Developed using the GRADE methodology, these EAACI guidelines provide evidence-based recommendations on the effectiveness of pollen reduction/avoidance strategies for allergic rhinitis (AR) and asthma, the utility of biomarkers for monitoring pollen-induced asthma and the efficiency of mitigation measures and of public health strategies. Systematic and narrative reviews and health economic analysis support the recommendations. According to GRADE, the certainty of evidence was moderate to very low, therefore conditional recommendations are provided to guide healthcare professionals, patients, and policymakers in developing personalized, preventive, and scalable interventions. Reducing/avoiding exposure to pollen should be recommended to reduce the risk of severe asthma exacerbations. Lung function decrease and exhaled nitric oxide increase may be predictive for pollen-induced asthma exacerbations. Real-time pollen monitoring and pollen concentration-based forecast may be recommended for managing pollen-induced AR and/or asthma. Pollutant information should be included in pollen information systems. Combined forecast (weather, pollen, pollutants) and warning systems might reduce the impact of thunderstorm asthma (TA). Emergency department/asthma-related services should be strengthened during pollen season and in TA. Personalized frameworks covering the types and allergenic potential of pollen, the coaggressors and the vulnerability of each patient are needed in daily practice. The fundamental role of prevention should be further prioritized.

The EAACI Guidelines used the GRADE approach to evaluate the impact of major indoor air pollutants (dampness and mould, cleaning agents, volatile organic compounds and pesticides) on the risk of new-onset asthma and on asthma-related outcomes. The guideline also acknowledges the synergies among indoor air pollutants and other components of the indoor exposome (allergens, viruses, endotoxins). Very low to low certainty of evidence was found for the association between exposure to indoor pollutants and increased risk of new-onset asthma and asthma worsening. Only for mould exposure there was moderate certainty of evidence for new-onset asthma. Due to the quality of evidence, conditional recommendations were formulated on the risk of exposure to all indoor pollutants. Recommendations are provided for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management. For policymakers and regulators this evidence-informed guideline supports setting legally binding standards and goals for indoor air quality at international, national and local levels. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but community and governmental measures for improved indoor air quality are needed to achieve significant impact.

Exposure to air pollution has been associated with up to 9 million premature deaths per year worldwide, with the respiratory system a key site for its effects. Air pollution exposure is a well-established risk factor for the development and exacerbation of airways diseases and lung cancer, however relatively little is known regarding the risks associated with air pollution interacting with areas of gas exchange - the alveoli and pulmonary interstitium. In recent years, evidence has emerged identifying a role in the development and progression of sub-clinical interstitial lung abnormalities as well as progression and risk of exacerbation of fibrotic interstitial lung diseases. This review outlines the epidemiologic evidence that air pollution perturbs alveolar health. It considers the different components of ambient air pollution, how penetration to the alveoli is determined by particle size and whether the response to alveolar exposure may be modulated by personal susceptibility factors. We discuss potential acute and chronic pathogenic mechanisms of injury upon the pulmonary interstitium and how these may contribute to the development and/or progression of interstitial processes. Finally, we explore current knowledge gaps and the potential for air pollution interventions in vulnerable individuals to support alveolar homeostasis and so prevent disease development and/or progression.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Almost 5 years ago, in my ‘letter from the UK’, I expressed concerns about BREXIT. What has happened since its declaration 1 year later has hardly been a success story either economically or in respect of the UK's contributions to health and science. After several years of toing and froing, on 4 December 2023, the EU and UK completed the final step towards association to Horizon Europe. At the same time in December 2023, according to Statista,1 55% of UK people thought that it was wrong to leave the EU compared with 33% who still considered it was the right decision. In the 2016 referendum, Leave comprised 51.9% percent of the votes and Remain 48.1%. This considerable reversal of national opinion has generated its own apt descriptor—Bregret. The last 5 years has witnessed the world becoming much more unstable and, with slowing of economic growth and conflict, a large increase in migration. This instability and economic decline have been exacerbated by the COVID-19 pandemic, the first documented case in the UK being on 31 January 2020 with, over the next 2 years, large waves of infection to follow. Hardly a single country has been spared the ravages of this disease, though it seems now as if every country had different views on its prevention and management. Among a range of inputs by UK scientists and clinicians,2 I had the privilege of chairing three Academy of Medical Sciences Working Groups to help develop effective management strategies. The advice emerging from the interdisciplinary advisory groups were requested by the Government's Scientific Advisory Group for Emergencies (SAGE) but, as the current COVID Enquiry is revealing, this advice came too late and was playing catch-up. Put simply, the UK was totally unprepared for the impact that SARS CoV-2 virus was to have on the population, particularly the vulnerable and disadvantaged members of society. However, what COVID-19 did demonstrate in the UK and in all countries faced with such a huge and unexpected challenge, was the remarkable courage and resilience of the health professions. Respiratory, Intensive Care and Infectious Disease specialists were at the leading edge of COVID-19 management—and all credit to them—in many cases putting their own lives at risk for the benefit of others. COVID-19 has not gone away, and our greatest enemy now is complacency. One effect of the pandemic was that the scientific community worked more closely together, both in academia and industry—establishing collaborations seemed so much easier. This led to the rapid development of point-of care diagnostics, coordinated trials of both repurposed and novel therapies (including large adaptive platform trials) and, of course, the SARS CoV-2 vaccines (especially the DNA vaccines) with accelerated clinical trial role out. Lockdown restrictions in the UK were lifted in July 2020 and while there have been further SARS CoV-2 waves, the high proportion of the vaccinated population coupled with viral mutations have reduced disease severity (with viral tropism more directed to the conducting airways rather than the alveoli). With continued top-up vaccination for the more vulnerable, there are now no COVID-related restrictions in the UK. The latest Omicron XBB SARS CoV-2 lineage variant JN.1, a descendent of BA 2.86 (Pirola) remains sensitive to current vaccines which more closely target the Omicron XBB lineage. However, with the rate at which this virus is mutating over time, it is highly likely that further updating of vaccines will be needed, especially if the virus mutates to become more virulent. Then there remains the enigma of the post-viral syndrome (Long COVID or post-acute sequelae of SARS-CoV-2 [PASC]) affecting 3% of the UK population with a range of debilitating symptoms, both organ-specific and less specific. The latter symptoms, which include persistent fatigue, myalgias and arthralgias, post-exertion malaise (PEM), cognitive problems (e.g. "brain fog"), headaches, disrupted sleep and orthostatic intolerance are similar, if not identical to, those experienced in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),3 a greatly misunderstood multi-system post-viral disorder effecting at least 250,000 adults and children in the UK and 17 million worldwide. Hopefully, understanding the mechanisms behind PASC (including PEM4) will also provide insights into those of ME/CFS, and enable effective therapeutic interventions to be developed for both disorders. One effect of the COVID-19 pandemic has been a much-needed greater focus on the importance of lung disease research which, in the UK (and I am sure in other countries), has not been well funded as compared to other organ-based disease.5 The reasons for this are in part historical (lung disease linked to tobacco smoking, industrial exposures and poverty) and in diseases like COPD and IPF, the symptom of breathlessness does not appear until a substantial amount of working lung tissue is lost. One positive step towards greater lung research in the UK has been the merger of our two main lung charities—the British Lung Foundation and Asthma UK—into a single new charity—Asthma + Lung UK (A + LUK) along with an ambitious and progressive research strategy aimed at reducing respiratory morbidity and mortality by 20% over the next 5 years. The COVID-19 pandemic has shone a light upon the importance of the ‘breathed environment’, both indoors and outdoors. In my 2019 ‘Letter’, I had hoped that BREXIT would have created the opportunity for a new Clean Air Act. However, difficult politics (3 Prime Ministers in 3 months!) has made progress towards cleaning up the air more difficult. However, not all is lost. A second inquest of Ella Adoo Kissi-Debrah, a 9-year-old London girl who died of catastrophic asthma, established an important role of air pollution in her death and, for the first time, air pollution was listed as a contributing cause on a death certificate. Her Mother, Rosamund (now a WHO BreatheLife Ambassador) has worked alongside A + LUK and our Medical Royal Colleges to raise the profile of air pollution in the UK and the right for all to breathe clean air (Figure 1). In October 2023, her tireless efforts catalysed the creation of a Clean Air (Human Rights) Bill (Ella's Law, a Private Members Bill) which was finally laid before parliament on December 7 2023. Let us hope that whatever government we eventually get later this year sees this as a major public health priority, as happened in 1956 when a new government secured the Clean Air Act and the world's first coordinated national air pollution monitoring network again, following a Private Members Bill. Going forward, there is optimism that cleaner air can be achieved here, and in other countries, especially if health professionals become more actively engaged in making the case for the substantial health benefits, as they did so effectively in 2007 with the UK ban on smoking in closed public spaces. After all, if COVID-19 has taught us one thing, our lives depend upon whatever is in the air we breath. Stephen T. Holgate is a cofounder and non-executive Director of Synairgen, consultant to Dyson and Clean Air Technologies, is a UKRI Clean Air Champion and Special Advisor to the Royal College of Physicians on air quality.

The EAACI Guidelines on the impact of short-term exposure to outdoor pollutants on asthma-related outcomes provide recommendations for prevention, patient care and mitigation in a framework supporting rational decisions for healthcare professionals and patients to individualize and improve asthma management and for policymakers and regulators as an evidence-informed reference to help setting legally binding standards and goals for outdoor air quality at international, national and local levels. The Guideline was developed using the GRADE approach and evaluated outdoor pollutants referenced in the current Air Quality Guideline of the World Health Organization as single or mixed pollutants and outdoor pesticides. Short-term exposure to all pollutants evaluated increases the risk of asthma-related adverse outcomes, especially hospital admissions and emergency department visits (moderate certainty of evidence at specific lag days). There is limited evidence for the impact of traffic-related air pollution and outdoor pesticides exposure as well as for the interventions to reduce emissions. Due to the quality of evidence, conditional recommendations were formulated for all pollutants and for the interventions reducing outdoor air pollution. Asthma management counselled by the current EAACI guidelines can improve asthma-related outcomes but global measures for clean air are needed to achieve significant impact.

Abstract Background Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. Methods In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Results In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. Conclusions Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. Trial registration EU clinical trials register (2017-003679-75), 6 October 2017.

Background: Interferon beta (IFN-β), a key host antiviral mediator, can be suppressed by virus or host factors locally at the site of infection. Inhaled SNG001 (IFN-β-1a nebuliser solution) aims to restore lung IFN-β levels. In a Phase 2 trial hospitalised COVID-19 patients receiving SNG001 were more than twice as likely to recover, supporting progression to the Phase 3 SPRINTER trial in hospitalised patients and inclusion of SNG001 in the ACTIV-2 Phase 2/3 trial in non-hospitalised volunteers (Figure 1). The SPRINTER study did not meet its primary efficacy endpoints, hospital discharge and recovery, likely due to improved standard of care reducing the window to show a treatment effect. An encouraging signal for the key secondary endpoint, prevention of progression to severe disease or death (26% RRR;OR 0.71(0.44,1.15);p=0.161), was observed and supported by post hoc analyses of at risk groups. Results: In ACTIV-2 there were no statistically significant differences between SNG001 and placebo for the primary outcomes of safety (SNG001 was well-tolerated), symptom resolution, or virology. However, fewer participants required hospitalisation following SNG001 treatment (N=1/110, [1%]) compared to placebo (N=7/110, [6%]), 86% RRR (P=0.07). IDSMB recommended progression to Phase 3. Conclusions: SNG001 was well tolerated across trials and should continue to be investigated for COVID-19 in the home and hospital settings.

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.

AllergyAccepted Articles OBITUARY IN MEMORIAM : Lawrence M. Lichtenstein (1934-2022) Gianni Marone, Corresponding Author Gianni Marone marone@unina.it Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy Center for Basic and Clinical Immunology Research (CISI), Naples, Italy Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy Correspondence Gianni Marone, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy Email: marone@unina.itSearch for more papers by this authorMassimo Triggiani, Massimo Triggiani Division of Allergy and Clinical Immunology, University of Salerno, Fisciano, SA, ItalySearch for more papers by this authorVincenzo Casolaro, Vincenzo Casolaro orcid.org/0000-0001-9810-0488 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, ItalySearch for more papers by this authorCristiana Stellato, Cristiana Stellato orcid.org/0000-0002-1294-8355 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, ItalySearch for more papers by this authorAmato de Paulis, Amato de Paulis Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy Center for Basic and Clinical Immunology Research (CISI), Naples, ItalySearch for more papers by this authorStephen T. Holgate, Stephen T. Holgate Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, UKSearch for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, SwitzerlandSearch for more papers by this authorStephen J. Galli, Stephen J. Galli orcid.org/0000-0001-5736-5340 Department of Pathology and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, California Department of Microbiology and Immunology, Stanford University School of Medicine, CaliforniaSearch for more papers by this author Gianni Marone, Corresponding Author Gianni Marone marone@unina.it Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy Center for Basic and Clinical Immunology Research (CISI), Naples, Italy Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (CNR), Naples, Italy Correspondence Gianni Marone, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy Email: marone@unina.itSearch for more papers by this authorMassimo Triggiani, Massimo Triggiani Division of Allergy and Clinical Immunology, University of Salerno, Fisciano, SA, ItalySearch for more papers by this authorVincenzo Casolaro, Vincenzo Casolaro orcid.org/0000-0001-9810-0488 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, ItalySearch for more papers by this authorCristiana Stellato, Cristiana Stellato orcid.org/0000-0002-1294-8355 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, ItalySearch for more papers by this authorAmato de Paulis, Amato de Paulis Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy World Allergy Organization (WAO), Center of Excellence (CoE), Naples, Italy Center for Basic and Clinical Immunology Research (CISI), Naples, ItalySearch for more papers by this authorStephen T. Holgate, Stephen T. Holgate Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, UKSearch for more papers by this authorCezmi A. Akdis, Cezmi A. Akdis orcid.org/0000-0001-8020-019X Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, SwitzerlandSearch for more papers by this authorStephen J. Galli, Stephen J. Galli orcid.org/0000-0001-5736-5340 Department of Pathology and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, California Department of Microbiology and Immunology, Stanford University School of Medicine, CaliforniaSearch for more papers by this author First published: 11 October 2022 https://doi.org/10.1111/all.15549 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/all.15549 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Background Despite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-β is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-β1a formulation delivered to the lungs via nebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygen via nasal prongs or mask. Methods Patients were randomised double-blind to SNG001 (n=309) or placebo (n=314) once daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001 versus placebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary end-points were progression to severe disease or death, progression to intubation or death and death. Results Median time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio (HR) 1.06 (95% CI 0.89–1.27); p=0.51); time to recovery was 25.0 days in both groups (HR 1.02 (95% CI 0.81–1.28); p=0.89). There were no significant SNG001–placebo differences for the key secondary end-points, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; OR 0.71 (95% CI 0.44–1.15); p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively. Conclusions Although the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary end-points analysis suggested that SNG001 may have prevented progression to severe disease.

The Cambridge Structural Database (CSD) is a collection of over one million experimental three-dimensional structures obtained through crystallographic analyses. These structures are determined by crystallographers worldwide and undergo curation and enhancement by scientists at the Cambridge Crystallographic Data Centre (CCDC) prior to their addition to the database. Though the CSD is substantial and contains widespread chemical diversity across organic and metal–organic compounds, it is estimated that a significant proportion of crystal structures determined are not published or shared through the peer-reviewed journal mechanism. To help overcome this, scientists can publish structures directly through the database as CSD Communications and these structural datasets are made publicly available alongside structures associated with scientific articles. CSD Communications contribute to the collective crystallographic knowledge as nearly two thirds are novel structures that are not otherwise available in the scientific literature. The primary benefits of sharing data through CSD Communications include the long-term preservation of scientific data, the strengthening of a widely data-mined world repository (the CSD), and the opportunity for scientists to receive recognition for their work through a formal and citable data publication. All CSD Communications are assigned unique digital object identifiers (DOIs). Contributions as CSD Communications currently comprise about 3.89% of the total CSD entries. Each individual CSD Communication is free to view and retrieve from the CCDC website.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.

Abstract 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 levels. SG015 (NCT03570359) was a randomized, placebo-controlled Phase 2 clinical study of inhaled SNG001 conducted in COPD patients. Here we describe lung antiviral biomarker and sputum viral clearance data from Part 2 of the study which was conducted in patients with a confirmed RVI. Methods 109 COPD patients with worsening symptoms and a positive respiratory viral test were randomized 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e.,acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Sputum samples were collected on days 1, 4, 7, 10, 13, 17 and 28 for analysis of lung antiviral biomarker responses (interferon-stimulated genes (ISGs): Mx1, OAS1 and CXCL10) and lung viral load by RT-qPCR. Results Mx1 and OAS1 sputum cell gene expression were significantly upregulated on day 7, 10 and 13 (p< 0.05) overall and in Groups A and B with SNG001 treatment compared to placebo. CXCL10 sputum cell gene expression was significantly upregulated in the overall population with SNG001 treatment compared to placebo on days 7 and 10, in Group B on days 7, 10 and 13, and there was no significant difference in Group A. Patients had a broad range of RVIs, the most common being human rhinovirus. A post-hoc analysis was therefore conducted in the subgroup of patients who had detectable rhinovirus viral load in sputum. By Day 4 the proportion of patients receiving SNG001 who had detectable rhinovirus reduced to 40.0% (compared to 94.7% of patients receiving placebo; p=0.052), with a further reduction to 20.0% on Day 7 (versus 89.5% receiving placebo; p=0.014). Conclusion Inhaled SNG001 upregulated lung antiviral defenses as assessed using sputum cell biomarker responses and accelerated viral clearance, supporting the proposed mechanism of action as an antiviral treatment for severe viral lung infections. Disclosures Phillip D. Monk, PhD, Synairgen Research Plc: Employee of Synairgen Research Plc and has options on shares|Synairgen Research Plc: Stocks/Bonds Jody L. Brookes, BSc, Synairgen Research Ltd: Share options Victoria J. Tear, PhD, Synairgen Research Ltd.: Stocks/Bonds Marcin Mankowski, MD MFPM (Dis), Multiple companies: Advisor/Consultant|Synairgen: Advisor/Consultant Michael G. Crooks, MBChB (hons), MD, FRCP, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Chiesi: Advisor/Consultant|Chiesi: Honoraria|Gilead: Honoraria|Synairgen: Advisor/Consultant Dave Singh, MD, AstraZeneca: Advisor/Consultant|Chiesi: Advisor/Consultant|gsk: Advisor/Consultant|Novartis: Advisor/Consultant|Orion: Advisor/Consultant|Pulmatrix: Advisor/Consultant|Sanofi: Advisor/Consultant|Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support|Therevance: Advisor/Consultant Rekha Chaudhuri, MD, AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Chiesi: Honoraria|GSK: Honoraria|Novartis: Honoraria|Sanofi: Honoraria|Teva: Honoraria Sarah Dudley, N/A, PhD, Synairgen Plc: Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc|Synairgen Plc: Stocks/Bonds Felicity Gabbay, MbChb, Synairgen: Board Member Stephen T. Holgate, FMedSci, MD, Synairgen Research Plc: Board Member|Synairgen Research Plc: Stocks/Bonds Ratko Djukanovic, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|KyMab: Advisor/Consultant|Sanofi: Advisor/Consultant|Synairgen: Advisor/Consultant|Synairgen: Stocks/Bonds Tom Wilkinson, PhD, PhD, Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support|Synairgen: Honoraria

Air pollution is a public health emergencyThe UK government must commit to (much) cleaner air by 2030

In July 2021, the UK Office of Life Sciences (OLS) published a Life Sciences Vision for the UK highlighting key areas for action. The report specifically flagged reducing morbidity and mortality from respiratory disease as one of the seven healthcare mission priorities. In addition, the report emphasised more generally the need to support underpinning infrastructure to enable better use of health data and genomic data and increasing the efficiency of clinical research delivery to improve healthcare. The importance of a flourishing respiratory disease research community in the UK has also been bought into sharp focus by the COVID19 pandemic. The UK has achieved international acclaim for its ability to deliver definitive therapeutic trials in COVID19 and has also made major investments into research on long COVID19 through UKRI and NIHR which will further inform clinical practice. There remains however a key question: how well prepared is the respiratory research community to deliver on the OLS vision? Some further insights on the state of UK respiratory research can be gained from two recent consultation exercises. The first of these was designed to identify priority areas for attention and took place between 2017 and late 2019 by a group brought together under the informal auspices of the UK Respiratory Research Collaborative (UKRRC). It included two multidisciplinary open sessions held at the winter British Thoracic Society meeting and meetings with key stakeholders including major respiratory charities and a range of opinion leaders. Unfortunately, the pandemic intervened before this work was completed, but nevertheless it provided valuable stakeholder insights. A further highlevel round table meeting with government convened by Asthma+Lung UK reinforced the need for a new approach. In this article, we summarise the main messages which came out of the consultations undertaken by UKRRC and Asthma+Lung UK and review the changes brought about by the pandemic. We identify key areas on which, as a specialty, we should focus to ensure the UK is positioned to address the challenge thrown down by the OLS vision and make suggestions on how to address this challenge.

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) aims to restore lung IFN-β levels. SPRINTER (NCT04732949) was a RCT of inhaled interferon beta in hospitalised COVID-19. There was no effect of SNG001 on the primary endpoints of time to discharge or recovery most likely due to improvements in the standard of care. However, there was an encouraging signal for the key secondary endpoint of prevention of progression to severe disease or death (ITT 26% relative risk reduction [RRR]; Odds Ratio [95% CI]: 0.71 [0.44, 1.15]; Per Protocol 36% RRR; OR 0.63 [0.35, 1.13]). Post hoc analyses showed enhanced effects favouring SNG001 in subgroups at higher risk of progression. We report on the impact of SNG001 on long COVID symptoms in SPRINTER. Patients requiring low-flow oxygen were randomized to receive SNG001 (314) or placebo (309) once daily for 14 days, plus standard-of-care. Long COVID symptoms were assessed as a secondary endpoint at follow-up visits via telephone/video call on Day 60 and Day 90. The following patient reported outcome (PRO) measures were also assessed: General Anxiety Disorder 7 Questionnaire (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale and Brief Pain Inventory (Short Form). When compared to placebo, SNG001 reduced the relative risk of common symptoms of long COVID (fatigue/malaise [RRR=35.4%]; dyspnoea [RRR=28.3%]; loss of smell and/or taste [RRR=61.4%]). Analysis of the PROs is ongoing. Assessment of COVID symptoms at Day 60 and 90 follow up visits Effect of SNG001 treatment on long COVID symptoms Long COVID can leave patients with lingering cognitive, respiratory, and functional symptoms months after a SARS-CoV-2 infection. Given the shift from pandemic to endemic status for COVID-19 and the need for new treatments then these findings, suggesting SNG001 may be impacting common long COVID symptoms, provide additional support for the further investigation of SNG001. Phillip D. Monk, PhD, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Board Member|Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Victoria J. Tear, PhD, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Jody L. Brookes, BSc, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Marcin Mankowski, MD, MFPM (Dis), CytoDyn: Advisor/Consultant|Entasis: Advisor/Consultant|ImmuPharma: Advisor/Consultant|Menarini: Advisor/Consultant|Pfizer: Advisor/Consultant|Synairgen: Advisor/Consultant|Venatorx: Advisor/Consultant Ratko Djukanovic, MD, Synairgen: Advisor/Consultant|Synairgen: Honoraria|Synairgen: Stocks/Bonds Stephen T. Holgate, FMedSci, MD, Synairgen: Board Member|Synairgen: Non executive board director, patent on inhaled interferon beta|Synairgen: Stocks/Bonds chris brightling, FMedSci, Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support Tom Wilkinson, PhD, PhD, AZ: Grant/Research Support|AZ: Honoraria|My mhealth: Board Member|My mhealth: Ownership Interest|My mhealth: Stocks/Bonds|Synairgen: Grant/Research Support|Synairgen: Honoraria.