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)

Inhalation of nicotine (0-64 mg/ml) and capsaicin (2 x 10(-6)-2.5 x 10(-4) M) in 24 healthy nonsmoking subjects produced a concentration-dependent cough response. Two subjects coughed to capsaicin but not to nicotine. The mean (95% confidence interval) nicotine concentrations causing two and five coughs were 5.5 (3.5-8.7) and 15.8 (10.0-25.1) mg/ml, respectively, and were reproducible over 3 different days. Capsaicin inhalation did not alter the response to nicotine and vice versa. Both agents increased respiratory resistance, but the response was more rapid to capsaicin. Inhalation of nicotine (0-8 mg/ml) over 5 min caused increases in heart rate and blood pressure and a decrease in skin temperature. Inhaled ipratropium bromide (0.50 mg) had an antitussive effect and also inhibited the nicotine-induced bronchoconstriction, indicating a vagally mediated effect. Sodium cromoglycate (0.20 mg) did not affect cough or airway resistance changes caused by nicotine. This study shows that inhaled nicotine produces a concentration-dependent cough and airway obstruction in healthy subjects, probably because of stimulation of afferent nerve endings in the bronchial mucosa and mediated through parasympathetic cholinergic pathways. Respiratory reflexes evoked by nicotine are similar to those produced by capsaicin, but it is unclear whether these reflexes are mediated by the same type of sensory nerves.
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PMID:Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems. 792 66

The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones.
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PMID:A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. 821 71

We have studied the effects on FEV1 of inhaled capsaicin in concentrations of 3 x 10(-6) to 3 x 10(-1) mg/ml and methacholine (1 to 16 mg/ml) in 15 heart-lung transplant (HLT) patients who had undergone recent transbronchial lung biopsy to determine the relationships in chronically denervated lungs between these different forms of airway hyperreactivity and inflammation. A total of 10 normal subjects and 17 asthmatic subjects were included for comparison. Capsaicin caused bronchodilation in eight HLT patients (FEV1 rising by 6.4 to 26.8%) and bronchoconstriction in two (fall in FEV1 of 7.2 and 7.6%). By contrast, seven asthmatic subjects developed bronchoconstriction after capsaicin (fall in FEV1 5.6 to 40.4%); the remaining 10 asthmatic subjects showed no response. Bronchial hyperresponsiveness to methacholine was most evident in the asthmatic subjects, but six HLT patients demonstrated a > or = to 20% fall in FEV1 with < or = 8 mg/ml of methacholine. All normal subjects were nonresponsive to both agents, and all normal and asthmatic subjects, unlike HLT patients, coughed with capsaicin. No relationship existed between the methacholine and capsaicin responses. In the HLT patients neither form of airway responsiveness was related to the degree of inflammation seen on transbronchial lung biopsy. The results suggest that in normal subjects, although it provokes cough, inhaled capsaicin causes little airway narrowing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of inhaled capsaicin in heart-lung transplant patients and asthmatic subjects. 823 59

1. Capsaicin, prostaglandin E2 (PGE2) and histamine are potent stimuli for reflex coughing and bronchoconstriction in many species including man. We have studied the effects of solutions of capsaicin, PGE2 and histamine on airway sensory receptors when administered as inhaled aerosols to the lower respiratory tract in anaesthetized, paralysed and artificially ventilated cats. 2. Histamine, administered by aerosol (6 breaths of a 1 mg ml-1 solution) and intravenously (10 micrograms kg-1), caused an increase in the rate of discharge from rapidly adapting stretch receptors (RARs) and caused bronchoconstriction. 3. Six breaths of a capsaicin aerosol generated from solutions of 0.1 or 1 mg ml-1 stimulated six out of nine RARs tested. Bronchoconstriction occurred with and without RAR stimulation. The diluent for the capsaicin aerosol had no significant effect on pulmonary mechanics or rate of RAR discharge. 4. Administration of increasing concentrations (0.001-1 mg ml-1) of PGE2 aerosol given in six breaths (at 6 min intervals) caused a dose-dependent increase in the rate of discharge of eight RARs tested and caused bronchoconstriction. The diluent for the PGE2 aerosol had no effect on pulmonary mechanics or rate of RAR discharge. 5. Inhalation of aerosols of histamine (6 breaths of 1 mg ml-1 solution) and capsaicin (3 breaths of 0.1 mg ml-1 solution) stimulated all six lung C fibre endings studied (3 pulmonary and 3 bronchial). These aerosols of capsaicin and histamine also caused bronchoconstriction. 6. We conclude that solutions of capsaicin and PGE2, when delivered by aerosol to the airway epithelial surface, are not selective stimulants of C fibres. Both agents can stimulate RARs. Activation of some but not all RARs tested, by inhaled capsaicin, suggests that there are subpopulations of capsaicin-sensitive and -insensitive receptors. Stimulation of airway RARs by a range of pharmacologically active agents released by airway inflammation may contribute to reflex coughing and bronchoconstriction in man.
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PMID:Effects of aerosol-applied capsaicin, histamine and prostaglandin E2 on airway sensory receptors of anaesthetized cats. 827 Dec 11

Methacholine provocation test, bronchial reversibility test, aspirin inhalation test, and cough provocation test have been performed at our institute to examine pathophysiology and to diagnose bronchial diseases. Bronchial responsiveness to methacholine correlated to baseline pulmonary functions, especially to % predicted value of forced expiratory volume in 1 second (%FEV1) in asthma and sinobronchial syndrome. Bronchial reversibility was greater with beta 2-agonists than with muscarinic antagonists in asthma while it was less with beta 2-agonists than with muscarinic antagonists in sinobronchial syndrome. Our protocol for aspirin inhalation test consists of a screening test and threshold measurement test and is useful for diagnosis of analgesics-induced asthma. Capsaicin provocation test to measure airway cough receptor sensitivity is used to diagnose chronic cough.
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PMID:[Bronchial provocation test in bronchial asthma]. 836 Oct 17

1. In animal studies monoamine oxidase (MAO) inhibition has been shown to reduce the cough response through elevation of 5-HT in the central nervous system. In this study the effect of selective inhibition of the two subtypes of MAO (MAO-A and MAO-B) was studied on human airway reflexes. 2. Capsaicin-induced cough and reflex increase in respiratory resistance were measured in nine normal volunteers before and after MDL 72394 (MAO-A inhibitor) 16 mg or MDL 72974A (MAO-B inhibitor) 12 mg. 3. Neither inhibitor altered capsaicin-induced cough. Following treatment with MDL 72394, however, the capsaicin-induced reflex increase in resistance was enhanced, by 5.97 +/- 2.1 fold of the placebo value at 1 h. 4. Thus, neurotransmitters in the central nervous system which are substrate for MAO-A (i.e. noradrenaline, 5-HT) may be involved in the control of capsaicin-induced reflex bronchoconstriction.
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PMID:Modulation of capsaicin induced airway reflexes in humans: effect of monoamine oxidase inhibition. 844 37

To examine the mechanisms of an angiotensin-converting enzyme (ACE) inhibitor-induced cough in perimenopausal and postmenopausal women, cough responses to aerosols of capsaicin and citric acid were examined in four groups of female guinea pigs treated orally with danazol (D) (an agent decreasing plasma estrogen levels), cilazapril (C) (an inhibitor of ACE), both danazol and cilazapril (C+D), or without either drug (control group) for 4 to 5 wk. Capsaicin caused dose-dependent increases in the number of coughs in all four groups. C or D alone shifted dose-response curves to capsaicin (from 10(-7) M to 10(-3) M) to lower concentrations compared with the control, and C+D further shifted them. Likewise, the number of coughs induced by citric acid (3 x 10(-1) M; 2 min) was highest in animals treated with C+D and significantly higher in animals treated with C or D than in the control group. Aerosols of a selective substance P (SP) receptor antagonist FK 888 (10(-5) M; 2 min) inhibited capsaicin-induced cough in all four groups, and dose-response curves to capsaicin did not differ significantly at any concentrations among the four groups in the presence of FK 888 (p > 0.10). D decreased cyclic AMP levels in the trachea, irrespective of the combination of C. A beta 2-adrenoceptor agonist, procaterol, which is thought to inhibit SP release by elevation of cyclic AMP in sensory nerves, dose-dependently inhibited the number of coughs induced by capsaicin (10(-3) M) in animals treated with D. The present study suggests that SP is a common mechanism mediating increases in the sensitivity of cough reflex induced by both ACE inhibition and a decrease in plasma estrogen levels, and the additive effects of the two events may explain the high incidence of cough during ACE inhibitor therapy in perimenopausal and postmenopausal women.
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PMID:Angiotensin-converting enzyme inhibitor and danazol increase sensitivity of cough reflex in female guinea pigs. 856 37

Cyclooxygenase products are released by chronic airway inflammation. Our working hypothesis for the present study was that prostanoids augment airway cough sensitivity. The effects of a cyclooxygenase inhibitor, indomethacin (100 mg.day-1 for 4 days), and a thromboxane synthesis inhibitor, OKY-046 (400 mg.day-1 for 4 days), on cough response to inhaled capsaicin were examined in eight patients with asthma, 10 patients with chronic bronchitis, and 10 normal subjects. Capsaicin cough threshold, the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. In asthmatics, the cough thresholds with indomethacin treatment (15.7 (GSEM 1.38) microM) and OKY-046 (10.2 (GSEM 1.20) microM) were significantly greater than the value with placebo (6.05 (GSEM 1.25) microM). In patients with chronic bronchitis, the cough threshold was significantly greater with indomethacin (5.94 (GSEM 1.50) microM) than with placebo (3.41 (GSEM 1.33) microM and OKY-046 2.97 (GSEM 1.43) microM). In normal subjects, the capsaicin cough threshold was not altered by indomethacin or OKY-046 treatment. These results support our hypothesis and suggest that thromboxane A2 may be one of the cyclooxygenase products augmenting airway cough sensitivity in asthma, but not in chronic bronchitis.
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PMID:Prostanoids and cough response to capsaicin in asthma and chronic bronchitis. 857 75

1. In eight hypertensive patients with ACE inhibitor-induced cough the resolution of the cough was examined in a prospective observational study over 4 weeks duration. Resolution of cough was measured by visual analogue scales and questionnaire at baseline and days 3, 7, 14 and 28. In addition changes in cough sensitivity to inhaled capsaicin, and skin responses to bradykinin and substance-P were measured at the same time points. 2. All patients recorded significant subjective improvement in cough questionnaire scores for severity and night time waking, and by visual analogue scales for severity and frequency of cough (all P < 0.0005 for trend from day 0-28). Significant changes in subjective measures were recorded by 3 to 7 days for most measures, but further reductions were observed up to day 28 (all P < 0.01 day 28 vs day 0). 3. The sensitivity to inhaled capsaicin fell over the 28 days of study after stopping enalapril. The potency of capsaicin relative to day 0 was reduced to 0.25 (95% CI 0.07-0.87) by day 14, and to 0.20 (95% CI 0.06-0.67) by 28 days. 4. After stopping enalapril there was a highly significant reduction in wheal area produced by intradermal bradykinin, with the majority of the effect seen by day 3 (P < 0.0005). The wheal area to intradermal substance-P also declined with time after stopping enalapril, but significant changes were not observed until 14 days (P < 0.01). 5. Multiple regression analysis of the rates of decline for the subjective and objective measures of cough showed significant associations between the response to inhaled capsaicin and the VAS scores for severity of cough (P = 0.005) and frequency of cough (P = 0.011). Capsaicin response was not related significantly to the severity of cough measured by self-administered questionnaire. 6. There was a significant association between bradykinin response and VAS scores for frequency of cough (P < 0.04) and severity of cough (P < 0.05), but not with cough by questionnaire or the capsaicin response. The response to substance-P did not relate significantly to any of the measures of cough. 7. Cough caused by enalapril improved markedly by 14 days but took up to 28 days to resolve. It was associated with increased sensitivity to inhaled capsaicin which decreased over 28 days, and which paralleled changes in subjective cough scores.
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PMID:Resolution of ACE inhibitor cough: changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and substance-P. 870 45

Asthmatic subjects cough and bronchoconstrict to various agents known to stimulate sensory nerves. A population of sensory nerves, the C fibres, contain the neuropeptides substance P, neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). Capsaicin, the principal ingredient of hot peppers, selectively stimulates C fibre afferents resulting in the release of these proinflammatory peptides. An upregulation in the function of sensory nerves may lead to augmented afferent and efferent function which, in asthma, could contribute to bronchial hyper-responsiveness, inflammation, and remodelling of the airway wall. Drugs specifically designed to attenuate the function of airway sensory nerves may prove useful in the treatment of asthma.
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PMID:Airway sensory nerves: a burning issue in asthma? 877 45


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