Stephen Holgate

• University of Southampton

Background Respiratory viral infections (RVIs) are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon beta (IFN-β) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-β-1a nebuliser solution) aims to restore lung IFN-β...

Background

Background Despite the availability of vaccines and therapies, patients are being hospitalised with COVID-19. Interferon-β is a naturally-occurring protein that stimulates host immune responses against most viruses, including SARS-CoV-2. SNG001 is a recombinant interferon-β1a formulation delivered to the lungs via nebuliser. SPRINTER assessed the e...

Background People with post-COVID conditions can have a wide range of symptoms lasting months and it can affect as many as one in five infected people. Interferon beta (IFN-β) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-β-1a nebuliser solution) aim...

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. Methods: We d...

Background: Maternal asthma is a risk factor for asthma and airway hyperresponsiveness (AHR) in children. The asthma susceptibility gene, ADAM33, has been associated with AHR and impaired lung function in early life. Aims and Objectives: Our aim was to study how a maternal allergic environment in pregnancy interacts with offspring-ADAM33 and the e...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to h...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work ade...

Dendritic cells (DCs) play a central role in regulating innate and adaptive immune responses. It is well accepted that their regulatory functions change over the life course. In order to study DCs function during early life it is important to characterize the function of neonatal DCs. However, the availability of neonatal DCs is limited due to ethi...

Background: Omalizumab improves clinical outcomes in patients with asthma. Several studies have shown lung function improvements with omalizumab; however, this has not been examined exclusively in adolescents. Objective: To assess the effect of omalizumab on lung function and eosinophil counts in adolescents with uncontrolled moderate-to-severe...

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the mini...

Reproducible science requires transparent reporting. The ARRIVE guidelines were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and rep...

In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy...

Objective To evaluate associations between early life air pollution and subsequent mortality. Design Geographical study. Setting Local government districts within England and Wales. Exposure Routinely collected geographical data on the use of coal and related solid fuels in 1951–1952 were used as an index of air pollution. Main outcome measures...

Asthma is widely accepted as a complex heterogeneous condition with diverse pathophysiological mechanisms, clinical presentations, comorbidities, physiological characteristics, pathology and outcomes that is typically best managed by a multidisciplinary team [1–4]. Severe asthma is recognised as a major unmet need with a high personal and social im...

Air pollution has become one of the major risks to human health because of the progressive increase in the use of vehicles powered by fossil fuels. While the risks of air pollution to health were thought to have been brought under control by the Clean Air Acts of the 1950s and 1960s, the situation of air pollution in the UK has now deteriorated to...

Background: Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and regulatory issues that deter progress of AR research and...

The past two decades have seen the creation of several European collaborations focusing on asthma and chronic obstructive pulmonary disease (COPD). The growth of the collaboration model for research began in the late 1990s with the Framework Programme (FP)-4-funded project on severe asthma, ENFUMOSA (European Network for Understanding Mechanisms of...

Background: CD48 is a membrane receptor (mCD48) on eosinophils and mast cells and exists in a soluble form (sCD48). CD48 has a pivotal role in murine asthma and in the proinflammatory interactions of mast cells with eosinophils via its ligand CD244. Thus CD48 might be important in human asthma. Methods: Therefore, two separate cohorts (IL and UK...

The fellowship programmes are fundamental to the European Respiratory Society's (ERS) mission to promote lung health and drive standards for respiratory medicine globally. These programmes have been considerably expanded over the past 3 years and offer a wide range of training opportunities to boost early career scientists' competitiveness, enhance...

The short-term health effects of air pollution are well-documented, but less is known as to whether early-life exposure to pollutants has long-term adverse effects. Daly used consumption of coal and related fuels in 1951-2 to estimate pollution from domestic and industrial sources in 83 major conurbations covering approximately one third of the Eng...

In July 2013 the European Respiratory Society (ERS) developed its 2013–2018 strategic plan to serve its members better and achieve its mission objectives (table 1) [1]. The outcomes of the previous 2006–2007 Strategy Meeting [2] summarising the ERS pillars (figure 1) and the recently published ERS Presidential plans were used as background material...

Why the RCP and the RCPCH are tackling this issue Each year in the UK, around 40,000 deaths are attributable to exposure to outdoor air pollution, with more linked also to exposure to indoor pollutants. Air pollution plays a role in many of the major health challenges of our day, and has been linked to cancer, asthma, stroke and heart disease, diab...

Asthma is a common but complex clinical syndrome affecting people of all ages, characterized by variable airflow obstruction, bronchial hyperresponsiveness and airways inflammation, and manifesting as differing phenotypes. The symptoms of asthma are non-specific, and diagnosis may not be straightforward in community settings. Episodic exacerbations...

This report from the RCP and the RCPCH examines the impact of exposure to air pollution across the course of a lifetime.

For decades, health care practitioners have relied on Middleton's Allergy as their go-to reference for comprehensive information on allergic disorders. Now Middleton's Allergy Essentials, by Drs. Robyn E. O'Hehir, Stephen T. Holgate, and Aziz Sheikh, offers a concise resource that's both easily accessible and highly authoritative. Perfect for clini...

Asthma is an inflammatory disorder of the conducting airways with strong genetic and environmental risk factors. Most asthma begins in childhood and has a strong association with a biased Th2-type helper T cell response linked to immunoglobulin E sensitization to common environmental allergens. However, the different clinical manifestations and nat...

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last...

Asthma is the most common inflammatory disease of the lungs. The prevalence of asthma is increasing in many parts of the world that have adopted aspects of the Western lifestyle, and the disease poses a substantial global health and economic burden. Asthma involves both the large-conducting and the small-conducting airways, and is characterized by...

High bronchodilator reversibility (HR) in adult asthma is associated with distinct clinical characteristics. This analysis compares lung function, biomarker profiles and disease control in HR and low reversibility (LR) asthma patients. A retrospective analysis was performed with data from 2 completed clinical trials of similar design (NCT01018550 a...

Drugs targeting the immune system such as corticosteroids, antihistamines and immunosuppressants have been widely exploited in the treatment of inflammatory, allergic and autoimmune disorders during the second half of the 20th century. The recent advances in immunopharmacological research made available new classes of clinically relevant drugs. The...

Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations.

Andolast is a new airway specific anti-inflammatory agent. The aim of the present multicentered, randomized, placebo controlled study is to investigate whether andolast produces a therapeutic response greater than placebo in asthmatic adult patients. 549 symptomatic patients with mild or moderate asthma were randomized to receive andolast at three...

Asthma represents an area of significant unmet medical need, with few new drugs making it to the clinic in the past 50 years. Much asthma research is currently carried out in non-human models. However, as asthma is a uniquely human condition, it is difficult to translate findings from these models to efficacious therapies. Based on the results of a...

In their Science &Society article ‘Scientometrics in a changing research landscape' [1] Lutz Bornmann and Loet Leydesdorff state that ‘the new UK Research Excellence Framework (REF) puts more emphasis on bibliometric data and less on peer review than did its predecessor’. Having overseen the UK Research Excellence Framework 2014 (http://www.ref.ac...

Asthma is a chronic inflammatory disease. Reticular basement membrane (RBM) thickening is considered feature of airway remodelling (AR) particularly in severe asthma (SA). Omalizumab, mAb to IgE is effective in SA and can modulate AR. Herein we describe protein profiles of bronchial biopsies to detect biomarkers of anti-IgE effects on AR and to exp...

IgE is central to the pathophysiology of allergic asthma. Omalizumab, a humanized anti-IgE mAb, specifically binds free IgE and interrupts the allergic cascade by preventing binding of IgE with its high-affinity FcεRI receptors on mast cells, antigen-presenting cells, and other inflammatory cells. The clinical efficacy of omalizumab has been well d...

IgE has long been known as a therapeutic target for allergic disease, but the difficulty has been in selecting agents that don't trigger cross linkage of IgE when bound to its high affinity receptor (FceR1) on mast cells and basophils. By "designing" a monoclonal antibody (mAb) which targets that part of IgE that binds to that binds to the a-chain...

Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity. Objectives: To compare the efficacy and safety of inhaled IFN-β with placebo administered to people with asthma after onset...

In the past, asthma was considered mainly as a childhood disease. However, asthma is an important cause of morbidity and mortality in the elderly nowadays. In addition, the burden of asthma is more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related q...

Unbiased genetic approaches, especially genome-wide association studies, have identified novel genetic targets in the pathogenesis of asthma, but so far these targets account for only a small proportion of the heritability of asthma. Recognition of the importance of disease heterogeneity, the need for improved disease phenotyping, and the fact that...

In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation. Primary bronchial epithel...

Diesel exhaust is associated with cardiovascular and respiratory mortality and morbidity. Acute exposure leads to increased IL-8 expression and airway neutrophilia, however the mechanism of this response is unknown. Objectives: As cigarette smoke-induced IL-8 expression by epithelial cells involves transactivation of the epidermal growth factor rec...

Rationale: IL-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment. Objectives: To determine efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody, in subjects with inadequately controlled mode...

My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we h...

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 al...

Asthma is an inflammatory disorder of the conducting airways that has traditionally been classified according to severity. While this has been helpful in guiding treatment with drugs that are currently available such as β2-adrenoceptor agonists and corticosteroids, it takes little account of disease heterogeneity and causal pathways. This review dr...

Background: Because TNF-α is increased in severe asthma, we hypothesized that TNF-α contributes to barrier dysfunction and cell activation in bronchial epithelial cells. We further hypothesized that src-family kinase inhibition would improve barrier function in healthy cells in the presence of TNF-α and directly in cultures of severe asthmatic cel...

Asthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness (BHR) and airflow obstruction. Airway structural changes or airway remodelling consist of epithelial injury, goblet cell hyperplasia, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. These chang...

Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biod...

While asthma is an inflammatory disorder of the conducting airways with strong allergic overtones, the variable and often low clinical response to selective treatments that target the Th2 pathway have been disappointing. Beyond mild disease, asthma is a disorder of epithelial damage and aberrant repair with recapitulation of regenerative pathways t...

AIM: While asthma is a chronic inflammatory disorder that is managed with inhaled controller and reliever drugs, there remains a large unmet need at the severe end of the disease spectrum. Here a novel stratified approach to its treatment is reviewed based upon identification of causal pathways with a focus on biologics. METHODS: A systematic searc...

The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells. Fo...

Background: IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) α2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13Rα2 can be regulated by IFN-γ, a type II interferon, we hypothesized that innate antiviral responses characterized...

Advances in basic research and research and development plans of pharmaceutical companies are radically changing the kind of available drugs and therapeutic targets. We are switching from predominantly chemical molecules, aimed at treating large populations of patients (blockbuster drugs), to a new generation of products, mostly biotech, aimed at m...

Personalised medicine promises prediction, prevention and treatment of illness that is targeted to individuals’ needs. New technologies for detailed biological profiling of individuals at the molecular level have been crucial in initiating the move to personalised medicine; further novel technologies will be necessary if the vision is to become a r...

In the review article by Dr Maria Garcia-Cruz and her colleagues in Mexico, AERD and the cyclooxygenase theory are discussed with special emphasis on rhinosinusitis, its diagnosis and its treatment. Pathophysiological mechanisms are reviewed including recent studies of cytokine and chemokine anomalies in AERD, particularly in relation to Staphyloco...

Air pollution: a global health issue Air pollution remains a major, global, public health issue. The World Health Organization estimates that outdoor air pollution contributes to 5% of death world-wide (1.3 million deaths per year), and indoor air pollution contributes to 2 million premature deaths in developing countries (1) . © 2012 The Authors....

It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, sug...

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in...

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of th...

Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of interferon regulatory factor 5 (IRF5) in innate and adaptive immunity, we investigated the preferential transmission patterns of ten IRF5 gene polymorphis...

The recognition that asthma is primarily an inflammatory disorder of the airways associated with T helper type 2 (T(H)2) cell-dependent promotion of IgE production and recruitment of mast cells and eosinophils has provided the rationale for disease control using inhaled corticosteroids and other anti-inflammatory drugs. As more has been discovered...

Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that...

Adenosine, an endogenous signaling nucleoside that modulates many physiological processes has been implicated in playing an ever increasingly important role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). All cells contain adenosine and adenine nucleotides and the cellular production of adenosine is greatly enhanced...

Drugs used to treat asthma have a long history, beginning with the bronchodilators and evolving into compounds that suppress airway inflammation. Guidelines for treatment of asthma are largely based on disease severity and control, rather than underlying mechanisms. However, identification of biomarkers in the causal pathways of asthma is enabling...

Distinct phenotypes within asthma show differences in underlying pathophysiology, risk factors, clinical characteristics, natural history and response to treatment. Variations in treatment response may be due to differences in pathophysiology, including environmental, immunological or genetic factors. Individualized therapy according to phenotype i...

Asthma is a common chronic inflammatory disease of the airways that has received significant attention in recent years and around which there has developed substantial literature. This fifteen-chapter book represents a significant enhancement to that knowledge base. The Editors have brought together international experts to create a well rounded co...