Airway generation

The estimated number of tubes in each airway generation depends on the bifurcation model used in describing the tracheobronchial tree. Though bronchial bifurcations are asymmetric, symmetric models, exemplified by Weibel, or asymmetric models, such as one suggested by Horsfield, can... 

Airway generation Theoretical representation of bronchi position within... 

Diffusion is the dominant mechanism of lung deposition for radon daughter aerosols. It is generally assumed that airflow is laminar in the smaller airways and that deposition in each airway generation can be calculated adequately (Chamberlain and Dyson, 1936 Ingham, 1975). However, there is no such consensus on the treatment of deposition in the upper bronchi. Some authors (Jacobi and Eisfeld, 1980 NCRP, 1984) have considered deposition to be enhanced by secondary flow, on the basis of experimental results (Martin and Jacobi, 1972). It has been shown that this assumption reduces the calculated dose from unattached radon daughters by a factor of two (James, 1985). 

The deposition of ultrafine particles has been measured in replicate hollow casts of the human tracheobronchial tree. The deposition pattern and efficiency are critical determinants of the radiation dose from the short lived decay products of Rn-222. The experimental deposition efficiency for the six airway generations just beyond the trachea was about twice the value calculated if uniform deposition from laminar flow is assumed. The measured deposition was greater at bifurcations than along the airway lengths for 0.2 and 0.15 ym diameter particles ... 

Mucociliary Clearance Mucociliary clearance operates by the coordinated movements of cilia, which sweep mucus out of the lungs towards the pharynx where it is swallowed. There is an inverse relationship between mucus velocity and airway generation, which relates to the lower percentage of ciliated cells, shorter cilia, lower ciliary beat frequency and lower number of secretory cells in the peripheral airways [121]. The reported tracheal mucociliary clearance... 

As noted earlier, air-velocity profiles during inhalation and exhalation are approximately uniform and partially developed or fully developed, depending on the airway generation, tidal volume, and respiration rate. Similarly, the concentration profiles of the pollutant in the airway lumen may be approximated by uniform partially developed or fully developed concentration profiles in rigid cylindrical tubes. In each airway, the simultaneous action of convection, axial diffusion, and radial diffusion determines a differential mass-balance equation. The gas-concentration profiles are obtained from this equation with appropriate boundary conditions. The flux or transfer rate of the gas to the mucus boundary and axially down the airway can be calculated from these concentration gradients. In a simpler approach, fixed velocity and concentration profiles are assumed, and separate mass balances can be written directly for convection, axial diffusion, and radial diffusion. The latter technique was applied by McJilton et al. 

Fleming, J.S. Nassim, M.A. Hashish, A.H. Bailey, A.G. Conway, J. Holgate, S. Halson, P. Moore, E. Martonen, T.B. Description of pulmonary deposition of radiolabeled aerosol by airway generation using a conceptional three dimensional model of lung morphology. J. Aerosol Med. 1995, 8 (4), 341-356. 

Figure 2 Graph of airway diameter and cross-sectional area as a function of airway generation.

Hashish AH, Fleming JS, Conway J, Halson P, Moore E, Williams TJ, Bailey AG, Nassim MN, Holgate ST. Lung deposition of particles by airway generation in healthy subjects three-dimensional radionuclide imaging and numerical model prediction. J Aerosol Sci 1998 29 205-215. 

Lee Z, Berridge MS, Finlay WH, Heald DL. Mapping PET-measured triamcinolone acetonide (TAA) aerosol distribution into deposition by airway generation. Int J Pharm 2000 199(1) 7-16. 

Calculation of surface area concentrations implies even distribution of particles on the airway wall, but this is probably not the case. Studies of deposition in lung models of large [12,13] and small airways [14] suggest that deposition on airway surfaces is uneven. At all airway generations, it is likely that flow kinetics cause heavy deposition at some points, especially at carinae but also along selected portions of the airways between branches. This creates hot spots and cold spots with respect to particle concentration on airway walls. The importance of uneven deposition with local hot spots with high drug concentration, and also cold spots with low concentration, is not known. That local deposition in the forms of hot spots could be detrimental is made plausible by the evidence that... 

Upper region, airway generation 0-5 middle region, airway generation 6-10 lower region, airway generation 11-15. 

Several investigators have modeled deposition within the Inng as a function of particle size. Gerrity related particle size and regional deposition on a per airway generation basis, as shown in Fig. 4 (15). His calculations took into account the Landahl equations (9) and the Weibel-A lung model (16). This model... 

Yeh and Shum developed a model for regional deposition on a per lobe basis instead of per airway generation. Airway dimensions to the terminal bronchioles were obtained from measurements of the cast of the lungs from a human cadaver. Information for generations beyond the terminal bronchioles... 

Targeting of therapeutic aerosol particles to specific airway generations is not possible because both monodisperse and polydisperse aerosols will deposit over several generations. 

Kim et al. developed a lung model based on the Weibel-A model in which they decreased airway diameter by 25 or 40% in both the peripheral and central airways (102). Then they calculated the increases in resistance and deposition. Their results are presented in Fig. 14A and B. The upper graph represents the situation after a diameter reduction of 25%, the lower one after a 40% reduction. It is clear from the graphs that there is no simple one-to-one relationship between the increase in resistance and deposition. This is to be expected, because resistance relates to airway diameter raised to the fourth power, while deposition does not. Nevertheless, from both graphs, it is clear that the model predicts that as resistance increases, the increase in deposition will occur mainly in the larger airways (generations 0-7). Deposition in generations 8-16 will be less affected by the inaease in resistance. 

Such differences could lead to a significant increase in dose of drug on a per-airway-generation basis in the larger, central airways of babies compared to adults. 

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