Stephen Holgate (physician)

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Sir

Stephen Holgate

Born
Stephen Townley Holgate

(1947-05-02) 2 May 1947 (age 76)
Heywood, Lancashire, England
OccupationPhysician
SpouseElizabeth Holgate
Children4

Sir Stephen Townley Holgate, CBE , FRCP , FRCPath , MAE , FMedSci (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.

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. [6] [7] [8]

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. [9]

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">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.

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, such as Chronic obstructive pulmonary disease (COPD).

<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">Bisoprolol</span> Beta-1 selective adrenenergic blocker medication used to treat cardiovascular diseases

Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

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

Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.

<span class="mw-page-title-main">ADAM33</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 33 is an enzyme that in humans is encoded by the ADAM33 gene.

<span class="mw-page-title-main">Firestone Institute for Respiratory Health</span>

The Firestone Institute for Respiratory Health (FIRH) is a center for the investigation and treatment of respiratory diseases. Based out of St. Joseph's Healthcare in Hamilton, Ontario, Canada, the institute is a clinical facility with strong research directions. FIRH faculty are also heavily involved at McMaster University with education at the undergraduate, graduate, post-graduate and continuing medical education levels.

<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>

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

Chronic Mycoplasma pneumonia and Chlamydia pneumonia infections are associated with the onset and exacerbation of asthma. These microbial infections result in chronic lower airway inflammation, impaired mucociliary clearance, an increase in mucous production and eventually asthma. Furthermore, children who experience severe viral respiratory infections early in life have a high possibility of having asthma later in their childhood. These viral respiratory infections are mostly caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV). Although RSV infections increase the risk of asthma in early childhood, the association between asthma and RSV decreases with increasing age. HRV on the other hand is an important cause of bronchiolitis and is strongly associated with asthma development. In children and adults with established asthma, viral upper respiratory tract infections (URIs), especially HRVs infections, can produce acute exacerbations of asthma. Thus, Chlamydia pneumoniae, Mycoplasma pneumoniae and human rhinoviruses are microbes that play a major role in non-atopic asthma.

<span class="mw-page-title-main">Richard Beasley (physician)</span> New Zealand medical researcher

Charles Richard William Beasley is a New Zealand academic physician, the founder and Director of the Medical Research Institute of New Zealand, and as of 2019 is a full professor at the Victoria University of Wellington.

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">Sejal Saglani</span> British medical researcher

Sejal Saglani is a British medical researcher who is Professor and Head of the Inflammation, Repair and Development Section at the National Heart and Lung Institute. Her research considers wheeze and severe childhood asthma. She serves as an Honorary Consultant in Paediatric Respiratory Medicine at the Royal Brompton Hospital.

<span class="mw-page-title-main">Asthma trigger</span>

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.

Anthony Barrington "Barry" Kay was a British immunologist known for his research in asthma and allergy. He was a professor at Imperial College London and a consultant immunologist to Royal Brompton Hospital.

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. 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.
  7. "Southampton respiratory drug discovery spin-out seeks partnership". sciencebusiness.net. Retrieved 25 July 2020.
  8. 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.
  9. "No. 63135". The London Gazette (Supplement). 10 October 2020. p. B2.