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)

We investigated the effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor antagonist, in 11 patients with severe bronchial asthma. The patients had been treated with 1600 micrograms/day of beclomethasone or 800-1600 micrograms/day of beclomethasone plus 2.5-20 mg/day of prednisolone, but remained symptomatic. After a 2-week baseline period, the patients received 225 mg of pranlukast twice daily for 8 weeks. Morning and evening peak expiratory flow rate (PEF) and symptom scores (cough, dyspnea, sleep) were recorded in an asthma diary. Ten patients completed the study. Symptom scores, especially dyspnea and sleep scores, and the number of rescue beta 2-agonist inhalations were significantly decreased. The morning PEF significantly improved from a mean baseline value of 311 to 341 L/min by the end of the study period. The evening PEF also improved, from 328 to 348 L/min, although the difference was not significant. These results suggest that pranlukast may be effective in treating patients with severe asthma who are refractory to corticosteroid therapy.
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PMID:Effect of pranlukast, a leukotriene receptor antagonist, in patients with severe asthma refractory to corticosteroids. 951 83

In patients with asthma, increased sensitivity of airway sensory nerves may be involved in producing bronchospasm and cough. To evaluate the effect of a leukotriene-modifying agent on cough reflex sensitivity, we measured the cough response to inhaled capsaicin before and after a 1 4-day course of therapy with zafirlukast, a cysteinyl leukotriene receptor antagonist, in a group of stable asthmatics. The concentration of capsaicin inducing two or more (C2) and five or more (C5) coughs was not altered by zafirlukast, even in those subjects demonstrating a significant change (increment or decrement) in forced expiratory volume in 1 sec (FEV1). These findings support previous evidence that cough and bronchoconstriction are modulated by distinct neural pathways.
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PMID:Effect of zafirlukast on cough reflex sensitivity in asthmatics. 1035 Feb 23

Cystic fibrosis (CF) lung disease is characterized by chronic endobronchial infection resulting in progressive pulmonary destruction; this is a major cause of mortality and morbidity. Neutrophils are the primary effector cells responsible for the progressive deterioration of lung function. Peptido-leukotriene B4 antagonists, new anti-inflammatory agents that block the neutrophil-dominated inflammation, could have had the potential for long-term use. A trial on the pharmacokinetics of amelubant administered orally as a single dose of up to 75 mg in pediatric patients with CF and 300 mg in adults, and as a repeated dose of 75 mg and 150 mg, respectively, once daily for 15 days provided evidence that amelubant metabolism in adult and pediatric patients with CF is similar to that in healthy adults. In another study using the same dosage regimen, amelubant appeared to be safe and well tolerated. Safety measures included physical examination, vital signs, spirometry, oximetry, ECG, and clinical laboratory testing. However, a randomized, double-blind, placebo-controlled, multinational, phase II trial (Boehringer Ingelheim 543.45) was conducted to investigate the clinical efficacy of 24 weeks of treatment with amelubant in patients with CF with mild-to-moderate lung disease. Two doses of amelubant (75 and 150 mg) were tested in adult patients (> or = 18 years) and one dose of amelubant (75mg) was tested in pediatric (6-17 years) patients. The trial was terminated early due to a statistically significant increase in the risk of pulmonary-related, serious adverse events in adults receiving amelubant. Cysteinyl leukotrienes, eosinophilic inflammation, and viral infections also contribute to progressive pulmonary destruction in CF. Cysteinyl leukotrienes are potential targets for cysteinyl leukotriene receptor antagonist use. A study on the pharmacokinetics of montelukast in children with CF provided evidence that the dose of montelukast and the administration interval does not need to be modified if the goal is to mimic the serum concentrations used to treat asthma. In a randomized, double-blind, crossover, placebo-controlled study, 16 children with mild CF (median age 9.5 years; vital capacity [VC] >70%) were treated with montelukast (5 to < or =14 years; 5 mg; >14 years; 10 mg) or placebo as a once-daily tablet for 21 days. There was a significant (p < or = 0.02) reduction in serum eosinophil cationic protein levels and eosinophils (p < or = 0.027) with montelukast. However, neither lung function tests (VC, forced expiratory volume in 1 second [FEV1], maximum expiratory flow at 25% of forced VC), nor clinical symptom scores changed significantly. In another study, 26 patients aged 6-18 years with moderate CF (VC between 40% and 69% predicted) received montelukast or placebo for 8 weeks in a 20-week, randomized, double-blind, crossover, placebo-controlled trial. After treatment with montelukast there was a significant improvement in FEV1, peak expiratory flow, and forced expiratory flow between 25% and 75%, and a significant decrease in cough and wheezing scale scores (p < 0.001 for all). Montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and interleukin-8 (IL-8), decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (p < 0.001 for all) compared with placebo. To date, clinical experience and research data on the anti-inflammatory effects of leukotriene receptor antagonists in CF are limited. Multicenter trials with longer observation periods and greater patient numbers are needed to prove the hypothesis that leukotriene receptor antagonists have the potential to ameliorate CF lung disease with long term use.
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PMID:Leukotriene receptor antagonists in children with cystic fibrosis lung disease : anti-inflammatory and clinical effects. 1635 23

Objectives Sceptridium ternatum is an expectorant in traditional Chinese medicine and is prescribed for the treatment of asthma. The study aim was to screen Sceptridium ternatum for ingredients with antitussive and antiasthmatic effects and to study their associated mechanisms. Methods Cough in mice was induced using ammonia. Cough latency and the number of coughs within 3 minutes were determined. Airway responsiveness was assessed using ovalbumin as a sensitizer and characteristic asthma indicators were measured. Results Chloroform and ethyl acetate extracts significantly reduced the number of coughs within 3 minutes, tidal volume, and the percentage of eosinophilic granulocytes, lymphocytes and neutrophils. All extracts decreased airway responsiveness in asthmatic mice compared with the untreated group. Petroleum ether, chloroform and n-butanol extracts lowered the Penh values of asthmatic mice. Petroleum ether and ethyl acetate extracts greatly reduced interleukin-4 expression and the interleukin-4/interferon gamma ratio. Compared with the model group, all extracts reduced mRNA expression of the cysteinyl leukotriene receptor-1 (CysLT1). Conclusions Chloroform extract and ethyl acetate extract displayed obvious antitussive effects and reduced airway inflammation. Thus, these two extracts contain the effective ingredients of Sceptridium ternatum. The active mechanism was ascribed to inhibition of mRNA expression of the CysLT1 receptor in mice with bronchial asthma.
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PMID:Screening of Sceptridium ternatum for antitussive and antiasthmatic activity and associated mechanisms. 2925 Dec 56