Impaction, inhaled particles

The probability of an inhaled particle being deposited by impaction is a function of the dimensionless Stokes number Stk, which relates particle properties (mass mP, diameter dP, and density, pP) to parameters of the airflow (air velocity vA, viscosity i)A, and airways radius rA) ... 

C. Inhalation. Inhalation of DU is the most significant mode of entry. DU particles can be dispersed in the air by fires involving DU or from DU ammunition impacting armored surfaces. Only very small particles can be inhaled. Of those inhaled particles, some will be soluble in lung fluid and others will not. Those particles that are soluble will be absorbed by the body to become a heavy metal poison (chemically toxic) primarily to the kidneys. The particles in the lungs that are not soluble will remain in the lungs and may be a radiation hazard. The body dispels insoluble particles that remain in the lungs very slowly. 

Because TCDO has a very low volatility, TCDD uptake via inhalation is directly related to the concentration of airborne dust due to wind-blown soil. It has been estimated that of all airborne, respirable particulates, only about 30-50% comes from soil, while the rest is apparently due to products of combustion, tire wear and other sources (32). Of the total suspended particulates, usually no more than 50% are respirable (i.e., particles less than 10 urn). Of these, about 50% of the respirable particles are deposited in the upper airways and ultimately swallowed while the rest reach the alveoli or are expired. An analysis of CDC s data indicates that CDC assumed that 100% of the TCDD present on all the inhaled particles would be retained and absorbed in the respiratory tract. In contrast, the EPA assessment (2) assumed that only 25% of the inhaled particles would be absorbed in the lower airways since at least 50% of the particles would be non-respirable (especially by weight) and these will be swallowed due to impaction in the throat and only about 50% of the respirable particles would be absorbed. In any assessment, it is important to recognize that of those particles swallowed, no more than 10-30% should be absorbed since they will pass through the G.I. tract (assuming 10-30% oral bioavailability). 

A number of recommendations can be made for the optimal use of spacers. Slow inhalation is preferable since the impaction of particles is proportional to velocity and particle size. A slow flow reduces the risk of impaction on valves and anatomic structures such as the pharynx or vocal cords. In addition, high flow rates enhance central airway deposition caused by inertial impaction and therefore reduce deposition in peripheral airways. 

The density of the particle also influences the amount of deposition and retention of particulate matter in the lungs upon inhalation. Particles of high density behave as larger particles of smaller density on passage down the respiratory tract by virtue of the fact that their greater mass and consequent inertia tend to impact them on the walls of the upper respiratory tract. Thus a uranium oxide particle of a density of 11 and 1 pm in diameter wiU behave in the respiratory tract as a particle of several microns in diameter, and thus its pulmonary deposition wiU be less than that of a low density particle of the same size. 

If metals and metal compounds are inhaled, water-soluble gases and vapors are readily dissolved in the mucous membranes of the nasopharyngeal and tracheobronchial region. Less soluble gases and vapors reach the terminal airways and the alveoli and then may pass into the bloodstream or lymph stream. Deposition of inhaled particles in the airways mainly occurs by impaction, sedimentation, and diffusion. 

The major means by which beryllium enters the body is by the respiratory tract. Since particles greater than 5 )im in diameter will usually be cleared by the mucociliary defense mechanism and either expectorated or swallowed, retention of beryllium is thought to occur only if particles less than 5 xm are inhaled. Particles of less that O.S p.m tend to remain in suspension and are not retained by the lungs. Thus, only particles between 5 and O.S p.m should be retained in the lungs. Both soluble and insoluble forms of beryllium will precipitate when they impact tissue in the distal lower airways. Beryllium appears to be cleared by the lungs in two phases. The first phase is fast with a half-life of several hours to 2 months. The second phase is slow with a half-life from one-half to several years [8-10]. It is probable that once inhalation of beryllium occurs, it is never completely eliminated. 

The fate of an orally inhaled particle is strongly dependent on its aerodynamic diameter. Generally, particles larger than ca. 5 pm will inertially impact the mouth or throat, and be swallowed. Particles in the range of ca. 3-5 pm in diameter will reach the upper or conducting airways of the lung and can deposit on the smooth muscle of these structures. Particles of approximately 1-3pm may follow the airstream all the way to the alveoli and be deposited, and particles less than about 1 pm may be exhaled. Thus, careful control of the particle size distribution of medical aerosols is essential for effective drug delivery. 

Monckedieck, M., Kamplade, J., Fakner, P., Steckel, H. (2015). The impact of particle shape on the dry powder inhaler performance of spray dried mannitol carrier particles. Respiratory Drug Delivery Europe, 2, 265-268. 

Particle deposition in the respiratory system is related to distinct physical mechanisms operating on inhaled particles. The most important of these mechanisms are gravitational sedimentation, impaction by inertial forces, and brownian diffusion (see Fig. 3). Electrostatic forces and interception, the latter being significant only for fibers, are generally less important. In this section the physical mechanisms are briefly introduced. Several excellent overviews are available in the literature (12-14). 

All inhaled particles evoke an inflammatory response in the lung. In most reported studies the initial inflammatory cells are polymorphonuclear leukocytes (PMNL), and these are followed by an influx of alveolar macrophages (1,41,49,64-68,78,89). In a few studies (55,70) only a macrophage response has been seen, at least when considering cells accumulating at the first alveolar duct bifurcations, the major site of particle impaction in these specific experiments. As a rule, and provided the point of overload (see following) is not reached, there is a reasonably good correlation between the number of particles deposited and... 

Warheit, D.B., Brock, W.J., Lee, K.P., Webb, T.R., and Reed, K.L. (2005) Comparative pulmonary toxicity inhalation and instillation studies with different Ti02 particle formulations impact of surface treatments on partide toxicity. Toxicological Sciences, 88 (2), 514-524. 

The DPI device presents medication to the patient as a dry powder in a form that can be inhaled orally for deliveiy to the target lung tissues. The delivery system should assist in the generation of very line particulates of medication in a way that enables them to avoid the impaction barriers that normally operate in the lung to prevent the ingress of potentially harmful particles. These barriers include the oropharynx and, for deep-lrmg delivery, the air-conducting bronchi and bronchioles. 

Studies have shown that in order to clear the oropharyngeal impaction barrier (comprising the mouth, throat, and pharynx), particles with aerodynamic diameters smaller than 5 pm are required [3,4]. Only particles with aerodynamic diameters less than 3 pm reach the terminal bronchi and the alveoli in significant numbers [5]. Therefore, the particle diameter required to be produced by the delivery system depends to a great extent on the intended target lung tissue. Lung deposition is also affected substantially by the specific inhalation dynamics of the patient, which in turn are influenced by the delivery device. This article addresses various attributes of the dry powder inhalation product, from intrinsic material properties to final product performance. 

Inertial impaction is most widely applied for the characterization of inhalation systems. The principles of particle separation on the basis of inertial and drag forces have been well described for many different applications. Theoretical cut-off diameters (for particles with 50% collection efficiency) of impactors can be calculated on the basis of Stokes numbers for nozzles of a particular design [8,120]. Many different designs are available, but only a few are described in the United States and European Pharmacopoeia [121,122]. 

A major reason for understanding the chemistry of the atmosphere is the impact that changes can have on human health and well-being. With respect to effects due to direct inhalation of gases and particles, exposure occurs not only outdoors but also indoors as well. Indeed, the vast majority of time for most people is spent indoors. As a result, understanding the nature of the indoor atmosphere and human impacts on it is important as well. 

Danesi et al.96 applied SIMS, in addition to X-ray fluorescence imaging, by using a microbeam (p-XRF) and scanning electron microscope equipped with an energy dispersive X-ray fluorescence analyzer (SEM-EDXRF) to characterize soil samples and to identify small DU particles collected in Kosovo locations where depleted uranium (DU) ammunition was employed during the 1999 Balkan conflict. Knowledge of DU particles is needed as a basis for the assessment of the potential environmental and health impacts of military use of DU, since it provides information on possible resuspension and inhalation. The measurements indicated spots where hundreds of thousands of particles may be present in a few mg of contaminated soil. The particle size distribution showed that most of the DU particles were < 5 pm in diameter and more than 50 % of the particles had a diameter of < 1.5 p.m.96... 

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