Caroline Wright

Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study

Background and objective:  Gastro‐oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on management suggest a therapeutic trial of anti‐reflux medication. Esomeprazole is a proton pump inhibitor licensed for the long‐term treatment of acid reflux in adults and we compared the effects of esomeprazole and placebo on patients with chronic cough.

Quantifying chronic cough: objective versus subjective measurements.

Background and objective:  The assessment of chronic cough has been improved by the development of objective ambulatory cough monitoring systems and subjective quality of life questionnaires. Experimental induction of cough is a useful tool in the assessment of the cough reflex. We wanted to assess the reproducibility of and association between these measurements.

Tussive challenge with ATP and AMP : does it reveal cough hypersensitivity?

Recent studies have demonstrated that blockade of P2X3 ATP receptors can profoundly inhibit chronic cough. We have considered whether inhaled ATP produces a tussive response and whether chronic cough patients are hypersensitive to inhaled ATP compared to healthy volunteers. A standardised inhalational cough challenge was performed with ATP and AMP. We randomised 20 healthy volunteers and 20 chronic cough patients as to the order of challenges. The concentration of challenge solution causing at least five coughs (C5) was compared for ATP and AMP. The study population consisted of six male and 14 female volunteers in each group. Two out of 19 healthy volunteers coughed with AMP (one volunteer could not take part in this challenge) and none reached C5. Eight out of 20 chronic cough patients coughed with AMP and two reached C5. Of the 20 healthy volunteers, 18 coughed with ATP, with 15 reaching C5. All 19 chronic cough patients completing the ATP challenge coughed with ATP and 18 reached C5. The chronic cough patients had a greater cough response at lower concentrations of ATP. The greater potency of ATP versus AMP in the inhalational challenge suggests that tussive responses are mediated through members of the P2X purinergic receptor family. This acute effect was, however, not sufficient to explain cough hypersensitivity syndrome. Chronic coughers have a heightened response to ATP but not sufficient to implicate ATP in cough hypersensitivity http://ow.ly/h15730699GA

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

AIMS The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. METHODS In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. RESULTS Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. CONCLUSIONS We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses.

Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Cough and sputum production are associated with adverse outcomes in COPD and are common during COPD exacerbation (AE-COPD). This study of objective cough monitoring using the Hull Automated Cough Counter and Leicester Cough Monitor software confirms that this system has the ability to detect a significant decrease in cough frequency during AE-COPD convalescence. The ability to detect clinically meaningful change indicates a potential role in home monitoring of COPD patients.

Is opiate action in cough due to sedation

Objectives: Opiates have been used for cough suppression for centuries. It is unclear whether this antitussive action is due to their known sedative effects. We aimed to assess correlation between cough suppression and opiate usage. Methods: We performed a post hoc analysis of two published trials with three opioids. In study one, patients with chronic cough were treated with 4 weeks of modified release morphine sulphate (5 mg twice daily) or placebo in a double-blinded placebo-controlled fashion. Cough suppression was assessed subjectively by the Leicester Cough Questionnaire and objectively by citric acid aerosol (CAA) induced cough challenge. In study 2, normal volunteers were given single doses of placebo, codeine 30 mg or dextromethorphan 50 mg and cough suppression assessed using the CAA-induced cough challenge. Sedation was contemporaneously assessed by direct questioning. Results: There were 14 episodes of patient-reported sedation; 2 with modified release morphine sulphate, 9 with codeine and 3 with dextromethorphan. There was no correlation between change in the Leicester Cough Questionnaire or the CAA-induced cough challenge and reported sedation. Conclusion: This observational study suggests that sedation is unlikely to underlie the antitussive properties of these opioids. Eliciting the mechanism of these medications in cough may be a target for future tailored drug development.

Serum LDH in chronic cough: a potential marker of airway inflammation

Introduction and Objectives:  Lactate dehydrogenase (LDH) is found in almost all tissues of the body and five different isoenzymes are known (LDH‐1 to LDH‐5). LDH can be elevated in many pathological conditions. We have observed serum LDH to be increased in patients with chronic cough. We wanted to confirm this finding, study the reproducibility and determine the origin of the LDH.

Neurological conditions presenting as airway reflux cough

To the Editor: The association of cough with neurological conditions is well described [1–4]. Herein, we report four patients with chronic cough who each presented to our cough clinic (Castle Hill Hospital, Cottingham, UK) with a different neurological diagnosis. Each of the patients had normal chest radiology and pulmonary function, they were not on angiotension converting enzyme inhibitors, and no obvious underlying respiratory pathology was identified. A summary of all the relevant investigations performed on each patient are detailed in table 1. View this table: Table 1. Summary of results of the four cases A 66-yr-old nonsmoking male presented with a non-productive cough for several years which was profound on rising from bed in the morning and associated with eating, but no symptoms of dyspepsia. Interestingly, he also complained of numbness over the left side of his head up to his mid upper arm. Clinical examination showed wasting of scapular muscles and biceps with absent sensations and areflexia in both lower limbs. Oesophageal pH monitoring and manometry were abnormal, with a DeMeester score of 18.3. Blood tests and cerebrospinal fluid analysis were normal. Anatomical and malignant pathology was excluded by radiological investigations. Neurophysiological studies revealed sensory polyneuropathy with a dorsal column lesion and focal radiculopathy at the right cervical (C)3, C4 and, possibly C6, levels. Autonomic testing of heart rate variability showed lack of variation of heart rate during inspiration and expiration (table 1). A diagnosis of mononeuritis multiplex was made and cough was probably secondary to vagal neuropathy causing …

Continuous Cough Monitoring Using Ambient Sound Recording During Convalescence from a COPD Exacerbation

PurposeCough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent exacerbations and increased mortality. Cough increases during acute exacerbations (AE-COPD), representing a possible metric of clinical deterioration. Conventional cough monitors accurately report cough counts over short time periods. We describe a novel monitoring system which we used to record cough continuously for up to 45 days during AE-COPD convalescence.MethodsThis is a longitudinal, observational study of cough monitoring in AE-COPD patients discharged from a single teaching hospital. Ambient sound was recorded from two sites in the domestic environment and analysed using novel cough classifier software. For comparison, the validated hybrid HACC/LCM cough monitoring system was used on days 1, 5, 20 and 45. Patients were asked to record symptoms daily using diaries.ResultsCough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significantly from mean ± SEM 272.7 ± 54.5 on day 1 to 110.9 ± 26.3 on day 9 (p < 0.01) before plateauing. The absolute cough count detected by the continuous monitoring system was significantly lower than detected by the hybrid HACC/LCM system but normalised counts strongly correlated (r = 0.88, p < 0.01) demonstrating an ability to detect trends. Objective cough count and subjective cough scores modestly correlated (r = 0.46).ConclusionsCough frequency declines significantly following AE-COPD and the reducing trend can be detected using continuous ambient sound recording and novel cough classifier software. Objective measurement of cough frequency has the potential to enhance our ability to monitor the clinical state in patients with COPD.

TRPV1 polymorphisms influence capsaicin cough sensitivity in men

Capsaicin, the hot component of chilli peppers, is a well-known tussive agent, which is regularly used as a tool to study cough and antitussives (1). Capsaicin is known to activate the transient receptor potential vanilloid 1 (TRPV1) cation channel which is thought to be involved in pain perception, inflammation, itch and cough (2-4). These functions within the body make TRPV1 an exciting target for research and drug development.