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PubMed2006

TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs.

We examined the molecular pharmacology and in vivo effects of a TRPV1 receptor antagonist, N-(4-Tertiarybutylphenyl)-4(3-cholorphyridin-2-yl)-tetrahydro-pyrazine1(2H) - carboxamide (BCTC) on the guinea pig TRPV1 cation channel. BCTC antagonized capsaicin-induced activation and PMA-mediated activation of guinea pig TRPV1 with IC50 values of 12.2 +/- 5.2 nM, and 0.85 +/- 0.10 nM, respectively. In addition, BCTC (100 nM) completely blocked the ability of heterologously expressed gpTRPV1 to respond to decreases in pH. Thus, BCTC is able to block polymodal activation of gpTRPV1. Furthermore, in nodose ganglia cells, capsaicin induced Ca2+ influx through TRPV1 channel was inhibited via BCTC in a concentration dependent manner. In in vivo studies capsaicin (10 - 300 muM) delivered by aerosol to the pulmonary system of non-sensitized guinea pigs produced an increase in cough frequency. In these studies, the tussigenic effects of capsaicin (300 muM) were blocked in a dose dependent fashion when BCTC (0.01-3.0 mg/kg, i.p.) was administered 30 minutes before challenge. The high dose of BCTC (3.0 mg/kg, i.p) produced a maximum inhibition of capsaicin-induced cough of 65%. We also studied the effects of BCTC (0.03 and 3.0) when administered 60 minutes before capsaicin. Under these conditions, BCTC (3.0 mg/kg, i.p) produced a maximum decrease in capsaicin-induced cough of 31%. In ovalbumin passively sensitized guinea pigs, we found that BCTC (1 and 3 mg/kg, i.p.) attenuated antigen ovalbumin (0.3%) cough responses by 27% and 60%, respectively. We conclude that TRPV1 channel activation may play role in cough mediated by antigen in sensitized guinea pigs. Our results supports increasing evidence that TRPV1 may play a role in the generation of the cough response.

Journal Article↗
PubMed1986

[Effects of naloxone on the cough depressant activities of antitussive drugs].

Effects of naloxone on the cough depressant action of antitussive drugs were investigated in pentobarbital anesthetized male and female cats. 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. An i.v. administration of morphine (1 mg/kg) significantly inhibited the cough reflex for at least 60 min. The antitussive effect of morphine was antagonized by naloxone (400 micrograms/kg). The inhibitory effect of morphine on the respiratory frequency was also antagonized by naloxone. The cough reflex was significantly inhibited by fominoben (5 mg/kg, i.v.) and dextromethorphan (3 mg/kg, i.v.). However, the respiratory frequency was increased by these two drugs. An i.v. administration of naloxone prevented the antitussive effects and the excitatory effects in respiratory frequency of fominoben and dextromethorphan. The present study suggests that the cough depressant actions of antitussive drugs may be mediated by endogenous opiates and/or by neurotransmitters which are modified by endogenous opiates.

Animals↗
PubMed1987

GABA-ergic mechanisms in the central control of cough.

The antitussive activity of gabalinoleamide (Gabalid U CB) was studied in 40 non-anaesthetized cats. The antitussive action of the substance was compared to that of codeine (Codein Spofa). Cough was induced by mechanical stimulation using a chronic tracheal cannula. Single cough parameters were evaluated from changes in the side tracheal pressure. When gabalinoleamide was administered in a dose of 100 mg/kg b.w. intramuscularly all the studied parameters of cough showed a statistically significant decrease, only the intensity of maximum cough effort remained unaffected. Gabalinoleamide administered in the same dose induced a statistically significant decrease of respiratory frequency and breathing amplitude, and prolonged the cycle of breathing by delaying the expiratory phase. Higher doses (200 and 300 mg/kg b.w.) did not have an increased cough suppressing effect. The quality and quantity of cough parameters were similar after codeine and gabalinoleamide.

Animals↗
PubMed2001

[Etiology of chronic cough in children: analysis of 100 cases].

In order to understand the epidemiological aspects of chronic cough, we analysed 100 patients' files referred for chronic cough in five pediatric-pulmonology consultations. The patients had a chronic cough for more than 3 weeks. The distribution of causes was: asthma, 56%; upper airway disorders, 16%; psychogenic, 4%; whooping cough, 4%; Mycoplasma pneumoniae pulmonary infection, 3%; Chlamydia pneumoniae pulmonary infection, 1%; bronchiectasis, 1%. In 15% of cases two or more causes were associated; In most cases, the clinical characteristics of the cough are evident enough to establish a diagnosis with few secondary explorations. The prognosis is on the whole favourable.

Adolescent↗
PubMed1999

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children.

Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.

Antibodies, Bacterial↗
PubMed1986

Long term respiratory sequelae of whooping cough in a nationally representative sample.

The long term respiratory consequences of whooping cough in childhood were sought among members of the National Survey of Health and Development. Peak expiratory flow rate was measured when the survey members were 36 years old and seven respiratory symptoms were reported at the same time. Peak expiratory flow rate was slightly reduced in those who had had whooping cough as a child, and this difference became non-significant when other factors were taken into account. Unexpectedly, chronic cough was significantly less likely to be reported by those who had had whooping cough, and this difference remained significant only among men after other factors had been taken into account. This study failed to show a long term detrimental effect of whooping cough on the respiratory system.

Adult↗
PubMed1954

Differential diagnosis and management of cough.

Cough is a complex defensive reflex whose purpose is protection of the respiratory tract. There are many nonrespiratory causes, particularly pulmonary congestion from heart disease. Coughs may be useful, useless, or harmful. Treatment based on etiology and type of cough requires only a few medications whose efficiency has been demonstrated. The meaning of cough as a symptom must be carefully determined before rational treatment can be planned. Recent researches on the physiology of the cough reflex, the bronchi, and the mechanisms of bronchial secretion have made it possible for a physician to plan a treatment program on a firm, scientific basis, rather than on tradition.

Bronchi↗
PubMed2006

[Whooping cough--an increasing problem in Norway].

BACKGROUND: The incidence of whooping cough has increased in recent years in Norway, especially amongst older children and adults; in 2004 it was 168/100,000. MATERIAL AND METHODS: This article is based on our own experience and a review of available literature, identified on Medline with the search word "pertussis". RESULTS AND INTERPRETATION: Whooping cough, a disease caused by the bacterium Bordetella pertussis, is transmitted via respiratory droplets. Sources of infection for infants are often their parents and siblings. Older children and adolescents contract whooping cough mostly in school, whereas adults usually get the disease from children or colleagues. The typical symptoms are bouts of violent coughing with the classic whoop and post-tussive vomiting. A milder clinical picture can be seen in vaccinated persons, reinfected patients, and in persons above the age of 15. Infants are most at risk of developing serious disease and have the highest numbers of hospitalizations, complications and mortality. But complications are also seen in adolescents and adults, including urinary incontinence, rib fractures and pneumonia. The diagnosis is made by culture or PCR in nasopharyngeal secretions, as well as by detection of antibodies to B. pertussis in serum. If treatment is indicated, macrolides are the drugs of choice; these shorten the duration of symptoms and the period of contagiousness if given in the early stages of the disease. To help combat whooping cough in Norway, from 2006 an extra vaccine booster dose will be given to children at the age of seven.

Adolescent↗
PubMed1995

Pertussis infection in adults with persistent cough.

OBJECTIVE: To determine the prevalence of Bordetella pertussis infection in adult patients with persistent cough. DESIGN: Prospective case series. SETTING: Urban university hospital emergency department. PATIENTS: Convenience sample of 75 patients aged 18 years or older with a cough lasting 2 weeks or longer. Serum specimens from 67 patients without respiratory complaints were used to develop reference values. INTERVENTIONS: In patients with cough, nasopharyngeal culture and direct fluorescent antibody testing for B pertussis were performed and serum samples were obtained at the first visit and 1 month later. Serum specimens were assayed for antibody to pertussis toxin (PT) and filamentous hemagglutinin (FHA). MAIN OUTCOME MEASURES: A subject with one or more of the following was defined as having a pertussis infection: a positive B pertussis culture result, a four-fold change in PT or FHA titer, and/or a single PT or FHA titer at least 2 SDs greater than the geometric mean of the control group. RESULTS: No subject tested culture positive for B pertussis. Sixteen (21%) (95% confidence interval [CI], 13% to 32%) of 75 subjects met the serologic criteria for pertussis infection; for 13 (81%; 95% CI, 54% to 96%) of the 16, the criteria were met by the initial serum specimen. In contrast, the geometric mean levels of antibody to PT and FHA for the remaining 59 subjects with cough did not differ from those of the control group. Clinical symptoms and the lymphocyte count did not differentiate patients with pertussis from those without the disease. CONCLUSION: Pertussis is a common cause of persistent cough in adults and should be considered in the differential diagnosis. Clinical symptoms, pertussis culture, direct fluorescent antibody testing, and lymphocytosis are of limited value in making the diagnosis.

Adult↗
PubMed1999

Urethral pressure response to cough and voluntary perineal contraction in men without previous pelvic surgery.

The aim of this study was to analyze the urethral pressure responses to cough in men to better characterize the neurogenic mechanisms of male urethral function. A prospective study was carried out on 41 men referred for urodynamic assessment. Urethral pressure profiles at rest and during coughing, and urethral pressure response to voluntary perineal contraction were recorded and analyzed in relation to the neurological status of the patients. Voluntary perineal contraction resulted in a urethral pressure increase (delta pU) of approximately 150 cm H2O in neurologically normal patients. Delta pU could be reduced to any degree in patients with either central or peripheral neurological lesions. Urethral pressure response to cough could be easily classified into two main patterns. Pattern I was characterized by a marked increase in urethral closure pressure during the cough (ratio of urethral to rectal pressure increase: 248 +/- 106%), occurring at the distal part of the posterior urethra. All the neurologically normal patients and the majority of those with upper motoneuron lesions had a pattern I response. Pattern II was defined by the absence of any significant increase in urethral closure pressure at any site of the posterior urethra and was observed in 80% of the patients with signs of lower motoneuron lesions. The pattern of the response to cough was significantly related to the neurological status of the patients (P < 0.001). It was dissociated from the response to voluntary contraction, as would be expected for a reflex versus a voluntary response in neurological patients.

Adult↗
PubMed2000

Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis.

The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2.5 mg qd) or placebo. Following the measurement of baseline clearance, patients were given a 7-day course of either rhDNase or placebo. The patient then returned on the seventh day for follow-up clearance measurements. This was followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucociliary clearance was initially measured for a period of 60 min (IC). This was followed by cough clearance (CC) measurements for 30 min, during which patients were requested to cough a total of 120 times. Post-cough clearance (PCC) was then measured for a further 60 min. Thirteen patients completed the study. Patients' age ranged between 18-38 years, and they had baseline values of FEV(1) of 27-103% of predicted values. Following completion of the course of rhDNase, there was a mean percent increase from baseline of 7.5% for FEV(1) and 5.4% for FVC% (P = 0. 03). There was a small, nonsignificant increase in IC (6.2 +/- 3.6%) on the rhDNase arm compared with the placebo arm (-2.3 +/- 2.9%), P = 0.1. No changes were seen in either CC (1.0 +/- 3.2% [rhDNase] vs. 1.9 +/- 2.4% [placebo], P = 0.9) or PCC (-0.7 +/- 1.5% [rhDNase] vs. 0.9 +/- 1.7% [placebo], P = 0.3). Patients who achieved a 10% or greater improvement in FEV(1) (n = 5) in response to rhDNase did not show any greater change in clearance than nonresponders. In conclusion, we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase. The mechanism of action of this drug in vivo remains uncertain.

Administration, Inhalation↗
PubMed2004

Inhaled anti-cholinergics for prolonged non-specific cough in children.

BACKGROUND: Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including inhaled anti-cholinergic medications. OBJECTIVES: To determine the efficacy of inhaled anti-cholinergic medications in the management of prolonged non-specific cough in children. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register and Cochrane Airways Group, MEDLINE and EMBASE databases were searched. Relevant pharmaceutical companies were contacted. The latest searches were performed in July 2003. SELECTION CRITERIA: All randomised controlled trials comparing inhaled anti-cholinergic medication with a placebo medication. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data were available for analysis. A single small trial in adults has been reported. MAIN RESULTS: No randomised-controlled trials that examined the efficacy of inhaled anti-cholinergic medications in the management of prolonged non-specific cough in children were found. REVIEWER'S CONCLUSIONS: There is currently no evidence to support the use of inhaled anti-cholinergics for symptomatic control of non-specific cough in children. Further research examining the effects of this intervention is needed.

Administration, Inhalation↗
PubMed2004

Inhaled cromones for prolonged non-specific cough in children.

BACKGROUND: Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including inhaled cromones. OBJECTIVES: To determine the efficacy of inhaled cromones in the management of prolonged non-specific cough in children. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases were searched. Australian representative of the relevant pharmaceutical company was contacted. The latest searches were performed in October 2003. SELECTION CRITERIA: All randomised controlled trials comparing inhaled cromones with a placebo medication. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. No eligible trials were identified and thus no data were available for analysis. One single arm open trial in children and one small randomised controlled trial in adults were reported. MAIN RESULTS: No randomised-controlled trials that examined the efficacy of inhaled cromones in the management of prolonged non-specific cough in children were found. In the non randomised trials above, a significant effect was seen within two weeks of therapy. REVIEWERS' CONCLUSIONS: There is currently an absence of evidence to support the routine use of inhaled cromones for symptomatic control of non-specific cough in children. Further research examining the effects of this intervention is needed.

Administration, Inhalation↗
PubMed2006

Indoor air modification interventions for prolonged non-specific cough in children.

BACKGROUND: Non-specific cough has been defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology and is common in childhood. These children are treated with a variety of therapies, including non-pharmacological treatments. There is a wide variety and a growing market for these non-pharmacological treatments that include air-modification modalities. OBJECTIVES: To determine the efficacy of air-modification modalities, (ionisers, vaporisers, humidifiers, air filters, regular vacuuming), in treating children with non-specific cough. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, OLDMEDLINE and EMBASE databases were searched by the Cochrane Airways Group. The latest searches were performed in November 2005. SELECTION CRITERIA: All randomised controlled trials comparing air-modification modalities with a placebo treatment, for any duration. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Five papers were considered for inclusion but no eligible trials were identified and thus no data was available for analysis. MAIN RESULTS: No randomised controlled trials that examined the efficacy of air-modification modalities in the management of prolonged, non-specific cough in children were found. AUTHORS' CONCLUSIONS: Based on the evidence currently available, a recommendation can not be given for air-modification interventions in the treatment of prolonged, non-specific cough in children.

Air Pollution, Indoor↗
PubMed1989

The positive association of cough with angiotensin-converting enzyme inhibitors.

Captopril, enalapril, lisinopril, ramipril, cilazipril, and quinipril have all been documented to induce cough with an estimated frequency of at least 15% of treated patients. Common descriptors include tickling, dry, nonproductive, and persistent. Onset usually occurs during the first week of therapy and lasts as long as the drug is taken, remitting within a few days after the agent is discontinued. Alternative angiotensin-converting enzyme (ACE) inhibitors replicate the cough. The mechanism seems related to stimulation of lung afferent C fibers, perhaps by prostaglandin E2. It may also be related to decreased breakdown of substance P, the neurochemical mediator of the cough reflex released in response to stimulation of C fibers and metabolized by ACE. The possible role of prostaglandins is supported by two anecdotal reports of cough disappearing in patients receiving nonsteroidal antiinflammatory agents. Future trials should recognize cough as a side effect of ACE inhibitor therapy, and prospective determination of its true frequency and cross-occurrence are necessary.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man.

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.

Administration, Inhalation↗
PubMed2002

Diagnosis and treatment of chronic cough due to gastro-esophageal reflux disease and postnasal drip syndrome.

Gastro-esophageal reflux disease (GERD) and postnasal drip syndrome (PNDS) are common causes of chronic cough. In patients with normal chest radiographs, GERD most likely causes cough by an esophageal-bronchial reflex. When GERD causes cough, there may be no gastrointestinal symptoms up to 75% of the time. While 24-h esophageal pH monitoring is the most sensitive and specific test in linking GERD and cough in a cause and effect relationship, it has its limitations. There is no general agreement on how to best interpret the test and it cannot detect non-acid reflux events. While some patients improve with minimal medical therapy, others require intensive regimens. Surgery may be efficacious when intensive medical therapy has failed. Because there are no pathognomonic findings of PNDS, the diagnosis is inferential and is based upon a combination of clinical findings, the results of ancillary testing, and the response to specific therapy. Specific therapy depends upon the rhinosinus disease(s) causing the PND. A common error in managing PNDSs is to assume that all H(1)-antagonists are equally efficacious. The second-generation, relatively non-sedating H(1)-antagonists have been found to be less effective than the first-generation agents in treating cough due to non-histamine-mediated PNDSs.

Antigens, Helminth↗
PubMed2002

Central nervous mechanisms of cough.

Cough is an airway defensive reflex substantially consisting in a modified respiratory act. Transection experiments have shown that the fundamental structures responsible for this reflex are located within the medulla oblongata. Electrical stimulation applied to the medulla failed to provide convincing evidence of a cough centre distinct from the brainstem respiratory network. In fact, electrical stimuli affect not only neuronal somata, but also intramedullary cough-related pathways. Studies on the behaviour of medullary respiratory neurones have led to the conclusion that the same respiratory neurones involved in the generation of the eupnoeic pattern of breathing also participate in the production of the cough motor pattern. These findings support the existence of multifunctional neural networks in the mammal brainstem. Bötzinger complex expiratory neurones with augmenting discharge patterns have been suggested to convey an excitatory drive to the expiratory bulbospinal neurones of the caudal ventral respiratory group and, hence, to expiratory motoneurones. The excitatory drive to caudal medullary expiratory neurones is mediated by ionotropic glutamate receptors. Recent lines of evidence indicate that the Bötzinger complex and the caudal ventral respiratory group have a crucial role in determining both the inspiratory and the expiratory components of the cough motor pattern.

Animals↗