Nitric Oxide Therapy Dosing for Respiratory Infections
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Solution Overview
Problem
Current methods for treating respiratory infections, particularly those caused by coronaviruses like COVID-19, are ineffective in preventing the progression to Severe Acute Respiratory Syndrome (SARS) due to challenges in determining correct dosing schedules for gaseous nitric oxide (NO) and reconciling dosing with toxicology outcomes, leading to potential side effects such as decreased oxygen transport and pulmonary injury.
Innovation Solution
The use of specific gaseous nitric oxide (NO) dosing regimens paired with monitoring of toxicology outcomes to enable the use of effective NO doses for treatment, along with a feedback loop method that measures parameters like methemoglobin levels and inflammatory cytokine plasma levels to adjust treatment, and the administration of NO followed by oxygen to inhibit viral replication and reduce harmful NOx species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of gaseous nitric oxide are administered to treat respiratory infections, then therapeutic effectiveness is improved, but toxic side effects such as methemoglobin formation and pulmonary injury worsen
Solution Approach 1:
The patent implements periodic action through cyclic administration of nitric oxide followed by oxygen. The method alternates between NO breath treatments (at concentrations of 20-500 ppm for 5-120 minutes) and oxygen breath treatments (at concentrations of 20-100% for 5-120 minutes), creating a rhythmic pattern that allows therapeutic accumulation of NO effects while providing periodic clearance periods that reduce toxic metabolite buildup in the body
Solution Approach 2:
The patent implements feedback mechanisms by monitoring toxicology outcomes such as methemoglobin levels and adjusting subsequent NO dosing accordingly. The method uses measured parameters including methemoglobin (metHb) levels, blood nitrate levels, oxygen saturation (SpO2), and inflammatory markers to dynamically modify treatment intensity and duration, creating a closed-loop control system that optimizes therapy while preventing toxicity
2Reliability
If correct dosing schedules for gaseous nitric oxide are determined, then treatment efficacy is improved, but dosing complexity and monitoring requirements worsen
Solution Approach 1:
The patent applies parameter changes by systematically varying multiple dosing parameters including NO concentration (20-500 ppm), treatment duration (5-120 minutes per breath), number of cycles (1-20+ cycles per day), and oxygen concentration (20-100%). These controlled parameter variations create a flexible dosing framework that can be tailored to disease severity while maintaining manageable complexity through standardized ranges and protocols
3Reliability
If nitric oxide is administered to inhibit viral replication, then antiviral effect is improved, but formation of harmful NOx species worsens
Solution Approach 1:
The patent converts the harmful interaction between nitric oxide and oxygen that produces toxic NOx species into a beneficial process. By administering oxygen immediately following nitric oxide treatments, the method promotes the conversion of accumulated NO and its reactive intermediates into nitrate metabolites that are safely excreted in urine. This transforms what would be a harmful oxidative reaction into a therapeutic elimination pathway that reduces viral load while preventing toxicity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively prevents the worsening of symptoms and progression to SARS by allowing for high and effective NO doses while minimizing side effects, potentially reducing the need for oxygen supplementation and preventing the need for intubation or mechanical ventilation.
Implementation Method 1
NO is inactivated through binding to sulfhydryl groups of cellular thiols or by nitrosylation of the heme moieties of hemoglobin to form methemoglobin (MetHb)
Implementation Method 2
MetHb reductase reduces NO to nitrates in the blood serum
Implementation Method 3
NO is inactivated through binding to sulfhydryl groups of cellular thiols or by nitrosylation of the heme moieties of hemoglobin
Data Source
AI summary
Methods for the treatment of a respiratory infection, for the prevention of worsening of symptoms associated with the infection, and for reducing the lethality of the infection such as but not limited to respiratory infections caused by a coronavirus. The present disclosure provides specific gaseous nitric oxide (NO) dosing regimens optionally paired with the monitoring of toxicology outcomes so as to enable the use of effective NO doses for treatment purposes. The present invention also discloses air circulation systems featuring NO for helping to prevent respiratory infections.