• Acute lung injury
• Acute respiratory distress syndrome
• Bronchoscopy
• Burn inhalation injury
• Burns
• Endotracheal intubation
• Heparin
• Mechanical ventilation
• Smoke inhalation injury

• Humans
• Acetylcysteine
• Burns/therapy
• Respiration, Artificial
• Heparin
• Lung Injury
• Albuterol

• British Journal of Anaesthesia (BJA)/Royal College of Anaesthetists (RCoA)

Wildfires are increasing in frequency and severity across the Western United States. Efforts to understand the health impacts on humans are widespread and expanding; however, very little is known about the impact of wildfires and smoke exposure on livestock. This work presents the results of a survey of cattle, sheep, and goat producers in California, Oregon, and Nevada, on their experiences during the 2020 wildfire season. While few direct impacts of fires were reported among the 70 responses, 26% of respondents reported they had to evacuate livestock and 19% reported pasture losses. Indirect losses from smoke exposure, including pneumonia and reproductive losses were reported more broadly. This preliminary work highlights the need to better understand impacts of wildfires on livestock and how policy changes can help support the livestock production industry through these crises.

Wildfires are increasing in frequency and severity across the Western United States. However, there is limited information available on the impacts these fires are having on the livelihood of livestock producers and their animals. This work presents the results of a survey evaluating the direct and indirect impacts of the 2020 wildfire season on beef cattle, dairy cattle, sheep, and goat, producers in California, Oregon, and Nevada. Seventy completed surveys were collected between May and July 2021. While dairy producers reported no direct impacts from the fires, beef, sheep, and goat producers were impacted by evacuations and pasture lost to fires. Only beef producers reported losses due to burns and burn-associated deaths or euthanasia. Dairy, beef, sheep, and goat producers observed reduced conception, poor weight gain, and drops in milk production. All but dairy producers also observed pneumonia. Lower birthweights, increased abortion rates, and unexplained deaths were reported in beef cattle, sheep, and goats. This work documents the wide-ranging impacts of wildfires on livestock producers and highlights the need for additional work defining the health impacts of fire and smoke exposure in livestock, as well as the policy changes needed to support producers experiencing direct and indirect losses.

• cattle
• livestock
• production losses
• smoke
• wildfires

The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.

• acute respiratory distress syndrome
• anticoagulation
• coagulation
• inflammation
• subphenotypes

• ARDS
• COVID-19
• Nebulised heparin
• SARS
• SARS-CoV-2
• Unfractionated heparin

• COVID-19
• Coronavirus Infections/drug therapy
• Heparin/administration & dosage
• Humans
• Nebulizers and Vaporizers
• Pandemics
• Pneumonia, Viral/drug therapy
• Randomized Controlled Trials as Topic
• Treatment Outcome

• SARS virus
• fibrin
• fibrinolysis
• plasminogen activator inhibitor 1
• respiratory distress syndrome (adult)
• tissue plasminogen activator

• Betacoronavirus/pathogenicity
• COVID-19
• Coronavirus Infections/blood
• Coronavirus Infections/diagnosis
• Coronavirus Infections/drug therapy
• Coronavirus Infections/virology
• Drug Repositioning
• Fibrinolysis/drug effects
• Fibrinolytic Agents/administration & dosage
• Fibrinolytic Agents/adverse effects
• Host-Pathogen Interactions
• Humans
• Pandemics
• Pneumonia, Viral/blood
• Pneumonia, Viral/diagnosis
• Pneumonia, Viral/drug therapy
• Pneumonia, Viral/virology
• SARS-CoV-2
• Thrombolytic Therapy/adverse effects
• Tissue Plasminogen Activator/administration & dosage
• Tissue Plasminogen Activator/adverse effects
• Treatment Outcome
• COVID-19 Drug Treatment

• FS/11/2/28579 British Heart Foundation
• PG/15/82/31721 British Heart Foundation
• PG/20/17/35050 British Heart Foundation
• FS/11/2/28579, PG/15/82/31721 British Heart Foundation

Smoke inhalation injury increases overall burn mortality. Locally applied heparin attenuates lung injury in burn animal models of smoke inhalation. It is uncertain whether local treatment of heparin is benefit for burn patients with inhalation trauma. We systematically reviewed published clinical trial data to evaluate the effectiveness of nebulized heparin in treating burn patients with inhalation injury.

A systematic search was undertaken in PubMed, the Cochrane Library, Embase, Web of Science, the Chinese Journals Full-text Database, the China Biomedical Literature Database and the Wanfang Database to obtain clinical controlled trails evaluating nebulized heparin in the treatment of burn patients with inhalation injury. Patient and clinical characteristics, interventions and physiological and clinical outcomes were recorded. Cochrane Risk of Bias Evaluation Tool and the Newcastle–Ottawa Scale were used to evaluate data quality. Potential publication bias was assessed by Egger’s test. A sensitivity analysis was conducted to assess the stability of the results. The meta-analysis was conducted in R 3.5.1 software.

Nine trials were eligible for the systematic review and meta-analysis. Nebulized heparin can reduce lung injury and improve lung function in burn patients with inhalation injury without abnormal coagulation or bleeding, but the findings are still controversial. Mortality in the heparin-treated group was lower than that of the traditional treatment group (relative risk (RR) 0.75). The duration of mechanical ventilation (DOMV) was shorter in the heparin-treated group compared to the traditional treatment group (standardized mean difference (SMD) −0.78). Length of hospital stay was significantly shorter than that in the traditional treatment group (SMD −0.42), but incidence rates of pneumonia and unplanned reintubation were not significantly different in the study groups (RRs 0.97 and 0.88, respectively). No statistically significant publication biases were detected for the above clinical endpoints (p > 0.05).

Based on conventional aerosol therapy, heparin nebulization can further reduce lung injury, improve lung function, shorten DOMV and length of hospital stay, and reduce mortality, although it does not reduce the incidence of pneumonia and/or the unplanned reintubation rate.

• Burns
• Heparin
• Inhalation injury
• Systematic review

Smoke inhalation injury increases overall burn mortality by up to 20 times. Current therapy remains supportive with a failure to identify an optimal or targeted treatment protocol for smoke inhalation injury. The goal of this review is to describe emerging therapies that are being developed to treat the pulmonary pathology induced by smoke inhalation injury with or without concurrent burn injury.

A comprehensive literature search was performed using PubMed (1995–present) for therapies not approved by the U.S. Food and Drug Administration (FDA) for smoke inhalation injury with or without concurrent burn injury. Therapies were divided based on therapeutic strategy. Models included inhalation alone with or without concurrent burn injury. Specific animal model, mechanism of action of medication, route of administration, therapeutic benefit, safety, mortality benefit, and efficacy were reviewed. Multiple potential therapies for smoke inhalation injury with or without burn injury are currently under investigation. These include stem cell therapy, anticoagulation therapy, selectin inhibition, inflammatory pathway modulation, superoxide and peroxynitrite decomposition, selective nitric oxide synthase inhibition, hydrogen sulfide, HMG-CoA reductase inhibition, proton pump inhibition, and targeted nanotherapies. While each of these approaches shows a potential therapeutic benefit to treating inhalation injury in animal models, further research including mortality benefit is needed to ensure safety and efficacy in humans.

Multiple novel therapies currently under active investigation to treat smoke inhalation injury show promising results. Much research remains to be conducted before these emerging therapies can be translated to the clinical arena.

• Burn inhalation injury
• Emerging therapy
• Review
• Smoke inhalation injury

• acute lung injury
• antithrombin
• heparin
• inflammation
• nebulization

• Acute Lung Injury/chemically induced
• Acute Lung Injury/drug therapy
• Animals
• Anticoagulants/pharmacology
• Antithrombins/pharmacology
• Blood Coagulation
• Bronchoalveolar Lavage Fluid
• Fibrinolysis
• Heparin/pharmacology
• Lung
• Rats

• airway casts
• inhalational acute lung injury
• perfluorochemicals
• plasminogen activators

Smoke-inhalation-induced acute lung injury (SI-ALI) is a leading cause of morbidity and mortality in victims of fire tragedies. SI-ALI contributes to an estimated 30% of burn-caused patient deaths, and recently, more attention has been paid to the specific interventions for this devastating respiratory illness. In the last decade, much progress has been made in the understanding of SI-ALI patho-mechanisms and in the development of new therapeutic strategies in both preclinical and clinical studies. This article reviews the recent progress in the treatment of SI-ALI, based on pathophysiology, thermal damage, airway obstruction, the nuclear-factor kappa-B signaling pathway, and oxidative stress. Preclinical therapeutic strategies include use of mesenchymal stem cells, hydrogen sulfide, peroxynitrite decomposition catalysts, and proton-pump inhibitors. Clinical interventions include high-frequency percussive ventilation, perfluorohexane, inhaled anticoagulants, and nebulized epinephrine. The animal model, dose, clinical application, and pharmacology of these medications are summarized. Future directions and further needs for developing innovative therapies are discussed.

• acute lung injury
• intervention
• pathophysiology of lung injury
• smoke inhalation

• Metabolic disturbances
• burn epidemiology
• burn progression
• infection
• reduced scarring
• smoke inhalation
• stem cells

• Animals
• Burns/drug therapy
• Burns/physiopathology
• Humans
• Wound Healing/drug effects

• R01 AI050875 NIAID NIH HHS
• R21 AI121700 NIAID NIH HHS

• inhalation injury
• burns

• Burns, Inhalation/pathology
• Burns, Inhalation/therapy
• Carbon Monoxide Poisoning/etiology
• Carbon Monoxide Poisoning/therapy
• Humans
• Hyperbaric Oxygenation/methods
• Respiration, Artificial/methods
• Smoke Inhalation Injury/complications
• Smoke Inhalation Injury/therapy

• P50 GM060338 NIGMS NIH HHS
• R01 GM056687 NIGMS NIH HHS
• R01 GM112936 NIGMS NIH HHS
• U48 DP000043 NCCDPHP CDC HHS

• Acute respiratory distress syndrome (ARDS)
• acute lung injury (ALI)
• coagulation
• fibrinolysis
• inhalation
• nebulization

• Nebulization
• anticoagulants
• lung injury

Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host’s haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury.

Twenty-seven South African meat merino/Border Leicester Cross ewes underwent instrumentation. Animals received either sham injury (n = 12) or S-ALI (n = 15). Control animal groups consisted of healthy controls (ventilation only for 24 h) (n = 4), ECMO controls (ECMO only for 24 h) (n = 8) and S-ALI controls (S-ALI but no ECMO for 24 h) (n = 7). The test group comprised S-ALI sheep placed on ECMO (S-ALI + ECMO for 24 h) (n = 8). Serial blood samples were taken for rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests. Animals were continuously monitored for haemodynamic, fluid and electrolyte balances and temperature. Pressure-controlled intermittent mandatory ventilation was used, and mean arterial pressure was augmented by protocolised use of pressors, inotropes and balanced fluid resuscitation to maintain mean arterial pressure >65 mmHg.

Rotational thromboelastometry, platelet aggregometry and routine coagulation laboratory tests demonstrated that S-ALI and ECMO independently induced changes to platelet function, delayed clot formation and reduced clot firmness. This effect was augmented with the combination of S-ALI and ECMO, with evidence of increased collagen-induced platelet aggregation as well as changes in factor VIII (FVIII), factor XII and fibrinogen levels.

The introduction of an ECMO circuit itself increases collagen-induced platelet aggregation, decreases FVIII and von Willebrand factor, and induces a transient decrease in fibrinogen levels and function in the first 24 h. These changes to haemostasis are amplified when a host with a pre-existing pulmonary injury is placed on ECMO. Because patients are often on ECMO for extended periods, longer-duration studies are required to characterise ECMO-induced haemostatic changes over the long term. The utility of point-of-care tests for guiding haemostatic management during ECMO also warrants further exploration.

• Coagulation
• Extracorporeal membrane oxygenation
• Fibrinogen
• Haemostasis
• Platelet aggregation
• Thromboelastometry

• smoke
• inhalation injury
• respiratory failure
• clinical management
• challenges in research

• Burns
• Humans
• Prognosis
• Research
• Smoke Inhalation Injury/diagnosis

• R01 HD049471 NICHD NIH HHS
• R01 GM056687 NIGMS NIH HHS
• P50 GM060338 NIGMS NIH HHS
• T32 GM008256 NIGMS NIH HHS
• UL1 TR001439 NCATS NIH HHS

• Assessment
• Burn
• Outcomes
• Pediatric
• Resuscitation

• anticoagulants
• blood coagulation
• burn
• critical care
• disseminated intravascular coagulation
• fibrinolysis

• Anticoagulants/chemistry
• Blood Coagulation
• Blood Coagulation Disorders/complications
• Blood Coagulation Disorders/immunology
• Blood Coagulation Disorders/therapy
• Burns/complications
• Burns/immunology
• Burns/therapy
• Coagulants/chemistry
• Fibrinolysis
• Hemodilution
• Hemostasis
• Humans
• Recombinant Proteins/chemistry
• Smoke Inhalation Injury

Antithrombin (AT) is a natural anticoagulant with anti-inflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.

• Antithrombin
• Burn trauma
• Burn injury
• Inhalation injury
• Recombinant antithrombin

In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies.

Smoke inhalation is a major source of morbidity and mortality. Heparin and N-acetylcysteine treatment has potential efficacy in inhalation injury. We investigated the impact of a heparin/N-acetylcysteine/albuterol nebulization protocol in adult patients with inhalation injury.

A retrospective review was performed of adult inhalation injury patients, admitted to a regional burn center between January 2011 and July 2012, who underwent a protocol of alternating treatments of heparin and N-acetylcysteine/albuterol nebulization every 4 hours. The study cohort was matched 1:1 by age, sex, and burn size to a control cohort admitted within 5 years before protocol implementation.

The study (n = 20) and control cohorts (n = 20) were well matched, with nearly identical age (50 vs 49 years), sex distribution (70% male), burn size (total body surface area, 22% vs 21%), and inhalation injury, except grade I injuries (79% vs 47%, P = 0.01). The protocol did not change mortality (30% vs 25%, P = 0.72) or duration of mechanical ventilation (8.5 vs 8.8 days, P = 0.9). There was no difference in development of sepsis (40% vs 33%, P = 0.7) or acute respiratory distress syndrome (15% vs 10%, P = 1); however, those who received the protocol were more likely to develop pneumonia (45% vs 11%, P = 0.03).

The implementation of a heparin/N-acetylcysteine/albuterol protocol did not reduce mortality or duration of mechanical ventilation in this cohort of adults with inhalation injury and resulted in a significant increase in pneumonia rates. Larger prospective studies are necessary, with close attention paid to minimizing the infection risk incurred from frequent administration of nebulized medications.

• inhalation trauma
• pulmonary coagulopathy
• nebulization
• heparin
• mechanical ventilation

• Administration, Inhalation
• Anticoagulants/administration & dosage
• Anticoagulants/adverse effects
• Belgium
• Clinical Protocols
• Double-Blind Method
• Heparin/administration & dosage
• Heparin/adverse effects
• Humans
• Intubation, Intratracheal
• Lung/drug effects
• Lung/pathology
• Lung/physiopathology
• Nebulizers and Vaporizers
• Netherlands
• Recovery of Function
• Research Design
• Respiration
• Respiration, Artificial
• Smoke Inhalation Injury/diagnosis
• Smoke Inhalation Injury/physiopathology
• Smoke Inhalation Injury/therapy
• Time Factors
• Treatment Outcome
• Ventilator Weaning

Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation.

Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data from European centers supports application of specific antidotes for cyanide toxicity. Consistent international support for this therapy is lacking. Even diagnostic criteria are not consistently applied though bronchoscopy is one diagnostic and therapeutic tool. Medical strategies under investigation for specific treatment of smoke inhalation include beta-agonists, pulmonary blood flow modifiers, anticoagulants and antiinflammatory strategies. Until the value of these and other approaches is confirmed, however, the clinical approach to inhalation injury is supportive.

Data from interventional trials of systemic anticoagulation for sepsis inconsistently suggest beneficial effects in case of acute lung injury (ALI). Severe systemic bleeding due to anticoagulation may have offset the possible positive effects. Nebulization of anticoagulants may allow for improved local biological availability and as such may improve efficacy in the lungs and lower the risk of systemic bleeding complications.

We performed a systematic review of preclinical studies and clinical trials investigating the efficacy and safety of nebulized anticoagulants in the setting of lung injury in animals and ALI in humans.

The efficacy of nebulized activated protein C, antithrombin, heparin and danaparoid has been tested in diverse animal models of direct (for example, pneumonia-, intra-pulmonary lipopolysaccharide (LPS)-, and smoke inhalation-induced lung injury) and indirect lung injury (for example, intravenous LPS- and trauma-induced lung injury). Nebulized anticoagulants were found to have the potential to attenuate pulmonary coagulopathy and frequently also inflammation. Notably, nebulized danaparoid and heparin but not activated protein C and antithrombin, were found to have an effect on systemic coagulation. Clinical trials of nebulized anticoagulants are very limited. Nebulized heparin was found to improve survival of patients with smoke inhalation-induced ALI. In a trial of critically ill patients who needed mechanical ventilation for longer than two days, nebulized heparin was associated with a higher number of ventilator-free days. In line with results from preclinical studies, nebulization of heparin was found to have an effect on systemic coagulation, but without causing systemic bleedings.

Local anticoagulant therapy through nebulization of anticoagulants attenuates pulmonary coagulopathy and frequently also inflammation in preclinical studies of lung injury. Recent human trials suggest nebulized heparin for ALI to be beneficial and safe, but data are very limited.

• obstruction
• alpha-tocopherol
• pulmonary function
• early excision

• Acute Lung Injury/drug therapy
• Acute Lung Injury/etiology
• Animals
• Burns/complications
• Female
• Nebulizers and Vaporizers
• Sheep
• Smoke Inhalation Injury/complications
• gamma-Tocopherol/administration & dosage
• gamma-Tocopherol/therapeutic use

• GM66312-01 NIGMS NIH HHS
• R01 GM060688-01A1 NIGMS NIH HHS
• P01 GM066312-01A2 NIGMS NIH HHS
• R01 GM060688 NIGMS NIH HHS
• T32 GM008256 NIGMS NIH HHS
• GM60668 NIGMS NIH HHS
• P01 GM066312 NIGMS NIH HHS

• acute lung injury
• fibrin
• fibrinolysis
• serpin
• smoke inhalation

• Acute Lung Injury/chemically induced
• Acute Lung Injury/metabolism
• Animals
• Cells, Cultured
• Female
• Fibrin/metabolism
• Lung/metabolism
• Lung/pathology
• Plasminogen Activator Inhibitor 1/genetics
• Plasminogen Activator Inhibitor 1/metabolism
• Pleura/metabolism
• Random Allocation
• Smoke/adverse effects
• Swine

• P01 HL076406 NHLBI NIH HHS
• R21 HL093547 NHLBI NIH HHS
• R-21-HL093547 NHLBI NIH HHS
• HL076406 NHLBI NIH HHS

• inhalation injury
• bronchial artery ligation
• bronchial circulation
• acute lung injury
• bronchial exudation
• airway cast formation
• ards

• Animals
• Bronchial Arteries/physiopathology
• Burns/physiopathology
• Exudates and Transudates/physiology
• Female
• Hemodynamics
• Oxygen/blood
• Pulmonary Circulation/physiology
• Random Allocation
• Sheep, Domestic
• Smoke Inhalation Injury/physiopathology

• R01 GM033324 NIGMS NIH HHS
• GM060688 NIGMS NIH HHS
• R01 GM060688 NIGMS NIH HHS
• P01-GM66312, NIGMS NIH HHS
• P01 GM066312 NIGMS NIH HHS

• Burns, Inhalation/diagnosis
• Burns, Inhalation/epidemiology
• Burns, Inhalation/therapy
• Gas Poisoning/diagnosis
• Gas Poisoning/epidemiology
• Gas Poisoning/therapy
• Humans
• Incidence

• acute lung injury
• anticoagulants
• antioxidants
• β₂-agonists
• carbon monoxide
• cyanide
• nitric oxide
• reactive oxygen species

• P01 GM066312 NIGMS NIH HHS
• R01 GM033324 NIGMS NIH HHS
• R01 GM060688 NIGMS NIH HHS