It is unlikely that oxygen supplementation in COPD patients with chronic respiratory failure reduce cardiac troponin level.

BACKGROUND: Cardiac troponin T (cTnT) is a biomarker of myocardial injury frequently elevated in COPD patients, potentially because of hypoxemia. This non-randomised observational study investigates whether long-term oxygen treatment (LTOT) reduces the cTnT level. METHODS: We compared cTnT between COPD patients who were candidates for LTOT (n = 20) with two reference groups. Patients from both reference groups were matched with the index group using propensity score.Reference groups consists of institutional pulmonary rehabilitation patients (short-term group) (n = 105 after matching n = 11) and outpatients at a pulmonary rehabilitation clinic (long-term group)(n = 62 after matching n = 10). Comparison was done within 24 h after LTOT initiation in first reference group and within 6 months after inclusion in the second group. RESULTS: The geometric mean of (standard deviation in parentheses) cTnT decreased from 17.8 (2.3) ng/L (between 8 and 9 a.m.) to 15.4 (2.5) ng/L between 1 and 2 p.m. in the LTOT group, and from 18.4 (4.8) ng/L to15.4 (2.5) ng/L in group (1) The corresponding long-term results were 17.0 (2.9) ng/L at inclusion (between 10 and 12 a.m.) to 18.4 (2.4) ng/L after 3 months in the LTOT-group, and from 14.0 (2.4) ng/L to 15.4 (2.5) ng/L after 6 months in group (2) None of the differences in cTnT during the follow-up between the LTOT-group and their matched references were significant. CONCLUSION: Initiation of LTOT was not associated with an early or sustained reduction in cTnT after treatment with oxygen supplementation.

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 NO3 -) or placebo (NO3 - -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 (SpO2), 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. CLINICAL TRIAL REGISTRATION: The activities of the Regional Committees for Medical and Health Research Ethics (REC) are founded on the Norwegian law on research ethics and medical research. This study was approved by NTNU/REK midt, Det medisinske fakultet, Postboks 8905, 7491 Trondheim (REK midt 2016/1360).

The severity of sleep hypoventilation in stable chronic obstructive pulmonary disease.

PURPOSE: An increase in PaCO2 is the element that defines sleep hypoventilation (SH). We queried if patients with SH, and those with PaCO2 increases during sleep for shorter time periods than SH (shamSH) differed from the patients without SH (noSH) in other ways. METHODS: This was a retrospective re-analysis of data from 100 stable inpatients with COPD with and without chronic hypercapnic respiratory failure. COPD was defined by criteria of the Global initiative for Chronic Obstructive Lung Disease (GOLD). For this study, SH was defined by an increase in PaCO2 ≥ 1.33 kPa to a value exceeding 6.7 kPa for ≥ 10 min (≥ 20 epochs of 30 s). Patients fulfilling the increase in PaCO2 for less than 10 min (1-19 epochs) were designated shamSH. All patients had daytime arterial blood gases, lung function tests, and polysomnography (PSG) with transcutaneous CO2 (PtcCO2). RESULTS: Of 100 patients, 25 had PtcCO2 increase ≥ 1.33 kPa. One never exceeded 6.7 kPa, 15 had SH, and 9 shamSH. SH and shamSH patients had extra CO2 load (= PtcCO2*time) both during and between the SH periods compared to the noSH group, the SH group more than the shamSH group. CONCLUSION: Using CO2 load as a measure of severity of sleep hypoventilation, SH patients have worse hypoventilation than the shamSH. Both shamSH and SH groups have extra CO2 load during and between SH periods, indicating that the SH/shamSH patients may represent a separate group of true hypoventilators during sleep.

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.

Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease.

PURPOSE: More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD. METHODS: Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50% of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2). RESULTS: Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19%) to 13 subjects (42%) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of -8.5 (7.8) (N = 11, P = 0.016). CONCLUSIONS: In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.

Alcohol at bedtime induces minor changes in sleep stages and blood gases in stable chronic obstructive pulmonary disease.

PURPOSE/BACKGROUND: The purpose of this study is to explore the effect of a moderate dose of alcohol on sleep architecture and respiration in chronic obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and hypoxic ventilatory drives in awake, normal individuals and reduces the amount of rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD subjects. METHODS: Prospectively designed, open-label interventional study in a pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients, median forced expiratory volume first second (FEV1) 40.5 % of predicted, median age 65 years, investigated by polysomnography including transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2) in randomized order of either control sleep or intervention with 0.5 g of ethanol/kilogram bodyweight, taken orally immediately before lights off. RESULTS: Alcohol induced a mean increase (95 % confidence interval, [CI]) in the mean ΔPtcCO2 of 0.10 kPa (0.002-0.206, P = 0.047) and a mean decrease (CI) in the REM-sleep percentage of total sleep time (REM % of TST) of 3.1 % (0.2-6.0), (P = 0.020). Six subjects with apnea/hypopnea index (AHI) ≥15 had fewer apneas/hypopneas during alcohol versus control sleep (mean reduction of AHI 11 (1-20), P = 0.046). Alcohol-sleep changes in SpO2, but not in ΔPtcCO2, correlated with daytime arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2). CONCLUSION: Occasional use of a moderate, bedtime dose of alcohol has only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution is appropriate as this study is small and higher doses of alcohol may result in major respiratory depressive and additional negative health effects.

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.

Acute exacerbation of COPD is associated with fourfold elevation of cardiac troponin T.

OBJECTIVE: To investigate if acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with myocardial injury, expressed as elevated high sensitive cardiac troponin T (hs-cTnT), and to identify determinants of hs-cTnT in chronic obstructive pulmonary disease (COPD) patients. DESIGN: In a cross-sectional study, hs-cTnT in patients hospitalised for AECOPD was compared with hs-cTnT in COPD patients in their stable state. SETTING: The study was conducted at a teaching and a pulmonary rehabilitation clinic. PARTICIPANTS: Consecutive admissions to participating units for the years 2010-2011 meeting objective, standardised criteria for AECOPD and stable COPD. MAIN OUTCOMES: Ratio of hs-cTnT in hospitalised AECOPD patients compared with stable COPD patients. Change in the ratio of hs-cTnT per unit increase of relevant covariables. RESULTS: The geometric mean of hs-cTnT in the index group was 25.8 ng/l (95% CI 21.1 to 31.7) compared with 4.55 ng/l (95% CI 3.72 to 5.67) in the reference group. After inclusion of relevant covariables, multiple linear regression analyses showed that the ratio between hs-cTnT in AECOPD patients and the references was 4.26 (95% CI 3.02 to 6.00) and that hs-cTnT increased 1.41-fold (95% CI 1.20 to 1.68), for each quartile increase in leucocyte count in stable COPD but not in AECOPD. Higher hs-cTnT levels were also associated with the presence of pathological q-waves (p=0.012) and electrocardiographic left ventricular hypertrophy (p=0.039), long-term oxygen treatment (p=0.002) and decreasing forced expiratory volume in 1 s (p=0.014). A significant univariable association between cTnT and arterial hypoxaemia was also found but this association was attenuated almost to a zero effect after inclusion of relevant covariates. CONCLUSIONS: AECOPD is associated with higher hs-cTnT as compared with stable COPD. In stable COPD, hs-cTnT appears to be positively associated with indices of COPD severity, whereas we were unable to identify significant determinants of hs-cTnT in AECOPD.