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Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis.

STUDY OBJECTIVE: The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies. STUDY DESIGN: The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period. SETTING: One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies. PATIENTS: Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. MEASUREMENTS AND RESULTS: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo. CONCLUSION: The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI.

Adolescent↗

Sensitivity of the cough reflex in patients with chronic cough.

Cough may occur in association with excess bronchial secretions and may, therefore, be productive. However, in a proportion of patients the cough is non-productive and a possible association with an enhanced response of the cough reflex has been postulated. Using the irritant capsaicin, the sensitivity of the cough reflex was measured in 363 individuals. A questionnaire was used to divide subjects into three groups: Group A) non-coughing controls; Group B) subjects with non-productive cough; and Group C) subjects with productive cough. The group means (+/- 99% confidence interval (CI)) of the log capsaicin concentration causing two or more coughs (C2) for groups A, B, C were 0.98 (+/- 0.08), 0.64 (+/- 0.09) and 1.04 (+/- 0.23), respectively. The log capsaicin concentration causing five or more coughs (C5) for groups A, B, C were 1.78 (+/- 0.1), 1.16 (+/- 0.12) and 1.54 (+/- 0.25), respectively. Group B was significantly more sensitive to inhaled capsaicin than the other groups (p less than 0.01). No significant difference was observed between groups A and C. Some differences were found when subgroups were examined within groups B and C. In group B, patients with post-nasal drip were found to have a normal sensitivity of the cough reflex and were, therefore, different from the remainder of patients with non-productive cough. In group C, patients with bronchiectasis and current infection showed an increase in the sensitivity of their cough reflex. It is concluded that cough can occur in association with either excess mucus production leading to productive cough or an increase in the sensitivity of the cough reflex, possibly leading to non-productive cough.

Administration, Inhalation↗

Resolution of ACE inhibitor cough: changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and substance-P.

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.

Adult↗

[Effects of inhaled anticholinergic agents and beta 2-agonists on distilled water induced cough in patients with chronic cough].

The purpose of this study was to evaluate the usefulness of ultrasonically nebulized distilled water (UNDW) inhalation for assessing cough receptor sensitivity and also the effects of inhaled anticholinergic agents and beta 2-agonists on the number of coughs induced by the UNDW inhalation in patients with chronic cough. All patients were non-smokers and had neither bronchial hyperreactivity nor atopic status. We studied the effects of inhaled oxitropium bromide (300 micrograms) and fenoterol hydrobromide (600 micrograms) on the number of coughs induced by UNDW inhalation for 3 minutes in 9 patients with chronic cough and the effects of inhaled fenoterol hydrobromide (400 micrograms) on the number of coughs induced by UNDW inhalation for 1 minute in 8 patients with chronic cough using a randomized, double-blind, cross-over method. There was no significant difference in pulmonary function test results before and after UNDW inhalation. In both the 3-minute and 1-minute UNDW inhalation studies, the number of coughs was greater in the patients than in normal subjects. Patients with chronic cough may have a high level of cough sensitivity, inhaled fenoterol significantly reduced the number of coughs in the patients in both the 3-minute and 1-minute UNDW inhalation studies (p < 0.05). However, compared with control, inhaled oxitropium did not reduce the number of coughs caused by the 3-minute UNDW inhalation in the patients. Tachyphylaxis was observed in normal subjects in the 3-minute UNDW inhalation study when repeated at a 30-minute interval. We conclude that 1-minute UNDW inhalation method may be safe and useful for measuring cough receptor sensitivity of patients with chronic cough and that inhaled beta 2-agonists may have an inhibitory effect on cough induced by irritation of cough receptors through unknown mechanisms other than the bronchodilator effect.

Administration, Inhalation↗

Clinical validation of efficacy and safety of herbal cough formula: study of herbal cough syrup.

OBJECTIVE OF THE STUDY: To clinically validate the efficacy and safety of herbal cough formula CORSHE-E of ayurvedic origin. PROCEDURE: An open label, uncontrolled clinical study was done on thirty patients with history of cough. The patients were given the cough syrup after they were enrolled in the study and were followed up for a period of seven days. The cough severity, frequency (as recorded on Visual Analogue Scale from 0 to 10 cm), chest discomfort, quantity and type of sputum were recorded at screening, on the fourth day and on the seventh day of treatment. The patient recorded the severity and frequency of cough on a Visual Analogue Scale which was divided into ten equal parts of 1 cm each. The patient marked the extent of symptoms on this scale at screening and after four days of consumption of the cough syrup. The scores were marked on these days and reduction in score was examined for efficacy evaluation of the cough syrup. The clinical and hematological safety parameters and parameters for acceptability of cough syrup (palatability, color, odor and consistency) were also studied. Global assessment by the patient and the physician was also carried out on the fourth day. RESULTS: Twenty-six of the thirty patients studied showed a significant decrease in the frequency and severity of cough (on Visual Analogue Scale). The sputum quantity and consistency also showed steady decrease and liquefaction respectively. Four patients who had longer duration of did not respond adequately to treatment. These patients had history of sub-acute to chronic cough with mean duration of cough being forty days (40 +/- 34 days), sore-throat and fever, highly suggestive of bacterial upper respiratory tract infection and a long duration of cough before initiation of therapy. Most of the patients found the cough syrup to be acceptable in terms of these criteria. Nineteen patients rated the cough syrup as excellent in palatability, two in color, four in odor and five in consistency. Six patients rated the syrup as good to taste, twenty-eight patients rated the natural color as good and twenty five and twenty patients rated the odor and consistency as good, respectively. Five patients described the taste as bad, none described the color as bad, one patient found the odor bad and five described the consistency as bad. All patients described a soothing effect of the study drug and appreciated the natural color and flavor of the same. Global assessment was based on improvement in symptoms, acceptability and overall efficacy and safety as reported by the physician and the patient. Thirteen of the thirty patients rated the trial medicine as excellent, thirteen rated it as good and four considered it poor. The investigator in charge of the patients rated the trial medicine as excellent in eighteen cases, good in eight cases, fair in two cases and poor in two cases. CONCLUSION: The test drug CORSHE-E is an effective and safe cough syrup that is highly acceptable for patients with cough of short duration.

Adolescent↗

Elevated substance P levels in nasal lavage fluids from patients with chronic nonproductive cough and increased cough sensitivity to inhaled capsaicin.

BACKGROUND: The exact mechanism of a chronic nonproductive cough is sometimes unclear when patients who are without symptoms or signs indicating the major causes of chronic cough remain undiagnosed. OBJECTIVE: We hypothesized that some neurochemical alterations in the sensory nerves in the cough reflex may occur in the upper airway of chronic nonproductive cough patients. METHODS: We took nasal lavage fluid (NLF) specimens from 38 patients with a chronic nonproductive cough as the sole presenting symptom. All 38 had normal chest radiography, spirometry, and bronchial responsiveness. We likewise took NLF specimens from 14 healthy control subjects. We used a capsaicin cough provocation test to determine cough sensitivity and considered the value of C5 (the lowest capsaicin concentration inducing 5 consecutive coughs) as an index of cough sensitivity. We measured levels of substance P of NLF specimens by using ELISA. In addition, we evaluated the clinical response of each patient after subsequent therapeutic trials with an antihistamine and decongestant for 2 weeks. RESULTS: By using capsaicin cough sensitivity as the basis for grouping the study subjects, we divided the patients into 2 groups: an increased cough sensitivity group (ICS, C5 <32 mumol/L) and a normal cough sensitivity (NCS) group. Patients with ICS showed an elevated SP concentration in NLF (median value, 408 pg/mL) compared with that of the NCS group (237 pg/mL) and the control subjects (138 pg/mL) (P <.01). The median value of the percentage of remnant cough after therapeutic trial compared with the cough status before treatment was significantly higher in the ICS subgroup (70%) than that of NCS (25%) (P <.05). CONCLUSIONS: Elevated substance P contents in NLF specimens were associated with ICS in patients with chronic nonproductive cough, suggesting a neurochemical abnormality in the upper airway.

Administration, Inhalation↗

Longitudinal decline in pulmonary function in atopic cough and cough variant asthma.

OBJECTIVE: Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non-productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough. METHODS: Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non-smokers. Of the 20 cough variant asthma patients, 13 were taking long-term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 +/- 58 micro g/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards. RESULTS: The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (- 0.029 +/- 0.007/year), atopic cough patients (- 0.021 +/- 0.022/year) and asymptomatic subjects (- 0.028 +/- 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 +/- 0.007 L/year, which was not significantly different from that in patients taking ICS (- 0.027 +/- 0.010 L/year). CONCLUSION: Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long-term ICS has no effect on the decline in cough variant asthma.

Asthma↗

Cough sensitivity in children with asthma, recurrent cough, and cystic fibrosis.

In adults, cough sensitivity is influenced by gender and is heightened in those with non-productive cough. This study examined if cough sensitivity is (i) altered in children with asthma, recurrent cough, and cystic fibrosis and (ii) influenced by age, gender, or forced expiratory volume in one second (FEV1). Cough sensitivity to capsaicin and spirometry were performed on 209 children grouped by the diagnosis of asthma, recurrent dry cough, cystic fibrosis, and controls. Cough sensitivity was increased in children with recurrent cough, and lower in children with cystic fibrosis when compared with children with asthma and controls. Age influenced cough sensitivity in the controls. In the asthmatics, FEV1 (% predicted) correlated to cough sensitivity measures. There was no gender difference in cough sensitivity. It is concluded that cough sensitivity is different among children with recurrent dry cough, asthma, and cystic fibrosis. In children, age, but not gender, influences cough sensitivity measures and when cough sensitivity is used in comparative studies, children should be matched for age and FEV1.

Adolescent↗

Bradykinin-induced cough reflex markedly increases in patients with cough associated with captopril and enalapril.

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on cough responses to bradykinin (BK), substance P (SP) and citric acid in a double blind, random study on 10 hypertensive patients receiving ACE inhibitors. Of these patients, five had reported cough with ACE inhibitors. Cough responses to citric acid were similar between patients with and without cough, and SP up to 10(-5) M did not cause cough in any of the subjects. BK caused cough at 13.4 +/- 1.2 (-log M) in 5 patients with cough associated with ACE inhibitors, but it did not cause cough at concentrations up to 10(-5) M in other 5 patients. One month after the withdrawal of ACE inhibitors, 5 patients were free from cough symptoms, and BK did not cause cough up to 10(-5) M in these patients, except for one who coughed at 10(-9) M, without changes in responses to citric acid. BK caused cough at 14.3 +/- 0.7 (-log M) although BK1-7, a major metabolite of BK by ACE, caused cough at 5.7 +/- 0.7 (-log M) in another 3 patients with cough associated with ACE inhibitor. These results suggest that impaired metabolism of BK induced by ACE inhibitors may relate to the manifestation of cough in hypertensive patients receiving ACE inhibitors.

Adult↗

Symptomatic treatment of the cough in whooping cough.

BACKGROUND: Whooping cough is an important cause of childhood morbidity and mortality. There are 20 to 40 million cases of whooping cough annually world-wide, 90% of which occur in developing countries, resulting in an estimated 200 to 300 000 fatalities each year. Much of the morbidity is due to the effects of the paroxysmal cough. Corticosteroids, salbutamol (beta 2 - adrenergic stimulant), and pertussis-specific immunoglobulin have been proposed as standard treatment for the cough. Antihistamines have also been administered. No systematic review of the effectiveness of any of these interventions or others has been performed. OBJECTIVES: To assess the effectiveness and safety of interventions used to reduce the severity of the coughing paroxysms in whooping cough in children and adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 2, 2003); MEDLINE (January 1966 to June 2003); EMBASE (1990 to June 2003) and LILACS (1982 to November 2001). We also scanned reference lists of identified trials and contacted authors of identified trials and relevant pharmaceutical companies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of any intervention aimed at suppressing the cough in whooping cough; excluding antibiotics and vaccines. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies and extracted data. Our primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis, development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Disagreements were resolved by discussion. MAIN RESULTS: Nine studies satisfied the inclusion criteria but four had insufficient data for meta - analysis of pre-specified outcomes. Studies were small and poorly reported. The largest study had a sample size of 49 and the smallest study 18. All studies were performed in industrialised settings. Eligible studies assessed diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol. No statistically significant benefit was found for any of the interventions. Diphenhydramine did not change coughing spells (mean increase of coughing spells per 24 hours 1.9 with 95%CI - 4.7 to 8.5) and pertussis immunoglobulin no change in hospital stay (0.7 days 95% CI -3.8 to 2.4), and a mean reduction of 3.1 whoops per 24 hours [95% CI -6.2; 0.02]. Dexamethasone did not show a clear decrease in hospital stay (-3.5 days 95% CI - 15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours [-0.22 95% CI - 4.13 to 3.69]. REVIEWER'S CONCLUSIONS: Insufficient evidence exists to draw conclusions about the effects of any intervention for the cough in whooping cough.

Adult↗

Cough headache: frequency, characteristics and the relationship with the characteristics of cough.

Cough headache (CH) is a relatively rare, but an important complication of cough. The aim of this cross-sectional clinical study was to evaluate the frequency, characteristics and etiology of CH among the patients referred to our Outpatient Department with the complaint of cough, and to investigate the relationship between their cough and headache characteristics. We evaluated 96 females and 69 males, a total of 165 patients with cough. Among those, 57 patients (34.5%) had one or more cough complications and 32 patients (19.3%) were diagnosed as CH. Although it was known that most of the patients with CH had benign headache characteristics, the ratio of the symptomatic CH was not low (37.5% of the CH patients and 7% of patients with cough). Also, there was a significant correlation between the frequency of cough and the severity of headache. Logistic regression analysis showed that the incidence of CH was increased 0.4-fold, when frequency of cough increased. Age, sex, tobacco use ad the duration of cough were not found to be predictive factors for CH. Logistic regression analysis showed that the rate of cough complications increased 2.08-fold, when the duration of cough was longer than eight weeks (p=0.03) and 0.4-fold when the frequency of cough increased (p=0.02). In conclusion, CH is a relatively rare, but an important complication of cough and it commonly has an effective treatment available. Radiological work-up was crucial in ruling out other causes of headache and to confirm that the CH was truly benign.

Adolescent↗

Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness.

BACKGROUND: It has been suggested that cough effectiveness can be improved by assisted techniques. The effects of manually assisted cough and mechanical insufflation on cough flow physiology are reported in this study. METHODS: The physiological actions and patient self-assessment of manually assisted cough and mechanical insufflation were investigated in 29 subjects (nine normal subjects, eight patients with chronic obstructive pulmonary disease (COPD), four subjects with respiratory muscle weakness (RMW) with scoliosis, and eight subjects with RMW without scoliosis). RESULTS: The peak cough expiratory flow rate and cough expiratory volume were not improved by manually assisted cough and mechanical insufflation alone or in combination in normal subjects. The median increase in peak cough expiratory flow in subjects with RMW without scoliosis with manually assisted cough alone or in combination with mechanical insufflation of 84 l/min (95% confidence interval (CI) 19 to 122) and 144 l/min (95% CI 14 to 195), respectively, reflects improvement in the expulsive phase of coughing by these techniques. Manually assisted cough and mechanical insufflation in combination raised peak expiratory flow rate more than either technique alone in this group. The abnormal chest shape in scoliotic subjects and the fixed inspiratory pressure used made effective manually assisted cough and mechanical insufflation difficult in this group and no improvements were found. In patients with COPD manually assisted cough alone and in combination with mechanical insufflation decreased peak expiratory flow rate by 144 l/min (95% CI 25 to 259) and 135 l/min (95% CI 30 to 312), respectively. CONCLUSIONS: Manually assisted cough and mechanical insufflation should be considered to assist expectoration of secretions in patients with RMW without scoliosis but not in those with scoliosis.

Adolescent↗

New non-invasive automatic cough counting program based on 6 types of classified cough sounds.

UNLABELLED: Cough consisting of an initial deep inspiration, glottal closure, and an explosive expiration accompanied by a sound is one of the most common symptoms of respiratory disease. Despite its clinical importance, standard methods for objective cough analysis have yet to be established. OBJECT: We investigated the characteristics of cough sounds acoustically, designed a program to discriminate cough sounds from other sounds, and finally developed a new objective method of non-invasive cough counting. In addition, we evaluated the clinical efficacy of that program. SUBJECTS AND METHODS: We recorded cough sounds using a memory stick IC recorder in free-field from 2 patients and analyzed the intensity of 534 recorded coughs acoustically according to time domain. First we squared the sound waveform of recorded cough sounds, which was then smoothed out over a 20 ms window. The 5 parameters and some definitions to discriminate the cough sounds from other noise were identified and the cough sounds were classified into 6 groups. Next, we applied this method to develop a new automatic cough count program. Finally, to evaluate the accuracy and clinical usefulness of this program, we counted cough sounds collected from another 10 patients using our program and conventional manual counting. And the sensitivity, specificity and discriminative rate of the program were analyzed. RESULTS: This program successfully discriminated recorded cough sounds out of 1902 sound events collected from 10 patients at a rate of 93.1%. The sensitivity was 90.2% and the specificity was 96.5%. CONCLUSION: Our new cough counting program can be sufficiently useful for clinical studies.

Cough↗

Efficacy and safety of Ascoril expectorant and other cough formula in the treatment of cough management in paediatric and adult patients--a randomised double-blind comparative trial.

The present study was undertaken to study the comparative safety and efficacy of two cough formulas viz, Ascoril expectorant and other cough formula in the management of cough associated with respiratory disorders. Fifty patients having cough associated with various respiratory disorders like bronchitis and upper or lower respiratory tract infections were randomly divided into 2 equal groups and were treated with one of the two cough formulas viz, Ascoril cough formula and other cough formula in double-blind manner over a period of 15 days. The evaluation of improvement was carried out by a rating scale using three clinical parameters--cough, sputum and breathlessness. The physicians were asked to rate the effectiveness of the therapy and patients were asked to rate the acceptability of therapy using pre-defined operational criteria. It was observed that the improvement and symptom relief was almost immediate, quicker and better in the group receiving Ascoril as compared to other group. On effectiveness parameter, 96% of the physicians rated Ascoril as having either 'very high effectiveness or high effectiveness' as opposed to only 34% of the physicians who rated other cough formula as having 'high' or 'very high effectiveness'. While on parameter of acceptability, 96% of the patients rated acceptability of Ascoril as 'high' or 'good' as opposed to only 24% of the patients who rated other cough formula 'high' or 'good'. The findings of this study suggests that Ascoril cough formula has better efficacy as well as better patient acceptability. Thus, Ascoril cough formula is superior to other cough formula in management of cough associated with respiratory disorders.

Adolescent↗

Effect of cough on heart rate and blood pressure in patients with "cough syncope".

BACKGROUND: "Cough syncope" is uncommon, and its mechanism remains controversial. OBJECTIVES: This study evaluated susceptibility to cough-triggered neural reflex hypotension-bradycardia among cough syncope patients. We hypothesized that individuals with cough syncope would manifest not only more profound cough-triggered hypotension than do other fainters but also an inappropriate chronotropic response accompanying cough-induced hypotension, thereby supporting the notion that a neural reflex hypotension-bradycardia contributes to the condition. METHODS/RESULTS: Three patient groups were studied. Group 1 patients (n = 9) had "cough syncope." The remaining patients had recurrent faints of other causes: group 2 (n = 13) had a positive head-up tilt test, and group 3 (n = 18) had a negative tilt test. With cough, group 1 patients exhibited a greater drop in systolic pressure (-51 +/- 19.3 mmHg) than did either group 2 (-23 +/- 11.1 mmHg, P < .04) or group 3 patients (-28 +/- 12.4 mmHg, P < .05). Recovery time to normalization of systolic pressure was greater in group 1 (25 +/- 9.1 seconds) than in group 2 or 3 (8 +/- 2.7 seconds and 9 +/- 6.1 seconds, respectively, both P < .01 vs group 1). The expected positive chronotropic response accompanying cough-induced hypotension was diminished in group 1 patients (0.16 +/- 0.21 bpm/mmHg) compared with that in either group 2 (0.74 +/- 0.60 bpm/mmHg, P < .05 vs group 1) or group 3 (0.33 +/- 0.15 bpm/mmHg, P = .06 vs group 1). CONCLUSION: Cough syncope patients not only exhibit more pronounced hypotension in response to cough than other fainters, but they also manifest an inappropriate cough-triggered blood pressure-heart rate relationship. These findings argue in favor of the importance of a neurally mediated reflex contribution to symptomatic hypotension in cough syncope.

Aged↗

Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. METHODS: Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.

Adult↗

Airway hyperresponsiveness and cough-receptor sensitivity in children with recurrent cough.

In children, recurrent cough is a common presenting symptom that may represent asthma. We tested the hypotheses that children with recurrent cough have increased cough-receptor sensitivity (CRS) or airway hyperresponsiveness (AHR). Skin prick testing, the capsaicin CRS test, and hypertonic saline (HS) challenge were performed in 44 children (median age: 8.9 yr) with recurrent dry cough (> or = 2 episodes of cough, each lasting > or = 2 wk, within a period of 12 mo) and 44 controls. Measures of CRS were the concentration of capsaicin required to stimulate > or = 2 coughs (Cth) and > or = 5 coughs (C5). During the coughing period, Cth (mean log: 0.62 [95% CI: 0.43 to 0.81]) and C5 (mean log: 1.15 [95% CI: 0.86 to 1.44]) of the subjects without AHR were significantly lower (p = 0.0026, 0.027, respectively) than Cth (mean log: 1.27 [95% CI: 0.88 to 1.66]) and C5 (mean log: 1.79 [95% CI: 1.21 to 2.37]) of the subjects with AHR and those of the controls (p = 0.0002 and 0.0001). During the cough-free period, there was no difference in CRS among the groups. In subjects who demonstrated AHR, the provocation dose causing a > or = 15% fall in FEV1 (PD15) during the cough period was significantly lower (p = 0.005) than that during the cough-free period. We conclude that AHR or increased CRS is present during the coughing phase in children with recurrent cough.

Adolescent↗

Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude.

The aim of this study was to determine the frequency of cough and the citric acid cough threshold during hypobaric hypoxia under controlled environmental conditions. Subjects were studied during Operation Everest 3. Eight subjects ascended to a simulated altitude of 8,848 m over 31 days in a hypobaric chamber. Frequency of nocturnal cough was measured using voice-activated tape recorders, and cough threshold by inhalation of increasing concentrations of citric acid aerosol. Spirometry was performed before and after each test. Subjects recorded symptoms of acute mountain sickness and arterial oxygen saturation daily. Air temperature and humidity were controlled during the operation. Cough frequency increased with increasing altitude, from a median of 0 coughs (range 0-4) at sea level to 15 coughs (range 3-32) at a simulated altitude of 8,000 m. Cough threshold was unchanged on arrival at 5,000 m compared to sea level (geometric mean difference (GMD) 1.0, 95% confidence intervals (CI) 0.5-2.1, p=0.5), but fell on arrival at 8,000 m compared to sea level (GMD 3.3, 95% CI 1.1-10.3, p=0.043). There was no relationship between cough threshold and symptoms of acute mountain sickness, oxygen saturation or forced expiratory volume in one second. Temperature and humidity in the chamber were controlled between 18-24 degrees C and 30-60%, respectively. These results confirm an increase in cough frequency and cough receptor sensitivity associated with hypobaric hypoxia, and refute the hypothesis that high altitude cough is due to the inhalation of cold, dry air. The small sample size makes further conclusions difficult, and the cause of altitude-related cough remains unclear.

Adult↗