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PubMed2002

Cough provocation tests: their clinical value.

Cough provocation testing was originally developed for testing new anti-tussive agents and still remains a mandatory tool in their development. The methodology has been developed into single breath and multiple breath techniques. Neither has been fully validated; however, single breath techniques have been used in a number of patient series of more than 100 patients. These studies show that the cough reflex is more sensitive in patients with cough and becomes normal on recovery. Studies in the common cold and in angiotensin converting enzyme inhibitor-associated cough suggest that this may be cause and effect. These results point to a utility for cough provocation testing in epidemiology but not in routine clinical practice. The one exception in clinical practice is in the assessment of patient post stroke where it is a better method, than voluntary cough testing, for assessing damage to the cough reflex. Other than use in epidemiology it remains an invaluable tool in hypothesis testing.

Cough↗

PubMed2005

Intravenous lidocaine 0.5 mg.kg-1 effectively suppresses fentanyl-induced cough.

PURPOSE: To evaluate the minimal dose of lidocaine required for suppression of fentanyl-induced cough. METHODS: 320 ASA I and II patients, non-smokers of both sexes scheduled for elective surgery between the ages of 18 to 60 yr were randomly allocated into four equal groups. The patients were assigned to receive lidocaine 0.5 mg.kg(-1) (Group I), 1.0 mg.kg(-1)(Group II), 1.5 mg.kg(-1) (Group III) or placebo (Group IV) over five seconds, one minute prior to the administration of fentanyl 3 microg.kg(-1) in a randomized and double-blind fashion. Any episode of cough was classified as coughing and graded as mild (1-2) moderate (3-4) or severe (5 or more). The data were analyzed by test of proportion. RESULTS: Eleven, 12, 11 and 28 patients (13.75%, 15%, 13.75% and 35%) had cough in Groups I, II, III and IV respectively (P < 0.05 Groups I, II, III vs IV). There was no significant difference in the incidence and severity of cough among the lidocaine pretreated groups (P > 0.05). CONCLUSION: The results of our study suggest that iv lidocaine 0.5 mg.kg(-1) is the minimal dose required to suppress fentanyl-induced cough when administered one minute prior to fentanyl. Any further increase in the lidocaine dose does not reduce the incidence or severity of fentanyl-induced cough.

Adolescent↗

PubMed2002

The association of gastroesophageal reflux disease with asthma and chronic cough in the adult.

Gastroesophageal reflux disease (GERD) is a common condition which is particularly prevalent in patients with asthma and chronic cough. Physiologic changes caused by asthma and chronic cough promote acid reflux. GERD is also considered by many investigators as a factor contributing to airway inflammation. An etiological relationship between GERD and asthma/chronic cough and vice versa has been supported by a large number of experimental and clinical findings and refuted by others. Although further controlled studies are needed to clarify this relationship, GERD and asthma/chronic cough appear to be linked to each other. The association of GERD with asthma and chronic cough involves nerve reflexes, cytokines, inflammatory and neuroendocrine cells and, in some patients, tracheal aspiration of refluxing gastric fluids. GERD may present with typical symptoms but can also be asymptomatic. Sensitive methods for diagnosing GERD are available, which include esophageal pH monitoring, acid provocative tests, modified barium swallow and endoscopy. Consideration of the association of GERD with asthma and chronic cough is of practical value in the management of chronic cough or asthma resistant to treatment. Treatment of GERD in patients with asthma has been consistently shown to improve respiratory symptoms but not necessarily pulmonary function tests. Surgical treatment can be a useful and cost-effective approach in selected patients with asthma and GERD.

Adolescent↗

PubMedDate not supplied

The influence of gastroesophageal reflux disease and its treatment on asthmatic cough.

Gastroesophageal reflux is known to cause chronic cough and is also implicated in worsening of asthma. We conducted a prospective study to examine the clinical significance of gastroesophageal reflux disease (GERD) in asthmatic patients with chronic cough to analyze the temporal relationship between reflux events and coughing and to assess the effect of esomeprazole treatment on respiratory symptoms and lung function in these patients. Asthmatic patients (126) with chronic dry cough were studied. Diagnosis of GERD was based on typical symptoms and the effectiveness of therapeutic test or on pH monitoring. Patients without GERD (negative pH results) consisted of the control group. The results of pH monitoring showed that 64% of cough episodes were related to acid reflux and in 91% of reflux events preceded coughing. Esomeprazole treatment (40 mg/day for 3 months) not only diminished GERD symptoms but also improved asthma outcome Baseline FEV(1) and PEF values increased significantly together with a decrease in symptom scores and the use of rescue medication. In most patients included in the extended part of the study for another 3 months, the dose of inhaled steroids could be reduced with sustained GERD therapy. Our data showing that reflux events preceded coughing in most cases and that treatment of GERD resulted in an improvement in different outcome measures of asthma suggest that GERD worsens asthma, and its treatment is of clinical importance to effectively manage these patients.

Adult↗

PubMed2002

Preoperative symptom evaluation and esophageal acid infusion predict response to laparoscopic Nissen fundoplication in gastroesophageal reflux patients who present with cough.

BACKGROUND: Most patients with cough and gastroesophageal reflux disease (GERD) improve on medical treatment with proton pump inhibitors (PPI). Nonresponders may be considered for antireflux surgery, but the selection of patients is difficult. METHODS: We have performed laparoscopic Nissen fundoplications (LNF) in 677 patients. Of these patients, 81% have undergone 6-month follow-up assessment with 24-h pH testing, esophageal manometry, symptom scores, and quality-of-life scores. RESULTS: LNF controlled heartburn in 93% and improved cough in 81%. Stepwise multiple regression showed that the preoperative cough score (r = 0.620, p <0.0001) and change in cough on and off PPI (r = 0.296, p = 0.0002) predicted improvement after surgery. A positive result on a randomized acid infusion test was associated with a greater improvement in cough after surgery (p = 0.0243). CONCLUSION: An acid infusion test and assessment of cough on and off PPI may be useful preoperative tools for the selection of patients with cough for LNF.

Cough↗

PubMed1993

The cough test is superior to the Valsalva maneuver in the delineation of right-to-left shunting through a patent foramen ovale during contrast transesophageal echocardiography.

A patent foramen ovale may result in paradoxical embolization and serious morbidity. Thus a sensitive method to diagnose a patent foramen ovale is important. It is unknown whether the cough test or the Valsalva maneuver is superior in delineating right-to-left shunting through a patent foramen ovale during contrast transesophageal echocardiography. Thus we studied 73 consecutive patients (53 men and 20 women), aged 54 +/- 16 years (range 18 to 79 years), during elective transesophageal echocardiography. Contrast transesophageal echocardiography was performed from a four-chamber view during quiet respirations, Valsalva maneuver, and cough test. In the entire group the incidence of a patent foramen ovale was higher during the cough test (32/73) as compared with the Valsalva maneuver (24/73, p < 0.025) and quiet respirations (18/73, p < 0.005). All subjects with a patent foramen ovale during the Valsalva maneuver had a positive contrast transesophageal echocardiogram during the cough test. In subjects (n = 55) without a patent foramen ovale during quiet respirations, the incidence of a patent foramen ovale was higher during the cough test (15/55) as compared with the Valsalva maneuver (9/55, p < 0.05). In a subgroup (N = 17) of patients with nonhemorrhagic stroke (n = 11), transient ischemic attack (n = 2), or peripheral embolus (n = 4), the cough test had a higher yield (9/17) in delineating a patent foramen ovale as compared with the Valsalva maneuver (7/17) but did not reach statistical significance. These data demonstrate that the cough test is superior to the Valsalva maneuver in delineating a patent foramen ovale during contrast transesophageal echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

Antitussive effect of moguisteine on the enhanced coughing associated with enalapril in guinea-pig.

The effect of moguisteine, a novel peripherally acting non-narcotic antitussive drug, on coughs associated with enalapril was examined in guinea-pigs. Chronic treatment with enalapril markedly enhanced the number of capsaicin-induced coughs. Moguisteine dose-dependently suppressed the number of coughs at doses between 3-30 mg/kg p.o., in both vehicle-treated and enalapril-treated animals. There was no significant difference in the antitussive ED50 (95% confidence limit) value of moguisteine between vehicle-treated (16.4 (13.7-19.7) mg/kg) and enalapril-treated (13.7 (3.9-47.6) mg/kg) animals. On the other hand, dihydrocodeine also dose-dependently suppressed the number of coughs in the same dose range as moguisteine in both vehicle-treated and enalapril-treated animals. There was no significant difference in the antitussive ED50 (95% confidence limit) of dihydrocodeine between vehicle-treated (11.7 (4.9-28.3) mg/kg) and enalapril-treated (11.2 (9.4-13.3) mg/kg) animals. Furthermore, the antitussive effect of moguisteine was identical to that of dihydrocodeine in both vehicle-treated and enalapril-treated animals. On the other hand, while chronic co-treatment with moguisteine significantly reduced the number of enhanced coughs associated with enalapril, chronic co-treatment with dihydrocodeine had no significant effect on the number of enhanced coughs associated with enalapril treatment. These results suggest that moguisteine may have a therapeutical benefit in reducing the coughing associated with treatment with inhibitors of angiotensin-converting enzyme.

Animals↗

PubMed2006

Involvement of ionotropic purinergic receptors in the histamine-induced enhancement of the cough reflex sensitivity in guinea pigs.

We examined the effect of inhaled histamine on citric acid-induced coughs and clarified the role of ionotropic purinergic receptors in the resulting changes. Although the inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to histamine, at concentrations of 0.3 to 1 mM, for 2 min concentration dependently increased the number of citric acid-induced coughs. This histamine-induced increase in the number of citric acid-induced coughs was dose dependently and significantly reduced when animals were pretreated with fexofenadine, a histamine H1 receptor antagonist. The histamine-induced increase in the number of citric acid-induced coughs was completely reduced when animals were co-pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP, 50 microM), a P2X receptor antagonist, and reactive blue 2, a P2Y receptor antagonist, for 2 min. Furthermore, the ATP-induced increase in the number of citric acid-induced coughs was dose dependently and significantly decreased when animals were pretreated with fexofenadine, at doses of 0.3, 1 and 3 mg/kg, p.o. These results suggest that histamine enhances the excitability of rapidly adapting receptors to tussive stimuli via modulation of ATP release in the airways. Furthermore, ATP might act not only on P2X receptors to directly activate rapidly adapting receptors, but also on P2Y receptors to increase histamine release, indirectly increasing the cough reflex sensitivity.

Adenosine Triphosphate↗

PubMed2004

Potential new cough therapies.

Cough is among the most common complaints for which patients seek medical attention. Consequently, enormous expenditures are made worldwide on prescription and non-prescription cough remedies. Multiple prospective studies have shown that specific antitussive therapy aimed at the underlying aetiology of cough is highly successful. The greatest current need therefore is for more effective nonspecific antitussive therapy, whose purpose is to suppress the cough reflex and provide symptomatic relief regardless of the underlying mechanism. Such therapy is particularly required for prolonged cough following upper respiratory tract infection, cough whose underlying aetiology is not easily treated, and idiopathic cough. Many areas of inquiry are currently ongoing that may lead to the development of novel and effective antitussive drugs.

Antitussive Agents↗

PubMed2006

Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.

Effects of the selective phosphodiesterase 3 (PDE3) inhibitor olprinone and the selective PDE4 inhibitor SB207499 were investigated on antigen-induced increase of cough reflex sensitivity and normal cough response to capsaicin in guinea pigs. Number of coughs elicited by inhalation of capsaicin (10(-8), 10(-6) and 10(-4)M) was counted 24h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10mg/kg) or SB207499 (1 or 10mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1h before the capsaicin provocation. SB207499, but not olprinone, significantly reduced both antigen-induced increase of cough response to inhaled capsaicin in sensitized animals and normal cough response in non-sensitized animals. SB207499, but not olprinone, also reduced the antigen-induced BAL eosinophilia. PDE4 inhibitors may be useful in treating cough associated with airway allergy via inhibiting both allergic airway inflammation and the common pathway of cough reflex.

Allergens↗

PubMed2006

Air pollutants and cough.

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze. Others, like irritant gases, appear to increase wheeze more than cough. For ETS, exposure during childhood is associated with cough and wheeze in adulthood, suggesting that the pollutant permanently alters some important aspect of the lungs, immune system or nervous system. We have shown in animal studies that pollutants change the neural control of airways and cough. Second hand smoke (SHS) exposure lengthened stimulated apnoea, increased the number of stimulated coughs, and augmented the degree of stimulated bronchoconstriction. The mechanisms included enhanced reactivity of the peripheral sensory neurones and second-order neurones in the nucleus tractus solitarius (NTS). NTS effects were due to a substance P mechanism at least in part. Ozone and allergen increased the intrinsic excitability of second-order neurones in the NTS. The animal studies suggest that the cough and wheeze experienced by humans exposed to pollutants may involve plasticity in the nervous system.

Adult↗

PubMed2006

Investigations in subjects with cough following upper respiratory tract infection.

The study aimed to investigate subjects with cough following acute upper respiratory tract infection (URTI), and to compare those subjects unable to suppress cough ("non-suppressors") with those who were able to suppress cough ("suppressors"). Forty-three URTI subjects participated, 31 with cough associated with acute URTI and 12 healthy controls; 21 of the coughing subjects were "suppressors", 10 were "non-suppressors". We obtained responses to chemical and mechanical stimulation of the nasal cavity or the pharynx using both psychophysical measures and event-related potentials. The study provided the following results: (1) "non-suppressors" did not exhibit significantly different intensity ratings or event-related potentials in comparison to "suppressors" in terms of responses to intranasal irritant, mechanical, or olfactory stimuli; (2) when pharyngeal mechanical stimuli were investigated "suppressors" rated the stimuli as more intense than "non-suppressors" and controls; (3) latencies of event-related potentials to pharyngeal stimuli were longest in "non-suppressors". Keeping in mind the relatively small sample size, it appears possible to differentiate certain types of cough during uncomplicated URTI. This may help to explain interindividual differences in responsiveness to cough medication.

Adolescent↗

PubMed2005

Mast cells in citric acid-induced cough of guinea pigs.

It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H(1) receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C(4), while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC(4) or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine.

Aerosols↗

PubMed2000

Psychological confounds in medical research: the example of excessive cough in asthma.

This experiment tested the hypothesis that the setting in which research is conducted may dominate symptom magnitude. Cough was induced with inhaled citric acid and its magnitude was influenced by changing the setting in 30 adolescents with asthma. Cough thresholds for citric acid were determined. The participants were assigned to a condition emphasising asthma, or a control condition, described as estimation of lemon flavors. All participants inhaled (in different order) thresholds for citric acid, 50% of these thresholds, or placebo. Results showed that both cough frequency and subjective 'cough tendency' were significantly higher in the asthma condition. State anxiety was higher in the asthma condition, but correlated only moderately with cough. Lung function, severity of asthma, trait anxiety, age or sex did not correlate with cough. It was concluded that patients with asthma cough more often in a situation which they have learned to associate with asthma.

Adolescent↗

PubMed1990

History of whooping cough in nonvaccinated Swedish children, related to serum antibodies to pertussis toxin and filamentous hemagglutinin.

The aim of this study was to examine whether there is a correlation between parental information on the child's history of whooping cough and the presence or absence of serum antibodies against two antigens of Bordetella pertussis, pertussis toxin and filamentous hemagglutinin, in nonvaccinated Swedish children. The parents of 266 Swedish children aged 1 to 4 years answered a questionnaire regarding the child's history of whooping cough, and a serum sample was obtained from the child for determination of IgG, IgM, and IgA antibodies to pertussis toxin and filamentous hemagglutinin. The study was performed from 1984 to 1986, five to seven years after the cessation of general vaccination against pertussis in Sweden; none of the children had received pertussis vaccine. Antibodies to both toxin and filamentous hemagglutinin increased with age. Of the children aged 4 years, 50% had antibodies to both antigens. Of all 266 children, 100 had antibodies to both antigens, 6 to toxin alone, and 49 to filamentous hemagglutinin alone. There was a good correlation between the presence of antibodies and a history of whooping cough. Of 91 children with a history of whooping cough, 77 had antibodies against both antigens and 13 against one antigen; only one child lacked detectable antibodies against both antigens. Of the 175 children with no history of whooping cough, 110 lacked detectable antibodies to both antigens, 23 had antibodies to both, 2 to toxin alone, and 40 to filamentous hemagglutinin alone. The data indicate that parental information on a previous history of whooping cough in their nonimmunized child is reliable, and that many infections with B. pertussis are subclinical or atypical. Exposure to other Bordetella species than B. pertussis, which is the only toxin-producing species, might be important for the development of FHA antibodies. A follow-up 2 to 4 years after the collection of serum samples of children without a history of whooping cough but with antibodies to one or both antigens indicated that serum antibodies to toxin, but not to filamentous hemagglutinin, may be protective against disease.

Age Factors↗

PubMed2004

[Mechanisms of chronic cough pathophysiology].

INTRODUCTION: In some situations such as post-virus or post whooping cough, a non productive subacute cough may occur without apparent local inflammation, epithelium abnormalities or bronchoconstriction. This subacute or chronic cough represents a real syndrome (cough disease) due to the central nervous system (CNS) and its ortho and parasympathic outputs. At the CNS level, functional disturbancies and neosynaptogenesis can be described, with the intervention of the NMDA-type glutamatergic receptors. STATE OF ART: The neurons located in the expiratory area of the breathing center (Pre-Boetzinger complex of the lower brainstem) present exagerated responses to stimuli, due to the repetitive stimulation of the NMDA receptors; this phenomenon is similar to long-term-potentiation (LTP), the molecular basis of learning, memory and neosynaptogenesis. The cough reflex is thus amplified and rapidly chronic and would justify any pharmacological intervention at the NMDA-receptors level. PERSPECTIVES: More recently 5TH4 receptors have been implied in the control of respiration; an overexpression of these receptors in the Pre-Boetzinger area could contribute to an increase of the cough reflex. CONCLUSION: The present review aims at summarizing the main rationale target to pharmacologically block the chronic cough.

Antitussive Agents↗

PubMed2001

[Chronic cough, asthma and allergy].

The medical approach of chronic cough suffers from the lack of a standardised definition. The most frequently encountered criterion is a recurrent cough observed during several consecutive months, each episode lasting at least 1 week. The link between recurrent cough and asthma is still discussed. Cough-related asthma diagnosis is facilitated when wheezing is clearly confirmed, or may be reminded by a nonproductive middle night cough, or an exercise-triggered cough, or the presence of personal or familial atopy. Conversely, an early morning and productive cough associated with tobacco exposure do not suggest asthma.

Asthma↗

PubMed1991

Veratrine-induced reflexes and cough.

With cats anaesthetized with sodium pentobarbital we studied how veratrine-induced reflexes interact with cough. Cough was elicited by mechanical stimulation of tracheobronchial mucosa and its intensity was evaluated from the changes in oesophageal pressure. Veratrine injected intravenously produced apnoea, bradycardia and long-lasting hypotension. With each dose the intensity of cough was significantly decreased during the apnoea. When the mechanical stimulus was repeated during the breathing following apnoea with remaining hypotension, cough intensity parameters were not changed from control. Veratrine injected intracardially caused bradycardia, hypotension, and decreases in respiratory rate and tidal volume. The intensity of cough elicited just after injection of veratrine was also significantly decreased. We suggest that veratrine-induced reflexes depress the cough reflex mainly by inhibitory reflexes arising from cardiac receptors. The inhibition of cough is probably mediated indirectly via the inhibition of medullary respiratory neurons.

Animals↗