Inclusive Research Representation and Blood Lactate as a Metabolic Biomarker of Vocal Function: Equitable Development of a Vocal Capacity Anaerobic Task

Abstract

Voice production is a highly coordinated motor-based task that involves the integration of three major anatomical and physiological skeletal muscle systems: respiratory, laryngeal (phonatory), and articulatory (oropharyngeal) systems. A voice disorder may exist if an individual expresses concern about their voice or voice quality being unable to meet their daily vocal demands, even if others do not perceive it as different. One of the most commonly reported vocal symptoms and precursors to laryngeal pathology and voice disorders is vocal fatigue, the sensation of feeling tired when speaking. Despite the prevalence of this vocal symptom in a diverse range of patients seen in clinical voice settings, there is limited evidence on the role of skeletal muscle metabolism and physiology in developing chronic, debilitating vocal fatigue. Voice scientists have primarily focused on indirect measures of vocal function (acoustic, aerodynamic, and perceptual measures), with frequent equivocal or inconsistent findings. It is hypothesized that such variability in the findings is due to the lack of direct measures to determine skeletal muscle function during vocal demand. In applied exercise science there is well-established methodology for the study of skeletal muscle adaptation with training and response to performance demand, including the use of metabolic blood biomarkers. This dissertation sought to address this gap in knowledge through the integration of exercise science methodology of investigating a well-studied metabolite, blood lactate, in the presence of a vocally demanding task hypothesized to be anaerobically challenging. This body of work also targeted the study of a diverse range of participants in terms of sex, race, ethnicity, and body composition to frame historical limitations and reporting of research volunteer diversity. This research was composed of three manuscripts: a meta-analysis, tutorial, and a prospective multimodality study, all of which seek to address different aims within the broad

objective. The purpose of this meta-analysis was to assess the frequency of sex, race, and ethnicity reporting and proportional representation in funded, non-cancerous voice clinical trials, to determine the state of compliance with National Institutes of Health (NIH) guidelines for inclusivity in clinical research. Clinical trials registered with the NIH U.S. National Library of Medicine between January 1988 and September 2021 were analyzed. Primary reports of the trials were obtained from clinicaltrials.gov and PubMed. The search yielded 46 research studies. After inclusion and exclusion criteria were applied and attempts to locate studies were conducted, 11 total papers were ultimately evaluated. Descriptively, there were more female subjects, yet overall, no significant difference in sex distribution (X2 = .07, P value = 0.75, 95% CI -0.25 to - 0.19). Race and ethnicity were only reported in two clinical trials. Black participants were underrepresented in one clinical trial (X2 = 4.93, P value = 0.02, 95% CI -0.11 to - 0.02), while Hispanic participants were underrepresented in a second trial (X2 = 11.27, P value < 0.00, 95% CI -0.20 to - 0.13). This preliminary analysis highlights the disparities in race and ethnicity recruitment and reporting in non-cancerous voice clinical trials. There is a need for strategic recruitment strategies and improved reporting practices to adhere to the NIH inclusivity directives. The purpose of the tutorial was twofold: 1) Present relevant exercise science literature on skeletal muscle metabolism and synthesize the limited available research on metabolism of the adult human speech musculature in an effort to elucidate the role of metabolism in speech production; and 2) Introduce a well-studied metabolic serum biomarker in exercise science, lactate, and the potential usefulness of investigating this metabolite, through well-established exercise science methodology, to better understand metabolism of the musculature involved in voice production. The tutorial synthesized the available research investigating metabolism of the

adult human speech musculature. The synthesis was followed by a proposed hypothesis of speech metabolism based on the voice science literature and the application of well-studied exercise science principles of muscle physiology. The tutorial concluded with a discussion of the potential usefulness of lactate in vocal function investigations to better understand the metabolism of the musculature involved in vocal demand tasks. The role of metabolism during speech (respiratory, laryngeal, articulatory) is an understudied yet critical aspect of speech physiology that warrants further study to better understand the metabolic systems that are used to meet vocal demands. The objective of the third and final manuscript was to investigate if a change in blood lactate was detectable in an anaerobically designed vocal demand task (VCAT60) and establish construct validity of the developed vocal demand task in assessing the anaerobic capacity of the speech musculature, similar to anaerobic power tests commonly used in applied exercise science. A prospective, multimodality repeated measures study quantified blood lactate concentrations prior to and following VCAT60 in vocally healthy adults. The secondary outcomes included determining correlations and predictors of the change in lactate including aerodynamic and anthropometric data as well as participant reported vocal fatigue. A significant change in lactate pre and post VCAT60was observed (p = 0.003). Body mass index (p = 0.003) and body mass (p = 0.005) were significant predictors of the lactate concentration shift. Evidence supported the hypothesis that blood lactate may be an effective metabolic biomarker in investigating the metabolism of the vocal muscles in vivo. The VCAT60 provides a means from which to understand metabolic adaptations that occur in the peripheral muscles of the speech mechanism, a valuable metric to further study vocal effort and vocal fatigue. Future investigations into the role of metabolic disease and body mass in vocal function are warranted given the findings.