Background: It is estimated that around 5% of people with asthma have severe asthma. Severe asthma typically presents with poor symptom control, impaired lung function and asthma exacerbations, despite regular inhaled steroids and additional controller medications. In the BEyond Allergic Th2-Severe Asthma clinical trials programme, we worked with severe asthma specialist centres in the United Kingdom to identify patients who experienced frequent asthma attacks (two or more per year), who were potentially eligible for stratified asthma treatments.

Objectives: There are currently two recognised subtypes of severe asthma which can be characterised by their level of eosinophils (a type of white blood cells). In the BEyond Allergic Th2-Severe Asthma clinical trial programme, we aimed to test whether a simple, once-daily oral antibiotic (doxycycline) can reduce asthma attacks in individuals with lower levels of eosinophils in peripheral blood (T2-Low arm: < 300 cells/µl). We also aimed to test whether a simple twice-daily oral drug (dexpramipexole) can reduce asthma attacks in individuals with high levels of eosinophils in peripheral blood (T2-High arm : ≥ 300 cells/µl). The trial was established using a master protocol and platform trial design with study protocols for the T2-High and T2-Low cohorts.

Study outcomes: The trial platform was successfully set up during the COVID-19 pandemic and opened across 13 sites in the United Kingdom for recruitment between August 2021 and September 2022, following a 12-month trial pause due to the pandemic. Several changes to the trial protocol were made to make the protocol easier to deliver due to pandemic restrictions. Due to capacity issues at National Health Service trusts in the United Kingdom following the pandemic, the trial was delayed in opening sites by approximately 4 months. Shortly after all sites were opened, a decision was made with the Trial Steering Committee and funders to close the dexpramipexole (T2-High) arm of the trial (October 2022), as the drug had moved on to definitive and confirmatory phase III trials. Recruitment into the doxycycline trial progressed slowly, largely in part due to challenges in finding people with asthma who had the required number of asthma attacks to be eligible, as attack rates in the United Kingdom fell during the pandemic. Furthermore, the trial was recruiting exclusively from severe asthma centres in the United Kingdom and did not have the funding required to change the recruitment model to include screening within primary care also. As a result of these factors, a decision was made by the sponsor of the trial to close the trial (April 2023), in line with National Institute for Health and Care Research post pandemic reset policy.

Limitations and future work: While no scientific conclusions can be drawn from this trial, following the pandemic a formal review of commercial clinical trials was commissioned by the government (Lord O’Shaughnessy review), with several recommendations to enhance clinical trial delivery in the United Kingdom. Many of the recommendations are applicable to non-commercial asthma trials. Furthermore, pivotal phase III trials of dexpramipexole are currently well underway. We would advocate the development of a Respiratory Clinical Trials Accelerator Platform for airways disease trials in the United Kingdom to support academic trials.

Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 16/71/05.

Background: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.

Aim: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).

Results: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.

Conclusions: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.

Chronic inflammation is an underlying feature of respiratory diseases such as chronic obstructive pulmonary disease (COPD). Novel therapies that target the inflammatory mechanisms driving acute exacerbations of COPD are required. The ST2 receptor, which binds the alarmin interleukin (IL)-33 to initiate an inflammatory response, is a potential target. Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, which binds with high affinity to ST2 to prevent binding of IL-33, is a potential therapy for COPD. However, targeting inflammatory pathways that form part of the immune system may have unintended consequences, such as implications for the response to infection and cardiovascular function. Therefore, an understanding of astegolimab's safety profile in clinical use is essential. This narrative review summarizes clinical safety data from published clinical trials of astegolimab with a focus on adverse events of interest, including infections and cardiac events. Astegolimab was shown to be well tolerated in > 580 patients with asthma, atopic dermatitis, COPD, and severe COVID-19 pneumonia who took part in Phase II trials. The frequency of adverse events (AEs) and serious AEs was similar between the astegolimab and placebo arms in each trial (AEs: 41-81% vs. 58-77%; serious AEs: 3-29% vs. 0-41%, respectively). The number of deaths was similar between treatment arms and there were no astegolimab-related deaths. Astegolimab did not increase the risk of infection or major adverse cardiac events. Ongoing Phase IIb and Phase III trials of astegolimab in patients with COPD who have a history of frequent acute exacerbation(s) of COPD will provide a future opportunity to confirm the safety profile of astegolimab.

Background/Objectives: The interplay between asthma and COVID-19 raises critical clinical questions, particularly regarding the risk of hematological complications in patients affected by both conditions. While COVID-19 is known to cause coagulopathy and thromboembolic events, it remains unclear whether asthma independently influences these risks. This systematic review aimed to synthesize existing evidence on hematological abnormalities-including D-dimer elevation, thrombocytopenia, and venous thromboembolism (VTE)-in asthmatic patients with confirmed SARS-CoV-2 infection. Methods: A systematic search was conducted in PubMed and Web of Science databases for studies published between January 2020 and May 2025. Inclusion criteria were studies reporting hematologic outcomes in asthmatic patients with COVID-19. After duplicate removal, 139 unique articles were screened, with 40 studies meeting inclusion criteria. These included observational cohorts, retrospective analyses, and clinical investigations. Data were synthesized in a systematic review with qualitative synthesis due to heterogeneity in design and reporting. Results: The review identified variable patterns of D-dimer elevation and thrombotic events among asthmatic COVID-19 patients. Some studies reported a higher incidence of ICU admission, elevated inflammatory and coagulation markers, and increased thromboembolic risk in asthmatic individuals-particularly those with poor disease control or non-allergic phenotypes. However, findings were inconsistent and often limited by the absence of asthma stratification, standardized outcome measures, and prospective designs. Conclusions: Current evidence does not support a definitive link between asthma and increased thrombotic risk in COVID-19. Further research with prospective, phenotype-stratified methodologies and harmonized hematologic endpoints is needed to clarify whether asthma modifies the hematologic trajectory of SARS-CoV-2 infection.

During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, concerns arose regarding the susceptibility of asthmatic children, one of the most common chronic conditions in childhood and a major cause of hospitalization in pediatric settings. Unexpectedly, evidences showed milder clinical courses and fewer asthma exacerbations in these patients, even if cases of critical and fatal infection, often related to specific clinical features of the patient, are not negligible. In this regard, obesity is considered not only an important comorbidity in patients with difficult-to-treat asthma but also a risk factor for more severe forms of COVID-19. These observations are of even greater concern in the context of an increase in childhood obesity that began even before the SARS-CoV-2 pandemic and has continued also as a consequence of it. Given asthma's heterogeneity, especially in children, an endotype-based approach is crucial. This is possible through a detailed analysis of the complex metabolic pathways that correlate asthma, COVID-19 infection and obesity thanks to new high-through-put technologies, especially metabolomics, which with minimally invasive sampling, including on exhaled breath condensate (EBC), can provide precise and unbiased evidence in support of existing endotypes, making it possible to identify not only the most vulnerable individuals and thus risk stratification through specific biomarkers, but also new molecular and therapeutic targets. This review explores asthma endotypes by highlighting their shared immunometabolic pathways with COVID-19. Findings suggest that metabolomics could enable more accurate risk stratification and guide personalized interventions during viral pandemics, especially in the presence of relevant comorbidities such as obesity.

Advances in wearable sensors and artificial intelligence have greatly enhanced the potential of digitised audio biomarkers for disease diagnostics and monitoring. In respiratory care, evidence supporting their clinical use remains fragmented and inconclusive. This study aimed to assess the current research landscape of digital audio biomarkers in respiratory medicine through a bibliometric analysis and systematic review (PROSPERO CRD 42022336730). MEDLINE, Embase, Cochrane Library and CINAHL were searched for references indexed up to 9 April 2024. Eligible studies evaluated the accuracy of sound analysis for diagnosing and managing obstructive (asthma and COPD) or infectious respiratory diseases, excluding COVID-19. A narrative synthesis was conducted, and the QUADAS-2 tool was used to assess study quality and risk of bias. Of 14 180 studies, 81 were included. Bibliometric analysis identified fundamental (e.g. "diagnostic accuracy"+"machine learning") and emerging (e.g. "developing countries") themes. Despite methodological heterogeneity, audio biomarkers generally achieved moderate (60-79%) to high (80-100%) accuracies. 80% of studies (eight out of ten) reported high sensitivities and specificities for asthma diagnosis, 78% (seven out of nine) reported high sensitivities and 56% (five out of nine) reported high specificities for COPD, and 64% (seven out of eleven) reported high sensitivity or specificity values for pneumonia diagnosis. Breathing and coughing were the most common biomarkers, with artificial neural networks being the most common analysis technique. Future research on audio biomarkers should focus on testing their validity in clinically diverse populations and resolving algorithmic bias. If successful, digital audio biomarkers hold promise for complementing existing clinical tools in enabling more accessible applications in telemedicine, communicable disease monitoring, and chronic condition management.

Background: In recent years, an increasing body of evidence has revealed a complex interplay between obesity and asthma, prompting academic and medical communities to intensify their focus on this area of research. The objective of this study is to undertake a comprehensive bibliometric analysis of the research literature pertaining to obesity-related asthma from 2004 to 2023. This analysis aims to provide precise and valuable insights, as well as to systematically reflect upon the current status and emerging trends within the field.

Methods: Literature data on obesity and asthma research was sourced from the Web of Science Core Collection database. CiteSpace and VOSviewer were utilized to visually analyze bibliometric indicators such as co-authorship, citation networks, and publication frequency of the data to facilitate the identification of patterns and trends.

Results: A total of 3,118 papers were included in the analysis, encompassing 2,539 articles and 579 reviews. Throughout the last 20 years, the volume of publications has shown a consistent upward trend. The United States and Harvard University are at the forefront of this research field. Professor Dixon Anne E. is recognized as a pioneer and leading figure in the cultivation of obesity-related asthma research. Keyword analysis identified topics such as "childhood asthma," "bariatric surgery," "physical activity," "gut microbiota," "COVID-19," "food allergy," "asthma control," "nutrition examination," and "severe asthma."

Conclusion: The research domain of obesity-related asthma has experienced a substantial growth, with the United States, the United Kingdom, and China leading the global landscape. The focus on asthma in obese adolescents and children, the role of bariatric surgery, and lifestyle interventions remains a consistent area of interest, with considerable potential for further study. These findings provide a scientific basis for the development of personalized treatment programs for obese asthma patients. In addition, this study highlights the importance of further research in the fields of gut microbiota, COVID-19, and food allergy, providing directions for future policymaking.

Since the onset of the COVID-19 pandemic, managing asthma has become significantly more challenging. Both national and international guidelines emphasize the importance of continuing prescribed medications to maintain asthma control and prevent exacerbations. However, the emergence of SARS-CoV-2 infection has raised concerns about the safety of biologic therapies during acute COVID-19 episodes, necessitating a careful and individualized approach to their use. Biologic therapies, including omalizumab, dupilumab, mepolizumab, reslizumab, benralizumab, and tezepelumab, which target specific pathways in severe asthma, have revolutionized asthma management by improving symptom control and reducing exacerbation rates. Despite their proven benefits, the intersection of biologic therapy and active SARS-CoV-2 infection has prompted questions regarding potential immunomodulatory effects and risks. This review aimed to synthesize the current literature on the antiviral effects and safety of biologic drugs in severe asthmatic patients with active SARS-CoV-2 infection, encompassing both pediatric and adult populations.

Respiratory diseases are major health concerns worldwide. Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide and some of the most common are chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases, and pulmonary hypertension. Despite having different etiology and characteristics, these diseases share several features, such as a persistent inflammatory state, chronic oxidative stress, impaired mucociliary clearance, and increased alveolar surface tension. CRDs are not curable; however, various forms of treatment, that help restore airway patency and reduce shortness of breath, can improve daily life for people living with these conditions. In this regard myo-inositol may represent a valid therapeutic adjuvant approach due to its properties. Being a redox balancer, an inflammation modulator, and, most importantly, a component of pulmonary surfactant, it may improve lung function and counteract symptoms associated with respiratory diseases, as recently evidenced in patients with COPD, COVID-19, asthma, and bronchiectasis. The aim of this review is to evaluate the potential therapeutic role of myo-inositol supplementation in the management of patients with respiratory diseases.

Asthma has long been associated with increased susceptibility to viral respiratory infections, leading to significant exacerbations and poorer clinical outcomes. Contrarily and interestingly, emerging data and research surrounding the COVID-19 pandemic have shown that patients with asthma infected with SARS-CoV-2 experienced decreased severity of disease, lower hospitalization rates, as well as decreased morbidity and mortality. Research has shown that eosinophils could enhance immune defense against viral infections, while inhaled corticosteroids can assist in controlling systematic inflammation. Moreover, reduced ACE-2 expression in individuals with asthma may restrict viral entry, and the Th2 immune response may offset the Th1 response typically observed in severe COVID-19 patients. These factors may help explain the favorable outcomes seen in asthmatic patients during the COVID-19 pandemic. This review highlights potential protective mechanisms seen in asthmatic patients, including eosinophilia, the use of inhaled corticosteroids, reduced ACE-2 expression, and a dominate Th2 immune response. Such a study will be helpful to better manage patients with asthma who have contracted COVID-19.