Background and objective

Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.

Methods

Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (P_crit ) and ventilation at CPAP level of 0 cmH₂ O (V_passive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHI<15 events/h on-therapy.

Results

Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1)  cmH₂ O vs 8.9 (8.4-10.4) cmH₂ O, P = 0.007), consistent with their reduced collapsibility (lower P_crit , P = 0.017, higher V_passive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both P_crit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and V_passive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH₂ O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.

Conclusion

Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and eszopiclone) for OSA.

Upper airway collapsibility is a key determinant of obstructive sleep apnea (OSA) which can influence the efficacy of certain non-continuous positive airway pressure (CPAP) treatments for OSA. However, there is no simple way to measure this variable clinically. The present study aimed to develop a clinically implementable tool to evaluate the collapsibility of a patient's upper airway. Collapsibility, as characterized by the passive pharyngeal critical closing pressure (Pcrit), was measured in 46 patients with OSA. Associations were investigated between Pcrit and data extracted from patient history and routine polysomnography, including CPAP titration. Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit (r2=0.51, p < .001) of all the variables investigated including apnea-hypopnea index, body mass index, sex, and age. Patients with a mildly collapsible upper airway (Pcrit ≤ -2 cmH2O) had a lower therapeutic CPAP level (6.2 ± 0.6 vs. 10.3 ± 0.4 cmH2O, p < .001) compared to patients with more severe collapsibility (Pcrit > -2 cmH2O). A therapeutic CPAP level ≤8.0 cmH2O was sensitive (89%) and specific (84%) for detecting a mildly collapsible upper airway. When applied to the independent validation data set (n = 74), this threshold maintained high specificity (91%) but reduced sensitivity (75%). Our data demonstrate that a patient's therapeutic CPAP requirement shares a strong predictive relationship with their Pcrit and may be used to accurately differentiate OSA patients with mild airway collapsibility from those with moderate-to-severe collapsibility. Although this relationship needs to be confirmed prospectively, our findings may provide clinicians with better understanding of an individual patient's OSA phenotype, which ultimately could assist in determining which patients are most likely to respond to non-CPAP therapies.

Background

Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death).

Methods

Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison.

Results

The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls.

Conclusions

Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.