Hyperoxia and acute lung injury

Abstract

TO THE EDITOR: The review by has misleading and potentially dangerous statements concerning the role of hyperoxia in human acute lung injury (ALI). Table 4 states "in normal human lungs, 100% oxygen has not induced lung injury . . . " The text states that most mammalian species develop respiratory distress and die with exposure to 100% oxygen, but the "same findings have not been reproduced in humans with normal lungs . . . " That statement is essentially true (fortunately) but mainly because very few studies of potentially lethal hyperoxia have been carried out in individuals with normal lungs, for obvious reasons. The one study referenced in the review (1) was carried out in patients with irreversible brain injury, which may have influenced the pulmonary response to hyperoxia, and indeed a subsequent similar study demonstrated significant lung injury (13). Studies of normal individuals exposed experimentally to 100% oxygen at normal pressure (i.e., 1 ATA) have shown evidence of tracheobronchitis and changes in vital capacity, diffusing capacity, and lung permeability (2-5, 7, 17). Inadvertent exposure of patients with normal lungs to prolonged hyperoxia resulted in clinical findings compatible with oxygen toxicity (12). Exposure of normal humans to oxygen at elevated pressure (that is, greater than 1 ATA O 2 ) has indicated a shorter duration of exposure for equivalent pulmonary symptoms and function changes (8,10,16,18). Pulmonary-related death has been reported for one patient in the normobaric O 2 exposure group (12) and another with hyperbaric exposure (9). Thus evidence of lung abnormalities with severity proportional to the partial pressure of oxygen has been demonstrated in normal human lungs similar to the findings with experimental animals. It is known that different species, and indeed strains of the same species as well as individuals from the same strain, show varying sensitivity to the toxic effects of oxygen (11). Rats exposed to 0.8 ATA O 2 become tolerant to 1 ATA O 2 but uniformly die when subsequently exposed to higher (1.5 ATA) O 2 partial pressures (14), emphasizing the importance of O 2 "dose." Parenthetically, the dose range for lethality (approximately 0.8 -1.5 ATA) is quite narrow compared with many toxicants where dose sensitivity of various species may vary by more than an order of magnitude. So the important question is, what is the dose range for human pulmonary oxygen toxicity? Based on the limited number of human studies but with analogy to nonhuman primates (6), the "average" human might require O 2 at 1.1 or 1.2 ATA to reach a lethal concentration. If that is the case, a large segment of the human population might be spared ALI and lethality with 100% oxygen at 1 ATA. However, that concentration of oxygen could prove to be lethal for that fraction of the population whose resistance to oxidant stress is less than the population mean. All indications are that hyperoxia in animals (with appropriate consideration of dose) does serve as a model for human ALI associated with oxidant...

Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3

“…High partial pressures of oxygen have long been known to be toxic to the lung (Aggarwal et al, 2010; Davis et al, 1983; Deneke and Fanburg, 1980; Deneke and Fanburg, 1982; Fisher and Beers, 2008) and contribute to the severity of ARDS and VILI. We found that oxidant injury (H 2 O 2 ) directly increases HMGB1 expression in EC suggesting a novel role for HMGB1 in pulmonary EC oxidant injury.…”

Differential Lung Uptake of 99mTc-Hexamethylpropyleneamine Oxime and 99mTc-Duramycin in the Chronic Hyperoxia Rat Model

“…However, prolonged exposure to high concentrations of O 2 can be toxic to the lungs (1,2,3). Although the mechanisms leading to pulmonary hyperoxic injury are not fully understood, there is ample evidence that the deleterious effects of high O 2 are the result of increased reactive oxygen species (ROS) formation, predominantly via mitochondrial pathways (3,4).…”

“…The chronic hyperoxia rat model of lung injury mimics key functional aspects of lung O 2 toxicity observed clinically (1,2,5-7). It is a well-documented acute lung injury model, especially for studies of oxidant-induced lung injury (2,5,6,8,9).…”

The Milieu of Damaged Alveolar Epithelial Type 2 Cells Stimulates Alveolar Wound Repair by Endogenous and Exogenous Progenitors

“…Subacute hyperoxia was used as an in vivo damage model in this study because it elicits well documented and reproducible responses in rodent AEC2s and can serve as a model for human acute lung injury associated with oxidant stress without inflammation (11). Our data herein show that the AEC2 in vivo hyperoxic milieu is sufficient to recapitulate the proliferation induced by in vivo hyperoxia when added to normoxic AEC2 ex vivo and can expedite alveolar epithelial wound healing through increased migration and proliferation.…”

“…In this study, we examined the milieu of AEC2s using two damage models, with an emphasis on cytokine/chemokine production. Hyperoxia was used as an in vivo epithelial damage model because subacute hyperoxia in rodents is a relevant model for human acute lung injury associated with oxidant stress without inflammation (11). BAL and lung extract from hyperoxic rats were used to represent AEC2s in vivo damage milieu and are reflective of autocrine contributions from many cell types.…”