SummaryBackgroundSince the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.MethodsThis randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.Findings313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the pr...

Although COPD is a common disorder of veterans who receive care from the Veterans Healthcare Administration (VHA), the perceptions of veterans with COPD about their disease, its effects on their lives, and their interactions with the VHA have not been determined. Utilizing qualitative methodology, we conducted focus groups of veterans with COPD at the Cincinnati VA Medical Center. Participants were selected by systematic sampling from the top quintile of veterans stratified by the cost of healthcare utilization related to a primary diagnosis of COPD and grouped by age and use of supplemental oxygen. All 42 participants were male and had a mean age of 65 years. Analysis of the focus group transcripts demonstrated five major themes: 1) Physical and Functional Limitations: work and employment constraints, recreation restrictions, limits on activities of daily living, reduced sexuality, concerns about housing and finances, and physical symptoms; 2) Restricted Social Interactions/Altered Social Networks: altered relationships with friends and family and reliance upon family and care givers; 3) Emotional Effects: reduced self-worth, vulnerability, depression, perseverance and adaptation, hopelessness, fear, pride, and lack of control; 4) Limitations in the Understanding of COPD: unawareness of diagnosis, triggers and reaction to disease manifestations, COPD management; and 5) Complex Healthcare Interactions. COPD pervasively and extensively affects all aspects of veterans' lives and causes significant consequences for their care and management.

Routine pulmonary function test results and clinical variables did not correlate with ED in patients with stable COPD. Dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.

open Scientific RepoRtS | (2020) 10:1238 | https://doi.org/10.1038/s41598-020-58326-7www.nature.com/scientificreports www.nature.com/scientificreports/ cytolytic response of NK cells. Activated cells release cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα), among others, which recruit and activate other immune system cells. Perforin release from NK cells causes pore formation in target cell membranes; proteases such as granzyme A and B can enter the cell to induce apoptosis by caspase cleavage as well as cleave other cellular targets. Therefore, aberrant and/or chronic activation of NK cells can result in chronic inflammation and tissue damage.Given the morbidities and economic burden of COPD and AECOPD, it is important to examine the immune function of these patients in greater detail than previous studies. In this study, we utilized polychromatic flow cytometry to measure the expression of an array of activating and inhibitory receptors on peripheral blood natural killer cells from never smokers, current smokers, and COPD patients. We identified >1,000 significant and unique NK cell subpopulations using the Scalable Weighted Iterative Flow-clustering Technique (SWIFT) 6-8 . These data reveal several changes in the expression of NK cell activating/inhibitory receptors and the size of the NK cell subpopulations associated with smoking and COPD. Furthermore, we demonstrate that logistic regression analysis using population size and receptor expression from peripheral blood NK cells is highly predictive of patients with a previous exacerbation. These findings provide an entry point to more closely examine the effects of smoking on NK cell phenotype and function, the role of NK cells in COPD exacerbations, and the use of NK cells as biomarkers for exacerbations. Scientific RepoRtS |(2020) 10:1238 | https://doi.

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Summary Background Chronic Obstructive Pulmonary Disease (COPD) is a common disorder of Veterans that causes significant morbidity and mortality. To measure Veterans’ perceptions about COPD, the effect of COPD on their lives and health, and their needs for improved health, we performed a postal survey. Methods 3263 Veterans with a diagnosis of COPD who received care at the Cincinnati Veterans Affairs Medical Center in 2008 were stratified into quintiles by Veterans Health Administration - associated COPD healthcare cost and uniformly sampled. Results 493 of 1000 surveys (49%) were completed and returned. COPD had different effects on respondents in top and bottom quintiles (highest and lowest COPD-related cost) for: knowledge of COPD diagnosis (89% vs 73%, p=0.03); activities affected by breathing, including work (69% vs 45%), recreation (85% vs 62%), change in living arrangements (36% vs 16%), and increased need for help (54% vs 25%) (p<0.05 for all comparisons); emotional effect of respiratory symptoms, including depression (53% vs 30%), fear (41% vs 15%), and helplessness (49% vs 24%) (p<0.05 for all comparisons). 91% of Veterans were prescribed inhalers and one quarter had difficulties using them. 25% of Veterans did nothing when they had symptoms of an exacerbation. Conclusions COPD has profound effects on Veterans’ breathing related activities and generates many negative emotions. Primary care providers are critical in conveying the diagnosis of COPD and providing information about the disease and its management. Veterans with COPD adhere poorly to their medications, and report little instruction about COPD or its management.

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