Theoretical models of carcinogenic particle deposition and clearance in children's lungs

Abstract

Introduction: Deposition and clearance of carcinogenic particles in the lungs of subjects belonging to four different age groups (infants, children, adolescents, and adults) were theoretically investigated. The study is thought to contribute to the improvement of our knowledge concerning the behaviour of inhaled particles in lungs that may be attributed to different stages of development.

Methods: Particle deposition and clearance were simulated by using a well established stochastic lung model, allowing the generation of nearly realistic scenarios. For the computation of particle deposition all main deposition forces were considered. Additionally, any influences on particle behaviour due to particle geometry were covered by using the aerodynamic diameter concept. Particle clearance was simulated by defining both a fast mucociliary clearance phase and a slow bronchial/alveolar clearance phase, the latter of which is based on previously published models and suggestions.

Results: As clearly provided by the modelling computations, lung deposition of particles with aerodynamic diameters ranging from 1 nm to 10 µm may significantly differ between the studied age groups. Whilst in infants and children most particles are accumulated in the extrathoracic region and in the upper bronchi, in adolescents and adults high percentages of inhaled particular substances may also reach the lower bronchi and alveoli. Although mucus velocities are significantly lower in young subjects compared to the older ones, fast clearance is more efficient in small lungs due to the shorter clearance paths that have to be passed. Slow clearance is commonly characterized by insignificant discrepancies between the age groups.

Conclusions: From the study presented here it may be concluded that particle behaviour in infants' and children's lungs has to be regarded in a different light with respect to that in adolescents and adults. Although young subjects possess natural mechanisms of protecting their lungs from hazardous aerosols (e.g., expressed by breathing behaviour and lung size), they are much more sensitive to any particle exposure, since particle concentrations per lung tissue area may reach alarming values within a short period of inhalation.

Keywords: Stochastic lung model; deposition force; mucociliary clearance; random walk; slow clearance.

Figure 1

Sketch illustrating those aerosol particle categories which are commonly known to have a hazardous effect on children. Besides the particles acting as triggers for infections and allergic reactions, some of these particular substances are also discussed to possess carcinogenic properties.

Figure 2

Graphs exhibiting the mathematical relationship between airway length and airway diameter for lung generations 1 to 16 (mean values ± standard deviations). Due to the constant scaling factor, being equally applied to each airway generation, the diameter-length correlations are nearly identical in infants (A), children (B) and adolescents (C), and adults (D).

Figure 3

Total, tubular (i.e., bronchial and bronchiolar), and alveolar deposition of particles and their dependence on the aerodynamic particle diameter: (A) infants (1 y), (B) children (5 y), (C) adolescents (15 y), and (D) adults.

Figure 4

Aerosol particle retention 24 h, 5 d, and 10 d after exposure and their dependence on the aerodynamic particle diameter: (A) infants (1y), (B) children (5 y), (C) adolescents (15 y), and (D) adults.