Compensatory responses to increased mechanical abnormalities in COPD during sleep

Abstract

Purpose To assess whether night-time increases in mechanical loading negatively impact respiratory muscle function in COPD and whether compensatory increases in inspiratory neural drive (IND) are adequate to stabilize ventilatory output and arterial oxygen saturation, especially during sleep when wakefulness drive is withdrawn. Methods 21 patients with moderate-to-severe COPD and 20 age-/sex-matched healthy controls (CTRL) participated in a prospective, cross-sectional, one-night study to assess the impact of COPD on serial awake, supine inspiratory capacity (IC) measurements and continuous dynamic respiratory muscle function (esophageal manometry) and IND (diaphragm electromyography, EMGdi) in supine sleep. Results Supine inspiratory effort and EMGdi were consistently twice as high in COPD versus CTRL (p < 0.05). Despite overnight increases in awake total airways resistance and dynamic lung hyperinflation in COPD (p < 0.05; not in CTRL), elevated awake EMGdi and respiratory effort were unaltered in COPD overnight. At sleep onset (non-rapid eye movement sleep, N2), EMGdi was decreased versus wakefulness in COPD (− 43 ± 36%; p < 0.05) while unaffected in CTRL (p = 0.11); however, respiratory effort and arterial oxygen saturation (SpO 2 ) were unchanged. Similarly, in rapid eye movement (stage R), sleep EMGdi was decreased (− 38 ± 32%, p < 0.05) versus wakefulness in COPD, with preserved respiratory effort and minor (2%) reduction in SpO 2 . Conclusions Despite progressive mechanical loading overnight and marked decreases in wakefulness drive, inspiratory effort and SpO 2 were well maintained during sleep in COPD. Preserved high inspiratory effort during sleep, despite reduced EMGdi, suggests continued (or increased) efferent activation of extra-diaphragmatic muscles, even in stage R sleep. Clinical trial informationThe COPD data reported herein were secondary data (Placebo arm only) obtained through the following Clinical Trial: "Effect of Aclidinium/Formoterol on Nighttime Lung Function and Morning Symptoms in Chronic Obstructive Pulmonary Disease" (https:// clini caltr ials. gov/ ct2/ show/ NCT02 429765; NCT02429765).

Ventilatory neural drive in chronically hypercapnic patients with COPD: effects of sleep and nocturnal noninvasive ventilation

“…L uo et al [ 18 ] demonstrated greater declines in EMG di during the transition from wakefulness to NREM and REM sleep in normocapnic COPD versus heathy controls despite consistently higher overall drive in COPD patients, concluding that such decreases in drive may contribute to hypoventilation and hypercapnia during sleep ( figure 3 a). This is supported by recent findings showing greater loss of EMG di in the transition from wakefulness to sleep in normocapnic COPD than in health [ 90 ]. Such nocturnal hypercapnia is predicted to precede the onset of persistent daytime hypercapnia [ 91 ].…”

“…It may also be postulated that the loss of this wakefulness drive could have exaggerated impacts on COPD patients as compared to the healthy population, due to impaired ability to compensate for the increasing mechanical and chemical deficits which we have described in hypercapnic COPD, thus increasing vulnerability to hypoventilation. Interestingly, decreases in EMG di in the transition to sleep may occur in the presence of preserved ventilatory effort (oesophageal and transdiaphragmatic pressure) in normocapnic COPD [ 90 ].…”

“…Hyperinflation, which is a hallmark of COPD, can worsen overnight ( figure 4 a) [ 90 , 105 ]. Combined with the deleterious impact of sleep on airway resistance, inspiratory muscle activity and breathing pattern, this hyperinflation can also lead to exaggerated hypoventilation and hypercapnia overnight [ 117 ].…”

Analysis and applications of respiratory surface EMG: report of a round table meeting

“…Neural respiratory drive has been shown to be correlated with dyspnea sensation [ 72 – 74 ], respiratory loading [ 2 , 75 , 76 ], clinical deterioration/exacerbations [ 77 ], recovery from exacerbations [ 4 ] and even mortality [ 78 ]. With increased loading, activation patterns of the diaphragm and accessory respiratory muscles change [ 11 , 76 , 79 , 80 ]. Parasternal and scalene activity has been shown to serve as surrogate for general respiratory activity in absence of diaphragm recordings, and high respiratory load changes the correlation between diaphragm and parasternal activity in both adult and pediatric patients [ 11 , 81 ].…”