Bronchial mucosa

During occupational exposure, respiratory absorption of soluble and insoluble nickel compounds is the major route of entry, with gastrointestinal absorption secondary (WHO 1991). Inhalation exposure studies of nickel in humans and test animals show that nickel localizes in the lungs, with much lower levels in liver and kidneys (USPHS 1993). About half the inhaled nickel is deposited on bronchial mucosa and swept upward in mucous to be swallowed about 25% of the inhaled nickel is deposited in the pulmonary parenchyma (NAS 1975). The relative amount of inhaled nickel absorbed from the pulmonary tract is dependent on the chemical and physical properties of the nickel compound (USEPA 1986). Pulmonary absorption into the blood is greatest for nickel carbonyl vapor about half the inhaled amount is absorbed (USEPA 1980). Nickel in particulate matter is absorbed from the pulmonary tract to a lesser degree than nickel carbonyl however, smaller particles are absorbed more readily than larger ones (USEPA 1980). Large nickel particles (>2 pm in diameter) are deposited in the upper respiratory tract smaller particles tend to enter the lower respiratory tract. In humans, 35% of the inhaled nickel is absorbed into the blood from the respiratory tract the remainder is either swallowed or expectorated. Soluble nickel compounds... 

Bentley, A.M. et al., Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma, J. Allergy Clin Immunol., 89, 821, 1992. 

Ilowite JS, Bennet WD, Sheetz WS, Groth ML, Nierman DM (1989) Permeability of the bronchial mucosa to mTc-DTPA in asthma. Am Rev Respir Dis 139 1139-1143. 

The limited availability of suitable human tissue for experimental studies and the rather low CYP expression level in the human lung, compared to that found in rodents [111], have notably limited identification of the lung CYP isoforms. By means of RT-PCR, it has been possible to qualitatively demonstrate the presence of several CYP mRNAs in the human bronchial mucosa, namely CYP1A1, 2A6, 2B6, 2C, 2E1 and 3A5, whereas the expression of CYP1A2, 2D6, 3A4 and 3A7 could be detected only in some samples (Table 10.1) [109, 111, 112], Immunohistochemical analysis has shown the significant expression of CYP enzymes in different pulmonary cells including... 

Enzyme Bronchial mucosa NHBE Calu-3 BEAS-2B... 

Expression of Phase II Enzymes in Tracheo-Bronchial Mucosa and Cell Cultures... 

Table 10.2 Expression profiles of phase II metabolic enzymes in human bronchial mucosa and in vitro cell culture models.

Mace K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM (1998) Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. Eur J Cancer 34(6) 914—920. 

Jahnsen FL, Moloney ED, Hogan T, Upham JW, Burke CM, Holt PG Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge. Thorax 2001 56 823-826. 

Hoogsteden HC Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients downreg-ulation by inhaled corticosteroids. Clin Exp Allergy 1996 26 517-524. 

Inhalation in the form of an aerosol (p. 12), a gas, or a mist permits drugs to be applied to the bronchial mucosa and, to a lesser extent, to the alveolar membranes. This route is chosen for drugs intended to affect bronchial smooth muscle or the consistency of bronchial mucus. Furthermore, gaseous or volatile agents can be administered by inhalation with the goal of alveolar absorption and systemic effects (e.g inhalational anesthetics, p. 218). Aerosols are formed when a drug solution or micron-ized powder is converted into a mist or dust, respectively. 

Dust particles inhaled in tobacco smoke, together with bronchial mucus, must be removed from the airways by the ciliated epithelium. Ciliary activity, however, is depressed by tobacco smoke mucociliary transport is impaired. This depression favors bacterial infection and contributes to the chronic bronchitis associated with regular smoking. Chronic injury to the bronchial mucosa could be an important causative factor in increasing the risk in smokers of death from bronchial carcinoma. 

Undesired effects. The magnitude of the antihypertensive effect of ACE inhibitors depends on the functional state of the RAA system. When the latter has been activated by loss of electrolytes and water (resulting from treatment with diuretic drugs), cardiac failure, or renal arterial stenosis, administration of ACE inhibitors may initially cause an excessive fall in blood pressure. In renal arterial stenosis, the RAA system may be needed for maintaining renal function and ACE inhibitors may precipitate renal failure. Dry cough is a fairly frequent side effect, possibly caused by reduced inactivation of kinins in the bronchial mucosa. Rarely, disturbances of taste sensation, exanthema, neutropenia, proteinuria, and angioneurotic edema may occur. In most cases, ACE inhibitors are well tolerated and effective. Newer analogues include lisinopril, perindo-pril, ramipril, quinapril, fosinopril, benazepril, cilazapril, and trandolapril. 

Exposure of rats to 800 ppm for 15 minutes was fatal, but nearly all survived when exposed for 13 minutes. There was severe inflammation of all exposed mucosal surfaces, resulting in lacrimation, corneal ulceration, and burning of exposed areas of skin. In another study, exposure of rats to 480 ppm for 40 minutes or to 96ppm for 3.7 hours was fatal in the latter group, effects were pulmonary edema and marked irritation of the bronchial mucosa. Chronic exposure of dogs and rats to about Ippm, 6 hours/day for up to 6 months caused severe pulmonary irritation and some deaths. ... 

Fjellbirkeland L, Bjerkvig R, Laerum OD (1998) Non-smaU-cell lung carcinoma cells invade human bronchial mucosa in vitro. In Vitro Cell Dev Biol Anim 34 333-340... 

It is naive to believe that the inhaled drug will not be absorbed to some extent. Ask any asthmatic about the effects they experience from two puffs of salbutamol from an inhaler and most will tell you about the fine tremor (sometimes bad enough to prevent them writing for a while) which they get. This must reflect systemic absorption from the bronchial mucosa and re-emphasises the point that many drugs can penetrate most body mucosae. 

The animals were killed and examined at 12 and 24 h and 3, 7, and 30 d. At the low exposure, one animal examined 12 h after exposure had superficial tracheitis, edema of the tracheal and bronchial mucosa, and beginning bronchorrhea. All others were free of lesions related... 

The bronchial mucosa and lungs are treated with inhalations, aerosols (in the form of fine powder with the help of nebulizer) e.g. salbutamol (ASTHALIN) inhaler. 

Respiratory system PGE is a powerful bronchodilator when given in aerosol form, but due to its irritant action on bronchial mucosa its clinical utility is limited. 

Many patients experience a dry cough, especially when beginning treatment. This may be due to the accumulation of bradykinin in the bronchial mucosa. Less frequent are angioedema, xanthelasma and bone marrow suppression. 

The causes of airway narrowing in acute asthmatic attacks (or "asthma exacerbations") include contraction of airway smooth muscle inspissation of viscid mucus plugs in the airway lumen and thickening of the bronchial mucosa from edema, cellular infiltration, and hyperplasia of secretory, vascular, and smooth muscle cells. Of these causes of airway obstruction, contraction of smooth muscle is most easily reversed by current therapy reversal of the edema and cellular infiltration requires sustained treatment with antiinflammatory agents. 

Corticosteroids have been used to treat asthma since 1950 and are presumed to act by their broad anti-inflammatory efficacy, mediated in part by inhibition of production of inflammatory cytokines (see Chapter 39). They do not relax airway smooth muscle directly but reduce bronchial reactivity and reduce the frequency of asthma exacerbations if taken regularly. Their effect on airway obstruction may be due in part to their contraction of engorged vessels in the bronchial mucosa and their potentiation of the effects of 13-receptor agonists, but their most important action is inhibition of the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells. 

Djukanovic, R., Wilson, J.W., Britten, K.M. et al. 1990. Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. Annu Res Respir Dis 142 863-871. 

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