Histamine airway responsiveness

Leukotrienes. Figure 2 Relative airway responses of asthmatic patients to inhaled cysteinyl leukotrines versus histamine. CysLTs have up to 1,000-fold greater potency in causing bronchoconstriction than histamine. Reprinted with permission from (2). 

Malo, J.L., Cartier, A., Pineau, L., Archeveque, J., Ghezzo, H. and Martin, R.R. (1986). Lack of acute effects of ascorbic acid on spirometry and airway responsiveness to histamine in subjects with asthma. J. Allergy Clin. Immunol. 78, 1153-1158. 

O Connor, B.J, Lecomte, J.M., Barnes, P.J., 1993. Effect of an inhaled histamine H3-receptor agonist on airway responses to sodium metabisulphite in asthma. Br. J. Clin. Pharmacol. 35, 55-57. 

The monofunctional tryptase inhibitor APC-366 (Axys Pharmaceuticals) reduces the acute airway response and histamine release to allergen in a pig model of allergen-induced asthma [19]. APC-366 is also effective in a sheep model of allergen-induced asthma but was only poorly effective in asthma patients (proof-of-principle) [8], The compound was in clinical development phase II for asthma (inhalative). Although highly selective for tryptase over plasmin and plasma kal-likrein, APC-366 was not selective against thrombin and trypsin [13], Another monofunctional tryptase inhibitor is bis(5-amidino-2-benzimidazol-yl)methane (BABIM) which has been shown to be effective in the sheep. Further development of the compound was, however, discontinued, maybe because of the lack of selectivity over trypsin [13, 16, 17] (Figure 3.2.2). 

Biggs, D.F. and Ladenius, R.C. (1990). Capsaicin selectively reduces airway responses to histamine, substance P and vagal stimulation. Eur. J. Pharmacol. 175, 29-33. 

DURHAM, S.R., GRANEEK, B.J., HAWKINS, R. NEWMAN TAYLOR, A.J. (1987) The temporal relationship between increases in airway responsiveness to histamine and late asthmatic responses induced by occupational agents. Journal of Allergy and Clinical Immunology, 79, 398 106. 

MAPP, C HARTIALA, J FRICK, O.L., SHIELDS, R.L. GOLD, W.M. (1985) Airway responsiveness to inhaled antigen, histamine, and methacholine in inbred, ragweed-sensitized dogs. American Review of Respiratory Disease, 132, 292-298. 

There have been no large-scale epidemiological studies, but a positive relationship between asthma mortality and regional purchases of table salt per person has been shown. In a randomized doubleblind crossover trial in subjects with moderately severe asthma, the airway response to histamine was related to urinary excretion of sodium in a dose-response way, but only in men. A low-salt diet is regarded as having a potentially positive effect in patients with asthma and may help to reduce the need for anti-asthma drugs. 

The nonallergic airway responsiveness is generally measured with inhalation provocation tests with either histamine or methacholine. This relationship is strong enough that the dose of allergen required to produce a target EAR can be predicted, albeit crudely, by measurement of skin test endpoint (related to the level of allergen-specific IgE) and the provocation concentration of hista-... 

Cockcroft DW, Murdock KY, Kirby J, Hargreave FE. Prediction of airway responsiveness to allergen from skin sensitivity to allergen and airway responsiveness to histamine. Am Rev Respir Dis 1987 135 264-267. 

Durham SR, Craddock CF, Cookson WO, Benson MK. Inaeases in airway responsiveness to histamine precede allergen-induced late asthmatic responses. J Allergy Clin Immunol 1988 82 764-770. 

Cockcroft DW, Killian DN, Mellon JJA, Hargreave FE. Bronchial reactivity to inhaled histamine a method and clinical survey. Clin Allergy 1977 7 235-243. Cockcroft DW, Swystun VA, Bhagat R. Interaction of inhaled P2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine. Am J Respir Crit Care Med 1995 152 1485-1489. 

Airway hyperresponsiveness is an exaggerated airway narrowing in response to a variety of unspecific stimuli. It can be measured by bronchial provocation with histamine, methacholine or adenosine. The reason for hyperresponsiveness may be stimulation of sensory nerves that are located within the epithelium. They become easily accessible after denudation of the... 

The human histamine Hi-receptor is a 487 amino acid protein that is widely distributed within the body. Histamine potently stimulates smooth muscle contraction via Hi-receptors in blood vessels, airways and in the gastrointestinal tract. In vascular endothelial cells, Hi-receptor activation increases vascular permeability and the synthesis and release of prostacyclin, plateletactivating factor, Von Willebrand factor and nitric oxide thus causing inflammation and the characteristic wheal response observed in the skin. Circulating histamine in the bloodstream (from, e.g. exposure to antigens or allergens) can, via the Hi-receptor, release sufficient nitric oxide from endothelial cells to cause a profound vasodilatation and drop in blood pressure (septic and anaphylactic shock). Activation of... 

Airway hyperresponsiveness is defined as the exaggerated ability of the airways to narrow in response to a variety of stimuli. Although AHR exists in patients without asthma, it is a characteristic feature of asthma and appears to be directly related to airway inflammation and the severity of asthma.1,3 Treatment of airway inflammation with inhaled corticosteroids attenuates AHR in asthma but does not eliminate it.1 Clinically, AHR manifests as increased variability of airway function. Although not commonly used to diagnose asthma, AHR can be evaluated clinically using a methacholine or histamine bronchoprovocation test. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Town GI, Holgate ST Comparison of the effect of loratadine on the airway and skin responses to histamine, methacholine, and allergen in subjects with asthma. J Allergy Chn Immunol 1990 86 886-893. 

There are other ways in which endotoxins may act to produce cotton dust induced airway disease. These include 1) an instrinsic toxicity due to lipid A, responsible for both pyro-genicity and tissue damage 2) a hypersensitivity reaction involving anti-lipid A antibodies. Further, changes in mechanical properties of the lung could be explained by the release of histamine or serotonin caused by endotoxins. 

Within 30 minutes of their administration, 6 -adrenergic drugs often reverse most of the functional deficit in Monday morning byssinotics. As there is no mucous secretion, airway smooth muscle contraction is considered the primary response. Exposure of man to histamine aerosols produces pulmonary function changes similar to those seen after exposure to dust extract. However, exposure to histamine aerosol invariably initiates constriction of smooth muscle more rapidly than exposure to cotton dust ( <15 minutes), and dissipates within minutes, while the acute effects of inhalation of cotton dust and dust extracts lasts for hours. The slowly developing and prolonged effects of dust and extracts suggest that mediators other than histamine are involved. 

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