The impact of dysphagia driven aspiration on lung pathophysiology in an animal model of term and preterm infants - feeding and respiration are fundamental and critical life functions

The National Institute of Child Health and Human Development awarded Northeast Ohio Medical University $626,200 on August 20, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate the impact of aspiration on lung pathophysiology in animal models of term and preterm infants.

The recipient will develop a predictive model linking feeding physiology, blood biomarkers, and aspiration frequency to measurable changes in lung pathophysiology. The work includes quantifying responses to varying aspiration levels in term and preterm infant models on normal and thickened milk, using high-resolution videofluoroscopy, histological assays, and in vivo blood biomarkers of inflammation to measure aspiration-driven lung damage. The project tests the hypothesis that a dose relationship exists between aspiration frequency and extent and histologically measurable lung damage, and examines whether physiologic measurements and lung-clearing ability contribute to pulmonary damage.

Performance occurs in Rootstown, Ohio. The award runs through May 31, 2031.

Failure to keep liquid out of the airway, aspiration, can be problematic, even pathological. However, the exact relationship between frequency and amount of aspiration and subsequent lung pathology is unknown. One standard compensatory treatment is thickening liquids; yet aspiration of such fluids has not been evaluated as an additional health burden on developing lungs and associated vascular tissues. The gold standard for assessing aspiration during swallowing, videofluoroscopy, presents ethical concerns for collecting data in both normal and compromised human infants. What is missing from both clinical and animal model data is a direct measurement of the impact of aspiration on lung physiology and histology. The goal of the proposed project is to use our validated animal model for infant dysphagia to develop a predictive model that links feeding physiology, blood biomarkers, and the amount of aspiration with measurable changes in lung pathophysiology. We propose to quantify the response to varying levels of aspiration, in term (SA1) and preterm (SA2) infants on normal and thickened (SA3) milk. Our animal models can generate variation in performance that can predict the extent of lung damage. Our predictive model will include physiologic measurements, as well as the ability to clear the lungs following a feed, to assess their contribution to pulmonary damage. We will measure aspiration lung damage in vivo dynamically through high resolution videofluoroscopy and post-mortem gross and histological assays, as well as in vivo blood biomarkers of inflammation. We hypothesize, supported by our preliminary data, that there will be a dose relationship between the frequency and extent of aspiration and histologically measurable lung damage. We hypothesize that the degree of aspiration will predict the lung damage response but will be different in term and preterm infants. We also hypothesize that both term and preterm infants will aspirate less frequently on thickened milk, but the impact of thickeners on lung physiology will produce more lung damage, as IT will be more difficult to clear such fluid post-feeding. The results from these experiments will determine the physiological impact of aspiration on the respiratory system in both term and preterm infants. We propose to quantify the impact of aspiration across infant development up to the time of weaning, something not possible in humans. Documenting the tissue level sequalae of aspiration, and its correlation with biomarkers, will provide the basis for subsequent clinical decisions on therapeutic interventions for infant airway protection.