Project Grant F31HL189248

PROFILES OF SALIVA, SWALLOWING, AND AIRWAY PROTECTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) EXACERBATION VULNERABILITY - ABSTRACT CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A PROGRESSIVE DISEASE AND A LEADING CAUSE OF DEATH WORLDWIDE, ASSOCIATED WITH SUBSTANTIAL MORBIDITY AND REDUCED QUALITY OF LIFE. EXACERBATIONS, EPISODES OF SUDDEN SYMPTOM WORSENING, REPRESENT A DEFINING FEATURE OF DISEASE PROGRESSION. THESE EVENTS ACCELERATE LUNG FUNCTION DECLINE, INCREASE HOSPITALIZATION RISK, AND WORSEN SURVIVAL. EMERGING EVIDENCE SUGGESTS THAT DYSPHAGIA (SWALLOWING DYSFUNCTION) AND IMPAIRED AIRWAY PROTECTION PLAY CRITICAL AND UNDERRECOGNIZED ROLES IN COPD EXACERBATIONS THROUGH ASPIRATION, THE ENTRY OF MATERIAL INTO THE LOWER AIRWAY. ASPIRATION, A DIRECT CONSEQUENCE OF DYSPHAGIA, MAY OCCUR PRANDIALLY (DURING SWALLOWING OF FOOD OR LIQUID) OR NON-PRANDIALLY (VIA SALIVA) DUE TO IMPAIRED SWALLOWING BIOMECHANICS SUCH AS INCOMPLETE AIRWAY CLOSURE OR IMPAIRED BOLUS CLEARANCE. SALIVA MAY CONTRIBUTE TO ASPIRATION RISK AND AIRWAY INFLAMMATION THROUGH ALTERATIONS IN ITS RHEOLOGICAL AND BIOCHEMICAL PROPERTIES, AND ITS INFLAMMATORY AND MICROBIAL CONTENT MAY PRECIPITATE EXACERBATIONS WHEN ASPIRATED. HOWEVER, DESPITE KNOWING THIS, THE INTERACTION BETWEEN SALIVARY CHARACTERISTICS, SWALLOWING PHYSIOLOGY, AND PROTECTIVE AIRWAY FUNCTION INFLUENCING EXACERBATION VULNERABILITY REMAINS UNKNOWN. THE CENTRAL HYPOTHESIS OF THIS PROPOSAL IS THAT VARIATIONS IN SALIVARY COMPOSITION, SWALLOWING PHYSIOLOGY, AND AIRWAY PROTECTIVE FUNCTION THAT CONTRIBUTE TO PRANDIAL AND SALIVARY ASPIRATION SERVE AS KEY DIFFERENTIATING FACTORS FOR COPD EXACERBATION OCCURRENCE. TO TEST THIS HYPOTHESIS, WE WILL RECRUIT INDIVIDUALS WITH LATER-STAGE COPD (GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE STAGES III-IV), GROUPING PARTICIPANTS AS EXACERBATORS OR NON-EXACERBATORS AND FOLLOW THEM FOR SIX MONTHS. THIS STUDY WILL ADDRESS THREE PRIMARY OBJECTIVES: 1) QUANTIFY DIFFERENCES IN SALIVARY COMPOSITION BETWEEN EXACERBATORS AND NON-EXACERBATORS. 2) COMPARE THE PREVALENCE OF PRANDIAL AND SALIVARY ASPIRATION BETWEEN GROUPS. 3) COMPARE DISTINCT SALIVA, SWALLOWING, AND COUGH IMPAIRMENT PROFILES CONTRIBUTING TO ASPIRATION IN EXACERBATORS VERSUS NON-EXACERBATORS. FINDINGS WILL ADVANCE MECHANISTIC UNDERSTANDING OF EXACERBATION VULNERABILITY AND INFORM DEVELOPMENT OF TARGETED PREVENTION STRATEGIES TO IMPROVE QUALITY OF LIFE AND OUTCOMES IN PATIENTS WITH LATER-STAGE COPD. THIS WORK ALIGNS WITH NIDCR'S MISSION BY UNDERSTANDING HOW ORAL AND SALIVARY HEALTH CONTRIBUTE TO DISEASE BURDEN AND TRANSLATING THESE FINDINGS TO INFORM FUTURE CLINICAL CARE. THIS WORK WILL USE QUANTITATIVE ANALYSIS OF SALIVARY BIOMARKERS, BOTH GOLD-STANDARD AND NOVEL IMAGING APPROACHES TO IDENTIFY ASPIRATION, WHILE SUPPORTING MY TRAINING GOALS OF STRENGTHENING TECHNICAL WET LABORATORY SKILLS AND CLINICAL RESEARCH SKILLS AT THE UNIVERSITY OF WISCONSIN-MADISON.