High Flow Nasal Cannula compared to Continuous Positive Airway Pressure: a bench and physiological study.

High-flow nasal cannula (HFNC) is extensively used for acute respiratory failure. However, questions remain regarding its physiological effects. We explored 1) whether HFNC produced similar effects to continuous positive airway pressure (CPAP); 2) possible explanations of respiratory rate changes; 3) the effects of mouth opening. Two studies were conducted: a bench study using a manikin's head with lungs connected to a breathing simulator while delivering HFNC flow rates from 0 to 60L/min; a physiological cross-over study in 10 healthy volunteers receiving HFNC (20 to 60L/min) with the mouth open or closed and CPAP 4cmH2O delivered through face-mask. Nasopharyngeal and esophageal pressures were measured; tidal volume and flow were estimated using calibrated electrical impedance tomography. In the bench study, nasopharyngeal pressure at end-expiration reached 4cmH2O with HFNC at 60L/min, while tidal volume decreased with increasing flow. In volunteers with HFNC at 60L/min, nasopharyngeal pressure reached 6.8cmH2O with mouth closed and 0.8cmH2O with mouth open; p<0.001. When increasing HFNC flow, respiratory rate decreased by lengthening expiratory time, tidal volume did not change, and effort decreased (pressure-time product of the respiratory muscles); at 40L/min, effort was equivalent between CPAP and HFNC40L/min and became lower at 60L/min (p=0.045). During HFNC with mouth closed, and not during CPAP, resistance to breathing was increased, mostly during expiration. In conclusion, mouth closure during HFNC induces a positive nasopharyngeal pressure proportional to flow rate and an increase in expiratory resistance that might explain the prolonged expiration and reduction in respiratory rate and effort, and contribute to physiological benefits.

Protective Effects of Quercetin on Livers from Mice Exposed to Long-Term Cigarette Smoke.

Cigarette smoke is highly toxic, and it can promote increased production of reactive species and inflammatory response and leads to liver diseases. Quercetin is a flavonoid that displays antioxidant and anti-inflammatory activities in liver diseases. This study aimed at evaluating the protective effects of quercetin on livers from mice exposed to long-term cigarette smoke exposure. Male C57BL/6 mice were divided into five groups: control (CG), vehicle (VG), quercetin (QG), cigarette smoke (CSG), quercetin, and cigarette smoke (QCSG). CSG and QCSG were exposed to cigarette smoke for sixty consecutive days; at the end of the exposures, all animals were euthanized. Mice that received quercetin daily and were exposed to cigarette smoke showed a reduced influx of inflammatory cells, oxidative stress, inflammatory reaction, and histopathological changes in the liver, compared to CSG. These results suggest that quercetin may be an effective adjuvant for treating damage to the liver due to cigarette smoke exposure.

Applying Positive End-Expiratory Pressure During Mechanical Ventilation Causes Pulmonary Redox Imbalance and Inflammation in Rats.

BACKGROUND: Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokines, inflammatory infiltration of neutrophils, and changes in the permeability of the alveolar-capillary barrier. The use of positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding alveolar collapse at the end of expiration. The present study aimed to analyze inflammatory response and redox imbalance in lungs of rats submitted to MV with and without PEEP. METHODS: Eighteen Wistar rats were divided into three groups: control (CG), PEEP group (PG), and zero PEEP (ZEEP) group (ZG). PG and ZG were submitted to MV for 60 min with or without PEEP, respectively. Subsequently, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. RESULTS: The number of neutrophils was higher in PG compared with CG. Leucocyte and neutrophil influx in bronchoalveolar lavage fluid was higher in PG compared with CG. PG showed an increase in alveolar area compared with the other groups. There were increases in the levels of chemokines, CCL3 and CCL5, in PG compared with CG. There were increases in oxidation of lipids and proteins in PG compared with other groups. There were increases in the activity of superoxide dismutase and catalase in PG compared with CG and ZG. However, there was a decrease in the ratio of glutathione to glutathione disulfide in PG compared with other groups. CONCLUSIONS: MV with PEEP caused redox imbalance and inflammation in lungs of healthy rats.

Disease Severity Prediction by Spirometry in Adults with Visceral Leishmaniasis from Minas Gerais, Brazil.

Visceral leishmaniasis (VL) is associated with interstitial pneumonitis according to histology and radiology reports. However, studies to address the functional impact on respiratory function in patients are lacking. We assessed pulmonary function using noninvasive spirometry in a cross-sectional study of hospitalized adult VL patients from Minas Gerais, Brazil, without unrelated lung conditions or acute infections. Lung conditions were graded as normal, restrictive, obstructive, or mixed patterns, according to Brazilian consensus standards for spirometry. To control for regional patterns of lung function, we compared spirometry of patients with regional paired controls. Spirometry detected abnormal lung function in most VL patients (70%, 14/20), usually showing a restrictive pattern, in contrast to regional controls and the standards for normal tests. Alterations in spirometry measurements correlated with hypoalbuminemia, the only laboratory value indicative of severity of parasitic disease. Abnormalities did not correlate with unrelated factors such as smoking or occupation. Clinical data including pulmonary symptoms and duration of therapy were also unrelated to abnormal spirometry findings. We conclude that the severity of VL is correlated with a restrictive pattern of lung function according to spirometry, suggesting that there may be interstitial lung involvement in VL. Further studies should address whether spirometry could serve as an index of disease severity in the management of VL.

Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype.

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-ß expression. Together, IL-6 and TGF-ß have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.

Alterações da histoarquitetura pulmonar de camundongos neonatos expostos à hiperóxia / Alterations in the pulmonary histoarchitecture of neonatal mice exposed to hyperoxia

OBJETIVOS: Analisar os efeitos da exposição à hiperóxia (100% de oxigênio) sobre a histoarquitetura pulmonar de camundongos neonatos. MÉTODOS: Camundongos neonatos da linhagem Balb/c foram expostos à hiperóxia (GH) (100% de oxigênio) (n = 10) em uma câmara (15 x 20 x 30 cm) por 24 horas, com fluxo de 2 L/min. O grupo controle (GC) (n = 10) foi exposto a normóxia em um mesmo tipo de câmara e pelo mesmo tempo. Após a exposição, os animais foram sacrificados por decapitação, os pulmões foram removidos para análise histológica e processados de acordo com a rotina do laboratório. Cortes de 3 µm de espessura foram corados com hematoxilina e eosina (H&E). A análise morfométrica foi realizada com o objetivo de analisar macrófagos presentes na luz alveolar, densidade de superfície (Sv) de trocas gasosas, densidade de volume (Vv) de parênquima pulmonar e áreas de atelectasias. RESULTADOS: Foi verificada diminuição do número de macrófagos alveolares (MØ) no GH (GH = 0,08±0,01 MØ/mm²; GC = 0,18±0,03 MØ/mm²; p = 0,0475), Sv de troca gasosa no GH (GH = 8,08 ± 0,12 mm² /mm³; GC = 8,65 ± 0,20 mm² /mm³; p = 0,0233), Vv de parênquima pulmonar no GH (GH = 54,7/33,5/83,5 %/mm²; GC = 75/56,7/107,9 %/mm²; p < 0.0001) quando comparado com o GC. Entretanto, houve aumento de áreas de atelectasias no GH (GH = 17,5/11,3/38,4 atelectasia/mm²; GC = 14/6,1/24,4 atelectasia/mm²; p = 0,0166) quando comparado com o GC. CONCLUSÃO: Nossos resultados indicam que a hiperóxia promoveu alterações na histoarquitetura pulmonar, aumentando áreas de atelectasia e hemorragia alveolar difusa.

OBJECTIVES: To analyze the effects of exposure to hyperoxia (100% oxygen) on the lung histoarchitecture of neonatal mice. METHODS: Neonatal Balb/c mice were exposed to hyperoxia (HG) (100% oxygen) (n = 10) in a chamber (15 x 20 x 30 cm) for 24 horas ours with a flow of 2 L/min. The control group (CG) (n = 10) was exposed to normoxia in the same type of chamber and for the same time. After exposure, the animals were euthanized by decapitation; the lungs were removed and processed for histological examination according to the laboratory routine. Three-mm thick sections were stained with hematoxylin and eosin (H&E). The morphometric analysis was performed with in order to analyze the macrophages present in the alveolar lumen, surface density (Sv) of gas exchange, volume density (Vv) of lung parenchyma, and areas of atelectasis. RESULTS: A decrease in the number of alveolar macrophages (MØ) was observed in the HG (HG = 0.08±0.01 MØ/mm², CG = 0.18±0.03 MØ/mm², p = 0.0475), Sv of gas exchange in HG (HG = 8.08±0.12 mm² /mm³, CG = 8.65±0.20 mm² /mm³, p = 0.0233), Vv of lung parenchyma in HG (HG = 54.7/33.5/83.5%/ mm²; CG = 75/56.7/107.9%/mm², p < 0.0001) when compared with the CG. However, there was an increase in areas of atelectasis in HG (HG = 17.5/11.3/38.4 atelectasis/mm², CG = 14/6.1/24.4 atelectasis/mm², p = 0.0166) when compared with the CG. CONCLUSION: The present results indicate that hyperoxia caused alterations in lung histoarchitecture, increasing areas of atelectasis and diffuse alveolar hemorrhage.

Alterations in the pulmonary histoarchitecture of neonatal mice exposed to hyperoxia.

OBJECTIVES: To analyze the effects of exposure to hyperoxia (100% oxygen) on the lung histoarchitecture of neonatal mice. METHODS: Neonatal Balb/c mice were exposed to hyperoxia (HG) (100% oxygen) (n= 10) in a chamber (15 x 20 x 30 cm) for 24 hours with a flow of 2 L/min. The control group (CG) (n = 10) was exposed to normoxia in the same type of chamber and for the same time. After exposure, the animals were euthanized by decapitation; the lungs were removed and processed for histological examination according to the laboratory routine. Three-mm thick sections were stained with hematoxylin and eosin (H&E). The morphometric analysis was performed with in order to analyze the macrophages present in the alveolar lumen, surface density (Sv) of gas exchange, volume density (Vv) of lung parenchyma, and areas of atelectasis. RESULTS: A decrease in the number of alveolar macrophages (MØ) was observed in the HG (HG = 0.08 ±0.01 MØ/mm(2), CG = 0.18 ± 0.03 MØ/mm(2), p=0.0475), Sv of gas exchange in HG (HG = 8.08 ± 0.12 mm(2)/mm(3), CG=8.65 ± 0.20mm(2)/mm(3), p = 0.0233), Vv of lung parenchyma in HG (HG = 54.7/33.5/83.5%/mm(2); CG = 75/56.7/107.9%/mm(2), p<0.0001) when compared with the CG. However, there was an increase in areas of atelectasis in HG (HG = 17.5/11.3/38.4 atelectasis/mm(2), CG = 14/6.1/24.4 atelectasis/mm(2), p=0.0166) when compared with the CG. CONCLUSION: The present results indicate that hyperoxia caused alterations in lung histoarchitecture, increasing areas of atelectasis and diffuse alveolar hemorrhage.

Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs.

In this study our aim was to investigate the time courses of inflammation, oxidative stress and tissue damage after hyperoxia in the mouse lung. Groups of BALB/c mice were exposed to 100% oxygen in a chamber for 12, 24 or 48 h. The controls were subjected to normoxia. The results showed that IL-6 increased progressively after 12 (P < 0.001) and 24 h (P < 0.001) of hyperoxia with a reduction at 48 h (P < 0.01), whereas TNF-α increased after 24 (P < 0.001) and 48 h (P < 0.001). The number of macrophages increased after 24 h (P < 0.001), whereas the number of neutrophils increased after 24 h (P < 0.01) and 48 h (P < 0.001). Superoxide dismutase activity decreased in all groups exposed to hyperoxia (P < 0.01). Catalase activity increased only at 48 h (P < 0.001). The reduced glutathione/oxidized glutathione ratio decreased after 12 h (P < 0.01) and 24 h (P < 0.05). Histological evidence of lung injury was observed at 24 and 48 h. This study shows that hyperoxia initially causes an inflammatory response at 12 h, resulting in inflammation associated with the oxidative response at 24 h and culminating in histological damage at 48 h. Knowledge of the time course of inflammation and oxidative stress prior to histological evidence of acute lung injury can improve the safety of oxygen therapy in patients.

Hyperoxia-induced lung injury is dose dependent in Wistar rats.

Oxygen is indispensable for aerobic respiration. However, the effects of hyperoxia on the lungs are poorly defined. The aim of the present study was to determine the effects of different oxygen concentrations on rat lungs. Rats (n = 6 per group) were exposed to hyperoxia for 90 minutes at 3 different concentrations: 50% (H50%), 75% (H75%), or 100% (H100%). Bronchoalveolar lavage (BAL) was performed and the right lungs were removed for histological analyses. The BAL samples were assayed for lipid peroxidation and antioxidant status using biochemical methods. Hyperoxia induced influxes of macrophages (1.8- to 2.3-fold) and neutrophils (7.0- to 10.2-fold) into the lungs compared to the control group (exposed to normoxia; n = 6). Histological analyses of the hyperoxic groups showed hemorrhagic areas and septal edema. A significant increase (2.2-fold) in lipid peroxidation was observed in the H100% group compared to the control group (P <.05). Glutathione peroxidase and superoxide dismutase activities were reduced to approximately 20% and 40% of the control values, respectively, in all 3 hyperoxic groups, and catalase activity was reduced in both the H75% (-0.6-fold) and H100% (-0.7-fold) groups. These results indicate a harmful effect of hyperoxia on the rat lung, with evidence of oxidant/antioxidant imbalance and histological damage.