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Effects of methysergide on the cough reflex.

The present study had two basic purposes: to observe the effect of methysergide on the cough reflex and to investigate the effect of methysergide on the antitussive effect of dextromethorphan. Male and female cats were anesthetized with pentobarbital-Na. Respiration and cough reflex were measured using a pneumotachograph via a cannula inserted into the trachea. The cough reflex was elicited by electrical stimuli to the superior laryngeal nerve. Methysergide (3 mg) injected into the vertebral artery increased the number of coughs and respiratory frequency. Dextromethorphan in a dose of 3 mg inhibited the cough reflex. Methysergide (1 and 3 mg) reduced the antitussive effect of dextromethorphan in a dose-dependent manner, but did not inhibit the excitatory effect on respiratory frequency. These findings might indicate that the central serotonergic system has an inhibitory role on the cough reflex and may be related to the antitussive mechanisms of dextromethorphan.

Animals↗

Difference in the incidence of cough induced by angiotensin converting enzyme inhibitors: a comparative study using imidapril hydrochloride and enalapril maleate.

To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12 wk (Period I) followed by enalapril for 12 wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p < 0.001). During Period I, decrease in blood pressure was observed in 63.9% (115/180) of Group IE and 64.6% (115/178) of Group EI patients. In approximately half of the patients in Group EI who developed cough during Period I and in whom the treatment was subsequently switched to imidapril, cough subsequently disappeared. It was concluded that the incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects of the two ACE inhibitors.

Administration, Oral↗

Chronic persistent cough and clearance of esophageal acid.

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

Chronic Disease↗

Intractable cough associated with the supine body position. Effective therapy with nasal CPAP.

We describe five patients with severe nocturnal cough and daytime somnolence in whom the coughing attacks are triggered by assuming the supine body position. Quantity and quality of the nocturnal cough were evaluated in the sleep laboratory with and without nasal continuous positive airway pressure (N-CPAP). Air flow characteristics were assessed using flow volume and airway resistance loops. Airway anatomy was evaluated bronchoscopically. In all five patients, the cough had a barking quality. Flow-volume loops showed an expiratory collapse phenomenon in two of the patients. Endoscopically, all five patients had signs of airway collapse. All patients had difficulty falling asleep because of coughing and were awakened by it frequently. Sleep times ranged from 2.5 to 4.5 h per night. With N-CPAP pressures ranging from 5 to 13 cm H2O, all five patients had clinically significant improvement in their symptoms. Their sleep times increased to a range of 5 to 7.5 h per night and the daytime somnolence markedly improved or resolved. All five patients requested a N-CPAP unit for home use. We conclude that a cough that is predominantly associated with or exacerbated by the supine body position may be treated effectively with N-CPAP.

Adult↗

Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.

STUDY OBJECTIVE: To determine (1) the spectrum and frequency of causes of chronic cough with a history of excessive sputum production (CCS) and (2) the response of these causes to specific therapy. STUDY DESIGN: Prospective study utilizing the anatomic diagnostic protocol originally developed to diagnose chronic cough. PATIENTS: Seventy-one immunocompetent adults who complained of expectoration of greater than 30 mL of sputum per day. LOCATION: University hospital pulmonary outpatient clinic. RESULTS: Patients were seen an average of 4.2 times over 4.6 months before a specific diagnosis was made. The cause of CCS was determined in 97%. It was due to one cause in 38%, 2 in 36%, and three in 26%. Postnasal drip syndrome (PNDS) was a cause 40% of the time, asthma 24%, gastroesophageal reflux disease (GERD) 15%, bronchitis 11%, bronchiectasis 4%, left ventricular failure 3%, and miscellaneous causes 3%. Among patients with a normal chest radiograph who were nonsmokers and not taking an angiotensin converting enzyme inhibitor; CCS was due to PNDS, or asthma, or GERD, or all three in 100% of cases. Chest radiograph, methacholine inhalation challenge, 24-h esophageal pH monitoring, bronchoscopy, and spirometry with bronchodilator each had a sensitivity and negative predictive value of 100%. Chest radiograph and barium swallow had positive predictive values of only 38% and 30%, respectively. CONCLUSIONS: (1) The anatomic diagnostic protocol for cough is also valid for CCS; (2) the major causes of chronic excessive sputum production and chronic cough are so similar that CCS should be considered a form of chronic cough; (3) the evaluation of CCS is more complicated and takes longer than the evaluation of chronic cough; (4) the major strength of the laboratory diagnostic protocol is that it reliably rules out conditions; (5) the outcome of specific therapy is almost always successful; and (6) the term "bronchorrhea" can be misleading if it is applied to excessive sputum production before a specific diagnosis of its source is made since the most common cause of excessive sputum that is expectorated (PNDS) is a disorder of the upper respiratory tract. Therefore, nonspecific therapies theoretically aimed at reducing mucus production in the lower respiratory tract are not likely to be helpful.

Adolescent↗

Daily oral care and cough reflex sensitivity in elderly nursing home patients.

BACKGROUND: Intensive oral care can reduce the incidence of pneumonia in elderly nursing home patients, but the mechanism is unknown. OBJECTIVE: To explore the effects of intensive oral care on impaired cough reflex sensitivity, which is a known risk factor of aspiration pneumonia. METHODS: Cough reflex sensitivity to citric acid was measured in elderly nursing home patients, who were randomly assigned to the intervention group (n = 30) and the control group (n = 29). The patients in the intervention group had their teeth and gingiva cleaned by caregivers after every meal for 1 month. The patients in the control group performed their own oral care during the same period. Serum substance P (SP) concentration, cognitive function, and activities of daily living (ADL) were also assessed. RESULTS: In the intervention group, cough reflex sensitivity at 30 days showed significantly higher sensitivity than baseline (p < 0.01). At 30 days, the cough reflex sensitivities in the intervention group were significantly higher than that of the control group (p < 0.05). Compared with the control group, the odds ratio of improvement of cough reflex sensitivity was 5.3 (95% confidence interval, 1.7 to 16.0; p < 0.005) for the intervention group. One month of intensive oral care did not have a significant effect on serum SP concentration, cognitive function, and ADL. CONCLUSION: Intensive oral care may reduce the incidence of pneumonia by improving cough reflex sensitivity in elderly nursing home patients.

Activities of Daily Living↗

Safety of capsaicin cough challenge testing.

BACKGROUND: Capsaicin, the pungent extract of red peppers, has achieved widespread use in clinical research because it induces cough in a dose-dependent and reproducible manner. Although > 2 decades of experience has led investigators to consider capsaicin cough challenge testing a safe diagnostic modality, this issue has not been specifically addressed in the literature. STUDY OBJECTIVES: To review the published experience with capsaicin inhalation challenge testing in terms of safety. DESIGN: Literature review and personal communication with study authors. SETTING: Academic medical center. RESULTS: One hundred twenty-two published studies since 1984 described 4,833 subjects (4,374 adults, 459 children) undergoing capsaicin cough challenge, with no serious adverse events reported. Subjects included healthy volunteers as well as patients with asthma, COPD, pathologic cough, and other respiratory conditions. Minor complaints described in a small fraction of studies consisted mainly of transient throat irritation. Personal communication with the authors of > 90% of the studies confirmed an absence of any serious adverse events. Furthermore, these investigators have performed thousands of additional capsaicin challenge studies not reported in the literature, also without any associated serious adverse events. CONCLUSIONS: A review of the 20-year clinical experience has failed to uncover a single serious adverse event associated with capsaicin cough challenge testing in humans. Given the need for better antitussive therapies, capsaicin represents a vital component of future scientific inquiry in the field of cough.

Administration, Inhalation↗

Chronic cough due to nonbronchiectatic suppurative airway disease (bronchiolitis): ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To review the role of nonbronchiectatic suppurative airway disease (bronchiolitis) in the spectrum of causes of cough and its management. DESIGN/METHODOLOGY: A MEDLINE search (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "causes of cough," "etiology of cough," "interstitial lung disease," "bronchiolitis," "bronchiolitis obliterans," "diffuse panbronchiolitis," and "inflammatory bowel disease" was performed. Case series and prospective descriptive clinical trials were selected for review. Any references from these studies that were pertinent to the topic were also obtained. RESULTS/CONCLUSIONS: In patients with cough in whom other more common causes of cough have been excluded, incomplete or irreversible airflow limitation, small airways disease seen on high-resolution CT scan, or purulent secretions seen on bronchoscopy, should suggest nonbronchiectatic suppurative airways disease (bronchiolitis) as a potential primary cause. Successful management depends on the identification of the specific underlying disorder.

Bronchiolitis↗

Chronic cough due to chronic interstitial pulmonary diseases: ACCP evidence-based clinical practice guidelines.

OBJECTIVES: To review the role of chronic interstitial pulmonary disease in the spectrum of causes of cough and its management. DESIGN/METHODOLOGY: A MEDLINE search (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "causes of cough," "etiology of cough," "interstitial lung disease," "idiopathic pulmonary fibrosis," "sarcoidosis," and "hypersensitivity pneumonitis" was performed. Case series and prospective descriptive clinical trials were selected for review. Any references from these studies that were pertinent to the topic were also obtained. RESULTS/CONCLUSIONS: In patients with cough, chronic interstitial pulmonary disease should be considered as a primary cause only after more common causes, such as upper airway cough syndrome and gastroesophageal reflux, have been excluded. Successful management depends on identification of the specific disorder.

Chronic Disease↗

Nonacid reflux in patients with chronic cough on acid-suppressive therapy.

BACKGROUND: It is generally accepted that extraesophageal gastroesophageal reflux disease (GERD) symptoms and their persistence despite acid-suppressive therapy are poor prognostic factors for antireflux surgery. Recent studies indicating that cough can be temporally associated with reflux episodes of pH 4 to 7 (ie, nonacid reflux) reinvigorates the need for a more careful workup in patients with cough suspected to be due to GERD. AIM: To evaluate the frequency of chronic cough associated with nonacid reflux and the response of these patients to laparoscopic Nissen fundoplication. METHODS: We retrospectively reviewed data from patients with persistent cough despite twice-daily proton pump inhibitor (PPI) with or without the use of nighttime regimens of histamine-2 receptor antagonist (H2RA), who had undergone combined multichannel intraluminal impedance and pH monitoring. The association of cough and reflux was evaluated by calculating the symptom index (SI) [positive if > or = 50%]. A subset of patients with positive SI values for impedance-detected reflux with therapy was referred for laparoscopic Nissen fundoplication. RESULTS: Of 50 patients (38 female patients; mean age, 43 years; age range, 6 months to 84 years) who were monitored while receiving therapy, 13 patients (26%) had a positive SI for cough. The SI-positive group had a lower percentage of female patients and patients of younger age compared to the SI-negative group. Laparoscopic Nissen fundoplication was performed in six SI-positive patients who became asymptomatic and stopped receiving acid-suppressive therapy during follow-up evaluations (median time, 17 months; range, 12 to 27 months). CONCLUSION: Impedance pH monitoring should be performed while receiving therapy in patients with persistent symptoms who are receiving PPI therapy. A positive SI for nonacid reflux may be helpful in selecting patients who will benefit from antireflux surgery.

Adolescent↗

Angiotensin-converting enzyme inhibitors and cough. Prevalence in an outpatient medical clinic population.

To determine the frequency of ACE inhibitor cough in an outpatient medical clinic population, a cross-sectional epidemiologic survey using mailed questionnaires was done. Patients were randomly selected from a computerized hospital pharmacy data base. The overall prevalence of cough was 19 percent in the ACE inhibitor groups compared with 9 percent in the hydrochlorothiazide-treated group. The observed odds ratio for cough among ACE inhibitor users was 2.3 (95 percent CI, 1.02 to 5.00). This study is the first systematic investigation of frequency and characteristics of ACE inhibitor cough that includes a control group. Our results suggest that cough may more frequently accompany treatment with ACE inhibitors than has been previously reported. We recommend that physicians specifically inquire about cough in patients taking an ACE inhibitor. Recognition of this side effect may prevent unnecessary testing and treatment of patients receiving ACE inhibitors.

Ambulatory Care↗

Adolescent cough medicine abuse in Hong Kong: implications for the design of positive youth development programs in Hong Kong.

This study examines the phenomenon of adolescent cough medicine abuse in Hong Kong. Quantitative data obtained from questionnaire survey with 225 adolescents showed that there were personal, peer, family and community factors influencing adolescent cough medicine abuse. Part 2 of the study obtained qualitative data from focus group interviews with cough medicine abusers (N = 8), their family members (N = 5) and service providers (N = 6). The accounts of the participants revealed that the primary factors accounting for adolescent cough medicine abuse were social pressure (peer and environmental influences), family (difficult relationships or harmful incidents), availability (ease of access), and ignorance (unaware of the consequence of cough medicine use and belief that cough medicine was non-addictive). The present findings provide useful pointers for the development of the positive youth development program supported by the Hong Kong Jockey Club Charities Trust.

Adolescent↗

Cough reflex by ventricular premature contractions.

A 72-year-old man was referred for further assessment of a chronic cough. He noticed an association between the episodes of coughing and palpitations. Electrocardiography (ECG) revealed normal sinus rhythm and sporadic unifocal ventricular premature contractions (VPCs). Each cough was preceded by a premature beat. Continuous wave Doppler echocardiography revealed a VPC-induced transient increase in the pulmonary artery blood flow. He was successfully treated for VPCs with oral disopyramide, resulting in subsidence of both the coughing and palpitations. We suspect that the VPC-induced hemodynamic changes in the pulmonary circulation might be responsible for coughing in our patient. Premature contractions should be considered as a possible cause of chronic dry cough in the clinical setting.

Anti-Arrhythmia Agents↗

Interaction of papaverine with the enalapril-induced cough in guinea pig.

BACKGROUND: Angiotensin Converting Enzyme Inhibitors (ACEIs) like enalapril are extremely effective in the treatment of hypertension and heart failure. One of the most important side-effects of these drugs which can lead to cessation of therapy is a persistant dry cough, induced because of increased bradykinin levels in the lung. Although antitussive alkaloids like codeine are effective in suppressing this cough, they too present a wide range of side-effects, most notably addiction. OBJECTIVE: In a previous work we were able to show that noscapine, a non-narcotic antitussive agent, was able to decrease enalapril induced cough in guinea pigs. In this work, papaverine, another non-narcotic alkaloid found in opium latex was tested in the guinea pig model for antitussive activity. METHOD: Cough was induced in enalapril pretreated guinea pigs by forcing the animals to inspire capsaicin aerosol in an air-tight chamber. Coughs were recorded in control animals and in those which had received different doses of papaverine. Characteristic changes in chamber air pressure, were detected by a pressure transducer. RESULTS: . At low doses (0.5 and 0.25 mg/kg) papaverine was able to decrease enalapril induced cough. CONCLUSION. This effect was not mediated by the action of the drug on mu receptors and was only observed in animals treated with enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

Treatment options in the child with a chronic cough.

Chronic cough is a common symptom in many different disease processes. Because the most effective way to eliminate a chronic cough is to identify and treat the underlying disease, the physician must approach the paediatric patient based on his or her knowledge of the differential diagnosis. The most common causes of cough in children are upper respiratory tract infections, asthma, rhinitis, sinusitis, and gastroesophageal reflux. By using a systematic approach, the cause of a chronic cough can almost always be found, and the cough successfully treated. Asthma is the cause of most undiagnosed chronic coughs but sinusitis, rhinitis, and gastroesophageal reflux must also be considered in difficult patients.

Antitussive Agents↗

Cough threshold to inhaled tartaric acid and bronchial responsiveness to methacholine in patients with asthma and sino-bronchial syndrome.

To evaluate the effect of chronic airway inflammation on cough sensitivity and bronchial responsiveness, we measured the cough threshold to tartaric acid and bronchial responsiveness to methacholine (PC20-FEV1) in 13 asthmatic, 13 bronchitic (sino-bronchial syndrome) and 49 healthy non-atopic subjects. All subjects were non-smokers. The geometric mean value of the cough threshold was 9.55, 5.62 and 12.3% in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly (p less than 0.02) lower than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.63 mg/ml) was significantly lower than those in bronchitic (8.7 mg/ml) (p less than 0.01) and normal subjects (21.4 mg/ml) (p less than 0.01). There was no correlation between cough threshold and PC20-FEV1 values [correlation coefficient (r) = 0.06, p greater than 0.1]. These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.

Adult↗

Bronchodilator-resistive cough in atopic patients: bronchial reversibility and hyperresponsiveness.

The number of atopic patients presenting only chronic non-productive cough appears to be increasing. This study was conducted to confirm the existence of non-asthmatic cough associated with atopy. We prospectively examined atopic findings, therapeutic effects of inhaled procaterol, azelastin, and/or glucocorticoids, improvement of FEV1 by bronchodilator therapy and bronchial responsiveness to methacholine in 20 patients. The cough was relieved by inhaled procaterol in 10 patients (Group 2) but not in the other 10 patients (Group 1). The increase in FEV1 by inhaled salbutamol following aminophylline injection was significantly less in Group 1 than in Group 2. Bronchial responsiveness to methacholine was normal in Group 1 while that in Group 2 was hyperreactive. These findings indicate that there is atopic non-asthmatic bronchodilator-resistive cough (Group 1) which is a different entity from bronchodilator-responsive cough (Group 2), or the so-called "cough variant asthma".

Adrenergic beta-Agonists↗

Longitudinal changes of pulmonary function and bronchial responsiveness in cough-variant asthma treated with bronchodilators alone.

Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as beta 2 adrenergic agonists. The aim of this study was to assess longitudinal changes of pulmonary function and bronchial responsiveness in CVA, which was treated with bronchodilators alone. Seventeen CVA patients recorded intensity and frequency of cough every day. Spirometry and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20) were measured in the run-in period and after cough almost completely relieved on therapy. Cough score had improved within 2 weeks after the initiation of bronchodilator therapy. Forced expiratory volume in one second (FEV1) was significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L after improvement of cough. However, the geometric mean (GSEM) PC20 value did not change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial responsiveness in CVA does not improve when only bronchodilator therapy is carried out. Because bronchial hyperresponsiveness has been shown to be a risk factor for typical asthma onset from CVA, the effect of inhaled corticosteroids on the longitudinal changes in bronchial responsiveness should be examined.

Asthma↗