Stephen Holgate (physician)

Last updated

Sir
Stephen Holgate
Born
Stephen Townley Holgate

(1947-05-02) 2 May 1947 (age 77)
Heywood, Lancashire, England
OccupationPhysician
SpouseElizabeth Holgate
Children4

Sir Stephen Townley Holgate (born 2 May 1947) is a British physician who specializes in immunopharmacology, respiratory medicine and allergies, and asthma and air pollution, based at the University of Southampton and University Hospital Southampton NHS Foundation Trust, UK. [1] [2] [3]

Contents

Education

Holgate was educated at The King's School in Macclesfield until 1965, when he joined Charing Cross Hospital Medical School, London (now incorporated into Imperial College London) where he received a BSc and MB BS. After completing postgraduate medical training in London at the National Hospital for Nervous Diseases and the Royal Brompton Hospital, he moved to Salisbury and Southampton where he completed his specialist higher medical training in general and respiratory medicine.

While a Clinical Lecturer at the University of Southampton, he researched the link between asthma death and over-use of beta-adrenergic bronchodilator inhalers. In 1978, Holgate received a Doctor of Medicine (MD) degree from the University of London. [4] [5]

In 1980, Holgate completed a two year post doctoral fellowship with K. Frank Austen at the Robert Brigham Hospital and Harvard University, Boston provided by the Dorothy Temple Cross MRC endowment and the Wellcome Trust. [ citation needed ]

Career and research

In 1980, Holgate began work at the University of Southampton researching the causes of human asthma and its treatment. After establishing the role that mast cells and other effector cells play in triggering the acute allergic inflammatory response in asthma, he examined the mechanisms of asthma chronicity and variability.

In 2002, Holgate collaborated with Donna Davies and Genome Therapeutics Corporation in Waltham, Mass, USA to identify the first novel asthma susceptibility gene of ADAM33 that encodes a metalloprotease linked to airway hyperresponsiveness and remodelling. This originated from the theory that in severe asthma, the airways behaved like a chronic wound with impaired epithelial repair and underlying tissue remodelling involving the deposition of new matrix, mucous metaplasia and proliferation of smooth muscle.

Holgate and his research group demonstrated the causal link between exacerbations in the autumn and winter months and respiratory virus infections. This led to the subsequent discovery that epithelial cells from those with moderate-severe asthma were deficient in their ability to generate an innate interferon beta response when infected by human rhinoviruses. [6]

In 2003 Holgate, Donna Davies and Ratko Djukanovic  [ Wikidata ] used this patented information to create the University spin-off company Synairgen to explore the potential therapeutic benefits of inhaled interferon beta in attenuating virus-induced exacerbations of asthma and COPD. Synairgen completed a Phase II placebo-controlled trial to treat COVID-19. [7] [8] [9]

Awards and honours

Holgate was appointed Commander of the Order of the British Empire (CBE) in 2011 and was knighted in 2020 for services to medical research. [10]

Related Research Articles

<span class="mw-page-title-main">Asthma</span> Long-term inflammatory disease of the airways of the lungs

Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise.

A bronchodilator or broncholytic is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be originating naturally within the body, or they may be medications administered for the treatment of breathing difficulties, usually in the form of inhalers. They are most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. Although this remains somewhat controversial, they might be useful in bronchiolitis and bronchiectasis. They are often prescribed but of unproven significance in restrictive lung diseases.

<span class="mw-page-title-main">Bronchospasm</span> Lower respiratory tract disease that affects the airways leading into the lungs

Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes difficulty in breathing which ranges from mild to severe.

<span class="mw-page-title-main">Fluticasone/salmeterol</span> Formulation used in the management of asthma and chronic obstructive pulmonary disease

Fluticasone/salmeterol, sold under the brand name Advair among others, is a fixed-dose combination medication containing fluticasone propionate, an inhaled corticosteroid; and salmeterol, a long-acting beta2‑adrenergic agonist. It is used in the management of asthma and chronic obstructive pulmonary disease (COPD). It is used by inhaling the medication into the lungs.

<span class="mw-page-title-main">Salmeterol</span> Chemical compound

Salmeterol is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchospasm include shortness of breath, wheezing, coughing and chest tightness. It is also used to prevent breathing difficulties during exercise.

<span class="mw-page-title-main">Aspirin-exacerbated respiratory disease</span> Chronic inflammatory disease affecting the sinuses and lungs

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated respiratory disease (N-ERD) or historically aspirin-induced asthma and Samter's Triad, is a long-term disease defined by three simultaneous symptoms: asthma, chronic rhinosinusitis with nasal polyps, and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell is extremely common, occurring in more than 90% of people with the disease. AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease.

Beta<sub>2</sub>-adrenergic agonist Compounds that bind to and activate adrenergic beta-2 receptors

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.

<span class="mw-page-title-main">Aminophylline</span> Chemical compound

Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate.

<span class="mw-page-title-main">Bronchoconstriction</span> Constriction of the terminal airways in the lungs

Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath.

Acute severe asthma, also known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators (inhalers) and corticosteroids. Asthma is caused by multiple genes, some having protective effect, with each gene having its own tendency to be influenced by the environment although a genetic link leading to acute severe asthma is still unknown. Symptoms include chest tightness, rapidly progressive dyspnea, dry cough, use of accessory respiratory muscles, fast and/or labored breathing, and extreme wheezing. It is a life-threatening episode of airway obstruction and is considered a medical emergency. Complications include cardiac and/or respiratory arrest. The increasing prevalence of atopy and asthma remains unexplained but may be due to infection with respiratory viruses.

<span class="mw-page-title-main">Pathophysiology of asthma</span> Medical condition

Asthma is a common pulmonary condition defined by chronic inflammation of respiratory tubes, tightening of respiratory smooth muscle, and episodes of bronchoconstriction. The Centers for Disease Control and Prevention estimate that 1 in 11 children and 1 in 12 adults have asthma in the United States of America. According to the World Health Organization, asthma affects 235 million people worldwide. There are two major categories of asthma: allergic and non-allergic. The focus of this article will be allergic asthma. In both cases, bronchoconstriction is prominent.

<span class="mw-page-title-main">Peter Barnes (respiratory scientist)</span> British pulmonary scientist and clinician

Sir Peter John Barnes, FRCP, FCCP, FMedSci, FRS is a British respiratory scientist and clinician, a specialist in the mechanisms and treatment of asthma and chronic obstructive pulmonary disease (COPD). He was Margaret Turner-Warwick Professor of Thoracic Medicine at the National Heart & Lung Institute, previous head of respiratory medicine at Imperial College and honorary consultant physician at the Royal Brompton Hospital London. He is one of the most highly cited scientists in the world

Airway basal cells are found deep in the respiratory epithelium, attached to, and lining the basement membrane.

Indacaterol/glycopyrronium bromide/mometasone, sold under the brand name Enerzair Breezhaler among others, is an inhalable fixed-dose combination medication for the treatment of asthma. It contains indacaterol as acetate, glycopyrronium bromide, and mometasone furoate.

Donna Elizabeth Davies is a British biochemist and professor of respiratory cell and molecular biology at the University of Southampton. In 2003, Davies was the co-founder of Synairgen, an interferon-beta drug designed to treat patients with asthma and chronic obstructive pulmonary disease.

Synairgen is a University spin-off and public limited company (plc) working in drug discovery and biotechnology. It was founded in 2003 by University of Southampton professors Stephen Holgate, Donna E. Davies and Ratko Djukanovic. The company is developing an inhaled formulation of interferon-beta for severe viral respiratory diseases including COVID-19.

<span class="mw-page-title-main">Asthma trigger</span> Factor that provokes symptoms of asthma

Asthma triggers are factors or stimuli that provoke the exacerbation of asthma symptoms or increase the degree of airflow disruption, which can lead to an asthma attack. An asthma attack is characterized by an obstruction of the airway, hypersecretion of mucus and bronchoconstriction due to the contraction of smooth muscles around the respiratory tract. Its symptoms include a wide range of manifestations such as breathlessness, coughing, a tight chest and wheezing.

John William Holloway is a geneticist based at the University of Southampton, where he is professor of allergy and respiratory genetics, and was appointed associate vice-president interdisciplinary research in 2021. He leads a research team based within the human genetics and medical genomics theme of the School of Human Development & Health, Faculty of Medicine. Holloway is a Fellow of the Higher Education Academy.

Anti-asthmatic agents refer to drugs that can aid in airway smooth muscle dilation to allow normal breathing during an asthma attack or reduce inflammation on the airway to decrease airway resistance for asthmatic patients, or both. The goal of asthmatic agents is to reduce asthma exacerbation frequencies and related hospital visits.

Jo A. Douglass or Jo Anne Douglass; is an Australian asthma researcher, Director of Research within the Royal Melbourne Hospital, James Stewart Professor of Medicine and she is also Department Head of Medicine within the Melbourne Medical School. She was awarded an Order of Australia, for her "distinguished service to medical research, to clinical immunology and allergy, to respiratory medicine, and to tertiary education."

References

  1. "Professor Stephen T. Holgate - King Faisal International Prize". Kfip.org. Retrieved 22 October 2017.
  2. "Professor Stephen Holgate". southampton.ac.uk. University of Southampton. Retrieved 22 October 2017.
  3. "Stephen Townley HOLGATE". London: Companies House.
  4. Holgate, Stephen Townley (1978). Beta-Adrenergic Resistance - The development and Mechanisms in normal man. london.ac.uk (MD thesis). University of London. OCLC   1006020949. EThOS   uk.bl.ethos.459448.
  5. "Professor Stephen Holgate CBE - AAIR Charity". Aaircharity.org. Retrieved 22 October 2017.
  6. "Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus". scholar.google.com. Retrieved 20 August 2024.
  7. Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F. (2015). "Drug development for airway diseases: looking forward". Nature Reviews Drug Discovery. 14 (6): 367–368. doi:10.1038/nrd4645. ISSN   1474-1776. PMID   26000726. S2CID   8539798.
  8. "Southampton respiratory drug discovery spin-out seeks partnership". sciencebusiness.net. Retrieved 25 July 2020.
  9. Neate, Rupert (24 July 2020). "'Major' breakthrough in Covid-19 drug makes UK professors millionaires". The Guardian . London. ISSN   0261-3077 . Retrieved 25 July 2020.
  10. "No. 63135". The London Gazette (Supplement). 10 October 2020. p. B2.