Standardized lung function reference values in rats for translational respiratory research.

Area of Science:

• Respiratory physiology and disease research
• Preclinical animal models
• Translational medicine

Background:

• Preclinical respiratory studies lack standardized reference frameworks, limiting translational impact.
• Clinical lung function is interpreted using prediction equations and z-scores, unlike preclinical absolute values.
• Comparability between preclinical studies is hampered by the absence of standardized interpretation methods.

Purpose of the Study:

• To establish reference equations for key respiratory parameters in rats.
• To enable the derivation of z-scores for individual preclinical measurements.
• To enhance the reproducibility and translational value of preclinical respiratory research.

Main Methods:

• Collected lung function data from 182 healthy Sprague Dawley and Wistar rats.
• Utilized generalized additive models for location, scale, and shape (GAMLSS) to model respiratory parameters.
• Modeled mean and variability as functions of body mass, sex, strain, and positive end-expiratory pressure.

Main Results:

• Established reference equations for airway resistance, tissue damping, tissue elastance, and end-expiratory lung volume.
• Models demonstrated excellent fit and cross-validation, allowing accurate z-score calculation.
• Significant influences of sex and strain on respiratory outcomes were identified.

Conclusions:

• Introduced clinical-style reference equations into preclinical respiratory research.
• The framework enhances reproducibility and aligns animal measurements with clinical standards.
• Open-source calculators are available for workflow integration, supporting computational models and study design.