Individual Variation in Dyspnea Severity During Free Breathing

Dyspnea is generally described as the sensation of unsatisfied breathing and is common in patients receiving care at both hospitals and tertiary facilities. Despite its prevalence, gaps remain in our understanding of the mechanisms underlying dyspnea severity and individual variation in its presentation. This has led to dyspnea often going unnoticed and untreated, particularly in noncommunicative patients. Leaving dyspnea untreated can lead to worse patient outcomes and has been linked to increased mortality rates in a variety of underlying pathologies. Furthermore, while the psychological harm that dyspnea can cause has been documented by several studies, the effect that an individual’s psychological state has on their experience and severity of dyspnea remains under evaluated. In this study, we employ a steady state, end-tidal forcing method to induce air-hunger related dyspnea in free-breathing healthy participants of varied age, sex, and psychological states. After completing a State Trait Anxiety Index (STAI) questionnaire, participants experienced 4-minute bouts of six distinct combinations of arterial partial pressures of oxygen and carbon dioxide (PO 2 , PCO 2 ) and indicated their self-reported dyspnea severity while several biomarkers were simultaneously recorded. We hypothesized that sex would play a role in dyspnea severity at controlled blood gas tensions. We also hypothesized that elevated anxiety would be associated with higher self-reported dyspnea scores. Preliminary findings show a significant difference in self-reported dyspnea severity between men and women in both moderate hypoxia (inspired PO 2 = 80 mmHg, end-tidal PCO 2 = 45 mmHg) (Men: 1.067 ± 1.452, Women: 2.549 ± 1.950, p = 0.013) and in a normoxic, hypercapnic state (inspired PO 2 = 149 mmHg, end-tidal PCO 2 = 52 mmHg) (Men: 2.166 ± 1.236, Women: 3.459 ± 2.242, p = 0.029). Dyspnea scores further increased under more severe conditions (inspired PO 2 = 80 mmHg, end-tidal PCO 2 = 52 mmHg; and inspired PO 2 = 68 mmHg, end-tidal PCO 2 = 52 mmHg) (p = 0.0013 and p < 0.001, respectively), with no significant impact of sex under these more challenging experimental treatments (Men: 3.157 ± 2.048, Women: 4.230 ± 2.401, p = 0.1073; and Men: 4.021 ± 2.192, Women: 4.982 ± 1.667, p = 0.1028, respectively). Preliminary findings also suggest that self-reported dyspnea severity was positively correlated with anxiety levels in men (r = 0.799, p = 0.0313). This data suggests that demographic and psychological factors may play a role in the onset and severity of air-hunger related dyspnea in freely breathing healthy individuals. Further study is necessary to determine if these relationships remain in a more diverse clinical population and to identify potential underlying mechanisms. This research was supported by the Dean's Collaborative Seed Grant at UC Riverside School of Medicine, a Regent's Faculty Fellowship for ECH, and the Burden Fellowship for KM. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.