Development of fatal bortezomib induced acute lung injury despite concurrent therapy with high-dose dexamethasone

2007 ◽  
Vol 48 (1) ◽  
pp. 212-213 ◽  
Author(s):  
Edward Chew ◽  
Robin Filshie ◽  
Andrew Wei
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Dose ◽  
Concurrent Therapy ◽  
High Dose Dexamethasone

Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation

1992 ◽  
Vol 72 (4) ◽  
pp. 1320-1325 ◽  
Author(s):  
J. M. Davis ◽  
J. Whitin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Tracheal Aspirate ◽  
Lung Compliance ◽  
Lung Damage ◽  
Control Group ◽  
High Dose ◽  
Albumin Concentration ◽  
High Dose Dexamethasone ◽  
Cell Counts

To determine if prophylactic corticosteroids would prevent acute lung injury caused by hyperoxia and barotrauma, 29 piglets (1.2 +/- 0.3 kg, 1–2 days of age) were studied. Ten piglets were hyperventilated [arterial PCO2 (PaCO2) 15–20 Torr] with 100% O2 for 48 h and compared with 10 piglets treated with the identical management but given 0.7 mg/kg of dexamethasone at time 0 and every 12 h for the 48-h study. Six piglets were normally ventilated (PaCO2 40–45 Torr) for 48 h with 21% O2 as an additional control group. Pulmonary function and tracheal aspirates were examined at time 0 and every 24 h. Bronchoalveolar lavage was performed for surfactant analyses at the conclusion of the study. In animals treated with hyperoxia and hyperventilation, lung compliance decreased 32% and tracheal aspirate polymorphonuclear leukocyte (PMN) chemotactic activity increased by 51%, cell counts by 204%, number of PMNs by 277%, elastase activity by 111%, and albumin concentration by 328% over 48 h (P less than 0.05). In contrast, dexamethasone-treated piglets had increases in only tracheal aspirate albumin concentration (206%) over the 48-h study. All cellular and biochemical variables were lower in dexamethasone-treated compared with hyperoxic hyperventilated piglets. Room air normal ventilation controls had only a 108% increase in tracheal aspirate albumin concentration noted. Despite quantitative differences in surfactant among the three groups, activity was unaffected. Results indicate that hyperoxia and hyperventilation for 48 h causes significant inflammatory changes and acute lung injury and that prophylactic high-dose dexamethasone significantly ameliorates this lung damage.

scholarly journals GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury

2018 ◽  
Vol 124 (4) ◽  
pp. 899-905 ◽  
Author(s):  
Nathan D. Putz ◽  
Ciara M. Shaver ◽  
Kobina Dufu ◽  
Chien-Ming Li ◽  
Qing Xu ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Oxygen Affinity ◽  
High Dose ◽  
Novel Therapy ◽  
Oxygen Affinity Of Hemoglobin

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8–15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1β, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.

scholarly journals Methotrexate induced lung injury in a patient with primary CNS lymphoma: A case report

2012 ◽  
Vol 4 (1) ◽  
pp. e2012020 ◽  
Author(s):  
Puneet Chhabra ◽  
Arjun Dutt law ◽  
Dr vikas Suri ◽  
Dr pankaj Malhotra ◽  
Dr subhash Varma
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Rare Event ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Connective Tissue Disorders ◽  
High Dose Regimen ◽  
Dose Methotrexate

Methotrexate is an antimetabolite commonly used in clinical practice for a variety of indications ranging from rheumatoid arthritis and other connective tissue disorders to high dose regimens in many malignancies. This folate antagonist has got a spectrum of toxicities among which gastrointestinal effects predominate . Lung injury is a well described but rare event and has been reported most often in patients who have been on long term oral therapy for rheumatic disorders. Acute lung injury in a patient receiving a high dose regimen for haematological malignancies has not been reported previously. We present one such case of methotrexate related acute lung injury in a patient of primary CNS lymphoma receiving high dose methotrexate.

scholarly journals Propofol Activation of the Nrf2 Pathway Is Associated with Amelioration of Acute Lung Injury in a Rat Liver Transplantation Model

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Weifeng Yao ◽  
Gangjian Luo ◽  
Guosong Zhu ◽  
Xinjin Chi ◽  
Ailan Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Content ◽  
High Dose ◽  
Lung Pathology ◽  
Lung Water ◽  
Sod Activity ◽  
Nrf2 Pathway ◽  
Lung Water Content

Objective. This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.Method. Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.Results. Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2and MDA levels, and improve the arterial PaO2and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.Conclusion. Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.

Acute Lung Injury Following Treatment With High-Dose Cyclophosphamide, Cisplatin, and Carmustine: Pharmacodynamic Evaluation of Carmustine

1993 ◽  
Vol 85 (8) ◽  
pp. 640-647 ◽  
Author(s):  
R. B. Jones ◽  
S. Matthes ◽  
E. J. Shpall ◽  
J. H. Fisher ◽  
S. M. Stemmer ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Dose

High-dose heparin fails to improve acute lung injury following smoke inhalation in sheep

2003 ◽  
Vol 104 (4) ◽  
pp. 349 ◽  
Author(s):  
Kazunori MURAKAMI ◽  
Perenlei ENKHBAATAR ◽  
Katsumi SHIMODA ◽  
Akio MIZUTANI ◽  
Robert A. COX ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Smoke Inhalation ◽  
High Dose ◽  
Dose Heparin

scholarly journals Bioactive Components from Qingwen Baidu Decoction against LPS-Induced Acute Lung Injury in Rats

Molecules ◽  
2017 ◽  
Vol 22 (5) ◽  
pp. 692 ◽  
Author(s):  
Qi Zhang ◽  
Hai-Min Lei ◽  
Peng-Long Wang ◽  
Zhi-Qiang Ma ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Polymorphonuclear Leukocytes ◽  
Principal Component ◽  
Hemorrhagic Fever ◽  
Pharmacological Effect ◽  
High Dose ◽  
Protective Effects ◽  
Pca Method

Qingwen Baidu Decoction (QBD) is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI) induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05). To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA) method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MSn and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs).

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