Abstract Rationale Negative effort dependence (NED) is a phenomenon in obstructive sleep apnea (OSA) where increasing inspiratory effort further reduces airflow, unlike non-NED obstruction where inspiratory flow limitation (IFL) plateaus regardless of effort. NED presence and severity vary among patients and reflect a distinct physiological feature of OSA. Quantifying NED by comparing changes in airflow at two points in the breath fails to capture full NED morphology. Tidal volume (TV) integrates airflow over the breath, allowing for better characterization of NED severity. We introduce a method to quantify NED and explored how NED severity relates to peak IFL across the pressure-flow relationship in OSA. We hypothesize that greater NED will correlate with greater airway collapsibility. Additionally, because prolonged inspiratory time permits greater negative effort buildup, we hypothesized that NED would be associated with higher inspiratory duty cycle (IDC). Methods Fifty-two patients (age 62±11yrs; 73% male; BMI 31.0±3.4 kg/m²; mean AHI4% 34.7±23.8events/hr) underwent drug-induced sleep endoscopy (DISE). Airflow and TV were measured via pneumotachometer, effort via supraglottic pressure and thoracoabdominal belts, and airway collapse visualized with an endoscope. Continuous positive airway pressure (CPAP) titration determined non–flow-limited (Popen) and zero-flow (Pcrit) pressures. IDC was calculated as inspiratory time divided by total breath time. NED was quantified as the percentage reduction in observed TV compared with an idealized non-NED breath (Figure 1). NED was compared to peak inspiratory flow (VI) across CPAP levels, and peak NED values defined severity: low (≤30%), medium (31–60%), or high (61–100%). ANOVA and post-hoc tests assessed group differences. Linear regression assessed the correlation between peak NED and Popen. Pearson correlation assessed the relationship between NED and IDC. Results Across the pressure–flow curve, NED peaked at intermediate levels of IFL, diminished toward apnea, and resolved at non–flow-limited breathing. Popen differed significantly across NED severity (p = 0.025), driven by high vs. low NED (11.1±3.4cmH2O vs. 7.9±2.9cmH2O, p = 0.022) groups, while Pcrit did not significantly differ. Peak NED correlated with Popen (R²=0.11, p = 0.018) and strongly with IDC (r = 0.67, p 0.001). Conclusions NED worsens ventilation at intermediate levels of IFL and exacerbates overall upper airway collapsibility. NED’s strong association with IDC suggests NED is a maladaptive manifestation of the respiratory compensatory response, where increased effort paradoxically amplifies airflow limitation and reduced ventilation. Further characterization of NED could inform individualized OSA management strategies.Figure 1: NED was quantified by comparing the observed breath (blue) to an idealized non-NED breath (red) with the same VI. This abstract is funded by: NCATS, NIH
Kane et al. (Fri,) studied this question.