Guidance for the Better Care of Patients with Chronic Obstructive Pulmonary Disease.
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ABSTRACT:
SUBMITTER: Calverley PMA
PROVIDER: S-EPMC7193847 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
Guidance for the Better Care of Patients with Chronic Obstructive Pulmonary Disease.
American journal of respiratory and critical care medicine 20200501 9
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Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
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Project description:Assessment of patients with chronic obstructive pulmonary disease (COPD) is important to establish an accurate diagnosis, assist in making therapeutic decisions, measuring outcomes for clinical and research purposes, and determining prognosis. Chest computed tomography (CT) scans are useful in patients who present with airflow limitation and clinical features suggestive of COPD but in whom other diagnoses are being considered. In such cases, a chest CT may indicate another diagnosis. The amount and distribution of emphysema can identify outcomes from lung volume reduction surgery, and chest CT scans are mandatory in assessment of patients for this surgery. Quantitative parameters from chest CT scans have been used to define longitudinal progression of disease. Assessment of patients with COPD for both clinical and research purposes should incorporate a variety of different outcomes. There are outcome measures that have been successfully incorporated in large clinical trials, and the design and outcomes of these trials can be used to plan future clinical investigations in COPD.
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Project description:RationaleAdaptive immune responses are present in patients with chronic obstructive pulmonary disease (COPD), and it has been postulated that these processes could be autoreactive.ObjectivesTo ascertain if humoral autoimmunity could play a role in COPD pathogenesis.MethodsCirculating IgG autoantibodies were detected by immunofluorescence and immunoprecipitation. Immunohistochemistry and immunofluorescence were used to evaluate intrapulmonary IgG and complement (C3) deposition in human lung explants. Autoantibody pathogenicity was also investigated with an antibody-dependent cell-mediated cytotoxicity assay.Measurements and main resultsThe prevalence of anti-HEp-2 epithelial cell autoantibodies in 47 smokers/former smokers with COPD (GOLD stages 1-4) was greater than among 8 subjects with a smoking history but normal spirometry and 21 healthy control subjects who had never smoked (68 vs. 13 vs. 10%, respectively; P < 0.0001). Antibodies against primary pulmonary epithelial cells were found in 12 of 12 patients with COPD versus 3 of 12 never-smoked control subjects (P < 0.001). Self-antigens immunoprecipitated from 34 of 35 (97%) of COPD plasmas (vs. 0/12 never-smoked controls). Antibodies against a particular 130-kD autoantigen (n = 7) were associated with decreased body mass index (23.2 +/- 2.1 vs. 29.5 +/- 1.0 kg/m(2), P = 0.007). Intrapulmonary immune complexes were present in six of six and C3 was seen in five of six COPD lung explants, unlike zero of six and one of six normals, respectively. Cytotoxicity of pulmonary epithelial cells by allogeneic mononuclear cells also increased 46% after incubation with COPD plasmas (n = 10), compared with identical treatments with eight normal specimens (P = 0.03).ConclusionsIgG autoantibodies with avidity for pulmonary epithelium, and the potential to mediate cytotoxicity, are prevalent in patients with COPD. Autoreactive adaptive immune responses may be important in the etiology of this disease.
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Project description:Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Single-cell RNA sequencing (scRNA-seq) provides gene expression profiles at the single-cell level. Hence, we evaluated gene expression in the peripheral blood of patients with COPD. Methods Peripheral blood samples from seven healthy controls and eight patients with COPD were obtained in this study. The 10X Genomics Chromium Instrument and cDNA synthesis kit was utilized to generate a barcoded cDNA library for single cell RNA-sequencing. We compared the scRNA-seq data between the COPD and control groups using computational analysis. Functional analyses were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Results scRNA-seq was used to analyze the transcriptome of peripheral blood mononuclear cells from seven normal controls and eight patients with COPD. We found increased numbers of monocyte macrophages in the COPD group compared to those in the normal control group. Among the differentially expressed genes (DEGs) in monocyte-macrophages, we identified five upregulated genes (HLA-DRB5, ITGB2, EGR1, CXCL8, and CCL4) and seven downregulated genes (FOLR3, RPS4Yq, CD52, LY6E, HLA-DQB1, G0S2, and CCL3L1) in the COPD group compared to the normal control group. Conclusions Using scRNA-seq, we found differences in cell type distribution, especially in monocyte macrophages. Several upregulated and downregulated genes were found in the monocyte-macrophages of the COPD groups.
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Project description:Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β(2) agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.
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