Respiratory-Responsive Vocal Biomarker for Asthma Exacerbation Monitoring: Prospective Cohort Study.

Background: Asthma exacerbations remain a major challenge in asthma management, often due to delayed recognition and limitations of conventional monitoring tools such as peak flow meters and symptom questionnaires. These tools are typically effort dependent or retrospective, making them less suited for continuous, real-time monitoring. A novel, smartphone-based respiratory-responsive vocal biomarker (RRVB) may offer an accessible and noninvasive approach for dynamic assessment of respiratory health. This RRVB has previously demonstrated generalizable performance in cross-sectional cohorts across multiple respiratory conditions, including asthma, chronic obstructive pulmonary disease, and COVID-19, in populations spanning India and the United States. This study extended this work by evaluating the real-world, longitudinal performance of the same RRVB tool for daily asthma exacerbation monitoring via smartphones in home settings.

Objective: This study aimed to evaluate the efficacy of the RRVB as a convenient real-time tool for monitoring asthma exacerbations and respiratory states in a real-world, longitudinal setting.

Methods: In this prospective cohort study, 84 adult patients with asthma were enrolled from an academic medical center and followed for 90 days. Participants submitted daily 6-second voice samples and conducted peak expiratory flow measurements and surveys, including symptom reports and asthma control assessments. RRVB scores were generated in real time on the app. Asthma states (normal function, mild event, and exacerbation) were defined based on both peak expiratory flow and self-reported well-being. Risk ratios were calculated to assess the predictive validity of RRVB scores for identifying exacerbation events. Engagement was measured via frequency of completed sessions, and participant experience was evaluated through exit surveys.

Results: RRVB scores significantly stratified asthma states. The risk of experiencing an exacerbation was 2.15 times higher (95% CI 1.62-2.85; P<.001) with elevated RRVB scores and 3.57 times higher (95% CI 2.70-4.73; P<.001) using normalized scores adjusted for individual characteristics. RRVB scores did not significantly correlate with the Asthma Control Test (risk ratio=1.17, 95% CI 0.96-1.44; P=.12), highlighting its role as a momentary signal rather than a proxy for longitudinal control. Engagement was moderate or higher (≥26 total app sessions) in 58% (49/84) of participants. Among survey respondents, 93% (43/46) found the app easy to use, 89% (41/46) reported a positive overall experience, and 87% (40/46) indicated that they would use a similar tool in the future. Fewer participants (32/46, 70%) reported understanding the RRVB scores, suggesting a need for improved score interpretability and user guidance in future implementations.

Conclusions: The RRVB tool demonstrated effective real-time detection of asthma exacerbations and dynamic respiratory states, supporting its potential as a noninvasive, user-friendly, and physiologically grounded digital biomarker for asthma monitoring. These findings provide foundational evidence for broader deployment and integration of voice-based tools to support proactive, real-world asthma management.

Trial registration: ClinicalTrials.gov NCT05850390; https://clinicaltrials.gov/study/NCT05850390.