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Background: Obesity hypoventilation syndrome (OHS) is associated with high morbidity and mortality. There is a paucity of data on whether there are gender differences in outcomes. Research Question Is female gender associated with worse outcomes in ambulatory and hospitalized patients with OHS?, Study Design and Methods: We performed post hoc analyses on two separate OHS cohorts: 1) stable ambulatory patients from the two Pickwick randomized controlled trials and 2) hospitalized patients with acute-on-chronic hypercapnic respiratory failure from a retrospective international cohort. We first conducted bivariate analyses of baseline characteristics and therapeutics between genders. Variables of interest from these analyses were then grouped into linear mixed effects models, Cox proportional hazards models or logistic regression models to assess the association of gender on various clinical outcomes., Results: The ambulatory prospective cohort included 300 patients (64% female) and the hospitalized retrospective cohort included 1,162 patients (58% female). For both cohorts, women were significantly older and more obese than men. Compared to men, baseline PaCO 2 was similar in ambulatory patients, but higher in hospitalized women. In the ambulatory cohort, in unadjusted analysis, women had increased risk of emergency room visits. However, gender was not associated with the composite outcome of emergency room visit, hospitalization, or all-cause mortality in the fully adjusted model. In the hospitalized cohort, positive airway pressure (PAP) prescription was less prevalent in women upon discharge. In unadjusted analysis, hospitalized women had a higher mortality at 3, 6, and 12 months after hospital discharge compared to men. However, after adjusting for age, gender was not associated with mortality., Interpretation: Although the diagnosis of OHS is established at a more advanced age in women, gender is not independently associated with worse clinical outcomes after adjusting for age. Future studies are needed to examine gender-related health disparities in diagnosis and treatment of OHS., (Copyright © 2024. Published by Elsevier Inc.)

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female sex as a significant risk factor. Increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EH ITSN ), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Herein, increased Xist expression was detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (EC PAH ) was studied in several lines of male EC PAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male EC PAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/XIST antisense RNA (Tsix) locus. Interestingly, Xist up-regulation in male EC PAH decreased the expression of Krueppel-like factor 2 (Klf2), via EH ITSN interaction with enhancer of zeste polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EH ITSN -triggered p38/ETS domain-containing protein Elk1/AP-1 transcription factor subunit (c-Fos) signaling is a pathologic mechanism central to EC PAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male EC PAH ., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The pathophysiological interplay between sleep-disordered breathing (SDB) and pulmonary hypertension (PH) is complex and can involve a variety of mechanisms by which SDB can worsen PH. These mechanistic pathways include wide swings in intrathoracic pressure while breathing against an occluded upper airway, intermittent and/or sustained hypoxemia, acute and/or chronic hypercapnia, and obesity. In this review, we discuss how the downstream consequences of SDB can adversely impact PH, the challenges in accurately diagnosing and classifying PH in the severely obese, and review the limited literature assessing the effect of treating obesity, obstructive sleep apnea, and obesity hypoventilation syndrome on PH., Competing Interests: Disclosure None of the authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a sex-biased disease with a poorly understood female prevalence. Emerging research suggests that nonhormonal factors, such as the XX or XY sex chromosome complement and sex bias in gene expression, may also lead to sex-based differences in PAH incidence, penetrance, and progression. Typically, one of females' two X chromosomes is epigenetically silenced to offer a gender-balanced gene expression. Recent data demonstrate that the long noncoding RNA X-inactive specific transcript, essential for X chromosome inactivation and dosage compensation of X-linked gene expression, shows elevated levels in female PAH lung specimens compared with controls. This molecular event leads to incomplete inactivation of the females' second X chromosome, abnormal expression of X-linked gene(s) involved in PAH pathophysiology, and a pulmonary artery endothelial cell (PAEC) proliferative phenotype. Moreover, the pathogenic proliferative p38 mitogen-activated protein kinase/ETS transcription factor ELK1 (Elk1)/cFos signaling is mechanistically linked to the sexually dimorphic proliferative response of PAECs in PAH. Apprehending the complicated relationship between long noncoding RNA X-inactive specific transcript and X-linked genes and how this relationship integrates into a sexually dimorphic proliferation of PAECs and PAH sex paradox remain challenging. We highlight herein new findings related to how the sex chromosome complement and sex-differentiated epigenetic mechanisms to control gene expression are decisive players in the sexual dimorphism of PAH. Pharmacologic interventions in the light of the newly elucidated mechanisms are discussed., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The existing coverage criteria for home noninvasive ventilation (NIV) do not recognize the diversity of hypoventilation syndromes and advances in technologies. This document summarizes the work of the hypoventilation syndromes Technical Expert Panel working group. The most pressing current coverage barriers identified were: (1) overreliance on arterial blood gases (particularly during sleep); (2) need to perform testing on prescribed oxygen; (3) requiring a sleep study to rule out OSA as the cause of sustained hypoxemia; (4) need for spirometry; (5) need to show bilevel positive airway pressure (BPAP) without a backup rate failure to qualify for BPAP spontaneous/timed; and (6) qualifying hospitalized patients for home NIV therapy at the time of discharge. Critical evidence support for changes to current policies includes randomized controlled trial evidence and clinical practice guidelines. To decrease morbidity and mortality by achieving timely access to NIV for patients with hypoventilation, particularly those with obesity hypoventilation syndrome, we make the following key suggestions: (1) given the significant technological advances, we advise acceptance of surrogate noninvasive end-tidal and transcutaneous Pco 2 and venous blood gases in lieu of arterial blood gases; (2) not requiring Pco 2 measures while on prescribed oxygen; (3) not requiring a sleep study to avoid delays in care in patients being discharged from the hospital; (4) remove spirometry as a requirement; and (5) not requiring BPAP without a backup rate failure to approve BPAP spontaneous/timed. The overarching goal of the Technical Expert Panel is to establish pathways that improve clinicians' management capability to provide Medicare beneficiaries access to appropriate home NIV therapy. Adoption of these proposed suggestions would result in the right device, for the right type of patient with hypoventilation syndromes, at the right time., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Because of the prevalence of extreme obesity in the United States, there has been an increase in prevalence of obesity hypoventilation syndrome (OHS). There is limited information on the characteristics and pattern of positive airway pressure (PAP) adherence in patients with OHS compared with eucapnic patients with obstructive sleep apnea (OSA). This article discusses in detail the impact of PAP therapy on outcomes in patients with OHS, compares adherence between continuous PAP and noninvasive ventilation in OHS, and compares PAP adherence in patients with OHS to patients with moderate to severe OSA enrolled in clinical trials designed to improve CPAP adherence., Competing Interests: Disclosure The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: OSA, a common comorbidity in interstitial lung disease (ILD), could contribute to a worsened course if untreated. It is unclear if adherence to CPAP therapy improves outcomes., Research Question: Does adherence to CPAP therapy improve outcomes in patients with concurrent interstitial lung disease and OSA?, Study Design and Methods: We conducted a 10-year retrospective observational multicenter cohort study, assessing adult patients with ILD who had undergone polysomnography. Subjects were categorized based on OSA severity into no/mild OSA (apnea-hypopnea index score < 15) or moderate/severe OSA (apnea-hypopnea index score ≥ 15). All subjects prescribed and adherent to CPAP were deemed to have treated OSA. Cox regression models were used to examine the association of OSA severity and CPAP adherence with all-cause mortality risk and progression-free survival (PFS)., Results: Of 160 subjects that met inclusion criteria, 131 had OSA and were prescribed CPAP. Sixty-six patients (41%) had no/mild untreated OSA, 51 (32%) had moderate/severe untreated OSA, and 43 (27%) had treated OSA. Subjects with no/mild untreated OSA did not differ from those with moderate/severe untreated OSA in mean survival time (127 ± 56 vs 138 ± 93 months, respectively; P = .61) and crude mortality rate (2.9 per 100 person-years vs 2.9 per 100 person-years, respectively; P = .60). Adherence to CPAP was not associated with improvement in all-cause mortality risk (hazard ratio [HR], 1.1; 95% CI, 0.4-2.9; P = .79) or PFS (HR, 0.9; 95% CI, 0.5-1.5; P = .66) compared with those that were nonadherent or untreated. Among subjects requiring supplemental oxygen, those adherent to CPAP had improved PFS (HR, 0.3; 95% CI, 0.1-0.9; P = .03) compared with nonadherent or untreated subjects., Interpretation: Neither OSA severity nor adherence to CPAP was associated with improved outcomes in patients with ILD except those requiring supplemental oxygen., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype., Research Question: Is NIV effective in OHS without severe OSA phenotype?, Study Design and Methods: In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups., Results: Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco 2 , pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms., Interpretation: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS., Trial Registry: ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities., Methods: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976., Findings: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups., Interpretation: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available., Funding: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In the surgical setting, OSA is associated with an increased risk of postoperative complications. At present, risk stratification using OSA-associated parameters derived from polysomnography (PSG) or overnight oximetry to predict postoperative complications has not been established. The objective of this narrative review is to evaluate the literature to determine the association between parameters extracted from in-laboratory PSG, portable PSG, or overnight oximetry and postoperative adverse events. We obtained pertinent articles from Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and Embase (2008 to December 2017). The search included studies with adult patients undergoing surgery who had OSA diagnosed with portable PSG, in-laboratory PSG, or overnight oximetry that reported on specific sleep parameters and at least one adverse outcome. The search was restricted to English-language articles. The search yielded 1,810 articles, of which 21 were included in the review. Preoperative apnea-hypopnea index (AHI) and measurements of nocturnal hypoxemia such as oxygen desaturation index (ODI), cumulative sleep time percentage with oxyhemoglobin saturation (Spo 2 ) < 90% (CT90), minimum Spo 2 , mean Spo 2 , and longest apnea duration were associated with postoperative complications. OSA is associated with postoperative complications in the population undergoing surgery. Clinically and statistically significant associations between AHI and postoperative adverse events exists. Complications may be more likely to occur in the category of moderate to severe OSA (AHI ≥ 15). Other parameters from PSG or overnight oximetry such as ODI, CT90, mean and minimal Spo 2 , and longest apnea duration can be associated with postoperative complications and may provide additional value in risk stratification and minimization., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary medicine specialists find themselves responsible for the diagnosis and management of patients with sleep disorders. Despite the increasing prevalence of many of these conditions, many sleep medicine fellowship training slots go unfilled, leading to a growing gap between the volume of patients seeking care for sleep abnormalities and the number of physicians formally trained to manage them. To address this need, we convened a multisociety panel to develop a list of curricular recommendations related to sleep medicine for pulmonary fellowship training programs., Methods: Surveys of pulmonary and pulmonary/critical care fellowship program directors and recent graduates of these programs were performed to assess the current state of sleep medicine education in pulmonary training, as well as the current scope of practice of pulmonary specialists. These data were used to inform a modified Delphi process focused on developing curricular recommendations relevant to sleep medicine., Results: Surveys confirmed that pulmonary medicine specialists are often responsible for the diagnosis and treatment of a number of sleep conditions, including several that are not traditionally considered related to respiratory medicine. Through five rounds of voting, the panel crafted a list of 52 curricular competencies relevant to sleep medicine for recommended inclusion in pulmonary training programs., Conclusions: Practicing pulmonary specialists require a broad knowledge of sleep medicine to provide appropriate care to patients they will be expected to manage. Training program directors may use the list of competencies as a framework to ensure adequate mastery of important content by graduating fellows., (Copyright © 2018 American College of Chest Physicians. All rights reserved.)

OSA is a chronic treatable sleep disorder and a frequent comorbidity in patients with type 2 diabetes. Cardinal features of OSA, including intermittent hypoxemia and sleep fragmentation, have been linked to abnormal glucose metabolism in laboratory-based experiments. OSA has also been linked to the development of incident type 2 diabetes. The relationship between OSA and type 2 diabetes may be bidirectional in nature given that diabetic neuropathy can affect central control of respiration and upper airway neural reflexes, promoting sleep-disordered breathing. Despite the strong association between OSA and type 2 diabetes, the effect of treatment with CPAP on markers of glucose metabolism has been conflicting. Variability with CPAP adherence may be one of the key factors behind these conflicting results. Finally, accumulating data suggest an association between OSA and type 1 diabetes as well as gestational diabetes. This review explores the role of OSA in the pathogenesis of type 2 diabetes, glucose metabolism dysregulation, and the impact of OSA treatment on glucose metabolism. The association between OSA and diabetic complications as well as gestational diabetes is also reviewed., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Obesity hypoventilation syndrome (OHS) is associated with a high burden of cardiovascular morbidity (CVM) and mortality. The majority of patients with OHS have concomitant OSA, but there is a paucity of data on the association between CVM and OSA severity in patients with OHS. The objective of our study was to assess the association between CVM and OSA severity in a large cohort of patients with OHS., Methods: In a cross-sectional analysis, we examined the association between OSA severity based on tertiles of oxygen desaturation index (ODI) and CVM in 302 patients with OHS. Logistic regression models were constructed to quantify the independent association between OSA severity and prevalent CVM after adjusting for various important confounders., Results: The prevalence of CVM decreased significantly with increasing severity of OSA based on ODI as a continuous variable or ODI tertiles. This inverse relationship between OSA severity and prevalence of CVM was seen in the highest ODI tertile and it persisted despite adjustment for multiple confounders. Chronic heart failure had the strongest negative association with the highest ODI tertile. No significant CVM risk change was observed between the first and second ODI tertiles. Patients in the highest ODI tertile were younger, predominantly male, more obese, more hypersomnolent, had worse nocturnal and daytime gas exchange, lower prevalence of hypertension, better exercise tolerance, and fewer days hospitalized than patients in the lowest ODI tertile., Conclusions: In patients with OHS, the highest OSA severity phenotype was associated with reduced risk of CVM. This finding should guide the design of future clinical trials assessing the impact of interventions aimed at decreasing cardiovascular morbidity and mortality in patients with OHS., Trial Registry: Clinicaltrial.gov; No.: NCT01405976; URL: www.clinicaltrials.gov., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: OSA is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first-line treatment for OSA, as well as for obesity hypoventilation syndrome (OHS), its most severe phenotype. However, the molecular and cellular mechanisms underlying OHS-induced morbidities and their response to PAP treatment remain unclear, and could be mediated, in part, by OSA-induced epigenetic changes., Methods: Blood was collected before starting PAP treatment (PRE group), as well as 6 weeks after PAP treatment (POST group) in 15 adult patients with OHS. DNA methylation profiles were studied by methylated DNA immunoprecipitation coupled to microarrays (MeDIP-chip) in six representative patients and further verified in a cohort of 15 patients by MeDIP-quantitative PCR., Results: We identified 1,847 regions showing significant differential DNA methylation (P < .001; model-based analysis of tiling arrays score, > 4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPARs). Single-locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR-responsive elements (PPAREs) of eight genes in the post-treatment samples (PRE/POST fold changes: ABCA1, 3.11; ABCG1, 1.72; CD36, 5.04; FABP4, 2.49; HMOX, 2.74; NOS2, 7.78; PEPCK, 9.27; and ADIPOQ, 1.73), suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPAR-γ complex and downstream gene expression., Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in patients with OHS who are responsive to PAP treatment., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

OSA is a commonly encountered comorbid condition in surgical patients. The risk of cardiopulmonary complications is increased by two to threefold with OSA. Among the different treatment options for OSA, CPAP is an efficacious modality. This review examines the evidence regarding the use of CPAP in the preoperative and postoperative periods in surgical patients with diagnosed and undiagnosed OSA., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The impact of OSA treatment with CPAP on percutaneous coronary intervention (PCI) outcomes remains largely unknown., Methods: Between 2002 and 2012, we identified 390 patients with OSA who had undergone PCI. OSA was diagnosed through in-laboratory sleep studies and defined by an apnea-hypopnea index ≥ 5 events/h. The cohort was divided into three groups: (1) moderate-severe OSA successfully treated with CPAP (n = 128), (2) untreated moderate-severe OSA (n = 167), and (3) untreated mild OSA (n = 95). Main outcomes included repeat revascularization, major adverse cardiac events (MACEs) (ie, death, nonfatal myocardial infarction, repeat revascularization), and major adverse cardiac or cerebrovascular events (MACCEs). The median follow-up period was 4.8 years (interquartile range, 3.0-7.1)., Results: The untreated moderate-severe OSA group had a higher incidence of repeat revascularization than the treated moderate-severe OSA group (25.1% vs 14.1%, P = .019). There were no differences in mortality (P = .64), MACE (P = .33), and MACCE (P = .76) among the groups. In multivariate analysis adjusted for potential confounders, untreated moderate-severe OSA was associated with increased risk of repeat revascularization (hazard ratio, 2.13; 95% CI, 1.19-3.81; P = .011)., Conclusions: Untreated moderate-severe OSA was independently associated with a significant increased risk of repeat revascularization after PCI. CPAP treatment reduced this risk.

Background: Systematic screening and treatment of sleep-disordered breathing (SDB) or obstructive sleep apnea (OSA) in presurgical patients would impose a significant cost burden; therefore, it is important to understand whether SDB is associated with worse postoperative outcomes. We sought to determine the impact of SDB on postoperative outcomes in patients undergoing four specific categories of elective surgery (orthopedic, prostate, abdominal, and cardiovascular). The primary outcomes were in-hospital death, total charges, and length of stay (LOS). Two secondary outcomes of interest were respiratory and cardiac complications., Methods: Data were obtained from the Nationwide Inpatient Sample database. Regression models were fitted to assess the independent association between SDB and the outcomes of interest., Results: The cohort included 1,058,710 hospitalized adult patients undergoing elective surgeries between 2004 and 2008. SDB was independently associated with decreased mortality in the orthopedic (OR, 0.65; 95% CI, 0.45-0.95; P = .03), abdominal (OR, 0.38; 95% CI, 0.22-0.65; P = .001), and cardiovascular surgery groups (OR, 0.54; 95% CI, 0.40-0.73; P &lt; .001) but had no impact on mortality in the prostate surgery group. SDB was independently associated with a small, but statistically significant increase in estimated mean LOS by 0.14 days (P &lt; .001) and estimated mean total charges by $860 (P &lt; .001) in the orthopedic surgery group but was not associated with increased LOS or total charges in the prostate surgery group. In the abdominal and cardiovascular surgery groups, SDB was associated with a significant decrease in adjusted mean LOS of 1.1 days and 0.35 days, respectively (P &lt; .001 for both groups), and adjusted mean total charges of $3,814 and $4,592, respectively (P &lt; .001 for both groups). SDB was independently associated with a significantly increased OR for emergent intubation and mechanical ventilation, noninvasive ventilation, and atrial fibrillation in all four surgical categories. Emergent intubation occurred significantly earlier in the postoperative course in patients with SDB. In the subgroup of patients requiring emergent intubation, LOS, total charges, pneumonias, and in-hospital death were significantly higher in those without SDB., Conclusions: In this large national study, despite the increased independent association of SDB with postoperative cardiopulmonary complications, the diagnosis of SDB was not independently associated with an increased rate of in-hospital death. SDB had a mixed impact on LOS and total charges by surgical category.

Background: Systemic symptoms are common in sarcoidosis and are associated with a decreased quality of life. Excessive daytime sleepiness (EDS) often is associated with obstructive sleep apnea (OSA) but may be a systemic symptom independently associated with sarcoidosis. The aim of this study was to assess the relationship between sarcoidosis and EDS., Methods: In a retrospective analysis, we used Epworth Sleepiness Scale scores to compare sleepiness in 62 patients with sarcoidosis with 1,005 adults without sarcoidosis referred for polysomnography for suspicion of OSA. Linear regression models controlled for covariates. In a subgroup analysis of patients with sarcoidosis, sleepiness scores and polysomnograms were compared between those with normal and those with abnormal pulmonary function based on total lung capacity., Results: EDS was more common in patients with sarcoidosis than in those without, and sarcoidosis remained an independent predictor of increased sleepiness after controlling for covariates. Compared with control patients referred for polysomnography, fewer patients with sarcoidosis had clinically significant OSA. However, among patients with sarcoidosis, OSA was more severe in those with abnormal lung function., Conclusions: Sarcoidosis is independently associated with EDS. Sleepiness may contribute to the morbidity of sarcoidosis and should be followed even after treating for potentially coexisting OSA or depression. Abnormal lung function in sarcoidosis may contribute to OSA, although the mechanisms for this are not known.

Background: The STOP-Bang questionnaire is a validated screening tool for the identification of surgical patients with obstructive sleep apnea (OSA). A STOP-Bang score ≥ 3 is highly sensitive but only moderately specific. Apnea/hypopnea during sleep can lead to intermittent hypercapnia and may result in serum bicarbonate (HCO₃⁻) retention. The addition of serum HCO₃⁻ level to the STOP-Bang questionnaire may improve its specificity., Methods: Four thousand seventy-seven preoperative patients were approached for consent and screened by the STOP-Bang questionnaire. Polysomnography was performed and preoperative HCO₃⁻ level was collected in 384 patients. Study participants were randomly assigned to a derivation or validation cohort. Predictive parameters (sensitivity, specificity, positive and negative predictive values) for STOP-Bang score and serum HCO₃⁻ level were calculated., Results: In the derivation cohort, with a STOP-Bang score ≥ 3, the specificity for all OSA, moderate/severe OSA, and severe OSA was 37.0%, 30.4%, and 27.7%, respectively. HCO₃⁻ level of 28 mmol/L was selected as a cutoff for analysis. With the addition of HCO₃⁻ level ≥ 28 mmol/L to the STOP-Bang score ≥ 3, the specificity for all OSA, moderate/severe OSA, and severe OSA improved to 85.2%, 81.7%, and 79.7%, respectively. Similar improvement was observed in the validation cohort., Conclusion: Serum HCO₃⁻ level increases the specificity of STOP-Bang screening in predicting moderate/severe OSA. We propose a two-step screening process. The first step uses a STOP-Bang score to screen patients, and the second step uses serum HCO₃⁻ level in those with a STOP-Bang score ≥ 3 for increased specificity.

Sleep-disordered breathing (SDB) comprises a diverse set of disorders marked by abnormal respiration during sleep. Clinicians should realize that SDB may present as acute cardiopulmonary failure in susceptible patients. In this review, we discuss three clinical phenotypes of acute cardiopulmonary failure from SDB: acute ventilatory failure, acute congestive heart failure, and sudden death. We review the pathophysiologic mechanisms and recommend general principles for management. Timely recognition of, and therapy for, SDB in the setting of acute cardiopulmonary failure may improve short- and long-term outcomes.

Background: Polysomnograms (PSGs) are routinely ordered by nonsleep specialists. However, it is unknown whether a sleep specialist consultation prior to a diagnostic PSG influences adherence to continuous positive airway pressure (CPAP) therapy., Methods: This study was done at the University of Chicago Sleep Disorders Center and included 403 patients with obstructive sleep apnea who had CPAP adherence data available. CPAP was set up at home, and objective adherence was remotely monitored during the first 30 days of therapy. Physicians who ordered PSGs were divided into two groups: sleep specialists and nonsleep specialists., Results: Patients were aged 52.5 ± 14 years, 47% were men, and 54% were African American. Mean daily CPAP use was greater in patients who were referred by sleep specialists (n = 105, 279 ± 179 min/d) than in patients referred by nonsleep specialists (n = 298, 219 ± 152 min/d, P = .005). In the linear regression model adjusting for several covariates, only two predictors were significantly associated with CPAP adherence. A sleep specialist consultation prior to the diagnostic PSG was associated with 58.2 min more per day (P = .002), and African American race was associated with 56.0 min less per day (P = .002) of CPAP use., Conclusions: In this cohort study, CPAP adherence was significantly higher with a sleep specialist consultation prior to the diagnostic PSG. In addition, African American race was associated with worse adherence to therapy. A better understanding of predictors of CPAP adherence may be useful in identifying patients who may benefit from a sleep specialist consultation prior to ordering a diagnostic PSG.

Over the last several decades, the prevalence of obesity has increased significantly worldwide. This has translated into an increased prevalence of obesity-associated morbidities including sleep-disordered breathing and metabolic disorders. While the medical management of obesity is relatively ineffective, bariatric surgery is the most successful method for sustained weight loss and markedly reduces obesity-related morbidity and mortality. The anatomical changes created with different types of procedures lead to variable weight loss and improvement of co-morbidities; however the latter does not appear to be exclusively dependent on the amount of weight loss. Bariatric surgery does not always lead to complete resolution of obstructive sleep apnea and age, gender and severity of the obstructive sleep apnea predict the residual disease after peak weight loss. Metabolic disorders and specifically diabetes often improve dramatically early after the procedure, before any significant weight loss has occurred. The modified gastrointestinal anatomy and physiology may explain this phenomenon., (Copyright © 2010. Published by Elsevier Ltd.)

Background: Inconsistent information exists about factors associated with daytime hypercapnia in obese patients with obstructive sleep apnea (OSA). We systematically evaluated these factors in this population., Methods: We included studies evaluating the association between clinical and physiologic variables and daytime hypercapnia (Paco(2), >or= 45 mm Hg) in obese patients (body mass index [BMI], >or= 30 kg/m(2)) with OSA (apnea-hypopnea index [AHI], >or= 5) and with a < 15% prevalence of COPD. Two investigators conducted independent literature searches using Medline, Web of Science, and Scopus until July 31, 2008. The association between individual factors and hypercapnia was expressed as the mean difference (MD). Random effects models were used to account for heterogeneity., Results: Fifteen studies (n = 4,250) fulfilled the selection criteria. Daytime hypercapnia was present in 788 patients (19%). Age and gender were not associated with hypercapnia. Patients with hypercapnia had higher BMI (MD, 3.1 kg/m(2); 95% confidence interval [CI], 1.9 to 4.4) and AHI (MD, 12.5; 95% CI, 6.6 to 18.4) than eucapnic patients. Patients with hypercapnia had lower percent predicted FEV(1) (MD, -11.2; 95% CI, -15.7 to -6.8), lower percent predicted vital capacity (MD, -8.1; 95% CI, -11.3 to -4.9), and lower percent predicted total lung capacity (MD, -6.4; 95% CI, -10.0 to -2.7). FEV(1)/FVC percent predicted was not different between hypercapnic and eucapnic patients (MD, -1.7; 95% CI, -4.1 to 0.8), but mean overnight pulse oximetric saturation was significantly lower in hypercapnic patients (MD, -4.9; 95% CI, -7.0 to -2.7)., Conclusions: In obese patients with OSA and mostly without COPD, daytime hypercapnia was associated with severity of OSA, higher BMI levels, and degree of restrictive chest wall mechanics. A high index of suspicion should be maintained in patients with these factors, as early recognition and appropriate treatment can improve outcomes.