Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iatrogenic respiratory disorders include bronchic manifestations (asthma, bronchospasm, cough) and bronchiolar manifestations (constrictive or proliferative bronchiolitis). Many pharmacologic agents can induce a bronchospasm. The bronchospasm induced by acetylsalicylic acid and nonsteroidal anti-inflammatory agents, often severe, is mediated by the inhibition of the cyclooxygenase enzyme; it can be prevented by eviction of the drug or desensitization. Leukotriene receptor antagonists and 5-lipoxygenase inhibitors may also be useful. Beta-blockers including cardioselective beta-blockers, cholinergic agonists, inhaled agents, angiotensin-converting enzyme inhibitors (ACE), vindesine, histamine liberators, etc..., can also induce a bronchospasm. Most of the same agents can also induce an isolated cough, particularly beta-blockers, inhaled agents, and ACE, which cause 75% of the reported cases of iatrogenic cough. ACE-induced cough usually disappears within 1 to 4 days after withdrawal of the treatment, confirming the diagnosis; ACE-induced cough may be prevented by sodium cromoglycate. The risk of obliterans bronchiolitis with expiratory airflow impairment during rheumatoid arthritis is increased by D-penicillamine. Many drugs can be involved in the pathogenesis of bronchiolitis obliterans organizing pneumonia, which presents with various clinical and radiological aspects. The physician has to keep in mind that bronchospasm, cough, or bronchiolitis of unknown origin, may have a iatrogenic cause.
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PMID:[Iatrogenic drug-induced bronchospasm, cough, and bronchiolitis. Etiologic and physiopathologic aspects]. 892 89

The environmental pollutant ozone, at sufficiently high levels, is known to induce pulmonary inflammation with resultant airway obstruction in normal subjects. Eicosanoids comprise one group of mediators released from alveolar macrophages which are involved in the pathogenesis of inflammatory lung diseases. We compared the effects of 2-h exposures to 0.4 ppm ozone and filtered air on pulmonary function and eicosanoid levels in bronchoalveolar lavage fluid in 11 normal healthy volunteers. Subjects were exposed to a 6-fold increase in minute ventilation using an adjusted work load on a cycle ergometer. All subjects complained of cough and dyspnea, and demonstrated increased airway obstruction, and increased specific airway resistance following ozone exposure as compared to air exposure. Bronchoalveolar lavage cell count demonstrated a 9-fold increase in the number of neutrophils with a lesser reduction in the number of alveolar macrophages following ozone exposure. Notably, bronchoalveolar lavage fluid leukotriene (LT) C4 (8-fold) and to a lesser extent LTB4 (1.5-fold) levels were higher following ozone exposure compared to air control, with no change in prostaglandins. In a subset of four subjects, alveolar macrophage arachidonic acid metabolism was studied in vitro following separate in vivo exposures to both ozone and air. Alveolar macrophages obtained following ozone exposure released more 5-lipoxygenase (1.5-fold) metabolites, with no change in cyclooxygenase metabolites, than did cells obtained following air exposure. These observations document activation of the 5-lipoxygenase pathway in the lung following ozone exposure, and suggest that alveolar macrophages may participate in the generation of LT, whose actions promote airway inflammation and obstruction.
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PMID:Increased 5-lipoxygenase metabolism in the lungs of human subjects exposed to ozone. 898 Jul 8

Asthma is a chronic inflammatory disorder of airways. It is characterised by bronchoconstriction, oedema and airways mucus hypersecretion. The main clinical features of asthma are dyspnea, cough, wheezing and heaviness in the chest. The pathology of asthma is characterised by presence of many inflammatory mediators, where the most important are cysteinyl leukotriens. Leukotriens C4, D4 and E4 are 1000 times more potent than histamine in contracting airways smooth muscles. Inhibitors of arachidonic acid metabolism have been used in asthma treatment. They can block the 5-lipoxygenase enzyme and/or 5-lipoxygenase-activating-proteine (FLAP), or can block the cysteinyl leukotriene receptors on the cell surface. Many inhibitors of arachidonic acid metabolism have been found during experimental trials. But only two are used as a drugs: zafirlukast and montelukast (leukotriene receptor inhibitors) montelukast and zileuton (5-lipoxygenase inhibitors) having the best efficacy in asthma treatment. Chronic treatment with these drugs results in a decrease of asthmatic symptoms, improvement of lung function (FEV1, PEF) and decreased usage of other medications--beta-adrenergic agonists and inhaled steroids. It has been proved that zafirlukast and zileuton show the high efficacy in mild-to-moderate asthma, exercise-induced asthma, allergen-induced asthma and aspirin-induced asthma. These oral drugs have been shown to course only mild adverse effects (such as temporary elevation in liver function tests, gastrointestinel disturbances, headache). Clinical usage of zafirlukast, montelukast and zileuton is limited in our country, they are hardly approachable on the market and the cost of treatment is high.
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PMID:[The use of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in bronchial asthma treatment]. 1010 12

Rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. To investigate the involvement of cysteinyl-leukotrienes and prostanoids in these symptoms, bronchial biopsy specimens from 9 normal subjects (nonatopic and with no history of chronic lung disease) were immunostained for 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16. 5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm(2); P <.05), and 5-LO-activating protein (FLAP)-positive cell counts increased 3.6-fold (from 1.8 to 6.5 cells/mm(2); P =.09). Levels of leukotriene A(4) hydrolase and leukotriene C(4) synthase were unchanged. COX-2--positive cell counts increased from 0 to 2.6 cells/mm(2) (P =.009), with no change in COX-1 levels. Increases of 3-4-fold were seen in levels of macrophages (P =.02) and mast cells (P =.07) but not of eosinophils (P >.4), and bronchoalveolar lavage fluid cysteinyl-leukotriene levels doubled (from 11.2 to 20.4 pg/mL; P =.13). Cold symptom scores correlated with bronchial immunostaining for FLAP (rho = 0.93; P =.001). In normal subjects, rhinovirus colds induce bronchial inflammation with markedly enhanced expression of 5-LO pathway proteins and COX-2.
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PMID:Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. 1219 64

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in urticaria and angioedema, is being observed with increasing frequency. Prevalence rates range from 0.1-0.3%, which is partly due to the large size of the exposed (at risk) population. Some predisposing factors for these cutaneous reactions have been identified, among them atopic diathesis, female sex, young adulthood, a history of chronic urticaria and the use of the NSAID for the relief of acute pain. The description of two different arachidonic acid cyclo-oxygenases (COX) about a decade ago, designated COX-1 and COX-2, and the incorporation into the therapeutic armamentarium of more selective enzyme inhibitors for the control of inflammation and pain, has led to an improved understanding of the pathogenesis of adverse reactions to NSAIDs. This has allowed investigators to study 'sensitive' individuals to see if they can safely receive these new pharmaceutical compounds. The reasons why some people react to NSAIDs are not completely clarified. The prevalent theory about the pathogenesis of urticaria and angioedema due to NSAIDs in cross-reactive patients assumes that the inhibition of COX-1 leads to a shunting of arachidonic acid metabolism towards the 5-lipoxygenase pathway, which results in an increased synthesis and release of cysteinyl leukotrienes. Although COX-2 inhibitors are well tolerated by the majority of classic NSAID-sensitive patients, cutaneous reactions to highly selective inhibitors of COX-2 have been described in some of these individuals, casting some doubts about the relevance of such hypotheses. On the other hand, in patients who react to a single NSAID and chemically similar products (single-reactors), specific immunoglobulin E antibodies to haptenated NSAID metabolites have been suspected, although these metabolites are not easily demonstrated by means of routine in vivo or in vitro techniques. Facial (periorbital) angioedema constitutes the most common form of clinical presentation, and one-third of the patients show a mixed clinical pattern of cutaneous (urticaria and/or angioedema) and respiratory symptoms which include upper respiratory tract edema, rhinorrhea, cough, breathlessness and tearing. When necessary, diagnosis is confirmed by means of controlled peroral drug challenges done by experienced physicians in the hospital setting and test results are helpful for clinical management, which will be based on strict avoidance, and the use of alternative tolerated medications. This approach is specially indicated in hypersensitive patients with chronic medical conditions who require continuous NSAID therapy, such as those with arthritis and coronary heart disease.
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PMID:NSAID-induced urticaria and angioedema: a reappraisal of its clinical management. 1244 2