Responses of the Respiratory Tract

Dungworth DL. 1989. Noncarcinogenic responses of the respiratory tract to inhaled toxicants. In McClellan RO, Henderson RF, eds. Concepts in inhalation toxicology. New York. NY Hemisphere Publishing Corporation. 

Montesano and Saffiotti (15A37) studied the carcinogenic response of the respiratory tract of Syrian golden hamsters to different doses of NDEA. They also summarized over two dozen previous studies with NDEA. 

The clearance of particles from the respiratory tract may be viewed as the first line of defense of the respiratory tract to protect the body from toxic effects of the deposited particles. The responses of the respiratory tract will also vary depending on where the particles are deposited, extending from the nares to the alveolar spaces (see Fig. 8). Although the clearance of particles and related activities are initiated as physiologically adaptive responses, they can progress and become pathological responses, as will be discussed later. 

Chlorine gas is a respiratory irritant and is readily detectable at concentrations of <1 ppm in air because of its penetrating odor. Chlorine gas, after several hours of exposure, causes mild irritation of the eyes and of the mucous membrane of the respiratory tract. At high concentrations and in extreme situations, increased difficulty in breathing can result in death through suffocation. The physiological response to various levels of chlorine gas is given in Table 19. 

The likelihood that materials will produce local effects in the respiratory tract depends on their physical and chemical properties, solubiHty, reactivity with fluid-lining layers of the respiratory tract, reactivity with local tissue components, and (in the case of particulates) the site of deposition. Depending on the nature of the material, and the conditions of the exposure, the types of local response produced include acute inflammation and damage, chronic... 

Bacterial catabolism of oral food residue is probably responsible for a higher [NHj] in the oral cavity than in the rest of the respiratory tract.Ammonia, the by-product of oral bacterial protein catabolism and subsequent ureolysis, desorbs from the fluid lining the oral cavity to the airstream.. Saliva, gingival crevicular fluids, and dental plaque supply urea to oral bacteria and may themselves be sites of bacterial NH3 production, based on the presence of urease in each of these materials.Consequently, oral cavity fNTi3)4 is controlled by factors that influence bacterial protein catabolism and ureolysis. Such factors may include the pH of the surface lining fluid, bacterial nutrient sources (food residue on teeth or on buccal surfaces), saliva production, saliva pH, and the effects of oral surface temperature on bacterial metabolism and wall blood flow. The role of teeth, as structures that facilitate bacterial colonization and food entrapment, in augmenting [NH3J4 is unknown. 

Pulmonary dynamics, the dimension and geometry of the respiratory tract and the structure of the lungs, together with the solubility and chemical reactivity of the inhalants greatly influence the magnitude of penetration, retention, and absorption of inhaled gases, vapors (Dahl, 1990), and aerosols (Raabe, 1982 Phalen, 1984). The quantity of an inhalant effectively retained in the pulmonary system constitutes the inhaled dose that causes pharmacotoxic responses. 

Upper respiratory tract irritation can occur from inhalation of a medicinal gas, vapor, or aerosol. For assessing the potential of an inhalant to cause URT irritation, the mouse body plethysmographic technique (Alarie, 1966, 1981a, b) has proven to be extremely usefid. This technique operates on the principle that respiratory irritants stimulate the sensory nerve endings located at the surface of the respiratory tract from the nose to the alveolar region. The nerve endings in turn stimulate a variety of reflex responses (Alarie, 1973 Widdicombe, 1974) that result in characteristic changes in inspiratory and expiratory patterns and, most prominently, depression of respiratory rate. Both the potency of irritation and the concentration of... 

The respiratory tract is exposed to chemicals in the inspired air. The two main factors that determine the tissue responses to chemicals are the functional anatomy of the respiratory tract and the physicochemical nature of the material. ... 

After acute mild insult the nonciliated cells proliferate and the epithelium regenerates to normal. In the airways, nonciliated basal cells are the main proliferating population. In the bronchioles, the Clara cell is the main precursor cell for regeneration. Because of the delicate nature of the respiratory tract epithelium and the close proximity of subepithelial blood vessels, an inflammatory response occurs to all but the mildest form of injury. Many lesions are therefore diagnosed as rhinitis, tracheitis, and bronchiolitis and qualified as acute, subacute, and chronic depending on the stage of the response. 

A second type of response to isocyanates is allergic sensitization of the respiratory tract. This usually develops after some months of exposure. The onset of symptoms may be insidious, becoming progressively more pronounced with continued exposure. Initial symptoms are often nocturnal dyspnea and/or nocturnal cough with progression to asthmatic bronchitis. 

Most of the information on the effects of air pollution on humans comes from acute pollution episodes such as the ones in Donora and London. Illnesses may result from chemical irritation of the respiratory tract, with certain sensitive subpopulations being more affected (1) very young children, whose respiratory and circulatory systems are poorly developed, (2) the elderly, whose cardiorespiratory systems function poorly, and (3) people with cardiorespiratory diseases such as asthma, emphysema, and heart disease. Heavy smokers are also affected more adversely by air pollutants. In most cases the health problems are attributed to the combined action of particulates and sulfur dioxides (SO2) no one pollutant appears to be responsible. Table 4.2 summarizes some of the major air pollutants and their sources and effects. 

Moxifloxacin has a broad spectrum of activity which includes Gram-positive cocci, atypical pathogens and anaerobic bacteria responsible, inter alia, for infections of the respiratory tract. Moreover, moxifloxacin is one of the most effective fluoroquinolones against pneumococci, including the penicillin- and macrolide-resistant strains. The development of resistance to moxifloxacin is slower than that of the other fluoroquinolones. 

An understanding of the respiratory tract and the immune response following nasal vaccination is necessary to understand how the antigen used in the vaccine interacts with the surfaces of the human body and how the different adjuvants may interact, modify, and aid in generating an immune response. The nose is a component of the upper respiratory tract, which is composed of the mouth, nasopharynx, and larynx. The nasal passages have an extensive surface area which is richly vascularized. 

However, the nasal epithelium has little ability to break down drugs. The extensive mucosal surface of the nose has a lining of pseudostratified epithelium as well as cilia and the goblet cells involved in the secretion of mucus. The lymphoid tissue primarily involved in the mucosal immune responses is the mucosal-associated lymphoid tissue (MALT). The different regions of the respiratory tract that play an influencing role in the immune system are as follows ... 

Q3 A type 1 hypersensitivity reaction is responsible for the development of the allergy. The symptoms are due to the effects of mast cell degranulation with the release of histamine. Mast cells are located in the nasal passages and the nasal mucosa is sensitive to the effects of histamine released from these cells, leading to inflammation of the mucous membranes of the nose. The inflammation is associated with oedema and swelling, vasodilation and an increase in the secretion of mucus. The mucous membrane of other sections of the respiratory tract (accessory sinuses, nasopharynx, and upper and lower respiratory tract) will also be affected by the allergic reaction. 

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