III. RESULTADOS
3.3. Aporte Práctico
LDSA is a very effective metric in refining the surface area metric as it pertains to human inhalation. From a health perspective the total surface area of a particle size distribution would not represent the actual surface area of particles that will interact with airway tissues and cells.
This is due to the fact that as particles travel through the airways, inertial and diffusion forces act upon particles, which will result in deposition in various regions of the airways. Hence, a deposition curve is required to relate the total surface area of particle to the deposited surface area of the particle. Hence, LDSA represents a surface area that takes into account the particle deposition factor for a human lung.
Traditionally LDSA could be calculated only by measuring the particle size distribution and number concentration to calculate the total surface area of spherically assumed particles followed by using deposition fractions to calculate LDSA. However, recent studies have shown that by coincidence, diffusion charging based instruments have been observed to produce a response that is very similar to LDSA. Wilson et al in their work with an electrical aerosol detector observed that the instrument response was well correlated with LDSA calculations (Wilson et al., 2007). The study used a TSI electrical aerosol detector (EAD) and scanning mobility particle sizer (SMPS) to measure particle size distribution and particle length. One of the important findings of the study was that it observed a strong correlation between the signal
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from the EAD and the calculated deposited surface area (particle number concentration multiplied by the deposition fraction for a certain diameter). The study further concluded that even with changes in particle size distribution, the signal from EAD correlated well with deposited surface area (Wilson et al., 2007). Hence, the EAD by itself could be a versatile instrument in directly suggesting the LDSA metric of a particle stream.
2.5.4.1 DEPOSITION FRACTION
Deposition fraction (DF) is an important parameter in discerning health effects of nanoparticles, and also to optimize respiratory drug delivery methods. DF defines the percent deposition of particle of various sizes during its transport within the human airway system, while being subjected to various forces such as gravitational settling, inertial settling and Brownian and diffusion movements. The respiratory tract consists of three regions namely: a) nose and head airways b) tracheobronchial region c) alveolar region. Deposition models have been a focus of research from early 1930s’. Findeisen developed the first lung deposition model in 1935. Since then the Findeisen model has undergone modifications in 1950 by Landahl and Beeckman in 1965 (Ensor, 2011). However, from the early 1960s the model developed by the International Commission on Radiological Protection (ICRP) has been the widely accepted model used for drug delivery and associating nanoparticle inhalation with health risks. The toal fraction of particles deposited in human lungs cab be estimated using Equation 3 (Ensor, 2011).
𝐷𝐹 = 0.0587 + 0.911
1 + exp (4.77 + 1.485𝑙𝑛𝐷𝑝) +
0.943
1 + exp (0.508 − 2.85𝑙𝑛𝐷𝑝) Equation 3 The above equation represents the deposition model for both men and women average for three types of physical activity that includes resting, light exercise and heavy exercise. The above equation was obtained through a curve fit of experimental data fitted to produce a deposition curve as a function of particle diameter Dp.
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Figure 2-7 Measured and theoretical curve for particle DF as adapted from (Ensor, 2011)
The type of particle diameter used in the model vary with the region in which the model is applicable. Gravitational and inertial settling and thermodynamic processes such as diffusion dominate particle deposition. Hence, in regional where gravitational settling and inertial settling are dominant, the aerodynamic diameter is used and in regions where diffusion is dominant, thermodynamic diameters are used. However, most particle instruments measure the electrical mobility diameter of the particle, which is closely approximated to stokes diameter for a spherical particle. Hence, while attempting to discern particle DF from mobility based instruments, diameter conversion is to be taken into account. Wilson et al. in their study suggest that electrical mobility agrees well with particle diameters associated with diffusion based measurements (Wilson et al., 2007). Hence, if Dp in the above equation is assumed to be stokes diameter, then the electrical mobility diameter measured directly from SMPS or EEPS can be used to represent DF as a function of particle diameter.
The subject of DF can be further extended to discern regional DF in the three regions mentioned earlier. The following equations represented in Equation 4, Equation 5 and Equation 6 signify the DF values for the different regions in the airway (Wu and Allen). The equations
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represented here are derived from the ICRP model as applicable to the different regions of the lungs.
a) Head Airways
𝐷𝐹ℎ𝑒𝑎𝑑 = 𝐼𝐹 � 1
1 + exp(6.84 + 1.183𝑙𝑛𝐷𝑝) +
1
1 + exp(0.924 − 1.885𝑙𝑛𝐷𝑝)�
Where
𝐼𝐹 = 1 − 0.5 ∗ � 1
1 + 0.00076𝐷𝑝2.8�
Equation 4 b) Tracheobronchial region
𝐷𝐹𝑇𝐵= �0.00352
𝐷𝑝 � ∗ �𝑒(−0.234(𝑙𝑛𝐷𝑝+3.40)2)+ 63.9 ∗ 𝑒(−0.819(𝑙𝑛𝐷𝑝−1.61)2)�
Equation 5 c) Alveolar region
𝐷𝐹𝐴𝐿 = �0.0155
𝐷𝑝 � ∗ �𝑒(−0.416(𝑙𝑛𝐷𝑝+2.84)2)+ 19.11 ∗ 𝑒(−0.482(𝑙𝑛𝐷𝑝−1.362)2)�
Equation 6
Figure 2-8 shows the percentage DF calculated from the ICRP model for two different breathing types as a function of particle diameter. The curves show that particles below the ultra fine size range (<100 nm) have a significant deposition fraction in the alveolar region.
Hence particles with smaller diameters can be viewed as a more potent threat to human health as they enter into the oxygen exchange regions of the lung. Particles in the accumulation region are observed to have a greater deposition in the tracheobronchial region, and as result might contribute to significant inflammatory responses in the cells of the respiratory path. Although the tracheobronchial region acts to filter most inhaled particles, greater surface area contribution combined with potent particle surface coating such as organics and transition metals can induce ROS responses in the cells and contribute to breakdown of the defense system.
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Figure 2-8 Percentage DF curve as function of particle diameter adapted from (Wilson et al., 2007) This study will present an analysis of the deposition fraction of nanoparticle emissions from heavy-duty natural gas engines and further correlate the toxicity responses to LDSA as calculated using particle size distribution and DF, in addition to measurements obtained from a TSI EAD.