Multispecies animal models often fail to reflect human nasal sinus anatomy and physiology in chronic rhinosinusitis research

Chronic rhinosinusitis (CRS) is a systemic, complicated, inflammatory disease which results in a significant burden on the patient's quality of life. Although the prevalence has been increasing worldwide, our therapeutic advances have been limited by the complexity of immune imbalance in addition to epithelial breakdown. Although murine models have always been the default of choice of mechanistic studies because of their relative affordability and genetic tractability, they are often insufficient to reflect the anatomical and physiological reality of the human nasal sinus. As an example, the sheep model provides a much more convincing explanation of the process of human sinus drainage, and porcine models offer a specialized perspective on the recalcitrant epithelial remodeling that characterizes severe CRS. In this review we go further than the listing of the species. Rather we focus on evaluating the efficiency of these models in representing specific human phenotypes, such as from eosinophilic overproliferation in type 2 inflammation to phenotypes in non-type 2 diseases. Through a new strategic decision framework, we would guide researchers out of paradigms of models of convenience, to models of clinical relevance, eventually facilitating the translation of bench discoveries to patient-centered therapy.