Hyperoxia Induced Pulmonary Inflammation and Organ Injury: a Human in Vivo Model
Study Details
Study Description
Brief Summary
Oxygen is the most commonly administered therapy in critical illness. Accumulating evidence suggests that patients often achieve supra-physiological levels of oxygenation in the critical care environment. Furthermore, hyperoxia related complications following cardiac arrest, myocardial infarction and stroke have also been reported. The underlying mechanisms of hyperoxia mediated injury remain poorly understood and there are currently no human in vivo studies exploring the relationship between hyperoxia and direct pulmonary injury and inflammation as well as distant organ injury.
The current trial is a mechanistic study designed to evaluate the effects of prolonged administration of high-flow oxygen (hyperoxia) on pulmonary and systemic inflammation. The study is a randomised, double-blind, placebo-controlled trial of high-flow nasal oxygen therapy versus matching placebo (synthetic medical air). We will also incorporate a model of acute lung injury induced by inhaled endotoxin (LPS) in healthy human volunteers. Healthy volunteers will undergo bronchoalveolar lavage (BAL) at 6 hours post-intervention to enable measurement of pulmonary and systemic markers of inflammation, oxidative stress and cellular injury.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Liquid medical oxygen Liquid medical oxygen will be administered using high-flow nasal cannula delivery system. |
Drug: Liquid oxygen
Liquid medical oxygen will be administered for 6 hours using high-flow nasal cannula delivery system with an Fi02 of 100% and flow rate of 60 litres per minute.
Other Names:
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Placebo Comparator: Synthetic medical air Synthetic medical air will be administered using high-flow nasal cannula delivery system. |
Drug: medical air
Synthetic medical air will be administered for 6 hours using high-flow nasal cannula delivery system with a flow rate of 60 litres per minute.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Bronchoalveolar lavage Interleukin-8 concentration [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar inflammatory response
Secondary Outcome Measures
- Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6 [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar inflammatory response biomarkers
- Bronchoalveolar lavage proteases and anti-proteases including but not limited to Matrix Metalloproteinases (MMP-2, MMP-8, MMP-9 and MMP-11), Tissue Inhibitors of Metalloproteinase (TIMPs 1-2) and neutrophil elastase [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar protease and antiprotease activity
- Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes) [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar cell populations
- Plasma cytokines including but not limited to IL-8, tumour necrosis factor alpha, IL-1 beta and IL-6 [6 and 24 hours post-intervention]
To determine the effects of hyperoxia on plasma inflammatory response biomarkers
- Bronchoalveolar lavage soluble programmed cell death receptor (SP-D) [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
- Bronchoalveolar lavage total protein [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
- Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE) [6 hours post-intervention]
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
- Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE) [6 hours post-intervention]
To determine the effects of hyperoxia on oxidative stress
- Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL) [6 hours post-intervention]
To determine the effects of hyperoxia on oxidative stress
- Plasma advanced glycation end products (AGE) [6 and 24 hours post-intervention]
To determine the effects of hyperoxia on oxidative stress
- Plasma oxidised low density lipoprotein (oxLDL) [6 and 24 hours post-intervention]
To determine the effects of hyperoxia on oxidative stress
- Plasma 4-hydroxy-2-nonenal (4-HNE) [6 and 24 hours post-intervention]
To determine the effects of hyperoxia on oxidative stress
Eligibility Criteria
Criteria
Inclusion Criteria:
- Healthy non-smoking subjects less than 45 years of age and BMI < 29 kg/m²
Exclusion Criteria:
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Age < 18 years
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On concomitant medications including over the counter medications excluding oral contraception and paracetamol
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Previous adverse reactions to LPS, lignocaine or sedative agents
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Pregnant or Breast-Feeding
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Participation in a clinical trial of an investigational medicinal product within 30 days
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Consent declined
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History of asthma or other respiratory conditions
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Smoking/ e cigarette use
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Marijuana use or other inhaled products with or without nicotine in the last 3 months
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Alcohol abuse, as defined by the Alcohol Use Disorders Identification Test (AUDIT)
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Subjects with history of prior conventional cigarette (> 100 cigarettes lifetime and smoking within 6 months) or electronic cigarette use.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Belfast Health and Social Care Trus | Belfast | United Kingdom |
Sponsors and Collaborators
- Belfast Health and Social Care Trust
Investigators
- Principal Investigator: Danny McAuley, MD, Queen's University, Belfast
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18129MS-AS