A5021984160- Respiratory and Cough-Related Research
- Asthma and respiratory diseases
- Ion Channels and Receptors
- Neuroscience of respiration and sleep
- Voice and Speech Disorders
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pediatric health and respiratory diseases
- Cannabis and Cannabinoid Research
- Air Quality and Health Impacts
- Noise Effects and Management
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuropeptides and Animal Physiology
- Vagus Nerve Stimulation Research
- Tracheal and airway disorders
- Immune Cell Function and Interaction
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pharmacological Receptor Mechanisms and Effects
- Phosphodiesterase function and regulation
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Air Quality Monitoring and Forecasting
- Heart Rate Variability and Autonomic Control
- Pulmonary Hypertension Research and Treatments
- Acoustic Wave Resonator Technologies
- Geography and Environmental Studies
Imperial College London
2013-2023
The London College
2019
Zero to Three
2017
Imperial Valley College
2015-2016
Lung Institute
2015
National Institutes of Health
2013-2014
Rationale: Heightened cough responses to inhaled capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, are characteristic of patients with chronic cough. However, previously, TRPV1 antagonist (SB-705498) failed improve spontaneous frequency in these patients, despite small reductions capsaicin-evoked cough.Objectives: XEN-D0501 (a potent antagonist) was compared SB-705498 preclinical studies establish whether an improved efficacy profile would support further clinical trial...
Most airway diseases, including chronic obstructive pulmonary disease (COPD), are associated with excessive coughing. The extent to which this may be a consequence of increased activation vagal afferents by pathology in the airways (e.g., inflammatory mediators, mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases dysfunction sensory nerves has potential identify novel therapeutic targets.To assess changes cough responses range inhaled irritants COPD...
BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, are a potent stimulus for airway narrowing asthmatic patients, but mechanisms involved not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed respiratory...
BackgroundDiesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms asthma exacerbations. Respiratory reflexes responsible for regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP activates airway afferents to elicit symptoms, such as cough bronchospasm.ObjectiveWe sought identify mechanisms involved activation sensory DEPs.MethodsIn this study...
BackgroundRecent studies have suggested that the long-acting muscarinic receptor antagonist tiotropium, a drug widely prescribed for its bronchodilator activity in patients with chronic obstructive pulmonary disease and asthma, improves symptoms attenuates cough preclinical clinical tussive agent challenge studies. The mechanism by which tiotropium modifies responses is not clear, but an inhibition of vagal tone consequent reduction mucus production from submucosal glands bronchodilation...
Mast cell–airway smooth muscle (ASM) interactions play a major role in the immunoglobulin (Ig)E- dependent bronchoconstriction seen asthma but less is known about IgE-independent mechanisms of mast cell activation. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activation causes contraction human ASM via release cysteinyl leukotrienes (cysLTs) mechanism unknown. The objective present study was to investigate for IgE-independent, cell–ASM interaction TRPV4-induced...
Prostaglandin D 2 (PGD ) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin receptor (DP is a target for numerous drug discovery programmes little known about actions of PGD on sensory nerves cough. We used human guinea pig bioassays, vivo electrophysiology conscious model assess effect 1 ), DP thromboxane antagonism responses. caused an increase calcium airway jugular ganglia. Using pharmacology receptor-deficient mice...
Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is most frequent reason consultation with a family doctor, options are limited. Determining how inhibits cough might lead development optimized compounds.We sought investigate inhibitory activity on vagal sensory nerve reflex.Using...
Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation cough reflex, so was hypothesised would produce antitussive activity <i>via</i> elevation endocannabinoids. Primary ganglia neurons, tissue bioassay, <i>in vivo</i> electrophysiology conscious...
Abstract Airway sensory nerves play an important defensive role in the lungs, being central mediating protective responses like cough and bronchoconstriction. In some cases, these become excessive, hypersensitive, deleterious. Understanding normal function of airway phenotype changes associated with disease will help developing new therapeutics for treating chronic obstructive pulmonary cough. Guinea pigs, to a lesser extent ferrets, are commonly employed studying reflex because they have...
Adenylyl cyclase (AC) is a key signalling enzyme for many GPCRs and catalyses the conversion of ATP to cAMP which, in turn, crucial determinant biological responses. β-Adrenoceptor agonists are prescribed as bronchodilators asthma chronic obstructive pulmonary disease, it commonly assumed that they elicit their actions via AC-dependent production cAMP. However, empirical evidence support this lacking exact mechanism by which these drugs acts remains elusive. This partly due existence at...
<h3>Introduction and objectives</h3> Activation of afferent fibres from the lungs are involved in cough reflex. <i>In vitro</i> studies guinea-pig have demonstrated that there various sub-types Aδ-fibres (RAR’s, nociceptive cough)<sup>1</sup> C-fibres (either nodose or jugular ganglia derived),<sup>1,2</sup> however, little is known about their equivalent characteristics <i>in vivo</i>. This study aims to characterise responsiveness airway sensory nerves, vivo,</i> ultimately providing a...
DiSodium Cromoglycate (DSCG) has been used as an effective asthma therapy for over 50 years with a good clinical safety history but poor pharmacokinetics. An analogue of DSCG more preferable profile could aid the development novel drugs, however, mechanism action is currently unknown. Previous pre-clinical data linked late asthmatic response (LAR) activation Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel on airway sensory nerves<sup>1</sup> and shown to inhibit this in...
<b>Introduction:</b> Cough is an essential defensive reflex, however excessive/chronic cough a problematic symptom of respiratory diseases. We have previously shown that inhaled LABA can attenuate responses by suppressing airway sensory nerves. As LABAs are commonly prescribed to asthmatic patients where coughing persists, we hypothesised this beneficial property may be lost due tachyphylaxis as seen in smooth muscle (ASM) (Finney <i>et al</i>, BJP, 2001). <b>Methods:</b> Guinea pigs were...
In chronic lung diseases, activation of airway sensory nerves initiate respiratory reflexes including cough for which there is currently no safe and effective treatment. Ion channels on afferents can activate these as such are attractive therapeutic targets. The ion channel TRPM3 a sensor noxious heat (Vriens J.<i>et al.</i>Neuron.2011:70.482-494), activated by hypoosmolarity expressed in somatosensory neurons from dorsal root trigeminal ganglia. We aimed to characterise the role nerve...
<h3>Introduction</h3> Asthma is a debilitating disease of the airways characterised by symptoms such as bronchoconstriction, hyperresponsiveness and cough. Current therapies are associated with significant side effects ineffective in severe highlighting need for novel treatments. Menthol, cooling compound found medicinal products, commonly thought to activate thermo-sensing cation-permeable Transient Receptor Potential Melastatin 8 (TRPM8) channel. Furthermore, menthol known its beneficial...
Asthma is a debilitating disease of the airways characterised by symptoms such as bronchoconstriction, hyperresponsiveness and cough. Current therapies are ineffective in severe highlighting need for novel treatments. Menthol, cooling compound found medicinal products several OTC medications, commonly thought to activate Transient Receptor Potential Melastatin 8 (TRPM8) channel has been reported possess beneficial effects bronchodilation suppression cough, however mechanism action unknown....
Activation of TRPV4 causes vagal nerve depolarisation, single airway fibre firing and reflex cough in the guinea pig (GP) through activating nodose derived Aδ fibres(Belvisi M.<i>et al.</i>AJRCCM:2013.A5265). Ca<sup>2+</sup> signal demonstrated a short delay prior to activation, suggesting an indirect mechanism. possibly on urothelium has been linked ATP release activation P2X3 receptors bladder afferents (Aizawa N.<i>et al</i>. Neuro Urod,2010<i>:</i>148-55), so aim this study was...
Chronic cough, a reflex driven by sensory nerves, is major symptom of chronic lung diseases. A study has identified the P2X3 antagonist AF-219 to inhibit cough counts in patients (AbdulqawiR.etal, Lancet.2011:1198-205), suggesting role for ATP, however mechanisms are not fully understood. Previous studies indicated that ion channel TRPV4 activates airway nerves via ATP-P2X3 axis (BonviniSJ.etal.JACI.2016:249-261) and data suggests activation TRPM3 partly involves this pathway. Hypoosmolar...