RESUMO
INTRODUCTION: 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: PaO2/FiO2 ≤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 µm, C:86.4 ± 33.3 µm, 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 PaO2/FiO2 (r2 = 0.34; P = 0.02) and a negative correlation with plateau pressure (r2 = 0.27; P = 0.04). The extension of denuded epithelium showed a negative correlation with PaO2/FiO2 (r2 = 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.
Assuntos
Remodelação das Vias Aéreas/fisiologia , Pulmão/patologia , Síndrome do Desconforto Respiratório/fisiopatologia , Adulto , Autopsia , Estudos de Casos e Controles , Matriz Extracelular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.
Assuntos
Bronquíolos/efeitos dos fármacos , Cocaína Crack/toxicidade , Exposição por Inalação/efeitos adversos , Nariz/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Administração por Inalação , Azul Alciano/metabolismo , Animais , Corantes/metabolismo , Cocaína Crack/administração & dosagem , Cocaína Crack/sangue , Cocaína Crack/farmacologia , Células Epiteliais/efeitos dos fármacos , Hemossiderina/análise , Imuno-Histoquímica , Macrófagos Alveolares/química , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação do Ácido Periódico de Schiff/métodos , Testes de Toxicidade CrônicaRESUMO
There is evidence indicating that oxidants play a pivotal role in determining air pollution-dependent lung injury. In the present study we explored the role of oxidants present in ambient particles in causing damage to the mucociliary epithelium. We explored the protective effects of pretreatment with three substances (n-propyl gallate, DL-alpha-tocopherol acetate, and EDTA) on the frog palate exposed to residual oil fly ash (ROFA). The parameters analyzed were mucociliary transport (MCT) and ciliary beating frequency (CBF) after 0, 10, 20, 30, 60, and 120 min of exposure. MCT was decreased significantly by ROFA (P < 0.001), with a significant interaction effect (P = 0.02) between the duration of exposure and treatment with antioxidants. The inhibitory effects on MCT of the substances tested were significantly different (P = 0.002); vitamin E was similar to control (Ringer) and different from all other groups. CBF showed no significant effect of duration of exposure (P = 0.465), but a significant interaction between duration of exposure and treatments was observed (P = 0.011). Significant differences were detected among treatments (P < 0.001), with ROFA and n-propyl gallate at concentrations of 50 microM presenting a short-lived increase in CBF, which was not observed in the remaining groups. The results showed that both MCT and CBF were affected within a short period (100 min) of exposure to ROFA and that the presence of antioxidant substances, such as vitamin E (4 mg/mL) and n-propyl gallate (300 microM), protected against the mucociliary impairment induced by ROFA on the frog palate.