Exposure to Air Pollution: How Particles Enter the Body

The ways through which micro- and nanoparticles are introduced into the body are various, and we have already discussed the topic in several publications, including the already mentioned books Nanopathology: The Health Impact of Nanoparticles (Pan Stanford Publishing, now Jenny Stanford Publishing, 2008) and Case Studies in Nanotoxicology and Particle Toxicology (Elsevier Academic Press), whose reading is essential for the best understanding of what follows.

The Inhalation/Respiration Pathway

When particles, particularly the smaller ones, are issued into the atmosphere, no matter how and from what source, their behaviour is, under many aspects, similar to a gas's. Because of their tiny size and mass, they can float suspended in the air and be inhaled. If their size is small enough (typically, though not exclusively, below about 0.5 pm), they can get as deep as the alveoli, the about 600 million hollow structures connected to the bronchioles located at the distal ends of the alveolar ducts. Around them, thin vessels bring venous blood whose content of carbon dioxide diffuses inside the alveolar cavity, while oxygen, arrived in the alveoli through inspiration,

Advances in Nanopathology: From Vaccines to Food

Antonietta Morena Gatti and Stefano Montanari

Copyright © 2021 Jenny Stanford Publishing Pte. Ltd.

ISBN 978-981-4877-29-9 (Hardcover), 978-1-003-05622-5 (eBook) w w w. j e n ny sta nf o rd. co m diffuses out to enrich the arterial blood, which is carried away from the lungs to reach all tissues. Expiration empties the alveoli of carbon dioxide.

Every day we breathe about 11,0001 of air (much more do active athletes), and inevitably, we inhale a huge quantity of particles suspended in the atmosphere. A considerable number of these particles are deposited in the respiratory tract, depending on their size, density, shape, electric charge and surface properties. The breathing pattern and the health state of the lungs of the individual are also of great influence on the phenomenon. Most particles entering the respiratory tract are expelled through expiration. This effect decreases its efficacy as the lungs and bronchi lose their functionality. If an excessive quantity of mucus coats the lower bronchial tracts, as can happen, for instance, in smokers, particles have greater probability to slide towards the cul-de-sac formed by the alveoli. Expulsion is even more problematic when the cilia present in the respiratory tract are shorter or, in any case, less functional or are not functional at all, conditions associated, among others, with tobacco smoking, with cancer or with genetic disorders (e.g. Kartagener syndrome).

Generally speaking, most particles with an aerodynamic diameter³ less than 10 pm stop in the nose or in the throat and cannot penetrate further in the respiratory tract.

Deposition in the lungs occurs by one of four different ways: interception, impaction, sedimentation and diffusion.

• • Interception happens when the particle travels so close to a surface of the airway passages that an edge of the particle touches their surface. This kind of deposition is typical of fibres (e.g. asbestos, cotton, etc.). The fibre length is crucial to determine where the particle is going to be intercepted.
• • Impaction: When particles travel inside the bronchial system, they do not follow the air when it bends in the airway system but tend to continue along their linear trajectory and impact against the bronchus wall, where they tend to stick. Particle’s mass and velocity influence the likelihood of impaction. The higher those two parameters, the higher the likelihood.
• -’Aerodynamic diameter is the diameter of a spherical particle which has the same settling velocity as another particle regardless of its shape, size or density.

• • Sedimentation: Gravity and air resistance will eventually exceed particle buoyancy, so particles will settle on an inner surface of the bronchi and the bronchioles. Sedimentation is an important factor with larger particles.
• • Nanoparticles tend to diffuse according to the Brownian motion and deposit on the bronchial walls mostly by chance. Diffusion is the prevalent mechanism for deposition in the small airways and alveoli, where only small particulate matter is present

Once particles are inside the alveoli, they cross their wall in a matter of a few tens of seconds entering the bloodstream. For that reason, they have little or no possibility to induce particular reactions involving the lungs.

In vivo studies of the University of Leuven verified that 100-nm-sized particulate matter, once inhaled, can cross the lung barrier in 60 s and disperse in the blood circulation [1-3]. Within an hour they can reach the liver and the kidneys. The percentage of particles not trapped in these organs can continue to travel throughout the body, reaching all organs, none excluded.

The entrapment can also occur in the upper respiratory tract (mouth, nose, trachea) where a pathology may originate.

The example of the nose cancer (Chapter 3) of the farmer living in the close vicinity of a waste incinerator is just one of many possible examples.

Of course, the particles which don’t enter the bloodstream and remain in the lungs can induce a pathology as well. The variety of lung tissue reactions ranges from granulomatosis to fibrosis to cancer. The type of reaction depends essentially on the characteristics of the particulate matter, namely morphology, size, chemical composition and degradation/corrosion. Peritoneal mesothelioma is a typical cancer of the serous membrane which wraps the lungs. The peculiarity of the lung mesothelioma induced by asbestos particulate matter depends on the morphology of the asbestos (a mineral fibre with one dimension at the nanoscale) and on its partial degradability once inside the extracellular fluids.

The following images (Fig. 4.1) give an example of what type of pollution can be found inside the lungs. The lungs collect everything of the environmental/industrial/occupational pollution inhaled, leaving a specific print. Beyond particles of ‘normal’ pollution

(tungsten, antimony, etc.), elements of rare earth are detected like shown in Fig. 4.1.

Figure 4.1 Examples of particulate matter entrapped in the lungs. The traditional histological image of optical microscopy of a lung tissue does not give the possibility of accurately identifying the content of solid and inorganic particles. The same tissue observed with the electron microscope shows the particles clearly and makes it possible to determine their elemental chemical composition.

Of particular interest are the studies of Oberddrster et al. showing that inhaled particles can have ‘access to the central nervous system and ganglia via translocation along axons and dendrites of neurons' [4].

This observation is particularly important because it could provide fundamental tips for the understanding of diseases such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, or, in any case, for understanding diseases involving a progressive paralysis such as the one we have described on page 142 of the book Nanopathology: The Health Impact of Nanoparticles (Pan Stanford Publishing, now Jenny Stanford Publishing, 2008).

A correlation between what had been inhaled and lung cancer was already made, and it is easy to find inside the cancer an important concentration of all the particulate matter inhaled and captured during the patient’s life, including urban, industrial and occupational pollution [5].

Recently, the World Health Organization (WHO) released a report [6] describing how every year 7 million deaths are due to the exposure to fine particles present in polluted air which lead to diseases such as stroke, heart failure, lung cancer, chronic obstructive pulmonary diseases and respiratory infections, including pneumonia.

The report only considers cardiopulmonary diseases, while particle pollution can affect virtually any organ.

A case which is rarely considered is that related to the small thrombi which the particles induce in the microcirculation, thus preventing the normal flow of blood to the tissue with all which follows from it

However, or, at least, in most instances, the particles carried by the bloodstream can reach any organ and tissue, whose general behaviour is very similar to that of any mechanical filter: they capture the particles without, then, as far as we know, being able to get rid of them.

The massive introduction of sub-micron- and nanosized particles in the environment, in food and in drugs increases the exposure of everyone to these stimuli which can interest the whole body. This novel bio-interaction is not yet well described in the books, even if many research projects of nanotoxicity were supported by the European Commission, research organisations and foundations.

Much of what results from the research depends on the cultural background of the researchers, a background which is often refined but equally often too specialised.

Biologists stress the biological aspect, biochemists the biomolecular, histopathologists the morphological, geneticists the DNA and environmentalists focus on particulate matter. As was to be expected, psychiatrists also come into play, according to whom many diseases derive from alterations of the psyche and for this reason are treated with psychotropic drugs. In parentheses, we have had experience of cases treated for years with anxiolytics, antidepressants, neuroleptics, sedatives, sleeping pills, tranquilizers, etc., because of the alterations in the behaviour of the patient (generally, though not always, a soldier) on which the diagnosis was made, when the problem was a brain tumour which had become intractable due to the loss of time. It is very sad to be right only on the autopsy table.

In any case, all contributions are welcome, and all those specialists, with different techniques, with different magnifications, with different ‘eyes' see a portion of the pathological phenomenon.

What is needed is synthesis through a multi-disciplinary approach, which is now largely missing, where everyone must be open and willing to accept that bacteria, viruses, chemicals, particles or psyche exist or matter, where each excludes or minimises the other.