The innate immune protein human surfactant protein D (SP-D) recognizes pathogens in the lungs via binding to carbohydrate surface structures. SP-D targets gram-negative bacterial lipopolysaccharide via calcium-dependent binding, preferentially to the inner core heptose (HepI). To further investigate this recognition, we have determined the high-resolution crystal structures of a trimeric recombinant fragment of human SP-D complexed with synthetic di-saccharide and trisaccharides, HepI-Kdo, HepIII-HepII-HepI, and HepII-HepI phosphorylated at either HepI or HepII, inner core lipopolysaccharide motifs common to many gram-negative bacteria. In contrast to acid-hydrolyzed lipopolysaccharide used in several previous studies, these synthetic saccharides allow the presentation of both the innermost Kdo in its natural pyranose form and heptose phosphorylation. The structures confirm the flexibility of SP-D to adopt alternative binding modes when the preferred epitope is not available, reveal a preference for recognition of the reducing terminal heptose (HepI) via the glyceryl group, indicate that a single Kdo attached to HepI does not have a significant role in ligand recognition, and provide evidence that heptose phosphorylation is a major determinant of recognition. The disaccharide with HepII O4' phosphorylation binds via the preferred HepI glyceryl-hydroxyls, while HepI O4' phosphorylation reveals HepII binding via the pyranose ring O3' and O4' hydroxyls, which would not be possible with the usual HepII O3' link to the outer core. The ability of HepI O4' phosphorylation to prevent preferred HepI recognition suggests a role for heptose phosphorylation in shielding the bacterial LPS inner core from immune recognition.

Introduction Early chronic obstructive pulmonary disease (COPD) is considered to represent the initial phase of the disease. However, inconsistent terminology and lack of standardised definitions hinders research and clinical application. This systematic review examined clinical research on early COPD, analysed terms and definitions used, and evaluated predictors of disease progression. This serves as a platform to reach consensus and direct future research to target early disease states and improve patient outcomes. Methods Utilising a standardised protocol, we systematically screened all clinical studies on early COPD. Titles and abstracts were reviewed and compared against inclusion and exclusion criteria. Stage 1 assessed terminology and definitions and stage 2 evaluated predictors of progression. Two independent people reviewed studies at each stage. Study quality was appraised using a modified Downs and Black checklist. Results We identified 4871 articles, 1759 were screened after duplicate removal. The terms used included PRISm (preserved ratio impaired spirometry) (104 articles), GOLD 0 (Global Initiative for Chronic Obstructive Lung Disease stage 0) (63), early COPD (37), at-risk COPD (35) and pre-COPD (30). Definitions were heterogeneous and proposed early COPD definitions were not routinely used. Stage 2 included 43 full-text articles from cohort studies, of which 93% were of good quality. Predictors of progression included age (n=13 articles), smoking history (12), symptoms (12), exacerbations (one), lung function measures (20), computed tomography metrics (14), risk tools (three) and machine learning approaches (three). Conclusion We demonstrate an urgent need for consensus on clinically applicable definitions of the early disease course of COPD, prior to diagnosis. We highlight predictors of progression; these need validation to enable stratification of individuals early in their disease trajectory for targeted management to halt or modify progression.

COPD remains a leading cause of morbidity and mortality, with outcomes stagnating relative to other long-term conditions. Current diagnostic pathways rely on spirometry, which detects airflow obstruction only after irreversible small airway and parenchymal damage has accrued, whereas pathogenic processes begin decades earlier. This review examines how understanding early pathogenic processes could inform alternative approaches to diagnosis and treatment. We highlight the contribution of developmental and environmental exposures, genetic susceptibility and epigenetic modification to disease initiation. We outline how these convergent mechanisms drive structural and functional abnormalities undetectable by conventional diagnostics but measurable with novel techniques. Advanced imaging-parametric response mapping, hyperpolarised gas magnetic resonance imaging and computed tomography-based vascular metrics-can detect emphysema, small airways disease and vascular pruning before spirometric thresholds are reached. Physiological tools including forced oscillation techniques and capnography show promise for early detection in primary care and may be scalable, affordable alternatives to spirometry. Biofluid-based platforms, including exhaled breath analysis, extracellular matrix neo-epitopes and blood-based inflammatory signatures, offer noninvasive phenotyping and risk stratification, though require validation and pathway integration. We argue for a shift from a spirometry-centric model to a multidimensional diagnostic framework integrating imaging, molecular, physiological and biomarker data. Recent longitudinal evidence, including diagnostic schemas combining imaging with symptom burden, indicates that such approaches identify high-risk individuals missed by spirometry alone. Proactive COPD detection in its earliest stages is therefore an essential step to altering disease trajectory and improving patient outcomes, and it is time our community looks beyond spirometry to deliver this.

Introduction:Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide and currently lacks effective disease-modifying therapies. Extracellular vesicles (EVs) are key mediators of intercellular communication and transport biologically active cargo, including microRNAs (miRNAs). We previously identified 8 differentially expressed EV miRNA (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p, miR-625-3p, miR-204-5p, miR-138-5p and miR-338-3p) that were differentially expressed in individuals with COPD compared with healthy volunteer ex-smoker controls (HV-ES). This study aimed to identify miRNA-mRNA interactions in diseased lung epithelium that may contribute to COPD pathogenesis. Methods:Gene expression was quantified by RNA sequencing of epithelial brushings obtained from 24 subjects with COPD and 20 HV-ES. In silico analyses were performed to identify target genes of the previously identified EV-derived miRNAs isolated from the same individuals. MiRNA-mRNA interactions were examined using negative correlation analysis and network-based approaches, and enrichment of biological processes was assessed using Cytoscape. Associations between computer tomography (CT) disease probability measures (DPM) and gene expression were assessed using Spearman correlation across the pooled cohort. Results:A total of 191 genes were differentially expressed in epithelial brushings from subjects with COPD compared with HV-ES. In silico analysis identified 121 miRNA-mRNA interactions involving these genes and the EV-associated miRNAs. Network analysis revealed miR-182-5p as a central hub, targeting multiple highly differentially expressed genes (DEGs). Expression of these DEGs correlated with CT DPM of emphysema and small airways disease (SAD). Exploratory pathway analyses suggested potential trends toward coordinated network regulation involving metabolic and immune -related processes; however, no biological processes remained significant after correction for multiple testing. Discussion:These findings highlight a potential role for EV-derived miRNA-mRNA regulatory networks in COPD pathogenesis, with miR-182-5p emerging as a putative regulator within this network. While exploratory analyses suggested possible associations with metabolic and immune-related pathways, these did not withstand multiple testing correction and should therefore be interpreted as hypothesis-generating. These findings support further mechanistic investigation of EV-derived miRNA-mRNA regulatory networks in COPD and may help inform future translational studies exploring their biological relevance.

Extracellular matrix (ECM) dysregulation is a key process in the pathology of COPD. However, an inability to characterise ECM remodelling in vivo has limited our understanding of its relationship with functional decline and disease mechanisms. We aimed to quantify in vivo ECM remodelling using probe-based confocal laser endomicroscopy (pCLE) and determine associations with physiological, radiological, histological, and serological markers of COPD. 16 patients with COPD and 20 controls underwent pulmonary function testing, CT imaging, bronchoscopy, and pCLE. Alveolar morphometrics and elastin linearity scores (ELS) were quantified using a novel automated algorithm. Bronchial biopsies were analysed for elastin and collagen content. Serum biomarkers of elastin and collagen turnover were measured in a combined cohort of 54 COPD patients and 61 controls. Compared with never-smoking controls, current smokers without airflow obstruction demonstrated larger alveolar dimensions including increased alveolar opening area (AOA) (46,282 ± 16,805 vs. 33,549 ± 2,595 μm², p = 0.003). Alveolar dimensions were further increased in COPD, with larger AOA (56,468 ± 11,079 vs. 46,282 ± 16,805 μm², p < 0.001) compared with all controls. COPD was also associated with greater elastin fibre disorganisation (ELS 54.9 ± 6.0 vs. 47.5 ± 10.7, p = 0.032). Across the cohort, ELS correlated with airflow obstruction and surrogate markers of small airway disease. Airway collagen content was increased in COPD and correlated with ELS (r = 0.665, p = 0.005). COPD was associated with higher circulating elastin and collagen degradation biomarkers, including ELP-3, C1M, C6M, and EL-CG (all p < 0.05), which correlated with pCLE morphometrics. Using an innovative lung imaging technique, we provide the first objective quantification of in vivo airway elastic fibre disorganisation and demonstrate quantifiable lung microstructural changes that may precede abnormalities detected by established techniques. These quantifiable signals relate to biomarkers of lung ECM turnover, offering a new platform for early disease detection and mechanistic understanding of COPD.

Acute non-invasive ventilation (NIV) is a lifesaving treatment for acute hypercapnic respiratory failure, particularly during exacerbations of chronic obstructive pulmonary disease (COPD), and is also an established therapy that improves outcomes in acute cardiogenic pulmonary oedema. Decisions regarding NIV initiation are complex and require careful consideration of patient-specific factors. With an aging population, with increasing multimorbidity, understanding the evolving acute NIV patient characteristics is critical to optimize NIV delivery. We audited all adult acute NIV patients at a tertiary centre, pre-COVID (April 2019-March 2020) and post-COVID (April 2023-March 2024) and performed a retrospective observational cohort analysis. We compared the Charlson Comorbidity Index (CCI) scores and outcomes using Chi-squared or Mann-Whitney U. Three hundred and twelve patients received acute NIV, 171 pre-COVID and 141 post-COVID. Post-COVID patients had higher comorbidity burden vs pre-COVID (median CCI 5 vs 4, p=0.002), and ward-based NIV ceiling of care frequency (83% vs 66%, p=0.009). Across the entire cohort, higher CCI score associated with increased NIV failure (p=0.007) and in-hospital mortality (p<0.001). Our demonstration of increasing multimorbidity in a real-world cohort, and the association of multimorbidity with NIV failure, provides insights to guide optimization strategies for acute NIV services. Further understanding the evolving patient characteristics and their impact on outcome is essential to determine how best to incorporate comorbidity assessment into clinical decision making for improved NIV delivery.

The innate immune protein human surfactant protein D (SP-D) recognizes pathogens in the lungs via binding to carbohydrate surface structures. SP-D targets gram-negative bacterial lipopolysaccharide via calcium-dependent binding, preferentially to the inner core heptose (HepI). To further investigate this recognition, we have determined the high-resolution crystal structures of a trimeric recombinant fragment of human SP-D complexed with synthetic di-saccharide and trisaccharides, HepI-Kdo, HepIII-HepII-HepI, and HepII-HepI phosphorylated at either HepI or HepII, inner core lipopolysaccharide motifs common to many gram-negative bacteria. In contrast to acid-hydrolyzed lipopolysaccharide used in several previous studies, these synthetic saccharides allow the presentation of both the innermost Kdo in its natural pyranose form and heptose phosphorylation. The structures confirm the flexibility of SP-D to adopt alternative binding modes when the preferred epitope is not available, reveal a preference for recognition of the reducing terminal heptose (HepI) via the glyceryl group, indicate that a single Kdo attached to HepI does not have a significant role in ligand recognition, and provide evidence that heptose phosphorylation is a major determinant of recognition. The disaccharide with HepII O4 ' phosphorylation binds via the preferred HepI glyceryl-hydroxyls, while HepI O4 ' phosphorylation reveals HepII binding via the pyranose ring O3 ' and O4 ' hydroxyls, which would not be possible with the usual HepII O3 ' link to the outer core. The ability of HepI O4 ' phosphorylation to prevent preferred HepI recognition suggests a role for heptose phosphorylation in shielding the bacterial LPS inner core from immune recognition.

Background: Accurate tools for patient stratification by likely outcome are needed to support complex decision-making and improve acute non-invasive ventilation (NIV) delivery. Objectives: To evaluate the potential of an emerging NIV outcomes (NIVO) score tool to predict in-hospital mortality to aid its validation in a real-world UK hospital population of ward-based NIV for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Design: This was a retrospective observational cohort study of all consecutive patient admissions with AECOPD managed with NIV for acute hypercapnic respiratory failure at a teaching hospital. Methods: Clinical parameters were collected as part of an ongoing quality improvement project. Patients were grouped based on their survival status at hospital discharge. First admission of each patient was included in the analysis. NIV failure, defined as NIV withdrawal or intubation requirement due to clinical deterioration on NIV, along with in-hospital mortality, was modelled using logistic regression. Results: There were 249 unique patient AECOPD admissions with ward-based NIV. Across first admissions, NIV failure rate was 37.3%, in-hospital mortality 26.5%, and 1-year mortality 47.0%. NIVO score was significantly associated with both NIV failure and in-hospital mortality, with odds ratios (95% Confidence intervals) of 1.33 (1.13–1.58, p < 0.001) and 1.52 (1.26–1.86), p < 0.001, respectively. A progressive increase in in-hospital mortality was observed with increasing NIVO scores ( p < 0.0001). Conclusion: This study demonstrates that the NIVO score shows promise as a predictive tool for in-hospital mortality in patients with AECOPD receiving ward-based NIV. Furthermore, it suggests that NIVO may be able to support decision-making for enhanced NIV delivery in new clinical pathways to address the growing burden of chronic obstructive pulmonary disease exacerbations.

Supplemental oxygen is an essential therapy during critical illness. However, patients with severe hypoxemic respiratory failure and/or acute respiratory distress syndrome often require high oxygen concentrations, exposing lungs to alveolar hyperoxia despite systemic hypoxemia, with consequent pulmonary oxygen toxicity. Pulmonary oxygen toxicity causes disruption of surfactant, which is essential for maintenance of alveolar functional anatomy, as well as efficient and effective gas exchange and immune regulation. This surfactant dysregulation can increase alveolar surface tension, causing alveolar collapse with atelectasis, resulting in poor lung compliance and impaired gas exchange. Hyperoxia-induced lung injury mechanisms may interact with mechanisms of harm associated with infections and mechanical ventilation. The intricate relationship between these different, interrelated stressors and altered surfactant metabolism and function is not yet delineated, particularly in humans. This review examines the current understanding of hyperoxia-induced surfactant dysregulation. We discuss potential mechanisms, including biochemical/compositional and functional changes to lipids and proteins including surfactant proteins A and D, epithelial atrophy, impaired surfactant synthesis/metabolism, redox imbalances, phospholipase A2, and altered macrophage clearance. Key areas for future research are outlined, emphasizing the need for clinically relevant human models that discriminate between the effects of oxygen therapy dose and duration, as well as other iatrogenic effects and underlying disease processes. We propose a roadmap to progress current knowledge and outline opportunities for well-designed human studies, novel surfactant preparations resistant to functional inhibition and breakdown, and technological developments, with the potential for leveraging these to identify innovative biomarkers, individualized therapeutic targets, and novel therapies in the future.

BACKGROUND:Bronchopulmonary dysplasia (BPD), the major chronic respiratory morbidity in extremely preterm infants, is largely driven by inflammation. Preterm lungs are deficient of surfactant protein D (SP-D), an immunomodulatory protein absent in current commercial surfactant preparations. We hypothesised that using a recombinant fragment of human SP-D (rfhSP-D) as an adjuvant to exogenous surfactant therapy would reduce ventilator-induced inflammation. METHODS:We utilised a preterm lamb model of ventilator-associated lung injury. Mechanically ventilated preterm lambs were randomised into control and two treated groups, receiving endotracheal surfactant at 15 min post-delivery. Physiological parameters were measured throughout the experiment. Lung tissue was analysed for changes in alveolar architecture and expression levels of pro-inflammatory cytokines. Bronchioalveolar lavage (BAL) was analysed for SP-D concentration, and inflammatory cells. RESULTS:Intratracheal administration of rfhSP-D improved respiratory outcomes, significantly increased airspace and lung compliance in treated groups. Treated lambs also showed a reduction in lung tissue gene expression of inflammatory cytokines and inflammatory cell counts. CONCLUSION:Intratracheal administration of rfhSP-D did not negatively impact standard surfactant therapy and appeared to complement it. The administration of rfhSP-D as an adjuvant to standard surfactant therapy effectively reduced lung inflammation supporting the potential therapeutic use of rfhSP-D for preterm infants at risk of developing BPD. IMPACT:We have successfully developed and tested a novel recombinant fragment of human surfactant protein D (rfhSP-D) capable of reducing ventilator-associated lung inflammation in a pre-term lamb model. These results suggest rfhSP-D may be a novel potentially useful therapy for Bronchopulmonary dysplasia (BPD) in combination with currently available surfactant replacement therapies and serves as justification for a first in human clinical trial in mechanically ventilated infants. If successful, rfhSP-D could become a therapeutic candidate to mitigate pulmonary inflammation and improve lung outcomes, potentially offering a novel therapeutic avenue in the prevention or management of BPD.

Introduction:Early in the COVID-19 pandemic, CT was demonstrated as a sensitive tool for diagnosing COVID-19. We undertook a detailed study of CT scans in COVID-19 patients to characterise disease distribution within lung parenchyma, respiratory airways, and pulmonary vasculature, aiming to delineate underlying disease processes. Methods:We characterised acute phase chest CT of 40 participants with COVID-19 from the REACT study, 31 with CT pulmonary angiography (CTPA), 4 with intravenous contrast enhanced CT and 5 with non-intravenous contrast enhanced CT. Participants had neither been vaccinated nor received systemic steroids. We further correlated the distribution of lung parenchymal damage on CT with contemporaneous chest radiographs. Results:Parenchymal lung damage was found in all subjects. However, airways inflammation was present in only 23% (9) and limited to small areas. Notably, vascular abnormalities were dominant and characterised by dilated peripheral pulmonary vessels supplying areas of lung damage in a gravity-dependent distribution bilaterally in 95% (38), basally in 90% (36), peripherally in 92.5% (37), and posteriorly in 90% (36). Macrothrombosis was demonstrated in 23% (7) of CTPAs. Wedge-shaped peripheral lung damage, resembling areas of pulmonary vascular congestion, were distinct in 53% (21) with or without visible macrothrombosis. Pleural effusions were seen in 28% (11). Notably, lung opacification distribution in 98% of the plain radiographs matched distribution on CT (39). Conclusion:Our study frames COVID-19 as a pulmonary vasculopathy rather than a more conventional pneumonia which may be important not only for guiding mechanistic study design but also for the development of novel targeted therapeutics.

The role of eosinophils in COPD and their utility as biomarkers for cytokine targeting monoclonal therapies remains unclear. We investigated the distribution of eosinophils across different tissue compartments in COPD and analysed gene expression to understand the possible mechanistic drivers of eosinophilic inflammation in COPD. Blood and BAL from ex-smoking volunteers with mild/moderate COPD (n = 31) and healthy ex-smoking controls (n = 20), and bronchial biopsy tissue in a subcohort (n = 19 and n = 8, respectively) was analysed. Differentially-expressed genes (DEGs) were characterised using RNASeq. Proteomic analysis of BAL was conducted using mass-spectrometry. COPD subjects had more eosinophils in blood and lung tissue compared to controls, with increased eosinophil protein CLC/Galectin-10 in BAL. However, peripheral blood eosinophil counts related poorly to numbers in lung tissue (rho = -0.09192, p = 0.3541) or proportions in BAL (rho = 0.01762, p = 0.4632). Tissue IL-5Rα expression was higher in frequent exacerbators and related to tissue eosinophils, but not peripheral blood eosinophils. Higher blood eosinophils were associated with DEGs that differed with compartment. Higher tissue eosinophil levels were associated with IL-13-induced DEGs including POSTN in bronchial brushes and CCL26 in bronchial biopsies. Gene-set enrichment analysis on data from brushings revealed significant enrichment of IL-4/IL-13, but not IL-5, pathways associated with eosinophil presence. Eosinophilic lung inflammation is related to exacerbation frequency, but lung eosinophils are not predicted by blood eosinophil counts in COPD. Our data suggest IL-13-mediated pathways may be responsible for the presence of tissue eosinophils in COPD. Further work to establish more predictive biomarkers of lung eosinophil biology are required to unlock this axis to optimised treatment.

The innate immune protein human surfactant protein D (SP-D) recognises pathogens in the lungs via binding to carbohydrate surface structures. SP-D has been shown to target gram-negative bacterial lipopolysaccharide via calcium-dependent binding, preferentially to the inner core heptose (HepI). To further investigate this recognition, we have determined the high-resolution crystal structures of a trimeric recombinant fragment of human SP-D complexed with synthetic di- and trisaccharides, HepI-Kdo, HepIII-HepII-HepI, and HepII-HepI phosphorylated at either HepI or HepII, inner core motifs common to the lipopolysaccharide of many gram-negative bacteria. In contrast to acid-hydrolysed lipopolysaccharide used in several previous studies, these synthetic saccharides allow presentation of both the innermost Kdo in its natural pyranose form and heptose phosphorylation. The structures confirm the flexibility of SP-D to adopt an alternative binding mode when the preferred epitope is not available, reveal a preference for recognition of the reducing terminal heptose (HepI) via the glyceryl group, indicate that a single Kdo attached to HepI does not have a significant role in ligand recognition, and provide evidence that recognition of phosphorylated inner core diheptosyl ligands varies dependent on whether HepI or HepII is phosphorylated. The disaccharide with HepII O4’ phosphorylation binds via the preferred HepI glyceryl-hydroxyls, while HepI O4’ phosphorylation reveals HepII binding via the pyranose ring O3’ and O4’ hydroxyls. The ability of the HepII O4’ phosphate to prevent preferred HepI recognition suggests a role for heptose phosphorylation in shielding the bacterial LPS inner core from immune recognition. ### Competing Interest Statement The authors have declared no competing interest. STFC / Diamond Light Source, MX14692, MX19880 Science Foundation Ireland, 08/IN.1/B2067, 13/IA/1959 MRC DPFS, MR/P026907/1

Introduction: The 'door-to-mask' time is a UK-wide quality metric for NIV services. We examined the utility of this metric in predicting in-hospital death, as the COVID pandemic resulted in a significant prolongation of this metric due to stringent infection control measures. Methods: Data was extracted for all acute NIV applications for hypercapnic respiratory failure pre and post 2020 (01 Apr-31 Dec, 2019 and 2021, respectively). Categorical and continuous variables were compared using Chi-squared and Mann-Whitney U tests, respectively. Logistic regression was used to predict in-hospital death adjusted odds ratios (OR) across both cohorts combined. Results: Total patients receiving NIV decreased by 26.2%, 2019 to 2021 (83 vs 45 patients). Age (69 vs 69, p=0.93) was not significantly different. NIV indication was not significantly different, the majority, 87 (66.9%) vs 63 (65.6%), received NIV for COPD, 2019 vs 2021, respectively. Door-to-mask-times increased, 327 to 651 mins (p<0.001), 2019 vs 2021. However, in-hospital death was not significantly different, 27 (20.8%) vs 28 (29.2%) (p=0.15). Age and pH did affect in-hospital mortality, OR ratio (95% CI), 1.037 (1.01, 1.07) (p=0.02) and 0.009 (0.00, 0.70) (p=0.03), respectively. However, door to mask time did not significantly affect OR of in-hospital mortality, 1.004 (1.00, 1.01), (p=0.07). Conclusions: Within our cohort, 'door-to-mask' time was not a strong predictor of mortality, hence we need to explore new metrics such as 'decision-to-mask time' and/or a surrogate of the physical quality of NIV application and synchronisation (e.g. Maximum pressures achieved) for our future quality improvement journey.

Objectives COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. Design and setting This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. Participants Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. Results The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%<lower limit of normal (LLN)). Increases in platelet counts and decreases in CRP, neutrophil:lymphocyte ratio (p<0.001), lactate dehydrogenase, neutrophil counts, urea and white cell counts (all p<0.01) were each associated with discharge. Conclusions Serial measurement of routine blood tests may be a useful prognostic tool for monitoring treatment response in hospitalised patients with COVID-19. Changes in other biochemical parameters often included in a 'COVID-19 bundle' did not show significant association with outcome, suggesting there may be limited clinical benefit of serial sampling. This may have direct clinical utility in the context of escalating healthcare costs of the pandemic.

Overuse of corticosteroids is an important problem not only in asthma but also the management of other airways diseases including bronchiectasis and COPD and results in associated risks of serious side effects and irreversible harm. We report a pilot using an in-reach solution to review patients, optimise their care and facilitate early discharge. We discharged >20% of our patients immediately, which is potentially a significant reduction in hospital bed use and, most importantly, through this approach we were able to establish early diagnosis and reduce inappropriate oral corticosteroid use.

Objectives: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. Methods: This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202,012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as the dominant strain). Results: Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47, [0.27,0.79],p = 0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86, [0.64, 1.15],p = 0.308). Conclusions: The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new treatments and ongoing concern over new COVID-19 variants.