A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Alyn H Morice - Top 30 Publications

Inhaled Corticosteroid use and the Risk of Pneumonia and COPD Exacerbations in the UPLIFT Study.

Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population.

Effect of Ivacaftor on Objective and Subjective Measures of Cough in Patients with Cystic Fibrosis.

Cough is a major symptom in cystic fibrosis. Ivacaftor is a novel drug which targets the G551D mutation and has been demonstrated to improve lung function and weight in the long term. It also improves symptoms of extra-oesophageal reflux. We wanted to evaluate the effect of ivacaftor on cough in cystic fibrosis.

Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis.

Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough.

Effect of aclidinium bromide on cough and sputum symptoms in moderate-to-severe COPD in three phase III trials.

Cough and sputum are troublesome symptoms in chronic obstructive pulmonary disease (COPD) and are associated with adverse outcomes. The efficacy of aclidinium bromide 400 µg twice daily in patients with stable COPD has been established in two phase III studies (ACCORD COPD I and ATTAIN) and a phase IIIb active-comparator study. This analysis evaluated cough-related symptoms across these studies.

TRPA1 Mediates Aromatase Inhibitor-Evoked Pain by the Aromatase Substrate Androstenedione.

Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, as the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of patients, we hypothesized that additional factors may cooperate to induce AIMSS. Here we report that the aromatase substrate androstenedione, unique among several steroid hormones, targeted TRPA1 in peptidergic primary sensory neurons in rodent and human cells expressing the native or recombinant channel. Androstenedione dramatically lowered the concentration of letrozole required to engage TRPA1. Notably, addition of a minimal dose of androstenedione to physiologically ineffective doses of letrozole and oxidative stress byproducts produces AIMSS-like behaviors and neurogenic inflammatory responses in mice. Elevated androstenedione levels cooperated with low letrozole concentrations and inflammatory mediators were sufficient to provoke AIMSS-like behaviors. The generation of such painful conditions by small quantities of simultaneously administered TRPA1 agonists justifies previous failure to identify a precise link between AIs and AIMSS, underscoring the potential of channel antagonists to treat AIMSS. Cancer Res; 76(23); 7024-35. ©2016 AACR.

Treating acute cough: wet versus dry - have we got the paradigm wrong?

It is time to abandon the dry/wet classification of acute cough due to URTI

Characterization of optimal resting tension in human pulmonary arteries.

To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations.

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review.

Fractional exhaled nitric oxide (Feno) is a safe and convenient test for assessing TH2 airway inflammation, which is potentially useful in the management of patients with chronic cough.

Ivacaftor and symptoms of extra-oesophageal reflux in patients with cystic fibrosis and G551D mutation.

Extra-oesophageal reflux (EOR) may lead to microaspiration in patients with cystic fibrosis (CF), a probable cause of deteriorating lung function. Successful clinical trials of ivacaftor highlight opportunities to understand EOR in a real world study.

Combating cough.

How does rhinovirus cause the common cold cough?

Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the host. The virus hijacks this natural defence mechanism in order to propagate itself through the population. Despite the resolution of the majority of cold symptoms within 2 weeks, cough can persist for some time thereafter. Unfortunately, the mechanism of infectious cough brought on by pathogenic viruses, such as human rhinovirus, during colds, remains elusive despite the extensive work that has been undertaken. For socioeconomic reasons, it is imperative we identify the mechanism of cough. There are several theories which have been proposed as the causative mechanism of cough in rhinovirus infection, encompassing a range of different processes. Those of which hold most promise are physical disruption of the epithelial lining, excess mucus production and an inflammatory response to rhinovirus infection which may be excessive. And finally, neuronal modulation, the most convincing hypothesis, is thought to potentiate cough long after the original stimulus has been cleared. All these hypotheses will be briefly covered in the following sections.

Idiopathic Pulmonary Fibrosis and Prothrombotic State.

Defining Chronic Cough: A Systematic Review of the Epidemiological Literature.

Recent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics.

Detection of pepsin in sputum: a rapid and objective measure of airways reflux.

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.

Over-the-counter cough medicines: New approaches.

The global market for over-the-counter (OTC) medicines in the category cough/cold is enormous amounting to 5.77 billion euro in 2014 (source IMS). Despite this enormous healthcare investment, mainly by direct consumer purchase, evidence for efficacy is poor by modern standards. Because of a lack of new drug development existing OTC medicines are supported by trials of inadequate design. This has led to the claim that cough medicines are inefficacious. Recent developments in measuring cough support some existing agents but investment in modern studies to provide comprehensive proof of efficacy has not happened. The switch from prescription medicine to OTC which has occurred in other markets will not occur in antitussives since novel therapies have yet to be developed. One area, that of herbal derived medicines, has seen innovation because it is less hampered by regulatory constraints.

Erratum to: The Impact of Chronic Cough: A Cross-Sectional European Survey.

Cough hypersensitivity syndrome: clinical measurement is the key to progress.

Radiotherapy for extensive stage small-cell lung cancer.

The impact of chronic cough: a cross-sectional European survey.

Studies that investigate the impact of chronic cough have largely focused on patients attending secondary care. Our aim was to investigate the opinions of the wider general population across Europe.

The global epidemiology of chronic cough in adults: a systematic review and meta-analysis.

The value of telehealth in the early detection of chronic obstructive pulmonary disease exacerbations: A prospective observational study.

We aim to establish the value of telemonitoring in the early detection of chronic obstructive pulmonary disease exacerbations. We followed up patients undergoing chronic obstructive pulmonary disease telemonitoring for 4 months. We studied changes in the telemonitored data in the week prior to admission or to community chronic obstructive pulmonary disease exacerbation. A total of 183 patients were studied. In all, 30 chronic obstructive pulmonary disease-related hospital admissions and 68 chronic obstructive pulmonary disease community exacerbations were recorded. Changes in telehealth parameters occurred in 80 per cent (24/30) of admissions and 82 per cent (56/68) of community exacerbations. Although changes in telehealth data occurred in the majority of exacerbations, most individual symptoms was present in less than half the exacerbations and almost 20 per cent of exacerbations were not preceded by any change in telemonitoring data. Cough created significantly more alerts by those treated in the community (p = 0.008), whereas a drop in oxygen saturation created significantly more alerts pre-hospitalisation (p = 0.049). We conclude that further work is required to develop methods of identifying impending chronic obstructive pulmonary disease exacerbations with greater sensitivity and specificity.

Developing antitussives the clinician's pipeline-what do we need?

The evolving concept of cough hypersensitivity, an over activity of the afferent sensory nerves in the upper airways, has given new insights into the pathophysiology underlying chronic cough. Armed with this new information drug development aimed at reducing cough reflex sensitivity to normal has, for the first time, led to successful clinical studies. This review outlines the concepts underlying the inflammatory processes leading to cough hypersensitivity and demonstrates how knowledge of the molecular pharmacology of hypersensitivity provides a lead into drug targets. Initial hope that antagonists of TRP receptors would reduce clinical cough has been disappointing. Drugs such as theobromine, thalidomide and AF 219 which all have activity on afferent sensory nerves have shown promise in clinical trials. Large-scale phase three clinical studies are required to confirm these exciting findings.

Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls.

A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response.

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10,032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60-69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation.

Is opiate action in cough due to sedation?

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.

Autonomic dysregulation: a mechanism of asthma death.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

On the definition of chronic cough and current treatment pathways: an international qualitative study.

The pathogenesis of chronic cough is not well understood and treatment options are limited. In this study we sought to explore the current understanding and management of chronic cough across an international group of specialists.

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

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.