Bone marrow characterization in COPD: a multi-level network analysis

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-β, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils

O desequilíbrio externo e a taxa de câmbio

O artigo possui duas partes. A primeira calcula qual seria o ajuste no dólar necessário para trazer o déficit em transações correntes no Brasil de 4,5% do PIB para 2,5% do PIB. Se isso fosse feito sem alterar o nível de atividade, seria necessária uma desvalorização do real entre 12,3% e 18,63%. Se se quisesse evitar a desvalorização mas cortar a atividade econômica, a renda deveria cair entre 11,5% e 14,88%. Para ao mesmo tempo recuperar o nível de pleno emprego e gerar o mesmo resultado no setor externo a desvalorização deveria ser de 18,5% a 28,56%. A segunda parte analisa criticamente a estratégia de política cambial seguida depois de 13.01.99 e tenta avaliar as consequências para a taxa de câmbio de equilíbrio para cinco possíveis cenários internacionais. O ajuste cambial médio varia de 23,36% para o cenário mais favorável a 99,56% para o menos favorável. O trabalho termina com uma análise comparativa entre os sistemas de câmbio livre, flutuação suja, currency board e dolarização

Bone marrow characterization in COPD: a multi-level network analysis

Abstract Background Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. Methods In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-β, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. Results We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. Conclusions Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils

Bone marrow characterization in COPD: a multi-level network analysis

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-β, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils

Additional file 2: of Bone marrow characterization in COPD: a multi-level network analysis

Figure S2. Multi-level correlation network of COPD patients with DLCO ≥60% or <60%. For further explanations, see text. Abbreviations: Abs: absolute count; HSC: Hematopoietic stem cells; EPC: Endothelial progenitor cells; TNF R80: Tumour necrosis factor receptor p80; TGF-ß: Transforming growth factor beta; HGF: Hepatocyte growth factor; VEGF: Vascular endothelial growth factor; IGF: Insulin-like growth factor; RBC: Red blood cells; Lympho: Lymphocytes; Segmented: segmented neutrophils; E. Polychrom: Polychromatic erythroblast; E. Ortochrom: Ortochromatic erythroblast; B cells: B lymphocytes; Plasmatic: Plasmatic cells; Hb: haemoglobin; Eos: Eosinophils; Mono/Macro: Monocyte/Macrophages; MFI: Mean fluorescence intensity; Mono: Monocyte; Neutro: Neutrophil; FEV1: forced expiratory volume in 1st second; DLCO: Diffusing capacity of the lung for carbon monoxide; BMI: body mass index. (JPG 60 kb

Additional file 3: of Bone marrow characterization in COPD: a multi-level network analysis

Table S1. Bone marrow characterization, inflammatory and repair markers (mean±SD or median [IQR]) in COPD patients with DLCO higher or lower than 60% of reference. Bolded italic text highlight variables with statistically significant differences ( p≤0.05). Table S2. Bone marrow characterization, inflammatory and repair markers (mean±SD or median [IQR]) in COPD patients with peripheral blood eosinophil counts <300 or ≥300/μL. Bolded italic text highlight variables with statistically significant differences (p≤0.05). (DOCX 42 kb

Additional file 4: of Bone marrow characterization in COPD: a multi-level network analysis

Figure S3. Multi-level correlation network of COPD patients with peripheral blood eosinophil counts <300/μL or ≥300/μL. For further explanations, see text. Abbreviations: Abs: absolute count; HSC: Hematopoietic stem cells; EPC: Endothelial progenitor cells; TNF R80: Tumour necrosis factor receptor p80; VEGF: Vascular endothelial growth factor; RBC: Red blood cells; WBC: White blood cells; Lympho: Lymphocytes; Segmented: segmented neutrophils; E. Ortochrom: Ortochromatic erythroblast; T cells: T lymphocytes; Plasmatic: Plasmatic cells; Mono/Macro: Monocyte/Macrophages; Mono: Monocyte; Neutro: Neutrophil; FEV1: forced expiratory volume in 1st second; DLCO: Diffusing capacity of the lung for carbon monoxide; BMI: body mass index. (JPG 53 kb