Validation of peripheral arterial tonometry as tool for sleep assessment in chronic obstructive pulmonary disease

Obstructive sleep apnea (OSA) worsens outcomes in Chronic Obstructive Pulmonary Disease (COPD), and reduced sleep quality is common in these patients. Thus, objective sleep monitoring is needed, but polysomnography (PSG) is cumbersome and costly. The WatchPAT determines sleep by a pre-programmed algorithm and has demonstrated moderate agreement with PSG in detecting sleep stages in normal subjects and in OSA patients. Here, we validated WatchPAT against PSG in COPD patients, hypothesizing agreement in line with previous OSA studies. 16 COPD patients (7 men, mean age 61 years), underwent simultaneous overnight recordings with PSG and WatchPAT. Accuracy in wake and sleep staging, and concordance regarding total sleep time (TST), sleep efficiency (SE), and apnea hypopnea index (AHI) was calculated. Compared to the best fit PSG score, WatchPAT obtained 93% sensitivity (WatchPAT = sleep when PSG = sleep), 52% specificity (WatchPAT = wake when PSG = wake), 86% positive and 71% negative predictive value, Cohen’s Kappa (κ) = 0.496. Overall agreement between WatchPat and PSG in detecting all sleep stages was 63%, κ = 0.418. The mean(standard deviation) differences in TST, SE and AHI was 25(61) minutes (p = 0.119), 5(15) % (p = 0.166), and 1(5) (p = 0.536), respectively. We conclude that in COPD-patients, WatchPAT detects sleep stages in moderate to fair agreement with PSG, and AHI correlates well.Obstructive sleep apnea (OSA) worsens outcomes in Chronic Obstructive Pulmonary Disease (COPD), and reduced sleep quality is common in these patients. Thus, objective sleep monitoring is needed, but polysomnography (PSG) is cumbersome and costly. The WatchPAT determines sleep by a pre-programmed algorithm and has demonstrated moderate agreement with PSG in detecting sleep stages in normal subjects and in OSA patients. Here, we validated WatchPAT against PSG in COPD patients, hypothesizing agreement in line with previous OSA studies. 16 COPD patients (7 men, mean age 61 years), underwent simultaneous overnight recordings with PSG and WatchPAT. Accuracy in wake and sleep staging, and concordance regarding total sleep time (TST), sleep efficiency (SE), and apnea hypopnea index (AHI) was calculated. Compared to the best fit PSG score, WatchPAT obtained 93% sensitivity (WatchPAT = sleep when PSG = sleep), 52% specificity (WatchPAT = wake when PSG = wake), 86% positive and 71% negative predictive value, Cohen’s Kappa (κ) = 0.496. Overall agreement between WatchPat and PSG in detecting all sleep stages was 63%, κ = 0.418. The mean(standard deviation) differences in TST, SE and AHI was 25(61) minutes (p = 0.119), 5(15) % (p = 0.166), and 1(5) (p = 0.536), respectively. We conclude that in COPD-patients, WatchPAT detects sleep stages in moderate to fair agreement with PSG, and AHI correlates well.publishedVersio

Assessment of nocturnal versus daytime gas exchange in stable COPD. With emphasis on hypoventilation during spontaneous sleep and in sleep influenced by alcohol or zopiclone

Background/purpose: Chronic hypercapnic respiratory failure (CHRF) is associated with increased mortality in patients with chronic obstructive pulmonary disease (COPD), and sleep hypoventilation (SH) has been proposed as a possible predictor for CHRF in COPD. SH was previously found in COPD patients with CHRF using long term oxygen therapy (LTOT). However, SH in normocapnic, non-LTOT subjects have not been described. More than half of COPD patients have difficulties in initiating or maintaining sleep or are excessively sleepy at daytime. Hypnotics and alcohol are often used although both are known to depress the respiratory drive to breathe, and little is known regarding SH due to these agents. We have explored the associations between sleep architecture and nocturnal and daytime blood gases in stable COPD, both in spontaneous sleep and during sleep influenced by alcohol or the hypnotic zopiclone. Material/methods: Paper I is an observational sleep study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients, mean FEV1 1.1 L (42% of predicted), mean age 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔptcCO2). Paper II and paper III presents data from interventional sleep recordings from 26 (9 male) and 31 (10 male) of the same subjects described in paper I, influenced by 0.5 mg ethanol/kg bodyweight or a pill of 5 mg zopiclone, respectively. Results: SH in spontaneous sleep was found in 15%, and although most had CHRF, six subjects were daytime normocapnic. Alcohol induced a mean (95% confidence interval) increase in the ΔptcCO2 during sleep of only 0.1 kPa (0.0-0.2, p=0.047) with no significant increase in the frequency of SH, whereas zopiclone increased the mean (SD) ΔptcCO2 with 0.23 (0.33) kPa, and the frequency of SH from 19% to 42% (p=0.020). Conclusions/consequences: SH is found both in hypercapnic and normocapnic COPD subjects. Whether it is a real predictor of CHRF should be investigated by prospective case-control studies. A moderate dose of alcohol has only minor effects on breathing at sleep whereas zopiclone increases the frequency of SH in COPD

Sleep hypoventilation and daytime hypercapnia in stable chronic obstructive pulmonary disease

Purpose: To explore the associations between sleep hypoventilation (SH) and daytime arterial pressures of carbon dioxide (PaCO2), sleep stages, and sleep apneas/hypopneas (AHI) in subjects with chronic obstructive pulmonary disease (COPD). SH has previously been found in COPD-subjects with chronic hypercapnic respiratory failure (CHRF) using supplementary oxygen (LTOT), and has been proposed as a possible predictor for CHRF. Patients and methods: A prospectively designed observational study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients with a mean forced expiratory volume in 1 second (FEV1) of 1.1 L (42% of predicted) and a mean age of 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2). Results: SH as defined by the American Academy of Sleep Medicine (AASM) was found in 15 of the subjects, seven of whom used LTOT. However, six had SH despite being normocapnic during the daytime (only one on LTOT). Subjects with SH had a greater ΔPtcCO2 increase from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep stages compared to non-SH subjects (mean [standard deviation] between-groups difference =0.23(0.20) kPa, P<0.0005). Subjects with apnea/hypopnea index ≥ 15 (overlap, N=27) did not differ from those with COPD alone (AHI <5, N=25) in sleep ΔPtcCO2 or daytime PaCO2. A regression model with the variables FEV1, LTOT, and sleep maximum ΔPtcCO2 explained 56% of the variance in daytime PaCO2 (F(3, 94) =40.37, P<0.001). Conclusion: In stable COPD, SH as defined by the AASM was found both in normocapnic, non-LTOT subjects and in hypercapnic, LTOT-using subjects. Between-sleep-stage increase in ΔPtcCO2 was higher in subjects with SH. Overlap subjects did not differ from simple COPD subjects in sleep ΔPtcCO2 or daytime PaCO2

Validation of peripheral arterial tonometry as tool for sleep assessment in chronic obstructive pulmonary disease

Obstructive sleep apnea (OSA) worsens outcomes in Chronic Obstructive Pulmonary Disease (COPD), and reduced sleep quality is common in these patients. Thus, objective sleep monitoring is needed, but polysomnography (PSG) is cumbersome and costly. The WatchPAT determines sleep by a pre-programmed algorithm and has demonstrated moderate agreement with PSG in detecting sleep stages in normal subjects and in OSA patients. Here, we validated WatchPAT against PSG in COPD patients, hypothesizing agreement in line with previous OSA studies. 16 COPD patients (7 men, mean age 61 years), underwent simultaneous overnight recordings with PSG and WatchPAT. Accuracy in wake and sleep staging, and concordance regarding total sleep time (TST), sleep efficiency (SE), and apnea hypopnea index (AHI) was calculated. Compared to the best fit PSG score, WatchPAT obtained 93% sensitivity (WatchPAT = sleep when PSG = sleep), 52% specificity (WatchPAT = wake when PSG = wake), 86% positive and 71% negative predictive value, Cohen’s Kappa (κ) = 0.496. Overall agreement between WatchPat and PSG in detecting all sleep stages was 63%, κ = 0.418. The mean(standard deviation) differences in TST, SE and AHI was 25(61) minutes (p = 0.119), 5(15) % (p = 0.166), and 1(5) (p = 0.536), respectively. We conclude that in COPD-patients, WatchPAT detects sleep stages in moderate to fair agreement with PSG, and AHI correlates well

Premature Ventricular Complex is More Prevalent During Acute Exacerbated than Stable States of Chronic Obstructive Pulmonary Disease, and Is Related to Cardiac Troponin T

During acute exacerbation of chronic obstructive pulmonary disease (AECOPD), myocardial stress may be aggravated. Sparse data exist concerning the prevalence and correlates of cardiac arrhythmias in the stable and exacerbated states of COPD. We hypothesized that AECOPD is associated with increased prevalence of cardiac arrhythmias independent of COPD-severity and co-morbidity, and explored possible mechanisms. A 24-hour Holter recording was obtained in 74 patients with stable COPD and 45 patients with AECOPD (mean age 54 years, 56% women). Any incidence of supraventricular tachycardia (SVT), frequent premature ventricular complex (PVC, >30/hour) and complex ventricular ectopy (bigeminy, trigeminy or non-sustained ventricular tachycardia) was recorded and compared between the two groups. Adjustments were made for by stable disease-related co-variates (demography, co-morbidity, COPD-severity) and by acute disease-related co-variates (heart rate, cardiac troponin T (cTnT), PO2, PCO2 and C-reactive protein (CRP)) in explorative analyses. The prevalence of SVT, frequent PVCs or complex ventricular ectopy was 40%, 27% and 33% in AECOPD, and 31%, 31% and 12% in stable COPD, respectively. Frequent PVC, but not SVT or complex ventricular ectopy, was significantly increased in AECOPD compared to stable COPD, odds ratio 3.03 (1.03–10.5, p = 0.039) when adjusted for stable disease-related co-variates. Higher heart rate, cTnT and CRP attenuated the association between AECOPD and frequent PVC to non-significant, while heart rate remained associated with frequent PVC. In conclusion, frequent PVC is more prevalent in exacerbated than in the stable states of COPD. Attenuation effects of cTnT, tachycardia and CRP suggest that cardiac stress or inflammation may be involved in mechanisms causing frequent PVC i AECOPD. © 2017 Taylor & Franci

Effect of dietary nitrate supplementation on sleep in chronic obstructive pulmonary disease patients

Purpose: Poor sleep quality in chronic obstructive pulmonary disease (COPD) is a result of oxygen desaturation secondary to compromised lung function. Nitrate supplementation with dietary beetroot juice is known to elevate plasma nitrate and to increase the efficiency of oxygen utilization in non-COPD individuals; whether it is of therapeutic benefit for sleep quality in COPD has not been reported. Patients and Methods: In a counterbalanced within-subjects design involving 15 COPD patients as subjects, the subjects consumed either beetroot juice containing nitrate (BJ; ∼ 6.2 mmol NO 3–) or placebo (NO 3– -depleted juice) immediately before a night of polysomnographic monitoring. Nitrate was measured in plasma collected immediately after waking. Results: While BJ consumption had no effect on the amount of time spent in any sleep stages, wake-to-N2 transitions and direct wake-to-rapid eye movement sleep (REMS) transitions, hallmarks of disordered sleep, were less frequent on the BJ night than on the placebo night. In the last two hours of the BJ night, percent time in REMS increased and delta power during deep (N3) non-REMS decreased, relative to the placebo night. Collectively, the reduced frequency of atypical transitions and the normalization of non-REMS/REMS dynamics after BJ are indicative of an improvement of sleep quality. BJ also resulted in sustained elevation of peripheral oxygen saturation (SpO 2), during episodes of wake after sleep onset. Plasma nitrate was elevated nearly tenfold on the morning after BJ relative to placebo. Conclusion: BJ has a normalizing effect on disordered sleep in COPD, which may be related to improved oxygen delivery.publishedVersio

The prognostic value of measurement of high-sensitive cardiac troponin T for mortality in a cohort of stable chronic obstructive pulmonary disease patients

Background Cardiovascular disease (CVD) is a common comorbidity in chronic obstructive pulmonary disease (COPD). Cardiac troponin (cTn) elevation, indicating myocardial injury, is frequent during acute COPD exacerbations and associated with increased mortality. The prognostic value of circulating cTnT among COPD patients in the stable state of the disease is still unknown. The purpose of the present study was to assess the association between circulating cTnT measured by a high sensitive assay (hs-cTnT) and all-cause mortality among patients with stable COPD without overt CVD. Methods In a prospective cohort study we included 275 patients from the Akershus University Hospital’s outpatient clinic and from Glittre, a pulmonary rehabilitation clinic. COPD-severity and cardiovascular risk factors were assessed, and time to all-cause death was recorded during a mean follow-up time of 2.8 years. Results One hundred-eighty patients (65%) had hs-cTnT concentrations ≥ the level of detection (5.0 ng/L) and 66 patients (24%) had hs-cTnT above the normal range (≥14.0 ng/L). In total, 47 patients (17%) died. hs-cTnT concentrations in the ranges <5.0, 5.0–13.9 and ≥14 ng/L were associated with crude mortality rates of 2.8, 4.4 and 11.0 per 100 patient-years, respectively. In adjusted analyses the hazard ratios (95% confidence intervals) for death were 1.7 (0.8–3.9) and 2.9 (1.2–7.2) among patients with hs-cTnT concentrations 5.0–13.9 and ≥14 ng/L, respectively, compared to patients with hs-cTnT <5.0 ng/L. Conclusions hs-cTnT elevation is frequently present in patients with stable COPD without overt CVD, and associated with increased mortality, independently of COPD-severity and other cardiovascular risk factors

Systemic inflammation induced by exacerbation of COPD or pneumonia in patients with COPD induces cardiac troponin elevation

Background Troponin is a biomarker of myocardial injury. In chronic obstructive pulmonary disease (COPD), troponin is an important determinant of mortality after acute exacerbation. Whether acute exacerbation of COPD (AECOPD) causes troponin elevation is not known. Here, we investigated whether troponin is increased in AECOPD compared to stable COPD. Methods We included 320 patients with COPD in the stable state and 63 random individuals from Akershus University hospital’s catchment area. All participants were ≥40 years old (mean 65·1 years, SD 7·6) and 176 (46%) were females. The geometric mean of high-sensitivity cardiac troponin T (hs-cTnT) was 6·9 ng/L (geometric-SD 2·6). They were followed regarding hospital admission for the subsequent 5 years. Results During the 5-year follow-up, we noted 474 hospitalisations: Totally, 150 and 80 admissions were due to AECOPD or pneumonia, respectively. The geometric mean ratio with geometric SE ( GSE) between cTnT at admission and stable state in AECOPD and pneumonia was 1·27 (GSE=1.11, p=0·023) and 1·28 (GSE=1.14, p=0·054), respectively. After inclusion of blood leucocyte count and C reactive protein at hospitalisation, these ratios attenuated to zero. However, we estimated an indirect of AECOPD and pneumonia on the ratio between hs-cTnT at admission and the stable state to 1·16 (p=0·022) and 1·22 (p=0·008), representing 91% (95% CI 82% to 100%) and 95% (95% CI 83% to 100%) of the total effects, respectively. Conclusion AECOPD and pneumonia in patients with COPD is associated with higher cTnT levels. This association appears to be mediated by systemic inflammation

Effect of dietary nitrate supplementation on sleep in chronic obstructive pulmonary disease patients

Purpose: Poor sleep quality in chronic obstructive pulmonary disease (COPD) is a result of oxygen desaturation secondary to compromised lung function. Nitrate supplementation with dietary beetroot juice is known to elevate plasma nitrate and to increase the efficiency of oxygen utilization in non-COPD individuals; whether it is of therapeutic benefit for sleep quality in COPD has not been reported. Patients and Methods: In a counterbalanced within-subjects design involving 15 COPD patients as subjects, the subjects consumed either beetroot juice containing nitrate (BJ; ∼ 6.2 mmol NO 3–) or placebo (NO 3– -depleted juice) immediately before a night of polysomnographic monitoring. Nitrate was measured in plasma collected immediately after waking. Results: While BJ consumption had no effect on the amount of time spent in any sleep stages, wake-to-N2 transitions and direct wake-to-rapid eye movement sleep (REMS) transitions, hallmarks of disordered sleep, were less frequent on the BJ night than on the placebo night. In the last two hours of the BJ night, percent time in REMS increased and delta power during deep (N3) non-REMS decreased, relative to the placebo night. Collectively, the reduced frequency of atypical transitions and the normalization of non-REMS/REMS dynamics after BJ are indicative of an improvement of sleep quality. BJ also resulted in sustained elevation of peripheral oxygen saturation (SpO 2), during episodes of wake after sleep onset. Plasma nitrate was elevated nearly tenfold on the morning after BJ relative to placebo. Conclusion: BJ has a normalizing effect on disordered sleep in COPD, which may be related to improved oxygen delivery