Standardized lung function reference values in rats for translational respiratory research

Abstract Preclinical models are essential for understanding respiratory physiology and disease, but their translational impact is limited by the absence of standardized reference frameworks. Unlike clinical practice, where lung function is interpreted using prediction equations and z-scores, preclinical studies report absolute values, hampering comparability. We established reference equations for airway resistance, tissue damping, tissue elastance, and end-expiratory lung volume in 182 healthy Sprague Dawley and Wistar rats. Using generalized additive models for location, scale, and shape (GAMLSS), we modeled mean and variability as functions of body mass, sex, strain, and positive end-expiratory pressure. The models showed excellent fit and cross-validation, enabling accurate z-score derivation at the individual level. Sex and strain significantly influenced outcomes. Open-source calculators support direct integration into workflows. This framework introduces clinical-style reference equations into preclinical respiratory research, enhancing reproducibility and aligning animal measurements with clinical standards, with implications for computational models, study design, and translational research.