NICOLE INFORSATO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
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bookPart Trauma vascular(2019) INFORSATO, Nicole; GRATãO, Tatiane Carneiro; MULATTI, GracebookPart Oclusão arterial aguda(2019) BENATTI, Fernanda Denadai; INFORSATO, Nicole; CUNHA, Victor Paro da; MARINO, Lucas Oliveira- Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue(2011) MORALES, Maina M. B.; PIRES-NETO, Ruy C.; INFORSATO, Nicole; LANCAS, Tatiana; SILVA, Luiz F. F. da; SALDIVA, Paulo H. N.; MAUAD, Thais; CARVALHO, Carlos R. R.; AMATO, Marcelo B. P.; DOLHNIKOFF, MarisaIntroduction: Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods: We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test. Results: Thirty-one ARDS patients (A: PaO(2)/FiO(2) <= 200, 45 +/- 14 years, 16 males) and 11 controls (C:52 +/- 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 +/- 27.2%, C:76.7 +/- 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 +/- 35.2%, C:21.8 +/- 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 +/- 54.3 mu m, C:86.4 +/- 33.3 mu m, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P = 0.03). The extension of normal epithelium showed a positive correlation with PaO(2)/FiO(2) (r(2) = 0.34; P = 0.02) and a negative correlation with plateau pressure (r(2) = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO(2)/FiO(2) (r(2) = 0.27; P = 0.04). Conclusions: Structural changes in small airways of patients with ARDS were characterized by epithelial denudation, inflammation and airway wall thickening with ECM remodeling. These changes are likely to contribute to functional airway changes in patients with ARDS.
bookPart Oclusão arterial aguda(2020) BENATTI, Fernanda Denadai; INFORSATO, Nicole; CUNHA, Victor Paro da; MARINO, Lucas OliveirabookPart Oclusão arterial aguda(2021) BENATTI, Fernanda Denadai; INFORSATO, Nicole; CUNHA, Victor Paro da; MARINO, Lucas OliveirabookPart Oclusão arterial aguda(2022) BENATTI, Fernanda Denadai; INFORSATO, Nicole; CUNHA, Victor Paro da; MARINO, Lucas Oliveira- Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome(2013) PIRES-NETO, Ruy Camargo; MORALES, Maina Maria Barbosa; LANCAS, Tatiana; INFORSATO, Nicole; DUARTE, Maria Irma Seixas; AMATO, Marcelo Britto Passos; CARVALHO, Carlos Roberto Ribeiro de; SILVA, Luiz Fernando Ferraz da; MAUAD, Thais; DOLHNIKOFF, MarisaPurpose: Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS. Materials and Methods: We studied the lungs of 31 patients with ARDS (PaO2/fraction of inspired oxygen <= 200, 45 +/- 14 years, 16 men) and 11 controls (52 +/- 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified. Results: Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 (P = .006) and an increased density of inflammatory cells expressing IL-6 (P = .004) and IL-8 (P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls. Conclusion: Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS.