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      Eosinopenia and neutrophil-to-lymphocyte count ratio as prognostic factors in exacerbation of COPD

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          Abstract

          Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPDs) are one of the most important clinical aspects of the disease, and when requiring hospital admission, they significantly contribute to mortality among COPD patients. Our aim was to assess the role of eosinopenia and neutrophil-to-lymphocyte count (NLR) as markers of in-hospital mortality and length of hospitalization (LoH) among patients with ECOPD requiring hospitalization. We included 275 patients. Eosinopenia was associated with in-hospital deaths only when coexisted with lymphocytopenia, with the specificity of 84.4% (95% CI 79.6–88.6%) and the sensitivity of 100% (95% CI 35.9–100%). Also, survivors presented longer LoH (P < 0.0001). NLR ≥ 13.2 predicted in-hospital death with the sensitivity of 100% (95% CI 35.9–100%) and specificity of 92.6% (95% CI 88.8–95.4%), however, comparison of LoH among survivors did not reach statistical significance (P = 0.05). Additionally, when we assessed the presence of coexistence of eosinopenia and lymphocytopenia first, and then apply NLR, sensitivity and specificity in prediction of in-hospital death was 100% (95% CI 35.9–100) and 93.7% (95% CI 90.1–96.3), respectively. Moreover, among survivors, the occurrence of such pattern was associated with significantly longer LoH: 11 (7–14) vs 7 (5–10) days (P = 0.01). The best profile of sensitivity and specificity in the prediction of in-hospital mortality in ECOPD can be obtained by combined analysis of coexistence of eosinopenia and lymphocytopenia with elevated NLR. The occurrence of a such pattern is also associated with significantly longer LoH among survivors.

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          T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.

          Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper lymphocytes, the nature of the 'help' provided to CTLs is unknown. One widely held view is that help for CTLs is mediated by cytokines produced by T-helper cells activated in proximity to the CTL precursor at the surface of an antigen-presenting cell (APC). An alternative theory is that, rather than being directly supplied to the CTL by the helper cell, help is delivered through activation of the APC, which can then prime the CTL directly. CD40 and its ligand, CD40L, may activate the APC to allow CTL priming. CD40L is expressed on the surface of activated CD4+ T-helper cells and is involved in their activation and in the development of their effector functions. Ligation of CD40 on the surface of APCs such as dendritic cells, macrophages and B cells greatly increases their antigen-presentation and co-stimulatory capacity. Here we report that signalling through CD40 can replace CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses. Blockade of CD40L inhibits CTL priming; this inhibition is overcome by signalling through CD40. CD40-CD40L interactions are therefore vital in the delivery of T-cell help for CTL priming.
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            Type 2 innate lymphoid cells control eosinophil homeostasis

            Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, 1 and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins, mediate eosinophil development and survival, 2 and tissue recruitment, 3 respectively, the processes underlying the basal regulation of these signals remain unknown. Here, we show that serum IL-5 is maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, 4 ILC2 co-express IL-5 and IL-13, which is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide (VIP) also stimulates ILC2 through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
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              Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.

              Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.
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                Author and article information

                Contributors
                adam.bialas@umed.lodz.pl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 February 2021
                26 February 2021
                2021
                : 11
                : 4804
                Affiliations
                [1 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, Department of Pneumology and Allergy, , Medical University of Lodz, ; Lodz, Poland
                [2 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, Department of General and Oncological Pulmonology, , Medical University of Lodz, ; Lodz, Poland
                [3 ]GRID grid.8267.b, ISNI 0000 0001 2165 3025, Department of Pathobiology of Respiratory Diseases, , Medical University of Lodz, ; 22nd Kopcińskiego Street, 90-153 Lodz, Poland
                Article
                84439
                10.1038/s41598-021-84439-8
                7910289
                33637803
                7553ebea-f92b-4be5-b445-0a87088fc902
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 June 2020
                : 16 February 2021
                Categories
                Article
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                © The Author(s) 2021

                Uncategorized
                diseases,medical research,risk factors
                Uncategorized
                diseases, medical research, risk factors

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