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For example, for a doctor in a pollution free rural area, sinusitis has exactly the same appearance as it would for a doctor in an area with severe air pollution. However, sinusitis clearly occurs more frequently in areas of high pollution than in low pollution areas [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11].

In a region with air pollution, environmental pollutants are thus involved in the emergence of sinusitis.

Xenobiotics and Inflammation

However, this is not immediately recognizable and in individual cases cannot be quantified, either. Analogous to this, employees in particular professions suffer more frequently from malignancies of the upper aerodigestive tract than the population average. This difference also remains significant if the effects of alcohol and tobacco consumption are compensated for [12]. Here, too, the job effect on the emergence of the illness is in individual cases not immediately apparent and usually difficult to quantify.

These examples show that environmental and occupational pollutants play a role in disorders of the head and neck. This has been demonstrated for acute and chronic inflammation of the nose and paranasal sinuses, the middle ear, the throat and the larynx, allergies of the respiratory tract, disorders of the sense of smell, of hearing and of balance, as well as head and neck tumours [13].

Only in individual cases are environmental and occupational pollutants the decisive causal factor. Mostly it is a case of cofactors that further the emergence of a disorder. For various poisons, toxicological mechanisms have been examined with classic pharmacological methods. This does not apply to the effect mechanisms of many inhalation pollutants occurring in the environment and workplace. Right up until only a few years ago it was above all the morphological and functional changes that were described in specialist literature, the actual damage mechanisms remained unknown.

Here, over the last few years a great deal of new knowledge has been gained through the use of cell biological techniques that are the subject of the present review.


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Those chemical substances that are relevant for diseases of the head and neck are predominantly absorbed via inhalation; we are dealing here with substances transmitted by air. On the one hand they appear as gasses. For the state of a substance at a particular temperature, its volatility is a decisive factor. Boiling point is a simple indicator for volatility. Gasses with environmental medical significance are SO 2 , NO x , ozone and formaldehyde. From an occupational medical point of view, volatile organic compounds VOC , volatile complex mixtures containing hydrocarbon and irritant gasses are of additional significance.

The second form of pollutants transmitted by air is aerosols. Aerosols are fine dispersions of liquids or solid substances in a gas, frequently in air. Fog is liquid dispersant aerosols, airborne dusts are particulate dispersal aerosols and fumes are aerosols from combustion processes. Air pollutants in the form of particles have the highest environmental and industrial medical relevance as inhaled noxae [ Fig.

Environmental dusts are complex particulate air pollutants from the real environment that emerge, for example, due to combustion processes, as a result of swirling up of dust from the ground, of condensation of gaseous air components or due to the mechanical rubbing off of various materials.

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Urban dusts are environmental dusts that collect in urban agglomeration zones. Combustion residue is a component of environmental and industrial dusts with particularly toxicological characteristics. They contain, amongst other things, polycyclic aromatic hydrocarbons PAH , nitroso compounds and aromatic amines. Coal fly ash CFA is a product of combustion from hard coal heating with a high level of quartz and aluminium hydroxide, residual oil fly ash ROFA derives from from oil heating and has a high metal content.

CFA and ROFA can be collected from the exhaust particles of coal- or oil-fired power stations for experimental investigations with appropriate filters. Diesel exhaust particles DEP come predominantly from motor vehicle traffic and can be produced for experimental purposes from the exhaust fumes of diesel engines. Bioorganic dusts come from organic materials that owe their origin biological processes.

Toxicologically, fragments of bacteria and fungi are of prime importance. The extremely inhomogeneous group of substances includes, for example, livestock dusts, laboratory animal dusts, feedstuff and grain dusts, food dusts, wood dusts as well as dusts containing mites and fungi, for example from biologic waste. Environmental dusts from ambient air, and in particular indoor dusts, also contain bioorganic pollutants bacteria, fungi pollen, spores, mite excrement that are related to health disorders.

Quartz and asbestos dusts belong to the common problem aerosols in industrial medicine. These are followed by, for example, combustion residue such as welding fumes, bioorganic dusts and cooling and lubrication agents. Toxicology is concerned with the harmful effects of chemical substances. Effects of radioactive or other radiation, as well as mechanical or thermal effects do not belong to toxicology in the narrow sense [14]. The harmful effect of a substance is dependent upon its concentration and duration of action at the structures affected.

These two factors are characterised by absorption, distribution, metabolic conversion and excretion and are the subjects of toxicokinetics. In pharmacological and toxicological texts books, toxicokinetics, main emphases are enteral absorption quota, first pass effect in the liver, distribution volumes as well as renal and biliary elimination. In the case of inhalative absorption, one has to differentiate between two cases.

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On the one hand it can lead to systemic effects following inhalative absorption, for example with inhalative anaesthesia. In this case, except for enteral absorption, the mechanisms described above apply. Local effects on the mucus membranes of the respiratory tract, however, are frequently in the foreground. These are the subjects of inhalation toxicology. Toxicokinetic factors of particular relevance in inhalation toxicology are listed in table 1 [ Tab.

Gasses can generally be inhaled. Under the influence of gravity gasses with a higher specific weight sink. For this reason the body size children or the position of the room cellar can influence the capacity of a gas to be inhaled. In the case of dusts, the mechanisms of inhalability are more complex.

The respiratory toxic effect of inhaled pollutants depends essentially upon the region of the respiratory tract they are either adsorbed or absorbed into. Here what is understood by adsorption is the attachment of a substance to a two-dimensional surface deposition ; what is understood by absorption is the intake into a three-dimensional matrix such as, for example, secretion or tissue. By resorption, absorption into the blood or lymph system is indicated. In the case of gasses, water solubility and reactivity are the main physical characteristics for absorption into the respiratory tract [16].

Gasses easily soluble in water are dissolved into the secretions of the upper respiratory tract and spread their effects here. In so far as they are not spread as aerosol droplets, only a small part of gasses easily soluble in water reach the lower respiratory tract. An overview of the absorption of a number of substances in the form of gas in the upper respiratory tract is provided in table 2 [ Tab.

In the case of aerosols, the deposition of particles is dependent upon the diameter, the form of the particles and their surface characteristics. Should one wish to describe the deposition by the particle size alone, then the influence of form and surface characteristics must be compensated for through calculation.

To this purpose the particle sizes are converted into equivalent spherical diameters. In which compartment of the respiratory tract the particles are predominantly deposited is dependent upon the aerodynamic diameter. It is used for a simple characterisation of a dust mixture. This corresponds with the above norm more or less to the alveolar fraction. The relation between aerodynamic diameter and deposition compartment in the respiratory tract according to DIN ISO in non-logarithmic presentation follows from illustration 3 [ Fig.

A significant factor for the harmful effect of an inhaled agent is first and foremost the concentration of the harmful substance in the air breathed in and the duration of exposure.

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In addition, the effect of inhaled pollutants is influenced by variable breathing parameters. Thus there are fundamental differences in the harmful effects of inhaled pollutants depending upon whether one is dealing with breathing through the nose or the mouth. The volume of breath and breathing frequency also play a considerable role. The surface of the mucous membrane with which the harmful substances inhaled come into contact is also relevant [19]. Due to this, the harmful effects of inhaled pollutants differ between children and adults and between rest or physical strain.

As first described by Lucas and Douglas in [21] , respiratory secretion consists of two layers. The lower low-viscous periciliar liquid layer sol phase is formed predominantly by transepithelial transport of ions and water from ciliated epithelia and brush cells [22]. What are dealt with here are similar and partly identical processes of water and ion transport as are found in the kidney. The highly viscous surface gel phase mucous layer shows a high share of integrated glycoproteins mucins.

They are formed predominantly in the submucous glands and the goblet cells. The kD large glycoproteins mucins have an amino acid framework on which various short chain sugars fucose, galactose and amino sugars N-acetylneuraminic acids, N-acetylglucosamine, N-acetylgalactosamine are either o-gylcosidic or n-glycosidic attached. Apomucins are peptides that form the central framework of the mucins [23] , [24].

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Discovering the route from inflammation to pancreatic cancer

The genes and their mRNAs are identified in epithelial cells of the submucous glands and in the goblet cells of the respiratory tract [25] , [26]. The regulation of the gene expression of different mucins is subject to species differences [27]. As well as this, the mucins Muc1 and Muc4 are involved in cellular signal transduction [28].

Numerous inhaled pollutants stimulate the mucin expression in the respiratory tract and thus contribute to hypersecretion [29] , [30].


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In the case of the exposure to noxious substances, the constant activation of mucin genes leads to goblet cell hyperplasia, a characteristic feature of chronic inflammation of the respiratory tract [31]. Consecutively, this leads to the dysregulation of mucus composition, with hyperviscous secretion. This impairs the mucocilliary transport and encourages colonization of pathogenic organisms. In order to gain access to the mucous membrane of the respiratory tract, a noxious substance must overcome the secretion barrier.

This process differs with noxious substances in the form of gas or particles. For lipophilic gasses, the watery respiratory secretion is to a large degree impenetrable. An insignificant solution of lipophilic substances in respiratory secretion can be conveyed through phospholipids with amphiphilic properties.

Water-soluble gasses go into solution in the respiratory secretion. At the same time, acids frequently form that can damage the epithelia of the respiratory tract. This is the case with SO 2 or NO 2 , for example.