Deciphering the Impact of Oral Hypofunction, Dysphagia, and the Airway Microbiome on Pneumonia Pathogenesis in Older Adults

/Abstract Pneumonia is the leading infectious cause of morbidity and mortality in older adults. The incidence of pneumonia increases exponentially with age, resulting in over 3 million US emergency department (ED) encounters and 1 million hospitalizations per year in individuals ≥65 years of age. Although aspiration pneumonia has traditionally been considered a distinct clinical entity, there is an emerging consensus that pneumonia should be considered on a continuum as aspiration of organisms from the oropharynx is a shared pathogenic mechanism for nearly all pneumonias. Oral hypofunction and dysphagia (swallowing dysfunction) are geriatric syndromes and established factors in oral dysbiosis and pneumonia risk. However, the prevalence and interaction between them has not been well characterized as it relates to the pathogenesis or microbial etiology of pneumonia in older adults. This knowledge gap represents a patient safety threat as diagnostic misclassification of pneumonias can result in poorly targeted antibiotic therapy and failure to refer for swallowing and/or oral rehabilitation. There is an urgent need to comprehensively characterize profiles of oral hypofunction and dysphagia in older adults with pneumonia of various bacterial etiologies and evaluate their role in pneumonia pathogenesis. Previous studies examining oral and swallowing profiles in adults with pneumonia are limited due to a lack of objective diagnostic evaluations or consideration of the upper airway microbiome. To address these knowledge gaps, we propose an observational study of older adults presenting to the ED with pneumonia that involves comprehensive assessments of both oral and swallowing function in combination with cutting edge metagenomic analyses and application of saliva to a microphysiological lung model of aspiration. Our overarching objective is to significantly advance the understanding of oral hypofunction and dysphagia in pneumonia pathophysiology in older adults as a foundational step towards reducing diagnostic error, improving targeted antibiotic therapy, optimizing referral to oral and swallowing rehabilitation, and reducing the significant morbidity and mortality observed in this population. Our multidisciplinary team of experts will achieve this objective via the following specific aims: 1a. Determine the prevalence and profiles of oral hypofunction and dysphagia among a cohort of older adults with pneumonia; 1b. Compare prevalence and severity of oral hypofunction and dysphagia between older adults with and without pneumonia and between patients with pneumonia due to normal respiratory flora vs. respiratory pathogens; 2. Compare microbiome profiles in older adults with pneumonia based on the presence of oral hypofunction and dysphagia; 3. Identify targetable mechanisms of saliva-induced lung bronchial epithelial injury in a lung microphysiological system. The proposed work is highly innovative as it will be the first to comprehensively assess oral and hypofunction to elucidate relationships with pneumonia development; include state of the art microbiome characterization of upper and lower respiratory sites; and utilize a microphysiological lung model to examine the impact of salivary characteristics on host response mechanisms. Project Number: 1R01AG097793-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Michael Pulia | Institution: UNIVERSITY OF WISCONSIN-MADISON, MADISON, WI | Award Amount: $646,358 | Activity Code: R01 | Study Section: Aging Systems and Geriatrics Study Section[ASG] View on NIH RePORTER: https://reporter.nih.gov/project-details/11278178