Cough Challenge Research Articles

Does inhaling menthol affect nasal patency or cough?

There is widespread use of menthol in over-the-counter medications, despite scant information on any beneficial effects. Our aim was to assess the effect of menthol on nasal air flow, perception of nasal patency and cough challenge testing. Subjects comprised 42 healthy children aged 10 and 11 in a school setting. We used a single-blind pseudo-randomized cross-over trial to compare the effect of an inhalation of either menthol or placebo(eucalyptus oil). Baseline and post-intervention measurements were made on each of 2 consecutive days. Main outcome measures were (i) nasal expiratory and inspiratory flows and volumes, measured by spirometer, (ii) perception of nasal patency, assessed with a visual analogue scale (VAS), and (iii) the number of coughs in response to nebulized citric acid. There was no effect of menthol on any of the spirometric measurements. Following menthol, there was a significant increase in the perception of nasal patency (mean difference in log VAS (menthol-placebo) = -0.207, 95%CI -0.329, -0.085). The cough count after menthol inhalation was reduced when compared to baseline but the change was not different from that after placebo (mean difference in cough count (menthol-placebo) = -1.71, 95%CI -4.11, 0.69). Menthol has no effect on objective measures of flow but significantly increases the perception of nasal patency. It may not be possible to extrapolate these findings to younger children and those with rhinitis. Extending the study of menthol to these groups, including investigations of the efficacy and safety profiles, will provide further valuable evidence for its common use.

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

Dextromethorphan is widely used as a cough suppressant in over the counter medications. Its efficacy in altering cough reflex sensitivity has been shown in healthy volunteers. In contrast evidence for an effect on clinically important cough is poor. A significant decrease in evoked cough was seen with dextromethorphan compared with placebo. However, both placebo and active treatment improved subjective data to a similar degree. We doubt the validity of currently used objective tests in the investigation of antitussives. Using an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo. The study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml(-1) dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose-response cough challenge. Dextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked 'placebo' effect. The objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences.

Simultaneous versus video counting of coughs in hypertonic cough challenges

BackgroundThe coughs occurring during cough provocation tests are usually counted at the same time when the test is being conducted, i.e., simultaneously. It is unknown whether cough counting from video recording might increase the accuracy of the cough counting. During recent years, cough challenges with hypertonic aerosols have been introduced. They often provoke very frequent coughing which may complicate the simultaneous cough counting.ObjectiveTo assess whether cough counting from video recording is superior to simultaneous cough counting in two different hypertonic cough challenges.MethodsThe analysis includes 82 hypertonic saline challenges performed on 66 subjects, providing 1984 observation minutes with both simultaneous and video cough counting. The cough sensitivity was expressed as the osmolality to provoke 15 cumulative coughs (CUM15). The analysis also includes 136 hypertonic histamine challenges performed on 114 subjects providing 5373 observation minutes with both simultaneous and video counting. The cough sensitivity was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). This challenge involved several additional measurements to cough counting.ResultsFor the saline challenge, the mean difference between the counting types was 0.0 coughs per minute with 95% limits of agreement of -1.2 to 1.2 coughs per minute. For the hypertonic histamine challenge the respective figures were 0.3 (-1.9 to 2.5) coughs per minute. At high coughing frequency the video counts tended to outnumber the simultaneous counts. The counting type had no effect on the hypertonic saline CUM15 and only a marginal effect on its repeatability. On the contrary, video counting resulted to significantly higher hypertonic histamine CCR values than simultaneous counting (p < 0.001).ConclusionThe agreement between simultaneous and video counting of coughs is generally good. However, as the coughing frequency increases, simultaneous counting may miss coughs, especially if the nurse has to share his/her attention to several activities simultaneously. Video recording is advisable for the hypertonic histamine challenge but unnecessary for the hypertonic saline challenge. To ensure reliable simultaneous cough counting, cough provocation tests should be performed in a quiet environment, applying as little unnecessary equipment and measurements as possible.

Cough reflex and oral chemesthesis induced by capsaicin and capsiate in healthy never-smokers

BackgroundMany tussive agents are components of foods, but little is known about the relationship between cough reflex and oral chemesthesis sensitivities. We investigated the relationships between cough reflex and oral chemesthesis in individuals using two transient receptor potential vanilloid 1 (TRPV1) agonists with different potencies: capsaicin and capsiate.MethodsTwenty-eight healthy never-smokers were allocated to evaluate cough and oral chemesthesis of capsinoids. Cough reflex sensitivities are estimated by the lowest concentrations generating five coughs by each TRPV1 agonist inhalation. Oral chemesthesis sensitivities are estimated by the lowest concentrations which generate a hot sensation when filter paper loaded with each TRPV1 agonist is placed on the tongue.ResultsThere were strong correlations between capsaicin- and capsiate-induced cough reflex sensitivities, and between capsaicin- and capsiate-induced oral chemesthesis sensitivities. However, there were no significant correlations between cough reflex and oral chemesthesis sensitivities induced by both capsaicin and capsiate. The cough reflex sensitivities are significantly greater in females than in males whereas there were no gender differences in oral chemesthesis.ConclusionThe results showed that the sensitivities of sensory afferents were different between cough reflex and oral chemesthesis, suggesting that TRPV1 sensitivities differ between organs within healthy individuals. Capsiate could be a tussigen for the cough challenge test.

ERS guidelines on the assessment of cough

### Cough 1) All basic scientific articles should refer to cough as a three-phase motor act. For the purposes of acoustic recordings in clinical studies, however, cough should be described as a forced expulsive manoeuvre or manoeuvres against a closed glottis that are associated with a characteristic sound or sounds. 2) All scientific articles should include a clear definition of what the authors have used as their definition of cough. ### Capsaicin and citric acid inhalation cough challenge 1) The methodology for the performance of inhalation cough challenge should be standardised so as to facilitate universal interpretation and comparison of data generated by different laboratories. 2) Comprehensive normal ranges need to be developed using the standardised methodology advocated in the present document. 3) The single-breath concentration–response method using a flow-limited dosimeter is recommended for most experimental protocols. 4) Both C2 and C5 should be recorded. 5) Since there is wide inter-individual variation, cough challenge data have no intrinsic significance, but may usefully be used to follow change in cough reflex sensitivity in an individual. ### Cough induced by inhalation of aqueous solutions 1) Aerosolised aqueous solutions represent a useful experimental tool in cough research. 2) The cough challenge with ultrasonic distilled water (fog) is difficult to standardise since it is highly dependent upon nebuliser output. 3) Consideration should be given to potential adverse events, such as bronchoconstriction and cross-infection. ### Cough monitors 1) No cough monitor is currently the gold standard. 2) Monitors should be developed that are ambulatory, are capable of being digitally processed and permit prolonged (24-h) recording. 3) There is little to commend any particular method of quantifying cough over any other. ### Assessment of quality of life of patients with chronic cough 1) Cough can have profound effects on health status, which can be assessed by cough-specific health status questionnaires. 2) Cough visual analogue scale (VAS, 0–100 mm) should be used to assess cough severity in patients with chronic cough. 3) Patients with chronic cough should be assessed with cough-specific quality-of-life questionnaires in clinical studies. ### Animal models of cough 1) The most useful animal model of cough is …

Chronic cough and Holmes-Adie syndrome

In April, 2006, a 45-year-old white man—a lifelong nonsmoker—was referred to the Royal Brompton Hospital Cough Clinic. In October, 2002, he had presented to his general practitioner with a persistent dry cough. The cough had started in March, 2002, after a bout of pneumonia. In addition, he claimed to have night sweats but no systemic symptoms. Auscultation of his chest, and a chest radiograph were normal, and he had a negative (grade 1) tuberculin skin test. In January, 2003, he was referred to his local chest clinic, where further inves tigations including lung function and CT of the chest were normal. He was reassured and discharged. In June, 2004, he presented to his local eye clinic complaining of blurred vision. Anisocoria was noted with an enlarged tonic left pupil (fi gure) and near light dissociation. Ankle tendon arefl exia was present on the right and elicited on the left only with reinforcement. He was diagnosed with Holmes-Adie syndrome—a condition of unknown cause characterised by tonic pupillary reactions and absent tendon refl exes. In August 2004, he was re-referred back to his local chest clinic because his dry cough persisted. Empirical treatment with omeprazole 20 mg daily was started and he underwent a normal barium swallow. Over the course of the following year, with no improvement in symptoms, he was prescribed an inhaled antimuscarinic bronchodilator (oxitropium bromide), an oral H1-anti histamine (loratadine), and he was given a trial of an H2-receptor antagonist (ranitidine) for 1 month, with no eff ect. When seen by us in April, 2006, his cough had persisted and he reported that during one coughing paroxysm he had experienced syncope. Direct questioning revealed truncal and right arm hyperhydrosis with excessive sweating in the right armpit. Respiratory, nasopharyngeal, and cardiovascular examinations were unremarkable. In particular, the patient had no evidence of dry eyes, dry mouth, or skin changes that might suggest a diagnosis of Sjogren’s syndrome. VDRL, autoantibody screen, and fasting blood sugar were negative. CT of the chest, full lung function (including histamine challenge, nitric oxide, and reversibility testing), nasolaryngo scopy, cinevideo fl uoroscopy, and 24-hour oesophageal pH monitoring were all normal. The patient declined fi breoptic bronchoscopy and capsaicin cough challenge. Treatment with high-dose inhaled corticosteroid (fl uticasone propionate 1000 μg daily) delivered from a pressurised metered-dose inhaler and spacer attachment, induced paroxysms of cough. Two separate courses of high dose oral steroids provided no improvement in either symptomatology or diurnal peak expiratory fl ow rate measurements. The addition of a non-selective oral H1-antihistamine treatment (chlorphenamine maleate 4 mg four times a day) was of no additional benefi t. As of September, 2006, the patient is still symptomatic and awaiting neurological consultation including cardiovascular autonomic testing. Kimber and colleagues, have reported an association between Holmes-Adie syndrome and chronic cough. Our patient showed early signs of autonomic neuropathy as his cough developed, including anisocoria, hyperhydrosis and syncope. The mechanism behind the cough is poorly understood, but it has been proposed that selective loss of thinly myelinated aff erent nerves in the lung, trachea, and larynx leads to denervation hypersensitivity of secondary neurons in the nucleus solitarius. Although the patient undoubtedly had a trigger episode precipitating his chronic cough (the original episode of pneumonia), the presence of an autonomic neuropathy may well explain the persistence of his symptoms. This case also highlights the diffi culty in treating patients with no apparent cause for their cough. Although chronic idiopathic cough and Holmes-Adie syndrome are both of unknown cause, recognition of this association has led to a more accurate diagnosis and, in this case, an appropriate tertiary specialist opinion.

Opiate Therapy in Chronic Cough

Cough is the most common complaint for which medical attention is sought, and chronic cough can be both physically and mentally debilitating. There is currently no evidence supporting the use of antitussives in chronic treatment-resistant cough. We tested the hypothesis that morphine sulfate in the dose of 5 mg twice daily would bring about a reduction in cough frequency and severity in patients failing to respond to specific measures. Patients recruited from the Hull Cough Clinic were enrolled into a randomized double-blind placebo-controlled study using 4 weeks of slow-release morphine sulfate and a corresponding period of matched placebo. An open-labeled extension of the core study allowed dose escalation to 10 mg twice daily. Cough was assessed using the Leicester Cough Questionnaire, daily symptom diary, and citric acid cough challenge. Twenty-seven patients completed the core study. A significant improvement of 3.2 points over baseline was noted on the Leicester Cough Questionnaire (p < 0.01). A rapid and highly significant reduction by 40% in daily cough scores was noted among patients on slow-release morphine sulfate (p < 0.01). Objective testing of the cough reflex using citric acid cough challenge tests did not show any significant changes. Eighteen patients continued into the extension study. Two-thirds of these patients opted to increase the morphine to 10 mg twice daily. At the end of 3 months, there was a similar improvement in cough between the 5- and 10-mg groups. Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily.

DISTRIBUTION OF VIBRATION ENERGY AMONG DIFFERENT MODES OF MECHANICAL VENTILATION

The relationships between objective cough rates, cough reflex sensitivity, subjective estimates of cough frequency, and cough-related quality of life in patients with COPD are poorly understood.Twenty-six patients with stable COPD who complained of cough (76.9% men; mean +/- SD age, 68.7 +/- 6.9 years; mean FEV(1), 54.2 +/- 12.0% of predicted; median smoking history, 42.4 pack-years [range, 13 to 135 pack-years]).Subjects performed a cough challenge test, ambulatory daytime and overnight sound recordings, scored the severity of cough (0 to 5 score and visual analog scale) for each recording period, and completed a cough-specific quality of life questionnaire (CQLQ). Coughs were counted manually and quantified in terms of cough seconds per hour (cs/h): the number of seconds within the recording that contain cough.Overall median time spent coughing was 7.5 cs/h (range, 2.7 to 23.1 cs/h; daytime median, 12.4 cs/h [range, 3.3 to 40.4 cs/h]; overnight, 1.9 cs/h [0.0 to 19.0 cs/h]) [p = <0.01]. Median log concentration of citric acid eliciting five coughs (C5) was - 0.9 mol/L (range, - 1.5 to 0.0 mol/L). Day time but not overnight time spent coughing was significantly correlated with log C5 (log C5 r = - 0.49, p = 0.02, and r = - 0.20, p = 0.37, respectively). Subjective cough scores and visual analog scales were moderately associated with objective time spent coughing: daytime (r = 0.37, p = 0.03, and r = 0.41, p = 0.03) and overnight (r = 0.48, p = <0.01, and r = 0.5, p = 0.01), respectively.Subjective measures of cough and cough reflex sensitivity are statistically related to time spent coughing in patients with COPD, but with low-to-moderate levels of correlation. These measures have insufficient predictive value to substitute for objective time spent coughing; however, in conjunction with the CQLQ, they may provide a qualitative dimension to the assessment of cough.

Changes in cough reflex sensitivity after cessation and resumption of cigarette smoking

Previous studies have shown that healthy cigarette smokers have diminished cough reflex sensitivity compared to healthy nonsmokers. We have recently demonstrated that cough reflex sensitivity is enhanced soon after smoking cessation, suggesting that diminished cough sensitivity in smokers results from chronic cigarette smoke-induced desensitization of airway cough receptors. In this study, we evaluated cough reflex sensitivity to capsaicin (C 5) in 11 chronic smokers who had discontinued smoking for at least 2 weeks, and then resumed smoking. Two weeks after smoking cessation there was a significant enhancement of cough reflex sensitivity; mean (±SEM) log C 5 decreased from 1.77±0.18 to 1.47±0.14 ( p=0.01). All subjects resumed smoking after 2–12 weeks of abstinence. Repeat capsaicin cough challenge was performed 14–23 days after resumption of smoking. Mean log C 5 increased compared to the last value obtained during the smoking cessation period: 1.42±0.15 vs. 1.77±0.16 ( p=0.0004). Mean log C 5 after resumption of smoking returned to almost exactly the baseline value. Our findings suggest that the sensitivity of airway cough receptors is a dynamic phenomenon, promptly affected and modulated by changes in environmental conditions, such as the presence or absence of cigarette smoke.

Cough in COPD: Correlation of Objective Monitoring With Cough Challenge and Subjective Assessments

Background The relationships between objective cough rates, cough reflex sensitivity, subjective estimates of cough frequency, and cough-related quality of life in patients with COPD are poorly understood. Subjects Twenty-six patients with stable COPD who complained of cough (76.9% men; mean ± SD age, 68.7 ± 6.9 years; mean FEV 1 , 54.2 ± 12.0% of predicted; median smoking history, 42.4 pack-years [range, 13 to 135 pack-years]). Methods Subjects performed a cough challenge test, ambulatory daytime and overnight sound recordings, scored the severity of cough (0 to 5 score and visual analog scale) for each recording period, and completed a cough-specific quality of life questionnaire (CQLQ). Coughs were counted manually and quantified in terms of cough seconds per hour (cs/h): the number of seconds within the recording that contain cough. Results Overall median time spent coughing was 7.5 cs/h (range, 2.7 to 23.1 cs/h; daytime median, 12.4 cs/h [range, 3.3 to 40.4 cs/h]; overnight, 1.9 cs/h [0.0 to 19.0 cs/h]) [p = r = − 0.49, p=0.02, and r = − 0.20, p=0.37, respectively). Subjective cough scores and visual analog scales were moderately associated with objective time spent coughing: daytime ( r = 0.37, p=0.03, and r = 0.41, p=0.03) and overnight ( r = 0.48, p= r = 0.5, p=0.01), respectively. Conclusions Subjective measures of cough and cough reflex sensitivity are statistically related to time spent coughing in patients with COPD, but with low-to-moderate levels of correlation. These measures have insufficient predictive value to substitute for objective time spent coughing; however, in conjunction with the CQLQ, they may provide a qualitative dimension to the assessment of cough.

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease

Codeine is the standard antitussive treatment to which novel agents are compared. Little is known about the objective effect of any treatments on cough in chronic obstructive pulmonary disease (COPD). To quantify the effect of codeine on objective cough frequency (quantified as time spent coughing: cough seconds, cs/h), citric acid cough threshold, and subjective measures in a double-blind, placebo-controlled crossover study in COPD. We studied 21 patients with physician-diagnosed, stable disease who complained of cough (76.9% male; mean age, 67.7 years; mean predicted FEV(1), 53.4%; median smoking history, 43.5 pack-years). Each subject performed a cough challenge (single breath, citric acid), 10-hour daytime ambulatory and overnight cough recordings, subjective cough scores, and visual analog scales at baseline and on 2 study days, 1 week apart. Codeine phosphate 60 mg or matched placebo were given, in random order, at the start of each cough recording (0 and 12 hours). Median time spent coughing at baseline was 8.27 cs/h (interquartile range [IQR], 5.94-11.67); after placebo treatment, 7.22 cs/h (IQR 4.42-10.40); and after codeine treatment, 6.41 cs/h (IQR 3.86-9.10). Codeine treatment had a significant effect on time spent coughing compared with baseline (P = .02) but not compared with placebo (P = .52). There were no significant differences in cough challenge thresholds (log concentration of tussive agent causing 2 coughs or log concentration of tussive agent causing 5 coughs) or subjective cough measures for codeine compared with placebo. In this study, codeine was no more effective than placebo in patients with COPD complaining of cough. Codeine is the antitussive agent to which we compare new treatments; however, in a group of stable patients with COPD, it had no effect on cough frequency over placebo.

Cough and Aspiration of Food and Liquids Due to Oral-Pharyngeal Dysphagia: ACCP Evidence-Based Clinical Practice Guidelines

Cough may be an indicator of aspiration due to oral-pharyngeal dysphagia. Relevant literature was identified by searching the Communication Sciences and Disorders Dome, the Cumulative Index to Nursing and Allied Health Literature, the Educational Resource Information Center, Health & Psychosocial Instruments, the American Psychological Association, and the National Library of Medicine databases from 1965 to 2004 using the terms "deglutition," "aspiration," and "cough." Aspiration was observed on radiologic evaluation in over one third of acute stroke patients and in >40% of patients undergoing cervical spine surgery. Cough while eating may indicate aspiration, but aspiration may be clinically silent. Subjective patient and caregiver reports of cough while eating are useful in identifying patients who are at risk for aspiration. Objective measures of voluntary cough and tussigenic challenges to inhaled irritants are under investigation to determine their capacity to predict the risk for aspiration and subsequent pneumonia. The treatment of dysphagic patients by a multidisciplinary team, including early evaluation by a speech-language pathologist, is associated with improved outcomes. Effective clinical interventions such as the use of compensatory swallowing strategies and the alteration of food consistencies can be based on the results of instrumental swallowing studies. The efficacy of swallowing exercises and electrical muscle stimulation is under study. Surgical interventions may be considered in selected patients, but studies proving efficacy are generally lacking. Patients who are at risk for aspiration can be identified, and appropriate interventions can reduce its associated morbidity.

Citric Acid Cough Threshold in Patients With Gastroesophageal Reflux Disease Rises After Laparoscopic Fundoplication

It has been reported that antireflux surgery can diminish chronic cough due to gastroesophageal reflux disease (GERD) that is resistant to pharmacologic therapy. The aim of this study was the assessment of citric acid cough threshold (CACT) in patients with chronic cough due to GERD before and 3 months after laparoscopic Toupet fundoplication. Thirty subjects (20 women and 10 men; median age, 45.3 years) with chronic cough due to GERD and 15 healthy volunteers underwent cough challenge with doubling concentrations of citric acid. Twenty subjects with GERD, a group of 14 women and 6 men (mean age, 45.5 years), underwent the same protocol 3 months after laparoscopic fundoplication. Daytime and nighttime cough score questionnaires (verbal category descriptive score) were completed in all groups. The geometric mean of CACT was significantly lower in GERD patients (9.62 mg/mL) than in healthy volunteers (50.8 mg/mL, p < 0.001). The results of cough score measurement significantly improved within 2 weeks after laparoscopic surgery. In 13 weeks of postoperative follow-up, cough disappeared or was greatly improved in 14 of the 20 patients (70%); in 3 other patients, cough resolved partially. In three patients. there was no improvement in cough. Cough challenge after surgery revealed a significant increase in mean cough threshold, from 8.28 to 19.03 mg/mL (p < 0.05). The results suggest that GERD influences CACT, which was significantly lower in GERD patients compared to healthy subjects. A significant correlation was found between subjective and objective measurements of cough in GERD patients. We found laparoscopic fundoplication to be objectively beneficial in GERD-induced chronic cough, as it reduced the CACT.

Safety of Capsaicin Cough Challenge Testing

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. To review the published experience with capsaicin inhalation challenge testing in terms of safety. Literature review and personal communication with study authors. Academic medical center. 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. 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.

Reproducibility and validity of a Yan-style portable citric acid cough challenge

Although many different methods of measuring cough reflex sensitivity have been published, few are simple enough to use outside of a hospital or laboratory environment. The aim of this study was to develop a simple, quick, and portable cough challenge, assess its reproducibility, and compare its results with those measured by an existing established hospital protocol. Twenty-five volunteers performed cough challenges based on an established hospital dosimeter protocol, and, on a separate occasion, by a protocol inhaling citric acid from DeVilbiss 40 hand-held nebulisers (citric acid concentrations of 10–3000 mM). Reproducibility of the hand-held cough challenge was assessed in 11 volunteers. Cough thresholds were consistently higher by the hand-held method than by the hospital dosimeter method. The geometric mean citric acid concentrations causing two coughs (threshold D 2) were 3.14 and 2.77 log mM, respectively ( p<0.001). The geometric mean (95% CI) difference between the tests was 0.51 log mM (0.18–0.83) of the average of the two values. Cough D 2 thresholds attained by the two techniques did, however, show significant correlation ( r=0.95, p<0.0001). The coefficient of repeatability for the hand-held method was 0.40 log mM. Administering citric acid from DeVilbiss 40 hand-held nebulisers offers a rapid, portable, and reproducible cough challenge in healthy volunteers. The results correlate well with an existing Mefar dosimeter challenge, but give two to three times greater cough thresholds.

Effects of enalapril and imidapril in the capsaicin cough challenge test and spirometry parameters in healthy volunteers

Background: Angiotensin-converting enzyme inhibitors are highly effective, welltolerated drugs, but are associated with respiratory adverse effects such as cough and wheezing. Objectives: In this double-blind, randomized, two-way crossover study, the effects of two angiotensin-converting enzyme inhibitors, enalapril and imidapril, in the capsaicin cough challenge test and spirometry parameters were investigated. Methods: The study involved two sequential 21-day periods separated by a 7-day washout period. In each period, volunteers received a once-daily oral dose of placebo during the first 7 days, imidapril 5 mg or enalapril 10 mg from days 8 to 14, and imidapril 10 mg or enalapril 20 mg from days 15 to 21. Cough challenge was performed at baseline and at the end of each week of treatment. Spirometry was performed before and immediately after the capsaicin challenge. Fourteen healthy subjects were enrolled, but one was withdrawn while taking enalapril due to dry cough. Results: Neither enalapril nor imidapril significantly altered the capsaicin cough threshold. A small but significant reduction in forced expiratory volume in 1 sec and forced vital capacity was demonstrated after treatment with enalapril (p = 0.017 and p = 0.018, respectively), but not with imidapril. Capsaicin cough challenge was not associated with bronchospasm. Conclusion: Studies in asthmatics are needed to assess the clinical relevance of these data.

Effects of enalapril and imidapril in the capsaicin cough challenge test and spirometry parameters in healthy volunteers

Effects of enalapril and imidapril in the capsaicin cough challenge test and spirometry parameters in healthy volunteers

Effect of salbutamol on smoking related cough

Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough when attempting smoking cessation. We investigated the use of smokers cough as a model for testing anti-tussive agents. The effect of salbutamol was compared with placebo in healthy adult smokers. In a randomised double blind crossover study the effect of 400 μg salbutamol via MDI plus spacer versus placebo was studied. Cough was assessed before and after the first cigarette of the day (received at 20 mintes) and throughout the day. Cough frequency, citric acid cough challenge, change in cough symptoms and peak flow were recorded. Salbutamol reduced the mean cough frequency between 0 and 20 min. A mean of 4.5 compared to 6 on placebo ( p<0.05). A significant reduction in cough followed cigarette consumption in those on placebo. Mean pre-cigarette 6 compared to 3.9 post-cigarette ( p<0.02). The citric acid concentration causing two coughs (C2) at 60 min increased on salbutamol. Geometric mean 278.8 compared to 190.4 mM on placebo ( p<0.03). Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that β agonists have modest activity in smoking related cough and that smokers cough represents a sensitive model to test anti-tussive activity.

Effect of Guaifenesin on Cough Reflex Sensitivity

Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Academic medical center. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Cough reflex testing with inhaled capsaicin in the study of chronic cough

Objectives: To assess the utility of capsaicin test in the differential diagnosis of non-productive causes of chronic cough and to examine the effects of treatment on this reflex. Participants: 86 healthy volunteers and 101 patients with chronic cough: asthma ( n: 54), gastroesophageal reflux ( n: 35) and post-nasal drip syndrome ( n: 12). Design: Prospective intervention trial. Spirometry, bronchoprovocation test with histamine (PC 20), and cough challenge with ascending concentrations of capsaicin (0.49–500 μM) were initially performed in all subjects. Patients were treated for 3 months according to the origin of the cough. Concentrations that elicited two ( C 2) and five or more coughs ( C 5) were determined before and after treatment. Results: In healthy subjects, cough sensitivity to capsaicin was not influenced by gender or smoking status; however, women with chronic cough were more sensitive to cough challenge than men. C 2 and C 5 were significantly lower in patients with asthma or gastroesophageal reflux than in post-nasal drip syndrome. No significant correlation was observed between the capsaicin cough threshold and PC 20. Cough sensitivity did not improve significantly in most patients with asthma or gastroesophageal reflux despite adequate medical treatment during 3 months. Discriminative value of capsaicin test to differentiate healthy subjects from patients with asthma or reflux was poor. Conclusions: Cough sensitivity to inhaled capsaicin is a safe and reproducible tool in the study of chronic cough. However, its usefulness for the management and differential diagnosis is limited.