Sleep disorders in chronic kidney disease.

Sleep disorders are highly prevalent in chronic kidney disease (CKD) but are often under-recognized. Restless legs syndrome, which is common in CKD owing to issues with dopamine metabolism and is exacerbated by iron deficiency and uraemia, can lead to poor sleep quality and increased daytime fatigue. Insomnia is also prevalent in CKD, particularly in patients requiring dialysis, with increased sleep latency and sleep fragmentation being reported. The cause of insomnia in CKD is multifactorial - poor sleep habits and frequent napping during dialysis, uraemia, medications and mood disorders have all been suggested as potential contributing factors. Sleep apnoea and CKD are also now recognized as having a bi-directional relationship. Sleep apnoea is a risk factor for accelerated progression of CKD, and fluid overload, which is associated with kidney failure, can lead to both obstructive and central sleep apnoea. The presence of obstructive sleep apnoea in CKD can exacerbate the already heightened cardiovascular morbidity and mortality in these patients, as well as leading to daytime fatigue and reduced quality of life. Increased awareness, timely diagnosis and appropriate therapeutic interventions are essential to reduce the negative impact of sleep disorders in patients with kidney disease.

Obstructive sleep apnea in the patient with atrial fibrillation: current knowledge and remaining uncertainties.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with atrial fibrillation and plays a causal role for OSA in the pathogenesis of atrial fibrillation. The presence of OSA in atrial fibrillation is associated with increased symptom burden and increased risk of hospitalizations. Furthermore, untreated OSA is associated with an increased risk of atrial fibrillation recurrence post ablation or cardioversion, and observational studies suggest that continuous positive airway pressure (CPAP) therapy can attenuate this risk. This review describes our current understanding of the relationship between OSA and atrial fibrillation with an emphasis on emerging evidence. RECENT FINDINGS: Recent studies have identified novel screening questionnaires, which may be superior to traditional questionnaires in identifying OSA in atrial fibrillation populations. Significant night-to-night variability in OSA severity has been shown in atrial fibrillation patients, which has implications for diagnostic testing. While several small, randomized control trials (RCTs) have not shown CPAP therapy to be effective in reducing atrial fibrillation burden, one RCT did show CPAP can attenuate the atrial substrate with implications for long-term outcomes. SUMMARY: Further RCTs, appropriately powered, and focused on well defined cohorts, are required to guide management decisions regarding screening and treatment of OSA in atrial fibrillation populations.

Impact of the COVID-19 pandemic on diagnosis of sleep apnea: an observational study of a hybrid virtual care clinical pathway.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been a reduction in patient uptake of in-person care, likely in part, due to patients' fear of contracting COVID infection. We aimed to examine changes in the proportion of patients assessed in a sleep clinic who subsequently underwent in-lab polysomnography before and during the pandemic. A retrospective study was conducted, comparing the periods September 2018-April 2019 (pre-pandemic) and September 2020-April 2021 (pandemic). Among the patients who were referred to an ambulatory sleep clinic in Toronto, Ontario for assessment of possible sleep apnea, the number of patients who underwent diagnostic PSG within 90 days from the first consultation with a physician was analyzed. Significantly lower number of patients underwent PSG in the pandemic than the pre-pandemic period [122/229 patients (53.3%) vs. 169/208 patients (81.3%), p < 0.001]. Older age and having a consultation in the months of full-blown pandemic, which was defined as month with its average of newly confirmed COVID-19 positive cases in Ontario > 1000 cases/day, were associated with declining PSG in the pandemic period. Among patients who underwent PSG, sleep apnea was found in 114/169 (67.5%) and 85/122 (69.7%) patients in the pre-pandemic and the pandemic period, respectively (p = 0.69). During the pandemic, there was a dramatic reduction in uptake of in-lab PSG. It is very likely that a significant proportion of patients in this cohort had sleep apnea that went undiagnosed with significant implications for health outcomes.

Prevalence of elevated hemoglobin and hematocrit levels in patients with obstructive sleep apnea and the impact of treatment with continuous positive airway pressure: a meta-analysis.

OBJECTIVES: Obstructive sleep apnea (OSA) is reported to be a cause of secondary polycythemia. The present study (i) reviewed the literature reporting the prevalence of secondary polycythemia in patients with OSA and (ii) determined the effect of continuous positive airway pressure (CPAP) therapy on hemoglobin and hematocrit levels in patients with OSA. METHODS: We searched MEDLINE, Embase and Cochrane for studies of adult patients with OSA that reported hemoglobin and/or hematocrit levels. We performed summary estimates of (i) polycythemia prevalence and a subgroup analysis according to OSA severity, and (ii) change in hemoglobin and hematocrit levels following treatment with CPAP. RESULTS: Synthesis of seven studies including 3,654 patients revealed an overall polycythemia prevalence of 2% (95% CI 1-4%); 2% (95% CI 1-3%) in mild-to moderate and 6 % (95% CI 3-12%) in severe OSA. In the pooled analysis of ten single-arm trials including 434 patients, CPAP treatment reduced hemoglobin by 3.76 g/L (95% CI -4.73 to -2.80 g/L). Similarly, pooled analysis of ten single-arm trials including 356 patients without baseline polycythemia showed that CPAP treatment reduced hematocrit by 1.1% (95% CI -1.4 to -0.9%). CONCLUSION: Our pooled analysis supports an increased prevalence of secondary polycythemia in OSA. This estimated prevalence is likely underestimated due to the change in the polycythemia diagnostic criteria in 2016. Future randomized controlled trials are needed to evaluate the effect of CPAP in patients with baseline polycythemia. HIGHLIGHTS: Pooled analysis shows OSA is associated with an increased prevalence of secondary polycythemiaPrevalence of polycythemia is greater in severe OSACPAP treatment for OSA reduces both the hemoglobin and hematocrit.

Quality of virtual care for ambulatory care sensitive conditions: Patient and provider experiences.

BACKGROUND: The COVID-19 pandemic and the need for physical distancing has led to rapid uptake of virtual visits to deliver ambulatory health care. Despite widespread adoption, there has been limited evaluation of the quality of care being delivered through virtual modalities for ambulatory care sensitive conditions (ACSCs). OBJECTIVE: To characterize patients' and providers' experiences with the quality and sustainability of virtual care for ACSCs. DESIGN: This was a multi-method study utilizing quantitative and qualitative data from patient surveys, provider surveys, and provider focus groups at a large academic ambulatory care hospital between May 2020 and June 2021. We included patients and providers utilizing telephone or video visits for the following ACSCs: hypertension, angina, heart failure, atrial fibrillation, diabetes, chronic obstructive pulmonary disease, or asthma. MAIN MEASURES: Quantitative and qualitative patient and provider survey responses were mapped to the Six Domains of Healthcare Quality framework. Provider focus groups were coded to identify themes within each quality domain. KEY RESULTS: Surveys were completed by 110/352 (31%) consenting patients and 20/61 (33%) providers. 5 provider focus groups were held with 14 participants. Patients found virtual visits to be generally more convenient than in-person visits for ACSCs. The perceived effectiveness of virtual visits was dependent on the clinical and social complexity of individual encounters. Respondents reported difficulty forming effective patient-provider relationships in the virtual environment. Patients and providers felt that virtual care has potential to both alleviate and exacerbate structural barriers to equitable access to care. CONCLUSIONS: In a large academic ambulatory care hospital, patients and providers experienced the quality of virtual visits for the management of ACSCs to be variable depending on the biopsychosocial complexity of the individual encounter. Our findings in each quality domain highlight key considerations for patients, providers and institutions to uphold the quality of virtual care for ACSCs.

Outpatient visit trends for internal medicine ambulatory care sensitive conditions after the COVID-19 pandemic: a time-series analysis.

BACKGROUND: The COVID-19 pandemic led to a dramatic shift in the delivery of outpatient medicine with reduced in-person visits and a transition to predominantly virtual visits. We sought to understand trends in visit patterns for ambulatory care sensitive conditions (ACSCs) commonly seen in internal medicine clinics. METHODS: We included adult outpatients seen for an ACSC between March 15th, 2017 and March 14th, 2021 at a single-centre in Ontario, Canada. Monthly visits were assessed by visit type (new consultation, follow-up), diagnosis, and clinic. Time series analyses compared visit volumes pre- and post-pandemic. Proportion of virtual visits were compared before and during the pandemic. Patient and visit factors were compared between in-person and virtual visits. RESULTS: 8274 patients with 34,021 visits were included. Monthly visits increased by 15% during the pandemic (p <  0.0001). New consultations decreased by 10% (p = 0.0053) but follow-up visits increased by 21% (p <  0.0001). Monthly heart failure visits increased by 43% (p <  0.0001) whereas atrial fibrillation visits decreased. Pre- pandemic, < 1% of visits were virtual compared to 82% during the pandemic (p <  0.0001). Less than half of heart failure visits were virtual whereas > 95% of diabetes visits were virtual. CONCLUSIONS: We found a significant increase in overall visits to internal medicine clinics driven by increased volumes of follow-up visits, which more than offset decreased new consultations. There was variability in visit trends and uptake of virtual care by visit diagnosis, which may indicate challenges with delivery of virtual care for certain conditions.

Obstructive sleep apnea and nocturnal attacks of paroxysmal atrial fibrillation.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly seen in patients with atrial fibrillation (AF), but it is unclear to what extent this relationship is one of causation or association. We examined a cohort of patients with paroxysmal AF to determine whether the presence of OSA (apnea-hypopnea index ≥ 15 events/h) affects the time of onset of symptomatic AF episodes. METHODS: Patients with a recent emergency department visit for a symptomatic episode of paroxysmal AF were recruited from an AF clinic. The time of onset of the AF attack was classified as occurring in "sleeping hours" or "waking hours" based on direct history from the patient and emergency department visit documentation. RESULTS: Of 152 patients with paroxysmal AF, 67 underwent polysomnography; 1 (1.5%) had central sleep apnea, 46 (68.7%) had mild or no OSA, and 20 (29.8%) had OSA. In the OSA group, 14/20 (70.0%) had their symptomatic AF attack during sleeping hours compared to 12/46 (26.1%) in the mild or no OSA group (P = .001). Compared with those who had a paroxysmal AF attack during waking hours, and adjusting for confounders, those who had a paroxysmal AF attack during sleeping hours had almost 6 times the odds of having OSA (odds ratio, 5.53; P = .007). CONCLUSIONS: Compared to patients with paroxysmal AF with mild or no OSA, those with OSA were far more likely to have a symptomatic AF attack during sleeping hours, supporting a causal role for OSA in the pathogenesis of AF in this population. These findings strongly suggest that patients who have nocturnal AF attacks should be evaluated for OSA. CITATION: Lin C-H, Timofeeva M, O'Brien T, Lyons OD. Obstructive sleep apnea and nocturnal attacks of paroxysmal atrial fibrillation. J Clin Sleep Med. 2022;18(5):1279-1286.

Changes in pulmonary restrictive parameters by intensive home hemodialysis: a case report.

BACKGROUND: Patients with End-Stage Renal Disease (ESRD) are at an increased risk for restrictive lung disease due to accumulation of uremic toxins and volume overload. Hemodialysis is the preferred treatment for improving lung function in dialysis patients. However, the effects of fluid removal and solute clearance by hemodialysis on lung function remain unclear. CASE PRESENTATION: We report a case of restrictive lung disorder in a hemodialysis patient, who showed improvement in both clinical and spirometric lung function after initiation of intensive home hemodialysis (32 h per week). CONCLUSION: Intensive hemodialysis augments fluid removal and solute clearance, which in turn may improve restrictive lung function.

Effect of Ultrafiltration on Sleep Apnea and Cardiac Function in End-Stage Renal Disease.

RATIONALE: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. METHODS: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. -Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no-sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. CONCLUSIONS: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect.

Sleep Apnea and Chronic Kidney Disease: A State-of-the-Art Review.

Patients with chronic kidney disease have increased morbidity and mortality, mainly due to cardiovascular disease. Compared with the general population, patients with chronic kidney disease have an increased prevalence of both OSA and central sleep apnea, and the presence of sleep apnea in this population has been associated with an increased risk of cardiovascular events and mortality. Although OSA can lead to an increase in the rate of kidney function decline, there is also evidence that the presence of end-stage renal disease can lead to worsening of sleep apnea, indicating a bidirectional relation between sleep apnea and chronic kidney disease. The objective of this review was to describe the epidemiology of sleep apnea in chronic kidney disease, understand the pathophysiological mechanisms by which OSA can lead to progression of chronic kidney disease, and consider the role of treatment with CPAP in this regard. The review also explores the pathophysiological mechanism by which end-stage renal disease can lead to sleep apnea and considers how intensification of renal replacement therapy or extra fluid removal by ultrafiltration may attenuate the degree of sleep apnea severity in this population.

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure.

STUDY OBJECTIVES: In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), stroke volume (SV) falls during hyperpnea of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). We have identified two distinct patterns of hyperpnea: positive, in which end-expiratory lung volume (EELV) remains at or above functional residual capacity (FRC), and negative, in which EELV falls below FRC. The increase in expiratory intrathoracic pressure generated by the latter should have effects on the heart analogous to external chest compression. To test the hypotheses that in HFrEF patients, CSR-CSA with the negative pattern has an auto-resuscitation effect such that compared with the positive pattern, it is associated with a smaller fall in SV and a smaller increase in cardiac workload (product of heart rate and systolic blood pressure). METHODS: In 15 consecutive HFrEF patients with CSR-CSA during polysomnography, hemodynamic data derived from digital photoplethysmography during positive and negative hyperpneas were compared. RESULTS: Compared to the positive, negative hyperpneas were accompanied by reductions in the maximum and mean relative fall in SV of 30% (p = 0.002) and 10% (p = 0.031), respectively, and by reductions in the degree of increases in heart rate and rate pressure product during hyperpnea of 46% (p < 0.001) and 13% (p = 0.007), respectively. CONCLUSIONS: Our findings suggest the novel concept that the negative pattern of CSR-CSA may constitute a form of auto-resuscitation that acts as a compensatory mechanism to maintain SV in patients with severe HF.

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk, mediated through pathophysiological mechanisms that include intermittent hypoxia, excessive sympathetic nervous activation and exaggerated swings in negative intrathoracic pressure (2, 3). While it has previously been established from randomized controlled trials (RCT) that treatment of OSA with continuous positive airway pressure (CPAP) reduces blood pressure, with the most marked effects seen in drug-resistant hypertension (4), data to support a role for CPAP therapy to reduce cardiovascular mortality comes largely from observational studies (5, 6). To address this, McEvoy et al. conducted a multicentre, randomized, parallel-group trial to evaluate the efficacy of CPAP in reducing cardiovascular mortality in patients with moderate-to-severe OSA (oxygen desaturation index ≥ 12) and a history of coronary artery disease or cerebrovascular disease , who were mildlyor non-sleepy (Epworth Sleepiness Scale less or equal to 15) (1). Patients were excluded if they had severe hypoxia (oxygen saturation <80%) or if they had a Cheyne-Stokes respiration pattern. The primary endpoint included a composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for unstable angina, heart failure or transient ischemic attack. 2687 subjects were randomized to either "usual care" (n=1341) or "usual care" plus CPAP (n=1346). After a mean follow up of 3.7 years, there was no significant difference in the occurrence of the primary endpoint between the groups (hazard ratio (HR) with CPAP added, 1.10; 95% confidence interval (CI) 0.91 to 1.32; p = 0.34). Mean duration of adherence to CPAP therapy was 3.3 hours per night. A one-to-one propensity score analysis performed to compare 561 adherent patients (CPAP used for more than 4h/night) and 561 patients in the usual care group, showed no significant difference in the primary endpoint (HR 0.80; 95% CI : 0.60-1.07; p = 0.13), but a lower risk of cerebrovascular events among the CPAP group (HR 0.52; 95% CI : 0.30-0.90; p = 0.02). The results of this relatively large RCT are clearly an important addition to the current knowledge base and certainly, on the basis of this one study, CPAP cannot be recommended as a therapy in moderate to severe OSA patients with established cardiovascular disease if the sole purpose is to reduce cardiovascular complications. This trial affirms the results of other studies in highlighting the uncertain efficacy of CPAP therapy in the reduction of cardiovascular risk in non-symptomatic OSA patients over the short to medium term, and also highlights the challenge of CPAP adherence (7, 8). However, it is important that these results are not extrapolated to those OSA patients who do have excessive daytime sleepiness or significant hypoxia given these patients were excluded from the study. (AU)

Obstructive sleep apnea and chronic kidney disease.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review describes our current understanding of the bi-directional relationship between OSA and CKD. RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia may lead to worsening of kidney function. One potential mechanism is activation of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP therapy. In ESRD, fluid overload plays an important role in the pathogenesis of OSA and fluid removal by ultrafiltration leads to marked improvements in sleep apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney function. In patients with ESRD, fluid overload plays an important role in the pathogenesis of OSA.

Distinct Patterns of Hyperpnea During Cheyne-Stokes Respiration: Implication for Cardiac Function in Patients With Heart Failure.

STUDY OBJECTIVES: In heart failure (HF), we observed two patterns of hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive pattern where end-expiratory lung volume remains at or above functional residual capacity, and a negative pattern where it falls below functional residual capacity. We hypothesized the negative pattern is associated with worse HF. METHODS: Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea, apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and left ventricular ejection fraction (LVEF) were assessed. RESULTS: Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a negative hyperpnea pattern. There was no difference in age, body mass index, and apnea-hypopnea index between groups. Patients with a negative pattern had longer hyperpnea time (39.5 ± 6.4 versus 25.8 ± 5.9 seconds, P < .01), longer cycle time (67.8 ± 15.9 versus 51.7 ± 9.9 seconds, P < .01), higher NT-proBNP concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York Heart Association class (P = .02) than those with a positive pattern. LFCT and LVEF did not differ between groups. CONCLUSIONS: Patients with HF and a negative CSR-CSA pattern have evidence of worse cardiac function than those with a positive pattern. Greater positive expiratory pressure during hyperpnea is likely generated during the negative pattern and might support stroke volume in patients with worse cardiac function. COMMENTARY: A commentary on this article appears in this issue on page 1227. CLINICAL TRIAL REGISTRATION: The trial is registered with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and Clinical Trials (www.clinicaltrials.gov; NCT01128816).

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

INTRODUCTION: Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. AIM: ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. METHODS: ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. CONCLUSION: The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality.

The effect of fluid overload on sleep apnoea severity in haemodialysis patients.

As in heart failure, obstructive and central sleep apnoea (OSA and CSA, respectively) are common in end-stage renal disease. Fluid overload characterises end-stage renal disease and heart failure, and in heart failure plays a role in the pathogenesis of OSA and CSA. We postulated that in end-stage renal disease patients, those with sleep apnoea would have greater fluid volume overload than those without.End-stage renal disease patients on thrice-weekly haemodialysis underwent overnight polysomnography on a nondialysis day to determine their apnoea-hypopnoea index (AHI). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance.28 patients had an AHI ≥15 (sleep apnoea group; OSA:CSA 21:7) and 12 had an AHI <15 (no sleep apnoea group). Total body extracellular fluid volume was 2.6 L greater in the sleep apnoea group than in the no sleep apnoea group (p=0.006). Neck, thorax, and leg fluid volumes were also greater in the sleep apnoea than the no sleep apnoea group (p<0.05), despite no difference in body mass index (p=0.165).These findings support a role for fluid overload in the pathogenesis of both OSA and CSA in end-stage renal disease.

Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma.

In asthma, supine posture and sleep increase intrathoracic airway narrowing. When humans are supine, because of gravity fluid moves out of the legs and accumulates in the thorax. We hypothesized that fluid shifting out of the legs into the thorax contributes to the intrathoracic airway narrowing in asthma. Healthy and asthmatic subjects sat for 30 min and then lay supine for 30 min. To simulate overnight fluid shift, supine subjects were randomized to receive increased fluid shift out of the legs with lower body positive pressure (LBPP, 10-30 min) or none (control) and crossed over. With forced oscillation at 5 Hz, respiratory resistance (R5) and reactance (X5, reflecting respiratory stiffness) and with bioelectrical impedance, leg and thoracic fluid volumes (LFV, TFV) were measured while subjects were seated and supine (0 min, 30 min). In 17 healthy subjects (age: 51.8 ± 10.9 yr, FEV1/FVC z score: -0.4 ± 1.1), changes in R5 and X5 were similar in both study arms (P > 0.05). In 15 asthmatic subjects (58.5 ± 9.8 yr, -2.1 ± 1.3), R5 and X5 increased in both arms (ΔR5: 0.6 ± 0.9 vs. 1.4 ± 0.8 cmH2O·l-1·s-1, ΔX5: 0.3 ± 0.7 vs. 1.1 ± 0.9 cmH2O·l-1·s-1). The increases in R5 and X5 were 2.3 and 3.7 times larger with LBPP than control, however (P = 0.008, P = 0.006). The main predictor of increases in R5 with LBPP was increases in TFV (r = 0.73, P = 0.002). In asthmatic subjects, the magnitude of increases in X5 with LBPP was comparable to that with posture change from sitting to supine (1.1 ± 0.9 vs. 1.4 ± 0.9 cmH2O·l-1·s-1, P = 0.32). We conclude that in asthmatic subjects fluid shifting from the legs to the thorax while supine contributed to increases in the respiratory resistance and stiffness.NEW & NOTEWORTHY In supine asthmatic subjects, application of positive pressure to the lower body caused appreciable increases in respiratory system resistance and stiffness. Moreover, these changes in respiratory mechanics correlated positively with increase in thoracic fluid volume. These findings suggest that fluid shifts from the lower body to the thorax may contribute to overnight intrathoracic airway narrowing and worsening of asthma symptoms.