Craniofacial Adaptation and Upper Respiratory Function among High‐Altitude Inhabitants
Authors: Butaric Lauren Nicole , Klocke Ross Patrick 
Published: November 2023

High‐altitude (HA; >2500m) dwellers face several environmental pressures, including hypoxic conditions and cold‐dry temperatures, which create greater respiratory demands to not only obtain more oxygen but to warm and humidify inspired air. While cardiovascular and pulmonary adaptations to these pressures have been extensively studied, adaptations of upper‐respiratory structures (nasal cavity, paranasal sinuses) remain untested. In terms of upper‐respiratory adaptation, an overall larger nasal cavity would augment oxygen intake, while a tall‐narrow nasal cavity would serve in conditioning cold/dry air. To assess these possible HA adaptations in nasal morphology, this study investigates craniofacial variation among three HA and two low‐altitude (LA) samples (n=110): LA‐Peruvians; HA‐Peruvians; LA‐Chinese; LA‐Mongolians/Buriats; HA‐Tibetans. Using computed tomographic (CT) scans, 44 landmarks assessing shape of the external midface, internal nasal cavity, and maxillary sinuses were obtained; centroid sizes were also calculated. Analyses of variance indicate no significant differences in nasal size (p=0.03), but HA‐Tibetans and LA‐Mongolians/Buriats display significantly larger sinuses (p<0.0001) compared to remaining samples. Canonical variate (CV) analysis on Procrustes‐aligned coordinates indicates distinct grouping along CV1 (48.10% variance), with HA‐Tibetans and LA‐Mongolians/Buriats exhibiting larger sinuses and taller/narrower nasal cavities in taller facial skeletons; both Peruvian samples display the opposite pattern, with smaller sinuses and shorter/wider nasal cavities in shorter facial skeletons; LA‐Chinese display an intermediate pattern. A two‐block partial least squares (2B‐PLS) analysis, using midfacial (Block1) and nasal/sinus (Block2) landmarks, indicates strong covariation between the external and internal structures (RV=0.42; p<0.0001). Plots for the PLS1 (50.80% covariance; r=0.79; p=0.007) and PLS2 (27.73% covariance; r=0.73; P<0.001) scores indicate similar patterns illustrated by CV1 groupings. Overall, analyses were unable to discern specific upper‐respiratory adaptations for the HA‐Peruvians; this lack of discernible craniofacial adaptation among Peruvians may be due to their recent migration history into the New World and accompanying neutral genetic processes. Differences among the three Asian samples likely relate to differential climates: LA‐Chinese display a nasal‐sinus morphology typical for warmer, wetter environments (wider nasal cavities, smaller maxillary sinuses), while LA‐Mongolians/Buriats and HA‐Tibetans display typical cold‐adapted morphology assisting in air conditioning processes (taller/narrower nasal cavities, larger maxillary sinuses). We hypothesize that relatively large maxillary sinuses among Tibetans could also explain their well‐documented, increased levels of nitric oxide. This gas, produced and stored in the sinuses, acts as an aerocrine messenger and pulmonary vasodilator to alleviate hypoxic stress and is considered an adaptation unique among Tibetans.