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Alyn H Morice - Top 30 Publications

Pharmacology of cough in palliative care.

Cough is a common and distressing symptom. It has a marked decrement on quality-of-life particularly in the arena of palliative care where coexisting symptoms such as pain may be exacerbated. Whilst local definitive treatment may alleviate coughing it usually requires general measures. The purpose of the review is to assess the current evidence relating to the pharmacological management of cough.

Response to Risks and Cough-Aggravating Factors in Prolonged Cough.

Lipid Laden Macrophages in Respiratory Disease.

TRPA1 receptors in chronic cough.

TRPV1 polymorphisms influence capsaicin cough sensitivity in men.

Point prevalence and epidemiological characteristics of chronic cough in the general adult population: The Korean National Health and Nutrition Examination Survey 2010-2012.

Cough is frequently self-limiting, but may persist longer in certain individuals. Most of previous studies on the epidemiology of chronic cough have only measured period prevalence, and thus have afforded limited information on the burden and natural course. We aimed to investigate the epidemiology of chronic cough by using a point prevalence measure in a large-scale general population.We analyzed cross-sectional data collected from 18,071 adults who participated in the Korean National Health and Nutrition Examination Survey 2010-2012. Presence and duration of current cough was ascertained by structured questionnaires, and cough was classified into acute (<3 weeks), subacute (3-8 weeks), or chronic cough (≥8 weeks). Demographic and clinical parameters were examined in relation to chronic cough.The point prevalences of acute, subacute, and chronic cough were 2.5 ± 0.2%, 0.8 ± 0.1% and 2.6 ± 0.2%, respectively. The proportion of current cough showed a steep decrease after 1 week of duration. However, 2 peaks in the prevalence of current cough were revealed; cough durations of less than 1 week and longer than 1 year were most common (31.1% and 27.7% of current cough, respectively). Subacute and chronic cough were more prevalent in the elderly (≥65 years); the positive associations with older age were independent of other confounders, including current smoking and comorbidities.This is the first report on the epidemiology of cough using a point prevalence measure in a nationally representative population sample. Our findings indicate a high burden of chronic cough among adults with current cough in the community. The dual-peak of cough duration suggested that the pathophysiology of acute and chronic cough may differ. The preponderance of elderly people in the prevalence of chronic cough warrants further investigation. In addition, more sophistication and validation of tools to define chronic cough will help our understanding of the epidemiology.

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

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.

The effects of exogenous lipid on THP-1 cells: an in vitro model of airway aspiration?

Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid-laden macrophages (LLMs) within the airway may indicate aspiration secondary to GOR. The proposed mechanism, that lipid droplets from undigested or partially digested food are aspirated leading to accumulation in scavenging macrophages, led us to hypothesise that an activated population of LLMs could interact with other immune cells to induce bronchial inflammation. To test this, we generated an in vitro model using differentiated THP-1 cells, which were treated with a high-fat liquid feed. Here, we show that THP-1 cells can take up lipid from the high-fat feed independent of actin polymerisation or CD36-dependent phagocytosis. These cells did not exhibit M1 or M2 polarisation. Gene array analysis confirmed over 8000 genes were upregulated by at least twofold following high fat exposure, and IL-8 was the most upregulated gene. Pathway analysis revealed upregulation of genes known to be involved in chronic obstructive pulmonary disease (COPD) pathophysiology. We suggest that aspiration and macrophage phagocytosis may be important mechanisms in the aetiology of diseases such as COPD and cystic fibrosis that are characterised by high levels of IL-8 within the airways.

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.