| 1. |
- Backer, Vibeke, et al.
(författare)
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Clinical characteristics of the BREATHE cohort–a real-life study on patients with asthma and COPD
- 2020
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Ingår i: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases.
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| 2. |
- Jiménez-Saiz, Rodrigo, et al.
(författare)
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Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease.
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| 3. |
- Jogdand, Prajakta, et al.
(författare)
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Eosinophils, basophils, and type 2 immune microenvironments in COPD-affected lung tissue
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 55:4
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Tidskriftsartikel (refereegranskat)abstract
- Although elevated blood or sputum eosinophils are present in many patients with chronic obstructive pulmonary disease (COPD), uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils, and eosinophil-promoting immune mechanisms in COPD-affected lungs. Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades GOLD I-IV; never-smokers/smokers served as controls. Automated immunohistochemistry and in-situ hybridization identified immune cells, the type 2 immunity marker GATA3, and eotaxins (CCL11, CCL24). Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+ cells, including Th2 lymphocytes and type 2 innate lymphoid cells. A similarly localised and IL-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11+ fibroblasts and CCL24+ macrophages. In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that will likely have implications for personalised treatment.
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| 4. |
- Nilsson, Johan S., et al.
(författare)
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Immune phenotypes of nasopharyngeal cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into “inflamed”, “excluded”, and “deserted” phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein–Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were “inflamed”, 29.8% were “excluded”, and 8.5% were “deserted”. While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of “inflamed” over “excluded” NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.
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