Imperial College London

Dr Sara Bonvini

Faculty of MedicineNational Heart & Lung Institute

Academic Visitor
 
 
 
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Contact

 

+44 (0)20 7594 8397sara.bonvini10

 
 
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Location

 

102Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

53 results found

Bonvini SJ, 2020, Cause or Effect? Stretching to Understand the Inflammatory Role of Elastin Fiber Breakdown in Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 63, Pages: 558-559, ISSN: 1044-1549

Journal article

Bonvini SJ, Birrell MA, Dubuis E, Adcock JJ, Wortley MA, Flajolet P, Bradding P, Belvisi MGet al., 2020, Novel airway smooth muscle-mast cell interactions and a role for the TRPV4-ATP axis in non-atopic asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 56, ISSN: 0903-1936

Journal article

Lahousse L, Bahmer T, Cuevas-OcaƱa S, Flajolet P, Mathioudakis AG, McDonnell M, Uller L, Schleich F, Dortas Junior S, Idzko M, Singh D, Ricciardolo FLM, Adcock IM, Usmani O, Spanevello A, Bonvini SJet al., 2020, ERS International Congress, Madrid, 2019: highlights from the Airway Diseases, Asthma and COPD Assembly, ERJ Open Research, Vol: 6, ISSN: 2312-0541

The European Respiratory Society (ERS) International Congress 2019 in Madrid, Spain, was a platform for scientific discussion of the highest quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses some of the high-quality research studies presented at that Congress, with a focus on airway diseases, including asthma, COPD, small airways, bronchiectasis and cough, presented through the Airway Diseases, Asthma and COPD Assembly (Assembly 5) of the ERS. The authors establish the key take-home messages of these studies, compare their findings and place them into context of current understanding.

Journal article

Smith JA, Wortley MA, Bonvini S, Birrell M, Belvisi MGet al., 2020, "Truth is ever to be found in simplicity, and not in the multiplicity and confusion of things" - Sir Isaac Newton, EUROPEAN RESPIRATORY JOURNAL, Vol: 55, ISSN: 0903-1936

Journal article

Wortley MA, Bonvini SJ, 2019, TGFβ1 - a novel cause of resistance to bronchodilators in asthma?, American Journal of Respiratory Cell and Molecular Biology, Vol: 61, ISSN: 1044-1549

Journal article

Schleich F, Bikov A, Mathioudakis AG, McDonnell M, Andersson C, Bonini M, Uller L, Idzko M, Singh D, Lopez-Campos JL, Bossios A, Adcock IM, Usmani O, Spanevello A, Bonvini SJet al., 2019, Research highlights from the 2018 European Respiratory Society International Congress: airway disease., ERJ Open Research, Vol: 5, ISSN: 2312-0541

The annual European Respiratory Society (ERS) International Congress (held in Paris in 2018) was once again a platform for discussion of the highest-quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses only some of the high-quality research studies presented at this year's Congress, with a particular focus on airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cough, as presented through Assembly 5 of the ERS (Airway Diseases: Asthma and COPD). The authors establish the key take-home messages of these studies, compare their findings and place them in the context of current understanding.

Journal article

Miles JHA, Dubuis E, Bonvini SJ, Wortley MA, Trevisani M, Villetti G, Patacchini R, Birrell M, Belvisi MGet al., 2019, Monitoring Cough in a Preclinical Guinea Pig Model of Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Wortley MA, Bonvini SJ, Adcock JJ, Dubuis ED, Maher SA, Penn RB, Belvisi MG, Birrell MAet al., 2019, Agonism of EP<sub>4</sub> Receptors Expressed on Airway Sensory Nerves Inhibits Cough, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Chen X, Bonvini SJ, Dubuis ED, Ariyasu T, Ushio S, Birrell MA, Belvisi MGet al., 2019, Cromoglycate Inhibits Oxidative Stress Triggered Airway Sensory Nerves Through Its Actions on the Ion Channel TRPV2: A New Insight into Biological Mechanism of Action, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Chen X, Bonvini SJ, Dubuis E, Birrell MA, Belvisi MGet al., 2018, Characterisation of TRPA1 activation on sensory nerves, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Wortley M, Bonvini SJ, Flajolet PLM, Belvisi MG, Birrell MAet al., 2018, The anti-tussive effects of an inhaled LABA are maintained after chronic treatment, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Andersson C, Bonvini SJ, Horvath P, Marquez E, Satia I, Kirkham P, Schleich F, Idzko M, Gosens R, Lopez-Campos JL, Bossios A, Usmani O, Spanevello A, Adcock IM, Mathioudakis AGet al., 2018, Research highlights from the 2017 ERS International Congress: airway diseases in focus, ERJ Open Research, Vol: 4, ISSN: 2312-0541

For another year, high-quality research studies from around the world transformed the annual ERS International Congress into a vivid platform to discuss trending research topics, to produce new research questions and to further push the boundaries of respiratory medicine and science. This article reviews only some of the high-quality research studies on asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and chronic cough that were presented during the congress through the Airway Diseases Assembly (ERS Assembly 5) and places them into the context of current knowledge and research challenges.

Journal article

Chen X, Bonvini SJ, Dubuis E, Cheng F, Birrell MA, Belvisi MGet al., 2018, Cromoglycate Inhibits Airway Sensory Nerves Through an Impact on NADPHase: A Novel Understanding of Its Biological Activity?, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Wortley MA, Adcock JJ, Dubuis ED, Bonvini SJ, Birrell MA, Belvisi MGet al., 2018, Key Role for TLR2 in Bacterial Activation of Airway Sensory Nerves, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Bonvini SJ, Wortley MA, Adcock JJ, Dubuis E, Bolaji J, D'Sa S, Ma J, Birrell MA, Belvisi MGet al., 2018, Oestradiol Triggers Airway Sensory Nerve Activation Via The TRPM3-P2X2/3 Ion Channel Axis, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Bolaji J, Bonvini SJ, Adcock JJ, Dubuis E, Birrell MA, Belvisi MGet al., 2018, Cleaning Agent Surfactant, 4-Octylphenol, Activates Airway Sensory Nerves and Triggers Respiratory Symptoms: Role in Occupational Asthma?, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Ma J, Bonvini SJ, Dubuis E, Adcock JJ, Wortley MA, Birrell MA, Belvisi MGet al., 2018, Investigation into the Mechanisms Driving Hypo-Osmotic Stress-Triggered Activation of Airway Sensory Nerves, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Wortley MA, Dubuis ED, Bonvini SJ, Birrell MA, Belvisi MGet al., 2017, BACTERIA CAN TRIGGER AIRWAY SENSORY NERVES VIA THE ACTIVATION OF TLR2, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A1, ISSN: 0040-6376

Conference paper

Bonvini SJ, Wortley MA, Adcock JJ, Dubuis E, Bolaji JA, D'Sa S, Ma J, Birrell MA, Belvisi MGet al., 2017, OESTROGEN: AN ENDOGENOUS AGONIST FOR TRPM3 TRIGGERED SENSORY NERVE ACTIVATION IN THE AIRWAY?, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A1, ISSN: 0040-6376

Conference paper

Wortley MA, Adcock JJ, Dubuis ED, Maher SA, Bonvini SJ, Delescluse I, Kinloch R, McMurray G, Perros-Huguet C, Papakosta M, Birrell MA, Belvisi MGet al., 2017, Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy, European Respiratory Journal, Vol: 50, Pages: 1-11, ISSN: 0903-1936

Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.Primary vagal ganglia neurons, tissue bioassay, in vivo electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents.FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels.These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.

Journal article

Bonvini S, Dubuis E, Adcock J, Wortley M, Birrell M, Belvisi Met al., 2017, Activation of transient receptor potential (TRP) channels by hypoosmolar solution: an endogenous mechanism of ATP release and afferent nerve activation, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Bonvini SJ, Belvisi MG, 2017, Cough and airway disease: the role of ion channels, Pulmonary Pharmacology and Therapeutics, Vol: 47, Pages: 21-28, ISSN: 1094-5539

Cough is the most common reason for patients to visit a primary care physician, yet it remains an unmet medical need. It can be idiopathic in nature but can also be a troublesome symptom across chronic lung diseases such as asthma, COPD and idiopathic pulmonary fibrosis (IPF). Chronic cough affects up to 12% of the population and yet there are no safe and effective therapies. The cough reflex is regulated by vagal, sensory afferent nerves which innervate the airway. The Transient Receptor Potential (TRP) family of ion channels are expressed on sensory nerve terminals, and when activated can evoke cough. This review focuses on the role of 4 TRP channels; TRP Vannilloid 1 (TRPV1), TRP Ankyrin 1 (TRPA1), TRP Vannilloid 4 (TRPV4) and TRP Melastatin 8 (TRPM8) and the purinergic P2X3 receptor and their possible role in chronic cough. We conclude that these ion channels, given their expression profile and their role in the activation of sensory afferents and the cough reflex, may represent excellent therapeutic targets for the treatment of respiratory symptoms in chronic lung disease.

Journal article

Robinson RK, Birrell MA, Adcock JJ, Wortley MA, Dubuis ED, Chen S, McGilvery CM, Hu S, Shaffer MSP, Bonvini SJ, Maher SA, Mudway IS, Porter AE, Carlsten C, Tetley TD, Belvisi MGet al., 2017, Mechanistic link between diesel exhaust particles and respiratory reflexes, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 1074-1084.e9, ISSN: 1097-6825

BackgroundDiesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm.ObjectiveWe sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs.MethodsIn this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus.ResultsWe demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers.ConclusionsThis study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.

Journal article

Grace MS, Bonvini SJ, Belvisi MG, McIntyre Pet al., 2017, Modulation of the TRPV4 ion channel as a therapeutic target for disease., Pharmacology and Therapeutics, Vol: 177, Pages: 9-22, ISSN: 0163-7258

Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury. A lack of observed side-effects in vivo has prompted a first-in-human trial for a TRPV4 antagonist in healthy participants and stable heart failure patients. If successful, this would open up an exciting new area of research for a multitude of TRPV4-related pathologies. This review will discuss the known roles of TRPV4 in disease, and highlight the possible implications of targeting this important cation channel for therapy.

Journal article

Bonvini SJ, Adcock JJ, Dubuis E, Wortley M, Vriens J, Voets T, Birrell MA, Belvisi MGet al., 2017, Trpm3: A Regulator Of Airway Sensory Nerves And Respiratory Reflexes Via Distinct Mechanisms, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Bonvini SJ, Wortley M, Birrell MA, Belvisi Met al., 2017, Identification Of Endogenous, Disease Relevant Activators Of Trpv4 In The Airways, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Belvisi MG, 2016, Transient receptor potential cation channel, subfamily V, member 4 and airway, sensory afferent activation: role of adenosine triphosphate, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 249-261.e12, ISSN: 1097-6825

BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.

Journal article

Belvisi MG, Birrell MA, Khalid S, Wortley MA, Dockry R, Coote J, Holt K, Dubuis E, Kelsall A, Maher SA, Bonvini S, Woodcock A, Smith JAet al., 2016, Neurophenotypes in airway diseases: insights from translational cough studies, American Journal of Respiratory and Critical Care Medicine, Vol: 193, Pages: 1364-1372, ISSN: 1535-4970

Rationale: 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 of vagal afferents by pathology in the airways (e.g. inflammatory mediators, excessive mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases are associated with dysfunction of airway sensory nerves has the potential to identify novel therapeutic targets. Objectives: To assess the changes in cough responses to a range of inhaled irritants in COPD, and model these in animals to investigate the underlying mechanisms. Methods: Cough responses to inhaled stimuli in patients with COPD, healthy smokers, refractory chronic cough, asthma and healthy volunteers were assessed and compared with vagus/airway nerve and cough responses in a cigarette smoke (CS) exposure guinea-pig model. Measurements and Main Results: Patients with COPD had heightened cough responses to capsaicin but reduced responses to PGE2 compared with healthy volunteers. Furthermore, the different patient groups all exhibited different patterns of modulation of cough responses. Consistent with these findings, capsaicin caused a greater number of coughs in CS-exposed guinea-pigs than in controls; similar increased responses were observed in ex-vivo vagus nerve and neuron cell bodies in the vagal ganglia. However, responses to PGE2 were decreased by CS-exposure. Conclusions: CS exposure is capable of inducing responses consistent with phenotypic switching in airway sensory nerves comparable to the cough responses observed in patients with COPD. Moreover, the differing profiles of cough responses support the concept of disease-specific neuro-phenotypes in airway disease.

Journal article

Robinson RK, Birrell MA, Wortley MA, Dubuis ED, Chen S, McGilvery CM, Hu S, Bonvini SJ, Maher SA, Adcock JJ, Mudway I, Porter AE, Tetley TD, Belvisi MGet al., 2016, Diesel Activates Airway Sensory Nerves To Initiate Respiratory Symptoms, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Wortley MA, Dubuis E, Bonvini SJ, Wong S, Shala F, Maher SA, Adcock JJ, Smith JA, Birrell MA, Belvisi MGet al., 2016, Making Sense Of Sensory Nerves: An In Vitro Characterisation Of Gene Expression Profiles Of Airway-Innervating Guinea-Pig Airway Neurons Using Single-Cell Analysis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

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