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Research paper thumbnail of Autonomic dysregulation: a mechanism of asthma death

European Respiratory Journal, 2014

Research paper thumbnail of Azithromycin for sarcoidosis cough: an open-label exploratory clinical trial

ERJ Open Research

BackgroundChronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Cont... more BackgroundChronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough.MethodsWe conducted a noncontrolled, open-label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analogue scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after 1 and 3 months of treatment.ResultsAll 21 patients were white, median age 57 years, 9 males, 12 females, median 3 years since diagnosis. Five were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients com...

Research paper thumbnail of Phenotyping patients with chronic cough: Evaluating the ability to predict the response to anti-inflammatory therapy

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Mar 1, 2018

Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-... more Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-inflammatory treatment in chronic cough is unknown. To explore whether the effectiveness of treatment with 10 mg of montelukast or 20 mg of prednisolone in patients with chronic cough is predicted by FeNO level. In this randomized, open-label, controlled pilot study conducted in the Clinical Trial Unit in Castle Hospital in the United Kingdom, 50 nonsmoking patients with a cough that lasted more than 8 weeks were sequentially enrolled in the study. Thirty patients with high FeNO levels (≥30 ppb) were randomized in a 1:1 ratio to receive 10 mg of montelukast or 20 mg of prednisolone for 2 weeks followed by 10 mg of montelukast for 2 weeks. Twenty patients with a low FeNO level (≤20 ppb) received 10 mg of montelukast. The primary objective was to determine the effectiveness of treatment on 24-hour cough counts. The 24-hour cough counts decreased in both groups by approximately 50% (P < ...

Research paper thumbnail of Inhaled beclomethasone/formoterol in idiopathic pulmonary fibrosis: a randomised controlled exploratory study

ERJ open research, 2017

We hypothesise that inflammation plays a role in idiopathic pulmonary fibrosis (IPF) and that the... more We hypothesise that inflammation plays a role in idiopathic pulmonary fibrosis (IPF) and that the harm associated with corticosteroid-containing regimens in IPF may relate to local beneficial effects being counterbalanced by deleterious systemic effects [1, 2]. Topical lung delivery could improve the poise between risk and benefit. Inhaled corticosteroids (ICS) are widely used in airway diseases to target inflammation, often in combination with long-acting β 2-adrenoceptor agonists (LABA). Human lung fibroblasts express β 2-adrenoceptors, and agonist-induced downregulation of collagen synthesis and myofibroblast differentiation has been demonstrated in vitro [3]. Inhibition of profibrotic mediator release in response to transforming growth factor-β1 has also been demonstrated [4]. Thus, there is a pharmacological rationale to study ICS/LABA combinations in IPF.

Research paper thumbnail of Does FeNO Predict Clinical Characteristics in Chronic Cough?

Lung, Feb 25, 2017

To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic ... more To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic cough patients based on their airway inflammatory phenotype. We have studied consecutive patients attending a specialist cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO (< 20 ppb) were recruited. There was a significant correlation between FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion of these patients were women (90%). LCQ scores were worse in the low FeNO group but it was not significant. A strong relationship between FeNO, blood eosinophils and sputum eosinophils confirming phenotypic identity was observed. Whether the observed gender disparity accounts for the different cough frequency characteristics is unknown.

Research paper thumbnail of TRPV1 polymorphisms influence capsaicin cough sensitivity in men

Journal of Thoracic Disease, 2017

Research paper thumbnail of Continuous Cough Monitoring Using Ambient Sound Recording During Convalescence from a COPD Exacerbation

Lung, Jun 28, 2017

Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent e... more Cough 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. This 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. Cough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significant...

Research paper thumbnail of The utility of remote cough monitoring in COPD

European Respiratory Journal, Sep 1, 2013

Research paper thumbnail of Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence

Lung, Jan 18, 2015

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwid... more 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.

Research paper thumbnail of A randomised placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

European Respiratory Journal, Sep 1, 2013

Research paper thumbnail of Autonomic dysregulation: a mechanism of asthma death

European Respiratory Journal, 2014

@ERSpublications Reduced lung function is a robust predictor of out-of-hospital sudden cardiac de... more @ERSpublications Reduced lung function is a robust predictor of out-of-hospital sudden cardiac death in middle-aged males

Research paper thumbnail of Dextromethorphan Attenuates Capsaicin Induced Cough In Healthy Volunteers

B69. AIRWAY STRUCTURE AND FUNCTION, 2012

Research paper thumbnail of Cough Hypersensitivity Syndrome: A Distinct Clinical Entity

Lung, 2011

We postulate that most patients with chronic cough have a single discrete clinical entity: cough ... more We postulate that most patients with chronic cough have a single discrete clinical entity: cough hypersensitivity syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2 months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen&amp;amp;#39;s kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (r = 0.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: cough hypersensitivity syndrome.

Research paper thumbnail of Is opiate action in cough due to sedation?

Therapeutic Advances in Chronic Disease, 2014

Opiates have been used for cough suppression for centuries. It is unclear whether this antitussiv... more 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. 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. 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. 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.

Research paper thumbnail of Cough Suppression By Opiates. Is It Due To Sedation?

Research paper thumbnail of Neurological conditions presenting as airway reflux cough

European Respiratory Review, 2012

Research paper thumbnail of Effect of salbutamol on smoking related cough

Pulmonary Pharmacology & Therapeutics, 2004

Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough w... more 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 microg salbutamol via MDI plus spacer versus placebo was studied. Cough was assessed before and after the first cigarette of the day (received at 20 minutes) 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that beta agonists have modest activity in smoking related cough and that smokers cough represents a sensitive model to test anti-tussive activity.

Research paper thumbnail of Dextromethorphan Attenuates Capsaicin Induced Cough In Healthy Volunteers

B69. AIRWAY STRUCTURE AND FUNCTION, 2012

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

The Clinical Respiratory Journal, 2011

Introduction and Objectives: Lactate dehydrogenase (LDH) is found in almost all tissues of the bo... more 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. Methods: Patients prospectively seen at the Hull Cough Clinic had total and specific LDH isoenzyme levels in serum determined. A subgroup of patients also had a serum creatine phosphokinase (CK) measured. Patients completed cough symptom scores and the Hull Airway Reflux Questionnaire (HARQ). Spirometry was performed. Results: Eighty-three patients were included. Forty-two percent had LDH values above the reference range and 78% had LDH values in the fourth quartile of the reference range or above. This increase in LDH was predominantly because of a rise in isoenzymes 4 and 5. The increase in LDH was found to be reproducible at 8 weeks. Ten percent had CK values above the normal range. There was no correlation observed between LDH values and the cough scores, HARQ scores or lung function. Conclusion: Serum LDH levels are elevated in a substantial proportion of patients with chronic cough. This rise is likely to be due to airway inflammation known to be associated with chronic cough.

Research paper thumbnail of Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study

Respirology, 2011

Gastro-oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on... more 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. This was a prospective, single-centre, randomized, double-blind, placebo-controlled, parallel group study conducted over 8weeks. Fifty adult non-smokers with chronic cough and normal spirometry were randomized. Patients completed cough-related quality-of-life and symptom questionnaires and subjective scores of cough frequency and severity at the beginning and end of the study. They also kept a daily diary of symptom scores. Citric acid cough challenge and laryngoscopic examination were performed at baseline and the end of the study. The primary outcome was improvement in cough score. There were no differences in cough scores in the placebo and treatment arms of the study although some significant improvements were noted when compared to baseline. In the cough diary scores there was a trend towards greater improvement in the treatment arm in patients with dyspepsia. Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough.

Research paper thumbnail of Autonomic dysregulation: a mechanism of asthma death

European Respiratory Journal, 2014

Research paper thumbnail of Azithromycin for sarcoidosis cough: an open-label exploratory clinical trial

ERJ Open Research

BackgroundChronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Cont... more BackgroundChronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough.MethodsWe conducted a noncontrolled, open-label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analogue scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after 1 and 3 months of treatment.ResultsAll 21 patients were white, median age 57 years, 9 males, 12 females, median 3 years since diagnosis. Five were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients com...

Research paper thumbnail of Phenotyping patients with chronic cough: Evaluating the ability to predict the response to anti-inflammatory therapy

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Mar 1, 2018

Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-... more Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-inflammatory treatment in chronic cough is unknown. To explore whether the effectiveness of treatment with 10 mg of montelukast or 20 mg of prednisolone in patients with chronic cough is predicted by FeNO level. In this randomized, open-label, controlled pilot study conducted in the Clinical Trial Unit in Castle Hospital in the United Kingdom, 50 nonsmoking patients with a cough that lasted more than 8 weeks were sequentially enrolled in the study. Thirty patients with high FeNO levels (≥30 ppb) were randomized in a 1:1 ratio to receive 10 mg of montelukast or 20 mg of prednisolone for 2 weeks followed by 10 mg of montelukast for 2 weeks. Twenty patients with a low FeNO level (≤20 ppb) received 10 mg of montelukast. The primary objective was to determine the effectiveness of treatment on 24-hour cough counts. The 24-hour cough counts decreased in both groups by approximately 50% (P < ...

Research paper thumbnail of Inhaled beclomethasone/formoterol in idiopathic pulmonary fibrosis: a randomised controlled exploratory study

ERJ open research, 2017

We hypothesise that inflammation plays a role in idiopathic pulmonary fibrosis (IPF) and that the... more We hypothesise that inflammation plays a role in idiopathic pulmonary fibrosis (IPF) and that the harm associated with corticosteroid-containing regimens in IPF may relate to local beneficial effects being counterbalanced by deleterious systemic effects [1, 2]. Topical lung delivery could improve the poise between risk and benefit. Inhaled corticosteroids (ICS) are widely used in airway diseases to target inflammation, often in combination with long-acting β 2-adrenoceptor agonists (LABA). Human lung fibroblasts express β 2-adrenoceptors, and agonist-induced downregulation of collagen synthesis and myofibroblast differentiation has been demonstrated in vitro [3]. Inhibition of profibrotic mediator release in response to transforming growth factor-β1 has also been demonstrated [4]. Thus, there is a pharmacological rationale to study ICS/LABA combinations in IPF.

Research paper thumbnail of Does FeNO Predict Clinical Characteristics in Chronic Cough?

Lung, Feb 25, 2017

To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic ... more To evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic cough patients based on their airway inflammatory phenotype. We have studied consecutive patients attending a specialist cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO (< 20 ppb) were recruited. There was a significant correlation between FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion of these patients were women (90%). LCQ scores were worse in the low FeNO group but it was not significant. A strong relationship between FeNO, blood eosinophils and sputum eosinophils confirming phenotypic identity was observed. Whether the observed gender disparity accounts for the different cough frequency characteristics is unknown.

Research paper thumbnail of TRPV1 polymorphisms influence capsaicin cough sensitivity in men

Journal of Thoracic Disease, 2017

Research paper thumbnail of Continuous Cough Monitoring Using Ambient Sound Recording During Convalescence from a COPD Exacerbation

Lung, Jun 28, 2017

Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent e... more Cough 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. This 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. Cough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significant...

Research paper thumbnail of The utility of remote cough monitoring in COPD

European Respiratory Journal, Sep 1, 2013

Research paper thumbnail of Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence

Lung, Jan 18, 2015

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwid... more 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.

Research paper thumbnail of A randomised placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

European Respiratory Journal, Sep 1, 2013

Research paper thumbnail of Autonomic dysregulation: a mechanism of asthma death

European Respiratory Journal, 2014

@ERSpublications Reduced lung function is a robust predictor of out-of-hospital sudden cardiac de... more @ERSpublications Reduced lung function is a robust predictor of out-of-hospital sudden cardiac death in middle-aged males

Research paper thumbnail of Dextromethorphan Attenuates Capsaicin Induced Cough In Healthy Volunteers

B69. AIRWAY STRUCTURE AND FUNCTION, 2012

Research paper thumbnail of Cough Hypersensitivity Syndrome: A Distinct Clinical Entity

Lung, 2011

We postulate that most patients with chronic cough have a single discrete clinical entity: cough ... more We postulate that most patients with chronic cough have a single discrete clinical entity: cough hypersensitivity syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2 months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen&amp;amp;#39;s kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (r = 0.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: cough hypersensitivity syndrome.

Research paper thumbnail of Is opiate action in cough due to sedation?

Therapeutic Advances in Chronic Disease, 2014

Opiates have been used for cough suppression for centuries. It is unclear whether this antitussiv... more 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. 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. 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. 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.

Research paper thumbnail of Cough Suppression By Opiates. Is It Due To Sedation?

Research paper thumbnail of Neurological conditions presenting as airway reflux cough

European Respiratory Review, 2012

Research paper thumbnail of Effect of salbutamol on smoking related cough

Pulmonary Pharmacology & Therapeutics, 2004

Smokers have an increased prevalence of chronic cough and may complain of exacerbation of cough w... more 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 microg salbutamol via MDI plus spacer versus placebo was studied. Cough was assessed before and after the first cigarette of the day (received at 20 minutes) 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). Cough frequency is reduced in smokers following a cigarette. The reduction in cough frequency and evoked cough after salbutamol suggests that beta agonists have modest activity in smoking related cough and that smokers cough represents a sensitive model to test anti-tussive activity.

Research paper thumbnail of Dextromethorphan Attenuates Capsaicin Induced Cough In Healthy Volunteers

B69. AIRWAY STRUCTURE AND FUNCTION, 2012

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

The Clinical Respiratory Journal, 2011

Introduction and Objectives: Lactate dehydrogenase (LDH) is found in almost all tissues of the bo... more 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. Methods: Patients prospectively seen at the Hull Cough Clinic had total and specific LDH isoenzyme levels in serum determined. A subgroup of patients also had a serum creatine phosphokinase (CK) measured. Patients completed cough symptom scores and the Hull Airway Reflux Questionnaire (HARQ). Spirometry was performed. Results: Eighty-three patients were included. Forty-two percent had LDH values above the reference range and 78% had LDH values in the fourth quartile of the reference range or above. This increase in LDH was predominantly because of a rise in isoenzymes 4 and 5. The increase in LDH was found to be reproducible at 8 weeks. Ten percent had CK values above the normal range. There was no correlation observed between LDH values and the cough scores, HARQ scores or lung function. Conclusion: Serum LDH levels are elevated in a substantial proportion of patients with chronic cough. This rise is likely to be due to airway inflammation known to be associated with chronic cough.

Research paper thumbnail of Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study

Respirology, 2011

Gastro-oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on... more 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. This was a prospective, single-centre, randomized, double-blind, placebo-controlled, parallel group study conducted over 8weeks. Fifty adult non-smokers with chronic cough and normal spirometry were randomized. Patients completed cough-related quality-of-life and symptom questionnaires and subjective scores of cough frequency and severity at the beginning and end of the study. They also kept a daily diary of symptom scores. Citric acid cough challenge and laryngoscopic examination were performed at baseline and the end of the study. The primary outcome was improvement in cough score. There were no differences in cough scores in the placebo and treatment arms of the study although some significant improvements were noted when compared to baseline. In the cough diary scores there was a trend towards greater improvement in the treatment arm in patients with dyspepsia. Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough.