The current standard of maintenance care for patients with moderate-to-severe asthma is the use of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) medications; some patients may also require additional therapies including long-acting muscarinic antagonists or biologics to establish disease control. Presently, there is a striking discrepancy between the positive outcomes reported in randomised clinical trials (RCTs) of these therapies and real-world outcomes that may be independent of treatment adherence. Patients with asthma included in RCTs are selected using stringent eligibility criteria, for example they have never been heavy smokers. Because current recommendations rely on results from such exclusive RCTs, this calls into question the extent to which these recommendations are applicable in daily practice. Therefore, generalising information from RCTs can be a difficult task for a number of reasons, including differences between ICS/LABAs, varied responses to medications among patients and the limited time busy general practitioners have to bridge the care gaps that exist. Factors in choosing a desirable ICS/LABA may include (a) considerations in clinical decision-making; (b) differences in pharmacokinetic and pharmacodynamic properties of ICS/LABA molecules, therapeutic index; (c) individual patient factors which may influence or facilitate successful adherence to treatment; (d) ease of inhaler use; (e) underlying inflammation; and (f) balancing efficacy and long-term safety, including adverse events and long-term exacerbation risk, based on data from both RCTs and real-world evidence. This review article discusses factors that healthcare professionals may utilise when selecting an ICS/LABA treatment for their patients, by considering data from RCTs and real-world evidence in addition to geographical/environmental, personal, and disease factors, which may also influence the decision process, such as availability and affordability. This article outlines treatments used to control moderate-to-severe asthma. Data from clinical trials and real-world studies were included. Current asthma medicines include combinations that reduce inflammation and open the airways: inhaled corticosteroids with long-acting β2-agonists (ICS/LABAs) plus other treatments for some individuals. Since there are many available combinations of ICS/LABAs (molecules and devices), selecting the most appropriate option requires important considerations from both patient and physician perspectives. In this paper, authors discuss these combinations alongside other important considerations, with the aim of encouraging doctors and patients to work together to choose the most appropriate treatment. Firstly, differences between ICS/LABA molecules mean they could have different effects in individual patients. This review discusses how physicians might identify these effects using different measures within the body. Secondly, findings from clinical trials and from patients in the ‘real world’, comparing specific ICS/LABA treatments, were discussed. Thirdly, balancing the safety of ICS/LABA treatments was explored along with how physicians can minimise the risk of side effects. Finally, individual patient requirements and preferences were explored, as these are important factors when doctors are deciding which inhaler device patients should have. This may help to ensure patients take the medicine as prescribed. This review demonstrates the importance of considering several factors when choosing the most appropriate inhaled medication. It highlights the need to focus on reducing underlying inflammation to prevent future asthma attacks (exacerbations) and minimising side effects. This can assist patients in achieving their long-term disease management goals and supporting continued treatment adherence.
Background:Higher blood eosinophil counts are associated with greater lung function decline in patients with COPD, and a relationship between higher sputum eosinophil counts and greater emphysema has been reported. The aim of the current study was to investigate a role for eosinophils in alveolar septal damage, which may contribute to emphysema and lung function decline in COPD patients. Methods:We quantified Luna positive alveolar septal eosinophil counts (ASEC) in peripheral lung tissue blocks from 48 COPD patients versus 27 smokers and 15 nonsmokers and examined the relationship between eosinophil numbers and alveolar tissue damage using histology techniques. Results:The numbers of ASEC were greater in COPD compared to controls (p≤0.02), and there was a significant correlation between ASEC and alveolar septal damage in a subgroup of COPD patients (rho=0.4, p=0.03). Conclusion:This association suggests a role for eosinophils in the pathogenesis of emphysema in a subset of COPD.
Type of the article: Research Article AbstractArtificial intelligence is diffusing across Gulf Cooperation Council insurance markets, yet disclosure-based evidence remains fragmented on whether adoption is associated with organizational change or localized automation. This study examines a purposive disclosure-based sample of 120 insurers from Saudi Arabia, the United Arab Emirates, Qatar, Kuwait, Oman, and Bahrain. Because inclusion required sufficient disclosure of artificial intelligence practices, the sample is not intended to represent the insurance market. The study examines whether disclosed artificial intelligence adoption is associated with organizational change through financial transparency and operational efficiency. The dataset is constructed from annual reports, audited financial statements, governance reports, environmental, social, and governance reports, investor materials, and regulatory documents. Documents from 2017 to 2023 are treated as an observation window, coded at the item level, and aggregated into one firm-level score per insurer for cross-sectional structural equation modeling. Results indicate positive associations from artificial intelligence adoption to financial transparency (β = 0.52, p < 0.001) and operational efficiency (β = 0.49, p < 0.001). Financial transparency (β = 0.41, p = 0.003) and operational efficiency (β = 0.38, p = 0.012) are associated with organizational change. The indirect paths through transparency and efficiency are statistically distinguishable from zero within the model. Because all variables are derived from similar disclosure evidence, the pattern is interpreted as disclosure co-patterning rather than proof of a mechanism. The findings are associational, not causal, representative, or longitudinal.
Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset of patients develop prolonged illness termed Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The pathophysiology underlying Long COVID remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play a role in Long COVID. In this context, we developed a method to quantify microclots and investigated the relationship between microclot counts and Long COVID. We show that as a cohort, platelet-poor plasma from Long COVID samples had a higher microclot count compared to control groups but retained a wide distribution of counts. Recent COVID-19 infections were also seen to be associated with microclot counts higher than the control groups and equivalent to the Long COVID cohort, with a subsequent time-dependent reduction of counts. Our findings suggest that microclots could be a potential biomarker of disease and/or a treatment target in some Long COVID patients. ### Competing Interest Statement AB is an employee of Agilent; and supported the design of the Cytation protocols using blinded data. The other authors have no competing interests to declare. ### Funding Statement Funding was provided by the Patient-Led Research Fund, a project of Balvi Filantropic Fund (Balvi) and Patient-Led Research Collaborative (PLRC) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for the study was obtained from the ethics committees of Sheffield Hallam University (reference number E39973246), and the North West Research Ethics Committee - Preston (reference number 10/H1016/25). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors
