightly different technique to measuring dead space (usingC18O2 as a tracer gas as opposed to nitrogen gas), the SBRD also showed promise as a method to use in patients with COPD.  However, the validation has to be generalized in future studies to patients with differing lung diseases and different breathing patterns as well as with different aerosol particle sizes.  

In conclusion, this study compared the SRBD technique with the CRD technique. Their results showed that both techniques yielded very similar results with respect to total and alveolar deposition.  The CRD method used the kinetics of particle clearance within the first 24 hours after inhalation to determine bronchial and alveolar deposition.  In contrast, the SBRD method used the longitudinal distribution of deposited inert test particles to calculate the particle fraction deposited within and distal to the dead space.  The authors suggested that because of controlled slow and deep inhalations, the alveolar deposition was as much as 50% in patients with COPD.  They concluded that SBRD should be considered an easy tool to study alveolar deposition in patients whose lung function is compromised.  

By: Arlene L. Weiss, MS DABT
Contributing Editor for Toxicology and Epidemiology

Source: P. Brand, T. Meyer, K. Sommerer, N. Weber, and G. Scheuch. 2002. Alveolar Deposition of Monodisperse Aerosol Particles in the Lung of Patients with Chronic Obstructive Pulmonary Disease. Experimental Lung Research 28:39-54 2002

 21 May 03