Preprint A Novel FiO2 Titration Protocol for Quantifying Pulmonary Oxygen Reserve Capacity : [...], 2025, Qiru

[Shiqiru]

A Novel FiO2 Titration Protocol for Quantifying Pulmonary Oxygen Reserve Capacity : Dynamic Assessment Framework for Infection-Associated Respiratory Dysfunction

Abstract
Background Progressive decline in pulmonary oxygen reserve capacity (ORC) is a hallmark of infection-associated respiratory dysfunction. Current tools (PaO2/FiO2 ratio, cardiopulmonary exercise testing [CPET], computed tomography [CT]) are limited in dynamic monitoring due to delayed responsiveness, operational complexity, or radiation risks, and other constraints.
Methods The ORC testing methodology integrates the dynamic load-incrementation logic of cardiopulmonary exercise testing (CPET) with the oxygenation quantification framework of PaO2/FiO2. Its operational paradigm comprises three phases:
➀Testing Protocol
Conducted under ventilation-locked conditions, a stepwise FiO2 titration protocol is applied, with termination triggered when SpO2
➁Parameter Definition
The minimum FiO2 required to maintain SpO2 ≥90% (FiO2-MIN) is recorded, and the oxygen reserve capacity is calculated as ORC = 0.21 - FiO2-MIN.
➂Dynamic Modeling
Through continuous monitoring throughout the entire disease course, ORC time-series data are acquired. A time-ORC curve is then fitted, and based on differential calculus (β = ΔORC/Δt, γ = Δβ/Δt), they collectively establish a quantitative respiratory compensation dynamics model in conjunction with the time-ORC curve.
Results The ORC test provides a novel non-invasive tool for dynamic quantification of respiratory reserve. Early warning of ARDS transformation during acute infection and quantitative dynamic tracking of lung dysfunction of long-COVID syndrome are its potential application scenarios. Its clinical utility requires prospective validation through multicenter trials integrated with CPET and CT quantitative analysis.

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[Shiqiru]

Hello everyone,
I am the author of the preprint discussing the ORC test. I'd like to take this opportunity to delve deeper into the potential significance of this testing tool.
In my view, the primary bottleneck in current ME/CFS and Long COVID research may not be the choice of research directions (such as viral persistence, autoimmunity, etc.), nor the lack of new microscopic molecular discoveries, or even the absence of novel treatment methods.
The current situation is more akin to astronomy before Kepler – we might not be short of good theories, but we lack the precise, objective observational data needed to validate them, much like the detailed observations and records meticulously collected by Tycho Brahe. Specifically, we are acutely missing quantifiable tools and corresponding continuous data for certain symptoms (which may be driven by specific microscopic molecular mechanisms).
While 2-day CPET is undoubtedly a valuable approach, its limitations and narrow scope of application restrict its broader use. The ORC test, introduced in our preprint, shares conceptual commonalities with CPET (or 6MWT), but it transforms the traditional exercise load challenge into a hypoxic load challenge. We believe this method holds the promise of significantly improving the test's precision, patient tolerability, resistance to interference, and overall applicability.
By continuously plotting the data curve of ORC – an objective, singular indicator – we aim to clearly capture the dynamic changes in the lung's oxygen conversion capacity throughout the disease course. This can provide more precise, objective, and continuous testing data support for future research.
Although preliminary small-scale studies with the ORC test have yielded promising results (I'm happy to share the data if there's interest), I am not a professional researcher in this specific field, and therefore lack the capacity to further expand the test's scope. To fully realize the potential of this testing method, broader collaboration and resources are essential.
Here, I sincerely hope to engage in a comprehensive discussion about this testing method with all of you. My hope is that through collective wisdom, we can collaboratively uncover its utility and explore how to promote its wider application, ultimately contributing to new breakthroughs in the diagnosis and research of ME/CFS and Long COVID.
Thank you again for your attention and valuable insights!

 

[Shiqiru]

It's also worth noting that this preprint is an early version. While the core findings are robust, there are areas where the content and presentation could be improved. Should there be interest, I'd be happy to provide an updated version.

 

[Shiqiru]

While the testing conditions for the ORC method, as described in the preprint, might appear stringent, this is primarily for ensuring methodological standardization and rigor.
In practice, however, much simpler alternative approaches can be adopted for testing. For instance, if one resides in an area with significant altitude variations, such as near mountains, an individual could perform tests at different altitudes using just a fingertip pulse oximeter. This is because changes in altitude directly correspond to changes in oxygen concentration. Thus, altitude itself (or its corresponding oxygen concentration) can directly serve as the testing standard.
Furthermore, the explicit control of ventilation during the described test is also primarily for standardization. In real-world applications, this strict requirement can often be relaxed. Instead, simply performing resting tests after a period of adequate rest each time would suffice.
And should altitude variation not be a feasible option, there are indeed many other alternative methodologies that could be explored. I would be very happy to discuss these possibilities further with anyone interested.