Sleep and COVID-19: considerations about immunity, pathophysiology, and treatment.

The fear and uncertainty caused by the coronavirus disease 2019 (COVID-19) pandemic, threats to survival are one of the main problems of everyday life; however, mental health care must also be considered a priority. During social isolation also called self-quarantine, the restricted mobility and social contact, concern about financial resources and availability of supplies, fear of infection, questions about the duration of self-quarantine, cause anxiety, depression, stress, insomnia and reduced the quality and quantity of sleep, that may present a greater risk to the health of the general population. Sleep disorders are increasingly becoming a major health issue in modern society, and are influenced by retinal stimulation by electronic devices, as well extended and/or night shift-work, which may aggravate the systemic and lung inflammation during viral infections. Sleep disorders can induce pro-inflammatory states and be harmful during the COVID-19 pandemic. The possible interactions between many drugs used to treat COVID-19, and those used to treat sleep disorders are unknown, mostly due to the lack of a standard protocol to treat these patients. Insufficient sleep or irregular sleep-wake cycles may impair health, immune system, induce pro-inflammation state, and may lead to increased vulnerability to viral infections, involving inflammatory and oxidative/antioxidant imbalance. In this sense, obstructive sleep apnea has been associated with recognized COVID-19 risk comorbidities and considered a risk factor for COVID-19. During the COVID-19 pandemic, health care cannot stop, and telemedicine has presented itself as an alternative method of delivering services. When a face-to-face visit is mandatory, or in locations with minimal community transmission where sleep centers have resumed activities, it is important that the sleep center facilities are properly prepared to receive the patients during the COVID-19 pandemic, and follow all relevant safety rules. In this work we gathered a group of researchers, specialists in aspects related to chronobiology, sleep, sleep disorders, and the immune system. Thus, we conducted a narrative review in order to address the relationship between COVID-19 and sleep, as well as its immunological aspects and strategies that may be applied in order to mitigate the harmful effects on health that affects everyone during the pandemic.

Impact of a Multimodal Telemonitoring Intervention on CPAP Adherence in Symptomatic OSA and Low Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: One of the major challenges in treating OSA is to achieve adequate CPAP adherence. Telemonitoring has the potential to provide individualized management and early recognition of problems during treatment. RESEARCH QUESTION: What is the effect of a multimodal telemonitoring intervention on treatment adherence, quality of life, and functional status in symptomatic patients with OSA and low cardiovascular risk? STUDY DESIGN AND METHODS: In a multicenter, randomized controlled trial, patients newly diagnosed with OSA were randomly assigned to multimodal telemonitoring for 6 months vs usual care (UC). Telemonitoring consisted of built-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks, or persistent residual events. The primary outcome was CPAP adherence (in hours per night). Secondary outcomes included daily symptoms such as fatigue and sleepiness, and quality of life measured by using self-reported questionnaires. RESULTS: A total of 206 patients with OSA and a median age of 50.6 years (interquartile range [IQR], 42.1; 58.1 years) were included in the study; they were predominantly male (63%) with a median BMI of 30.6 kg/m2 (IQR, 26.8; 35.1 kg/m2) and a median apnea-hypopnea index of 45.2 events/h (IQR, 34.0; 60.0 events/h). Of these, 102 received UC and 104 received telemonitoring. After 6 months of treatment, CPAP adherence was similar in the two groups when assessed either by mean duration of usage (4.73 ± 2.48 h per night in the telemonitoring group and 5.08 ± 2.44 h per night in the UC group; P = .30) or in percentage of patients adherent to treatment (> 4 h usage per night, > 70% nights; 64% in the telemonitoring group vs 72% in the UC group; P = .24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. INTERPRETATION: In patients with severe OSA and low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both the telemonitoring and UC groups, similar improvements in daytime symptoms were achieved. TRIAL REGISTRY: ClinicalTrials.gov; No.: 01796769; URL: www.clinicaltrials.gov.

Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number. METHODS AND ANALYSIS: Adult subjects with newly diagnosed OSA (Apnoea-Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student's t-test to compare changes in sympathetic tone between groups. ETHICS AND DISSEMINATION: The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03428516; Pre-results.

Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients.

BACKGROUND: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. STUDY OBJECTIVE: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. METHODS: We analyzed 183 stable CHF patients with optimized medical treatment in the "MARS" database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. RESULTS: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m2 (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO2 remained significant. CONCLUSION: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients.

Multimodal Remote Monitoring of High Cardiovascular Risk Patients With OSA Initiating CPAP: A Randomized Trial.

BACKGROUND: The management of patients with high cardiovascular risk and OSA must target not only improving adherence to CPAP, but should also include strategies aimed at reducing BP and increasing physical activity. The study aims to evaluate the effectiveness of an integrated intervention using remote patient telemonitoring in reducing BP in high cardiovascular risk patients with OSA. METHODS: In a multicenter, open, randomized trial, patients with OSA were randomly assigned at CPAP initiation to usual care or multimodal telemonitoring for 6 months. Telemonitoring used electronic equipment collecting information about BP, symptoms, CPAP side effects, and physical activity with home care providers prespecified protocoled actions. The primary effectiveness outcome was assessed using home self-measured BP on 3 consecutive days. Secondary outcomes included CPAP compliance, symptoms, and physical activity. RESULTS: Of 306 patients with a median age of 61.3 years [interquartile range, 54.1; 66.1], who were predominantly men, 226 (74%) with a BMI of 32.0 [28.7; 35.6] kg/m2 and an apnea-hypopnea index of 46 [35; 61] events/h, 149 received usual care and 157 received telemonitoring. After 6 months of CPAP, home self-measured BP did not differ significantly between groups. In secondary analyses, there was no significant difference in steps per day, but a significant increase in CPAP adherence and an improvement in daytime sleepiness and quality of life in favor of the multimodal telemonitoring. CONCLUSIONS: In OSA patients with high cardiovascular risk, multimodal telemonitoring was not superior to usual CPAP care for improving home BP; however, telemonitoring improved adherence and patient-centered outcomes.

Cerebral microvascular blood flow and CO2 reactivity in pulmonary arterial hypertension.

Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBFmicr) and cerebrovascular reactivity to CO2 (CVRCO2). Pulmonary arterial hypertension (PAH) is characteristically associated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We therefore determined CBFmicr (pre-frontal blood flow index (BFI) by the indocyanine green-near infrared spectroscopy methodology) during hypocapnia and hypercapnia in 25 PAH patients and 10 gender- and age-matched controls. Cerebral BFI was lower in patients than controls at similar transcutaneous PCO2 (PtcCO2) levels in both testing conditions. In fact, while BFI increased from hypocapnia to hypercapnia in all controls, it failed to increase in 17/25 (68%) patients. Thus, BFI increased to a lesser extent from hypo to hypercapnia ("Δ") in patients, i.e., they showed lower Δ BFI/Δ PtcCO2 ratios than controls. In conclusion, CBFmicr and CVRCO2 are lessened in clinically stable, mildly-impaired patients with PAH. These abnormalities might be associated with relevant clinical outcomes (hyperventilation and dyspnea, cognition, cerebrovascular disease) being potentially amenable to pharmacological treatment.

Eszopiclone versus zopiclone in the treatment of insomnia.

OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.

Eszopiclone versus zopiclone in the treatment of insomnia

OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.

Cerebral microvascular blood flow and CO2 reactivity in pulmonary arterial hypertension

Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBFmicr) and cerebrovascular reactivity to CO2 (CVRCO2). Pulmonary arterial hypertension (PAH) is characteristical lyassociated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We therefore determined CBFmicr (pre-frontal blood flow index (BFI) by the indocyanine green-near infrared spectroscopy methodology) during hypocapnia and hypercapnia in 25 PAH patients and 10 gender- andage-matched controls. Cerebral BFI was lower in patients than controls at similar transcutaneous PCO2(PtcCO2) levels in both testing conditions. In fact, while BFI increased from hypocapnia to hypercapnia inall controls, itfailed to increase in 17/25 (68%) patients. Thus, BFI increased to a lesser extentfrom hypo tohypercapnia (“”) in patients, i.e., they showed lower BFI/ PtcCO2 ratios than controls. In conclusion,CBFmicr and CVRCO2 are lessened in clinically stable, mildly-impaired patients with PAH. These abnormalities might be associated with relevant clinical outcomes (hyperventilation and dyspnea, cognition,cerebrovascular disease) being potentially amenable to pharmacological treatment...

Diagnostic accuracy of home-based monitoring system in morbidly obese patients with high risk for sleep apnea.

BACKGROUND: No previous studies have validated the use of portable monitoring (PM) for the diagnosis of obstructive sleep apnea (OSA) in morbidly obese individuals. Our aim was to investigate the accuracy of PM for detecting respiratory events in morbidly obese patients that will be undergoing bariatric surgery. METHODS: This was a prospective study involving patients with body mass index (BMI) ≥35 kg/m(2) who were recruited from the Sleep Clinic of Universidade Federal de São Paulo. Sleep-disordered breathing (SDB) was evaluated during full-night polysomnography (PSG). PM use was randomized and used on two consecutive nights: (1) at home (STDHome) and (2) at the sleep laboratory with PSG (PSG_STDLab). RESULTS: Although 58 participants initially underwent the recordings, 26 (45%) were excluded because of technical problems. The patients' mean age was 42.9 ± 10.9 (SD) years, and 56% were female. The mean BMI was 40.8 ± 5.2 kg/m(2). All patients had high risk for OSA, as defined by the Stop-Bang questionnaire, and the mean apnea-hypopnea index (AHI) was 46.9 ± 30.4/h. The intraclass coefficient of the correlation between AHI_PSG and AHI_STDLab was r = 0.92 (p = 0.0001); the intraclass coefficient for AHI_PSG and AHI_STDHome was r = 0.84 (p = 0.0001). The Kappa index was 0.87 (p > 0.0001) for severe cases. The sensitivity and the positive predictive value increased with the disease severity. A Bland-Altman analysis showed good agreement between the investigated methods. CONCLUSIONS: PM is an efficacious method for diagnosing OSA in obese patients who have a high clinical probability of the disease. The method displays good sensitivity and specificity in severe cases; nevertheless, the high rate of data loss must be taken into account.

Optimizing the evaluation of excess exercise ventilation for prognosis assessment in pulmonary arterial hypertension.

BACKGROUND: Increased ventilatory (.VE) response to carbon dioxide output (.VCO2) is a key finding of incremental cardiopulmonary exercise testing in both heart failure and pulmonary arterial hypertension (PAH). As with heart failure, measures of excessive exercise ventilation considering high-to-peak exercise .VE-VCO2 might have higher prognostic relevance than those restrained to sub-maximal exercise in PAH. DESIGN: Cross-sectional and observational study on a tertiary center. METHODS: Eighty-four patients (36 idiopathic and 48 with associated conditions) were followed up for up to five years. Excessive exercise ventilation was calculated as a slope (Δ .VE/Δ .VCO2 to the respiratory compensation point (RCP) and to exercise cessation (PEAK)) and as a ratio (.VE-VCO2 at the anaerobic threshold (AT) and at PEAK). RESULTS: Thirteen patients died and three had atrial septostomy. Multivariable regression analyses revealed that Δ .VE/Δ .VCO2(PEAK) <55 and .VE/.VCO2(PEAK) <57 were better related to prognosis than Δ .VE/Δ .VCO2(RCP) and .VE/.VCO2(AT) (p < 0.01). Δ oxygen uptake (.VO2)/Δ work rate >5.5 ml/min per W was the only other independent prognostic index. According to a Kaplan-Meier survival analysis, 96.9% (90.8% to 100%) of patients showing Δ .VE/Δ .VCO2(PEAK) <55 and Δ .VO2/Δ work rate >5.5 ml/min per W were free from a PAH-related event. In contrast, 74.7% (70.1% to 78.2%) with both parameters outside these ranges had a negative outcome. CONCLUSION: Measurements of excessive exercise ventilation which consider all data points maximize the usefulness of incremental cardiopulmonary exercise testing in the prognosis evaluation of PAH.

The use of portable monitoring for sleep apnea diagnosis in adults.

Due to increasing demand for sleep services, there has been growing interest in ambulatory models of care for patients with obstructive sleep apnea (OSA). The implementation of alternative approaches to the current management by full polysomnography (PSG) in the sleep laboratory is necessary for diagnosing this syndrome due to the high cost of full-night PSG. A good alternative option for OSA diagnosis is portable monitoring (PM), which is known for its accuracy, ease of management and lower cost when compared with full PSG. PM has not been well validated for OSA diagnosis in patients with medical comorbidities or in elderly individuals and children. PM may be recommended as an alternative method to PSG for patients with high clinical risk for OSA. In the present review, we describe the use of PM for OSA diagnosis and evaluate the current progress, costs, limitations and applications of these devices in various groups of patients, particularly for patients with comorbid diseases.

Factors influencing physical functional status in intensive care unit survivors two years after discharge.

BACKGROUND: Studies suggest that in patients admitted to intensive care units (ICU), physical functional status (PFS) improves over time, but does not return to the same level as before ICU admission. The goal of this study was to assess physical functional status two years after discharge from an ICU and to determine factors influencing physical status in this population. METHODS: The study reviewed all patients admitted to two non-trauma ICUs during a one-year period and included patients with age ≥ 18 yrs, ICU stay ≥ 24 h, and who were alive 24 months after ICU discharge. To assess PFS, Karnofsky Performance Status Scale scores and Lawton-Instrumental Activities of Daily Living (IADL) scores at ICU admission (K-ICU and L-ICU) were compared to the scores at the end of 24 months (K-24mo and L-24mo). Data at 24 months were obtained through telephone interviews. RESULTS: A total of 1,216 patients were eligible for the study. Twenty-four months after ICU discharge, 499 (41.6%) were alive, agreed to answer the interview, and had all hospital data available. PFS (K-ICU: 86.6 ± 13.8 vs. K-24mo: 77.1 ± 19.6, p < 0.001) and IADL (L-ICU: 27.0 ± 11.7 vs. L-24mo: 22.5 ± 11.5, p < 0.001) declined in patients with medical and unplanned surgical admissions. Most strikingly, the level of dependency increased in neurological patients (K-ICU: 86 ± 12 vs. K-24mo: 64 ± 21, relative risk [RR] 2.6, 95% CI, 1.8-3.6, p < 0.001) and trauma patients (K-ICU: 99 ± 2 vs. K-24mo: 83 ± 21, RR 2.7, 95% CI, 1.6-4.6, p < 0.001). The largest reduction in the ability to perform ADL occurred in neurological patients (L-ICU: 27 ± 7 vs. L-24mo: 15 ± 12, RR 3.3, 95% CI, 2.3-4.6 p < 0.001), trauma patients (L-ICU: 32 ± 0 vs. L-24mo: 25 ± 11, RR 2.8, 95% CI, 1.5-5.1, p < 0.001), patients aged ≥ 65 years (RR 1.4, 95% CI, 1.07-1.86, p = 0.01) and those who received mechanical ventilation for ≥ 8 days (RR 1.48, 95% CI, 1.02-2.15, p = 0.03). CONCLUSIONS: Twenty-four months after ICU discharge, PFS was significantly poorer in patients with neurological injury, trauma, age ≥ 65 tears, and mechanical ventilation ≥ 8 days. Future studies should focus on the relationship between PFS and health-related quality of life in this population.

Clinical usefulness of response profiles to rapidly incremental cardiopulmonary exercise testing.

The advent of microprocessed "metabolic carts" and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed.

Additive effects of non-invasive ventilation to hyperoxia on cerebral oxygenation in COPD patients with exercise-related O2 desaturation.

BACKGROUND: It is currently unknown whether potential haemodynamic improvements induced by non-invasive ventilation (NIV) would positively impact upon cerebral oxygenation (COx) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). OBJECTIVE: To investigate the effects of NIV on exercise COx in COPD patients presenting with exercise-related O(2) desaturation. METHODS: On a double-blind trial, 13 males (FEV1 = 48·8 ± 15·1% predicted) were randomly assigned to NIV (16 cmH(2)O IPS and 5 cmH(2)O PEEP) plus HOx (FiO(2) = 0·4) or sham NIV (7 cmH(2)O IPS and 5 cmH(2)O PEEP to overcome breathing circuit resistance) plus HOx during ramp-incremental exercise performed on different days. Near-infrared spectroscopy and impedance cardiography assessed changes (Δ) in COx and cardiac output (Q(T)), respectively. RESULTS: There were no significant between-intervention differences in peak work rate, ventilation and reported symptoms (P>0·05). Peripheral oxyhaemoglobin saturation remained above 98% throughout the tests. NIV + HOx was associated with larger increases in Δ COx, Δ Q(T) and Δ stroke volume at maximal and submaximal exercise (P<0·05). Increases in the area under the curve (to an iso-work rate) of Δ COx under NIV + HOx were significantly (P<0·01) correlated with improvements in Δ Q(T) (r = 0·82) and Δ stroke volume (r = 0·87). There was, however, no significant correlation between enhancement in these physiological responses with changes in peak work rate with NIV + HOx (P>0·05). CONCLUSIONS: NIV added benefit to HOx in improving central haemodynamics and COx in O(2) 'desaturators' with COPD. The clinical relevance of such beneficial effects on exercise tolerance, however, remains to be demonstrated.

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure.

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O(2)) delivery (Qo(2mv)) to O(2) uptake (Vo(2)) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo(2mv)-to-O(2) utilization matching and Vo(2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo(2), fractional O(2)extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo(2) kinetics (P < 0.05). Active treatment, however, failed to accelerate CO dynamics (P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo(2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular Qo(2mv)-to-Vo(2) matching with beneficial effects on Vo(2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.

Heart rate recovery in pulmonary arterial hypertension: relationship with exercise capacity and prognosis.

BACKGROUND: Delayed postexercise heart rate recovery (HRR) has been associated with disability and poor prognosis in chronic cardiopulmonary diseases. The usefulness of HRR to predict exercise impairment and mortality in patients with pulmonary arterial hypertension (PAH), however, remains largely unexplored. METHODS: Seventy-two patients with PAH of varied etiology (New York Heart Association classes I-IV) and 21 age- and gender-matched controls underwent a maximal incremental cardiopulmonary exercise test (CPET), with heart rate being recorded up to the fifth minute of recovery. RESULTS: Heart rate recovery was consistently lower in the patients compared with the controls (P < .05). The best cutoff for HRR in 1 minute (HRR(1 min)) to discriminate the patients from the controls was 18 beats. Compared with patients with HRR(1 min) ≤ 18 (n = 40), those with HRR(1 min) >18 (n = 32) had better New York Heart Association scores, resting hemodynamics and 6-minute walking distance. In fact, HRR(1 min) >18 was associated with a range of maximal and submaximal CPET variables indicative of less severe exercise impairment (P < .05). The single independent predictor of HRR(1 min) ≤ 18 was the 6-minute walking distance (odds ratio [95% CI] 0.99 [0.98-1.00], P < .05). On a multiple regression analysis that considered only CPET-independent variables, HRR(1 min) ≤ 18 was the single predictor of mortality (hazard ratio [95% CI] 1.19 [1.03-1.37], P < .05). CONCLUSIONS: Preserved HRR(1 min) (>18 beats) is associated with less impaired responses to incremental exercise in patients with PAH. Conversely, a delayed HRR(1 min) response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated (and costlier) analyses provided by a full CPET are not available.

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy.

BACKGROUND: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O(2) content (CaO(2)). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long-term O(2) therapy but present with exercise-induced hypoxaemia and (ii) improve with hyperoxia (FIO(2) = 0·4) in this specific sub-population. METHODS: A total of 20 non-hypercapnic men (FEV(1) = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold-changes from unloaded exercise in O(2)Hb) being determined by near-infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO(2)), and impedance cardiography estimated changes in cardiac output (ΔQT). RESULTS: Peak work rate and ΔCOx in normoxia were lower in eight O(2) 'desaturators' compared with 12 'non-desaturators' (P < 0·05). Area under ΔCOx during sub-maximal exercise was closely related to SpO(2) decrements in 'desaturators' (r = 0·92, P < 0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P < 0·05). Despite a trend to lower sub-maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for 'non-desaturators' and 'desaturators', respectively; P < 0·05). CONCLUSIONS: ΔCOx was impaired in non-hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO(2) rather than improved central haemodynamics. This indicates that O(2) supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O(2) therapy.

Patients admitted to the ICU for acute exacerbation of COPD: two-year mortality and functional status.

OBJECTIVE: To assess ICU patients with COPD, in terms of in-hospital characteristics, two-year mortality and two-year functional status of survivors. METHODS: A prospective cohort study involving patients with acute exacerbation of COPD admitted to the ICUs of two hospitals in the city of Porto Alegre, Brazil, between July of 2005 and July of 2006. At two years after discharge, survivors were interviewed by telephone in order to determine Karnofsky scores and scores on a scale regarding activities of daily living (ADL). RESULTS: The sample comprised 231 patients. In-hospital mortality was 37.7%, and two-year post-discharge mortality was 30.3%. Of the 74 survivors, 66 were interviewed (89%). The mean age at ICU admission was 74 ± 10 years, and the mean Acute Physiology and Chronic Health Evaluation II score was 18 ± 7. Two or more comorbidities were present in 87.8% of the patients. Of the 66 interviewees, 57 (86.3%) lived at home, 58 (87.8%) were self-sufficient, 12 (18.1%) required oxygen therapy, and 4 (6.1%) still required ventilatory support. There was a significant reduction in the quality of life and autonomy of the survivors, as evidenced by the Karnofsky scores (85 ± 9 vs. 79 ± 11, p = 0.03) and ADL scale scores (29 ± 5 vs. 25 ± 7; p = 0.01), respectively. CONCLUSIONS: In this patient sample, two-year mortality was quite high. Although there was a noticeable reduction in the functional status of the survivors, they remained self-sufficient.

Exacerbação aguda da DPOC: mortalidade e estado funcional dois anos após a alta da UTI / Patients admitted to the ICU for acute exacerbation of COPD: two-year mortality and functional status

OBJETIVO: Determinar a taxa de mortalidade de pacientes com DPOC e avaliar o estado funcional dos sobreviventes dois anos após a alta da UTI. MÉTODOS: Estudo de coorte prospectiva realizada nas UTIs de dois hospitais na cidade de Porto Alegre (RS) com pacientes com exacerbação aguda de DPOC e internados em UTI entre julho de 2005 e julho de 2006. Dois anos após a alta, os sobreviventes foram entrevistados via telefone. Os dados obtidos foram utilizados na determinação dos escores da escala de Karnofsky e de uma escala de atividades de vida diária (AVD). RESULTADOS: Foram incluídos 231 pacientes. A mortalidade hospitalar foi de 37,7 por cento e a mortalidade extra-hospitalar foi de 30,3 por cento. Dos 74 sobreviventes, foram entrevistados 66 (89 por cento). A média de idade dos pacientes no momento da internação na UTI era de 74 ± 10 anos e a do escore Acute Physiology and Chronic Health Evaluation II era de 18 ± 7. Tinham duas ou mais comorbidades 87,8 por cento dos pacientes. Dos 66 entrevistados, 57 (86,3 por cento) viviam em suas casas, 58 (87,8 por cento) eram capazes de realizar seu autocuidado, 12 (18,1 por cento) utilizavam oxigenoterapia, e 4 (6,1 por cento) necessitavam suporte ventilatório. Houve uma significante redução na qualidade de vida e na autonomia, segundo os escores da escala de Karnofsky (85 ± 9 vs. 79 ± 11; p = 0,03) e de AVD (29 ± 5 vs. 25 ± 7; p = 0,01), respectivamente. CONCLUSÕES: A mortalidade desta amostra de pacientes foi muito elevada nos primeiros dois anos. Embora houvesse evidente redução do estado funcional dos sobreviventes, os mesmos preservaram a capacidade de realizar seu autocuidado.

OBJECTIVE: To assess ICU patients with COPD, in terms of in-hospital characteristics, two-year mortality and two-year functional status of survivors. METHODS: A prospective cohort study involving patients with acute exacerbation of COPD admitted to the ICUs of two hospitals in the city of Porto Alegre, Brazil, between July of 2005 and July of 2006. At two years after discharge, survivors were interviewed by telephone in order to determine Karnofsky scores and scores on a scale regarding activities of daily living (ADL). RESULTS: The sample comprised 231 patients. In-hospital mortality was 37.7 percent, and two-year post-discharge mortality was 30.3 percent. Of the 74 survivors, 66 were interviewed (89 percent). The mean age at ICU admission was 74 ± 10 years, and the mean Acute Physiology and Chronic Health Evaluation II score was 18 ± 7. Two or more comorbidities were present in 87.8 percent of the patients. Of the 66 interviewees, 57 (86.3 percent) lived at home, 58 (87.8 percent) were self-sufficient, 12 (18.1 percent) required oxygen therapy, and 4 (6.1 percent) still required ventilatory support. There was a significant reduction in the quality of life and autonomy of the survivors, as evidenced by the Karnofsky scores (85 ± 9 vs. 79 ± 11, p = 0.03) and ADL scale scores (29 ± 5 vs. 25 ± 7; p = 0.01), respectively. CONCLUSIONS: In this patient sample, two-year mortality was quite high. Although there was a noticeable reduction in the functional status of the survivors, they remained self-sufficient.