Pathogenesis of obstructive sleep apnea in individuals with the COPD + OSA Overlap syndrome versus OSA alone

Abstract

Overlap syndrome (OVS) is the concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), and is associated with poor outcomes. We hypothesized that physiological changes in COPD may affect the pathogenesis of OSA in important ways. We therefore sought to measure the anatomical and nonanatomical OSA traits in individuals with OVS and compare to those with OSA alone. Patients with established OVS were recruited, along with age, gender, and BMI matched OSA only controls. Smoking and relevant comorbidities or medications were excluded. Subjects underwent baseline polysomnography followed by an overnight physiological research study to measure the OSA traits (Veupnea , Varousal , Vpassive , Vactive , and loop gain). Fifteen subjects with OVS and 15 matched controls with OSA alone were studied (overall 66 ± 8 years, 20% women, BMI 31 ± 4 kg/m2 , apnea-hypopnea index 49 ± 36/hr). Mixed-modeling was used to incorporate each measurement (range 52-270 measures/trait), and account for age, gender, and BMI. There were no significant differences in the traits between OVS and OSA subjects, although OVS subjects potentially tolerated a lower ventilation before arousal (i.e., harder to wake; p = .06). Worsened lung function was significantly associated with worsened upper airway response and more unstable breathing (p < .05 for all). Consistent differences in key OSA traits were not observed between OVS and OSA alone. However, worse lung function does appear to exert an influence on several OSA traits. These findings indicate that a diagnosis of OVS should not generally influence the approach to OSA, but that lung function might be considered if utilizing OSA trait-specific treatment.

Keywords: COPD; OSA; lung.

Conflict of interest statement

The authors have no relevant conflict of interest to disclose.

© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Figures

Figure 1

Measurement of OSA traits via a Series of Pressure Changes. OSA traits are measured by manipulating CPAP (Panel a) during supine non‐rapid eye movement (NREM) sleep and measuring the resultant changes in ventilation (Panel b). (i) Minute ventilation is taken over 30–60 s while on optimal CPAP settings (i.e., holding pressure) to measure Veupnea; (ii) The pressure is rapidly dropped to sequentially lower pressures. Minute ventilation (for Vpassive) and peak inspiratory flow (for Pcrit) is taken from the third through fifth breaths following a drop. Regression is used to determine ventilation at atmospheric pressure for Vpassive, and CPAP level at onset of zero peak inspiratory flow for Pcrit. (iii) CPAP is then gradually lowered until flow limitation starts and arousals occur intermittently. Ventilation just prior to arousal is defined as Varousal. During stable breathing between arousals under this maximally‐increased respiratory drive, CPAP is dialed down or up from this level to obtain Vactive (v) and loop gain (vi), respectively. Minute ventilation taken is from the second and third breath following a rapid drop from the minimum tolerable CPAP level and regression is used to determine ventilation at atmospheric pressure for Vactive. Loop gain is the ventilatory response (first breath overshoot in ventilation above Veupnea) divided by the ventilatory disturbance (preceding five breath reduction in ventilation below Veupnea). Adapted from (Edwards et al., 2016)

Figure 2

Comparison of OSA traits for subjects with OVS versus OSA alone. Circles represent mean values of each OSA trait for each subject. The dot and whisker plot shows the mixed modeling group estimated mean with associated [95% confidence interval]. There was no significant difference in (a) Veupnea (6.9 [6.3–7.4] vs. 7.2 [6.7–7.8] L/min; p = .38), (b) Varousal (5.1 [4.5–5.8] vs. 6.0 [5.4–6.6] L/min; p = .06), (c) Vpassive (1.5 [0–3.1] vs. 2.3 [0.6–4.1] L/min; p = .48), (d) Vactive (1.6 [−0.5 to 3.7] vs. 4.1 [2.1–6.0] L/min; p = .11), or (e) Loop gain (5.0 [3.1–6.8] vs. 3.8 [1.9–5.8]; p = .43)