Nasal resistance and inflammation: mechanisms for obstructive sleep apnea from chronic rhinosinusitis.

STUDY OBJECTIVES: We have previously estimated that the prevalence of obstructive sleep apnea (OSA) among World Trade Center (WTC) rescue and recovery workers is 75% and identified that having symptoms of chronic rhinosinusitis (CRS) is an independent risk factor for OSA in this population. Nasal inflammation and/or elevated awake nasal resistance that carried over into sleep could explain this association. To understand the mechanism(s) for the elevated risk of OSA observed in WTC responders with chronic rhinosinusitis (CRS) symptoms we examined if elevated awake supine nasal resistance was associated with OSA, CRS and/or nasal inflammatory biomarkers. METHODS: 601 individuals (83% male, average age 53 years, BMI=29.9 ± 5.5 kg/m2) enrolled in the WTC Health Program and without significant pre-9/11 snoring, underwent two nights of home sleep apnea testing, measurements of anterior rhinomanometry in the supine position, and nasal lavage. RESULTS: Awake supine nasal resistance was not associated with OSA; 74.8% and 74.4% of the participants with low and high nasal resistance respectively, had OSA (P=NS). Patients with CRS had elevated nasal inflammatory markers (IL6, IL8, ECP and Neut) but did not have high nasal resistance. Nasal inflammatory markers were not correlated with nasal resistance. CONCLUSIONS: As awake nasal resistance did not explain the relationship of CRS to OSA in this large and well characterized dataset, our findings suggest that either "sleep" nasal resistance or other factors such as increased supraglottic inflammation, perhaps through impairing upper airway reflex mechanisms, or systemic inflammation are involved in the pathophysiology of OSA in the WTC population.

Lack of association of impaired upper airway sensation with the presence or absence of obstructive sleep apnoea or chronic rhinosinusitis in World Trade Center responders.

OBJECTIVE: Examine sensory function of the upper airway in four groups of subjects recruited from the World Trade Centre General Responder Cohort (WTCGRC), with/without obstructive sleep apnoea (OSA), and with/without chronic rhinosinusitis (CRS). METHODS: Upper airway sensory function was determined using 2-point discrimination (2-PD) and vibration threshold (VT) in 163 WTCGRC subjects with both OSA and CRS (cases), OSA or CRS alone and without OSA or CRS (controls). Presence of OSA was determined from clinical sleep studies or home sleep testing. Presence of CRS was determined by nasal symptom questionnaire. The relationship between the presence of OSA and CRS and upper airway sensory impairment was assessed using linear regression analysis with each of 2PD and VT sensory threshold values as the dependent variable; OSA, CRS and their interaction were the independent variables. Age, gender and body mass index were covariates in the statistical model. The primary analysis was comparison of OSA+CRS versus controls (no OSA and no CRS) evaluated by linear contrasts. RESULTS: There were no differences in 2-PD or VT in those with OSA+CRS, OSA and CRS alone or controls. However, both 2-PD and VT were significantly higher in the WTCGRC controls compared with values seen in historical controls using the same methodology (median 2-PD 13.0; CI (11.0 to 13.5) vs 10.5; CI (8 to 11); VT: mean±SEM (9.3±0.6 vs 2.2±0.1)). CONCLUSION: While no differences were found in upper airway sensation between cases of OSA and CRS versus controls in the WTGRC population, there was evidence of impaired upper airway sensation in the WTGRC overall.

The overlap of chronic obstructive pulmonary disease and obstructive sleep apnea in hospitalizations for acute exacerbation of chronic obstructive pulmonary disease.

STUDY OBJECTIVES: This study examined in-hospital outcomes for patients with both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also known as COPD-OSA overlap syndrome, during hospitalizations for acute exacerbation of COPD. METHODS: The National Inpatient Sample was used to examine in-hospital mortality, length of stay, costs, and utilization of supportive ventilation in patients with COPD-OSA overlap during acute exacerbation of COPD hospitalizations. A 1-to-1 matched case-control design was utilized to match patients with and without OSA. Multivariate logistic regression modeling was used to examine mortality and ventilatory support, while controlling for potentially confounding diagnoses. RESULTS: COPD-OSA overlap was associated with longer median length of stay (4 days OSA, 3 days non-OSA; P < .001), higher mean costs ($32,197 OSA, $29,011 non-OSA; P < .001), increased utilization of noninvasive positive-pressure ventilation (13.92% OSA, 6.78% non-OSA; P < .001), and when required for greater than 96 hours, earlier initiation of mechanical ventilation (2.53 days OSA, 3.35 days non-OSA; P = .001). However, COPD-OSA overlap was associated with reduced mortality (0.81% OSA, 1.05% non-OSA; P < .001). These differences in mortality (adjusted odds ratio: 0.650; 95% confidence interval: 0.624-0.678) and noninvasive positive-pressure ventilation usage (adjusted odds ratio: 1.998; 95% confidence interval: 1.970-2.026) remained when adjusted for confounders. CONCLUSIONS: Patients with COPD-OSA overlap have higher utilization of supportive ventilation and longer length of stay during acute exacerbation of COPD hospitalizations, contributing to higher costs. The diagnosis of OSA is associated with reduced mortality in these hospitalizations, which may be related to greater utilization of supportive ventilation when OSA is recognized. CITATION: De la Fuente JRO, Greenberg P, Sunderram J. The overlap of chronic obstructive pulmonary disease and obstructive sleep apnea in hospitalizations for acute exacerbation of chronic obstructive pulmonary disease. J Clin Sleep Med. 2024;20(6):863-870.

The World Trade Center Health Program: Obstructive sleep apnea best practices.

The events of September 11, 2001 exposed nearly half a million community residents and workers engaged in rescue and recovery and clean-up to dust, debris and toxic chemicals, as well as psychologic and physical stressors. Early studies showed an excess of aerodigestive diseases including rhinosinusitis and gastroesophageal reflux. Several studies of World Trade Center (WTC) responders report an excess of obstructive sleep apnea among patients who developed new onset or worsening chronic rhinosinusitis. High quality clinical diagnostic and treatment guidelines are available from The American Academy of Sleep Medicine and the Department of Veterans Affairs/Department of Defense. For enrolled members, the WTC program covers diagnostic evaluation and treatment for sleep apnea in members diagnosed with WTC-related upper and lower respiratory disease and gastroesophageal reflux.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure.

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) improves sleepiness in patients with obstructive sleep apnea, but some patients remain sleepy. The objective of this study was to identify determinants that are associated with improvements in self-reported sleepiness in patients with obstructive sleep apnea on CPAP therapy. METHODS: A retrospective cohort study was performed in a clinic-based population to determine which variables contributed to the improvement in the Epworth Sleepiness Scale (ESS) in patients on CPAP therapy for OSA, stratified by baseline ESS score (< 11 or ≥ 11). Variables associated with ESS scores normalizing with CPAP were also assessed. RESULTS: Patients with a baseline high ESS score showed greater improvements in the ESS with CPAP. When looking at interactions between baseline ESS classification and changes in ESS, we found that a higher apnea-hypopnea index was only associated with improvement in the ESS among patients with a high baseline ESS. Other assessed factors or covariates were not significantly different. When looking at ESS normalization, we found that female sex and lower body mass index were associated with a lower likelihood of ESS normalization. The difference in the rate of ESS normalization between females and males was higher with more days on CPAP. CONCLUSIONS: Of all the assessed factors and covariates, only the apnea-hypopnea index was associated with the change in the ESS differently in patients with a high or normal baseline ESS score. ESS normalization rates were lower in females than in males, and this disparity was amplified by more days on CPAP. CITATION: Scharf MT, Zhang P, Walker NA, et al. Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure. J Clin Sleep Med. 2022;18(9):2273-2279.

Multi-feature Multi-Scale CNN-Derived COVID-19 Classification from Lung Ultrasound Data.

The global pandemic of the novel coronavirus disease 2019 (COVID-19) has put tremendous pressure on the medical system. Imaging plays a complementary role in the management of patients with COVID-19. Computed tomography (CT) and chest X-ray (CXR) are the two dominant screening tools. However, difficulty in eliminating the risk of disease transmission, radiation exposure and not being cost-effective are some of the challenges for CT and CXR imaging. This fact induces the implementation of lung ultrasound (LUS) for evaluating COVID-19 due to its practical advantages of noninvasiveness, repeatability, and sensitive bedside property. In this paper, we utilize a deep learning model to perform the classification of COVID-19 from LUS data, which could produce objective diagnostic information for clinicians. Specifically, all LUS images are processed to obtain their corresponding local phase filtered images and radial symmetry transformed images before fed into the multi-scale residual convolutional neural network (CNN). Secondly, image combination as the input of the network is used to explore rich and reliable features. Feature fusion strategy at different levels is adopted to investigate the relationship between the depth of feature aggregation and the classification accuracy. Our proposed method is evaluated on the point-of-care US (POCUS) dataset together with the Italian COVID-19 Lung US database (ICLUS-DB) and shows promising performance for COVID-19 prediction.

The age pattern of the male-to-female ratio in mortality from COVID-19 mirrors that of cardiovascular disease in the general population.

Males are at a higher risk of dying from COVID-19 than females. Older age and cardiovascular disease are also associated with COVID-19 mortality. To better understand how age and sex interact in contributing to COVID-19 mortality, we stratified the male-to-female (sex) ratios in mortality by age group. We then compared the age-stratified sex ratios with those of cardiovascular mortality and cancer mortality in the general population. Data were obtained from official government sources in the US and five European countries: Italy, Spain, France, Germany, and the Netherlands. The sex ratio of deaths from COVID-19 exceeded one throughout adult life, increasing up to a peak in midlife, and declining markedly in later life. This pattern was also observed for the sex ratio of deaths from cardiovascular disease, but not cancer, in the general populations of the US and European countries. Therefore, the sex ratios of deaths from COVID-19 and from cardiovascular disease share similar patterns across the adult life course. The underlying mechanisms are poorly understood and warrant further investigation.

PAP Adherence and Nasal Resistance. A Randomized Controlled Trial of CPAPflex versus CPAP in World Trade Center Responders.

Rationale: Continuous positive airway pressure (CPAP) adherence is often poor in obstructive sleep apnea (OSA) and may be influenced by nasal resistance. CPAP with a reduction of expiratory pressure (CPAPflex) may reduce discomfort in those with high nasal resistance and improve adherence in this subgroup.Objectives: To evaluate the association of positive airway pressure (PAP) treatment adherence to nasal resistance and examine if CPAPflex improves adherence over CPAP in subjects with high nasal resistance.Methods: A randomized double-blind crossover trial of 4 weeks each of CPAPflex versus CPAP in subjects exposed to World Trade Center dust with OSA stratified by nasal resistance, measured by 4-Phase Rhinomanometry.Results: Three hundred seventeen subjects with OSA (mean, apnea-hypopnea index with 4% O2 desaturation for hypopnea = 17 ± 14/h) were randomized. Overall, PAP adherence was poor, but adherence to CPAP (n = 239; mean hours per night [95% confidence interval (CI)]), 1.97 h (1.68 to 2.26) was greater than adherence to CPAPflex (n = 249; 1.65 h [1.39 to 1.91]; difference of 0.31 h [0.03; 0.6]; P < 0.05). Contrary to our hypothesis there was no correlation between nasal resistance and adherence to CPAP (r = 0.098; P = not significant) or CPAPflex (r = 0.056; P = not significant). There was no difference in adherence between CPAP and CPAPflex (mean Δ hours [95% CI]) in subjects with low resistance (0.33 h [-0.10 to 0.76]) or high nasal resistance (0.26 h [-0.14 to 0.66]). No significant differences were observed in any of the secondary outcomes between PAP modes.Conclusions: Contrary to expectations, our data do not show better adherence to CPAPflex than to CPAP in subjects with high or low nasal resistance and do show clinically insignificant better adherence overall with CPAP.Clinical trial registered with www.clinicaltrials.gov (NCT01753999).

In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study.

OBJECTIVES: To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19). DESIGN: Multicenter cohort study. SETTING: Intensive care units at 68 geographically diverse hospitals across the United States. PARTICIPANTS: Critically ill adults (age ≥18 years) with laboratory confirmed covid-19. MAIN OUTCOME MEASURES: In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality. RESULTS: Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation. Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest. Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years). The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status. Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older. CONCLUSIONS: Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.

Circadian Disruption in Critical Illness.

Circadian rhythms play a vital role in metabolic, hormonal, and immunologic function and are often disrupted in patients in the ICU. Circadian rhythms modulate the molecular machinery that responds to injury and illness which can impact recovery. Potential factors contributing to the alteration in circadian rhythmicity in intensive care unit (ICU) patients include abnormal lighting, noise, altered feeding schedules, extensive patient care interactions and medications. These alterations in circadian rhythms in ICU patients may affect outcomes and therefore, normalization of circadian rhythmicity in critically ill patients may be an important part of ICU care.

Clinical utility of the Epworth sleepiness scale.

PURPOSE: The Epworth sleepiness scale (ESS) is a widely used tool which has been validated as a measure of sleepiness. However, the scores within individual patients referred for clinical sleep services vary considerably which may limit the clinical use of the ESS. We sought to determine the test-retest reliability of the ESS if scores were classified as either normal or sleepy. METHODS: We measured the ESS in patients presenting to our sleep center at a clinical visit and again when a sleep study was done. Demographic and clinical information was extracted from the electronic medical record. RESULTS: Average ESS scores were similar on 2 administrations, mean (SD) of 9.8 (5.4) and 10.2 (6.2). Bland-Altman analysis showed upper and lower limits of agreement of 7.5 and - 6.7, respectively. No demographic or clinical variables were identified which contributed to the intra-individual variability. Of the patients who presented with an initial ESS < 11, 80% had a second ESS < 11. Of the patients who presented with an initial ESS ≥ 11, 89% had a second ESS ≥ 11. Cohen's kappa for the two administrations of the ESS was 0.67 (95% CI of 0.51-0.83). Using previously published reports, we calculated Cohen's kappa for polysomnographic determination of the apnea-hypopnea index (AHI) with values ranging from 0.26 to 0.69. CONCLUSIONS: Individual ESS scores varied considerably within individual patients, but with classification into either normal or sleepy, the test-retest reliability was substantial and in line with other clinical measures including polysomnographic determination of the AHI.

The Association between Health Conditions in World Trade Center Responders and Sleep-Related Quality of Life and Sleep Complaints.

Background: World Trade Center (WTC) dust-exposed subjects have multiple comorbidities that affect sleep. These include obstructive sleep apnea (OSA), chronic rhinosinusitis (CRS), gastroesophageal-reflux disorder (GERD) and post-traumatic stress disorder (PTSD). We examined the impact of these conditions to sleep-related outcomes. Methods: Demographics, co-morbidities and symptoms were obtained from 626 WTC (109F/517M), 33⁻87years, BMI = 29.96 ± 5.53 kg/m²) subjects. OSA diagnosis was from a 2-night home sleep test (ARESTM). Subjective sleep quality, sleep-related quality of life (QOL, Functional Outcomes of Sleep Questionnaire), excessive daytime sleepiness (Epworth Sleepiness Scale), sleep duration and sleep onset and maintenance complaints were assessed. Results: Poor sleep quality and complaints were reported by 19⁻70% of subjects and average sleep duration was 6.4 h. 74.8% of subjects had OSA. OSA diagnosis/severity was not associated with any sleep-related outcomes. Sleep duration was lower in subjects with all conditions (p < 0.05) except OSA. CRS was a significant risk factor for poor sleep-related QOL, sleepiness, sleep quality and insomnia; PTSD for poor sleep-related QOL and insomnia; GERD for poor sleep quality. These associations remained significant after adjustment for, age, BMI, gender, sleep duration and other comorbidities. Conclusions: Sleep complaints are common and related to several health conditions seen in WTC responders. Initial interventions in symptomatic patients with both OSA and comorbid conditions may need to be directed at sleep duration, insomnia or the comorbid condition itself, in combination with intervention for OSA.

Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers.

Sarcoid-like granulomatous diseases (SGD) have been previously identified in cohorts of World Trade Center (WTC) dust-exposed individuals. In the present studies, we analyzed lung and/or lymph node biopsies from patients referred to our clinic with suspected WTC dust-induced lung disease to evaluate potential pathophysiologic mechanisms. Histologic sections of lung and/or lymph node samples were analyzed for markers of injury, oxidative stress, inflammation, fibrosis, and epigenetic modifications. Out of seven patients examined, we diagnosed four with SGD and two with pulmonary fibrosis; one was diagnosed later with SGD at another medical facility. Patients with SGD were predominantly white, obese men, who were less than 50 years old and never smoked. Cytochrome b5, cytokeratin 17, heme oxygenase-1, lipocalin-2, inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, ADP-ribosylation factor-like GTPase 11, mannose receptor-1, galectin-3, transforming growth factor ß, histone-3 and methylated histone-3 were identified in lung and lymph nodes at varying levels in all samples examined. Three of the biopsy samples with granulomas displayed peri-granulomatous fibrosis. These findings are important and suggest the potential of WTC dust-induced fibrotic sarcoid. It is likely that patient demographics and/or genetic factors influence the response to WTC dust injury and that these contribute to different pathological outcomes.

Chronic Rhinosinusitis Is an Independent Risk Factor for OSA in World Trade Center Responders.

BACKGROUND: Many respiratory conditions have been attributed to toxic dust and fume exposure in World Trade Center (WTC) rescue and recovery workers, who frequently report symptoms of OSA. We examined the prevalence of new-onset OSA and tested if the prevalence and severity of OSA are related to the presence of chronic rhinosinusitis (CRS). METHODS: A total of 601 subjects (83% men; age, 33-87 years; BMI, 29.9 ± 5.5 kg/m2) enrolled in the WTC Health Program, excluding those with significant pre-September 11, 2001, snoring or prior CRS, underwent two nights of home sleep testing. OSA was defined as Apnea Hypopnea Index 4% ≥ 5 events/h or respiratory disturbance index of ≥ 15 events/h. CRS was assessed using nasal symptom questionnaires. RESULTS: The prevalence of OSA was 75% (25% no OSA, 46% mild OSA, 19% moderate OSA, and 10% severe OSA), and the prevalence of CRS was 43.5%. Compared with no CRS, new and worsening CRS was a significant risk factor for OSA with an OR of 1.80 (95% CI, 1.18-2.73; P = .006) unadjusted and 1.76 (95% CI, 1.08-2.88; P = .02) after adjustment for age, BMI, sex, gastroesophageal reflux disorder, and alcohol use. CONCLUSIONS: The high prevalence of OSA in WTC responders was not explained fully by obesity and sex. Possible mechanisms for the elevated risk of OSA in subjects with CRS include increased upper airway inflammation and/or elevated nasal/upper airway resistance, but these need confirmation.

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

RATIONALE: Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome. OBJECTIVES: To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers. METHODS: Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated. MEASUREMENTS AND MAIN RESULTS: In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota. CONCLUSIONS: We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

Comparison of two home sleep testing devices with different strategies for diagnosis of OSA.

PURPOSE: Home sleep testing devices are being widely used in diagnosis/screening for obstructive sleep apnea (OSA). We examined differences in OSA metrics obtained from two devices with divergent home monitoring strategies, the Apnea Risk Evaluation System (ARES™, multiple signals plus forehead reflectance oximetry) and the Nonin WristOx2™ (single channel finger transmission pulse oximeter), compared to differences from night-night variability of OSA. METHODS: One hundred fifty-two male/26 female subjects (BMI = 30.3 ± 5.6 kg/m2, age = 52.5 ± 8.9 years) were recruited without regard to OSA symptoms and simultaneously wore both ARES™ and Nonin WristOx2™ for two nights (n = 351 nights). Automated analysis of the WristOx2 yielded oxygen desaturation index (ODIOx2, ≥4% O2 dips/h), and automated analysis with manual editing of ARES™ yielded AHI4ARES (apneas + hypopneas with ≥4% O2 dips/h) and RDIARES (apneas + hypopneas with ≥4% O2 dips/h or arousal surrogates). Baseline awake oxygen saturation, percent time < 90% O2 saturation (%time < 90%O2Sat), and O2 signal loss were compared between the two methods. RESULTS: Correlation between AHI4ARES and ODIOx2 was high (ICC = 0.9, 95% CI = 0.87-0.92, p < 0.001, bias ± SD = 0.7 ± 6.1 events/h). Agreement values for OSA diagnosis (77-85%) between devices were similar to those seen from night-to-night variability of OSA using a single device. Awake baseline O2 saturation was significantly higher in the ARES™ (96.2 ± 1.6%) than WristOx2™ (92.2 ± 2.1%, p < 0.01). There was a significantly lower %time < 90%O2Sat reported by the ARES™ compared to WristOx2 (median (IQR) 0.5 (0.0, 2.6) vs. 2.1 (0.3, 9.7), p < 0.001), and the correlation was low (ICC = 0.2). CONCLUSIONS: OSA severity metrics predominantly dependent on change in oxygen saturation and metrics used in diagnosis of OSA (AHI4 and ODI) correlated well across devices tested. However, differences in cumulative oxygen desaturation measures (i.e., %time < 90%O2Sat) between the devices suggest that caution is needed when interpreting this metric particularly in populations likely to have significant hypoxia.

Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice.

Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region and the pre-Bötzinger complex (pre-BötC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O2) during 10 days of exposure to CIH in chronically instrumented awake wild-type (WT) and HO-1 null mice (HO-1-/-). HO-1 was induced within the C1 and pre-BötC regions after 1 day of CIH. There were no significant differences in the baseline respiratory parameters between WT and HO-1-/- Prior to CIH, acute hypoxia increased respiratory frequency in both WT and HO-1-/-; however, minute diaphragm electromyogram activity increased in WT but not HO-1-/- The hypoxic respiratory response after 1 and 10 days of CIH was restored in HO-1-/- CIH resulted in an initial significant decline in 1) the hypoxic sigh frequency response, which was restored in WT but not HO-1-/-, and 2) the baseline sympathetic activity in WT and HO-1-/-, which remained stable subsequently in WT but not in HO-1-/- We conclude that 1) CIH induces expression of HO-1 in the C1 and pre-BötC regions within 1 day and 2) HO-1 is necessary for hypoxia respiratory response and contributes to the maintenance of the hypoxic sigh responses and baseline sympathetic activity during CIH.

A comparison of CPAP and CPAPFLEX in the treatment of obstructive sleep apnea in World Trade Center responders: study protocol for a randomized controlled trial.

BACKGROUND: Following the World Trade Center disaster, a large number of individuals involved in rescue and recovery activity were exposed to significant amounts of dust, and reported symptoms of chronic nasal and sinus inflammation. An unusually high prevalence of obstructive sleep apnea (OSA) has also been observed in this World Trade Center Responder population. This project aims to examine the relationship between nasal pathology and OSA. Our hypothesis is that increased nasal resistance due to nasal inflammation predisposes to OSA in this population. Continuous Positive Airway Pressure (CPAP) is the standard therapy for OSA but despite its efficacy has poor adherence. Subjects with high nasal resistance may have greater difficulty in tolerating this therapy than those who do not have high nasal resistance. Reduction of excess expiratory positive pressure by the modality known as Cflex(™) during Continuous Positive Airway Pressure therapy (CPAP(Flex)) has been suggested to improve comfort without compromising efficacy. We will compare CPAP to CPAP(Flex) in subjects with OSA. STUDY DESIGN: Subjects with new onset habitual snoring will be screened for OSA using home sleep studies and rhinomanometry will be used to determine nasal resistance. In 400 subjects with OSA we will perform a randomized double blind cross-over study comparing CPAP to CPAP(flex), and relate nasal resistance to adherence to CPAP therapy. DISCUSSION: This is the first multicenter trial designed to test the hypothesis that adherence to CPAP therapy relates to nasal resistance and CPAP(Flex) will improve adherence to CPAP in those subjects with high nasal resistance. We anticipate the following results from this trial: 1. Increased nasal resistance is associated with decreased adherence to CPAP therapy. 2. Use of CPAP(Flex) improves adherence with CPAP therapy in subjects with high nasal resistance, but not in those with low nasal resistance. 3. The benefit of CPAP(Flex) on adherence is greatest when offered at CPAP therapy initiation rather than as a "rescue" therapy in subjects with high nasal resistance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01753999, Date: 12 December 2012.

Reduced Hospital Duration of Stay Associated with Revised Emergency Department-Intensive Care Unit Admission Policy: A before and after Study.

BACKGROUND: Emergency department (ED) and hospital crowding adversely impacts patient care. Although reduction methods for duration of stay in the ED have been explored, few focus on medical intensive care unit (MICU) patients. OBJECTIVE: To quantify duration of stay or mortality changes associated with a policy intervention that changed the role of an MICU resident to "screen" and write MICU admission orders in the ED to instead meet the patient and write orders in the MICU if there was an available bed. The intervention moved "screening" bed management-appropriateness discussions to the MICU attending or fellow level. METHODS: We performed a retrospective before and after study at an urban, level 1 trauma center of adults admitted to the MICU from the ED during the first 6 months in 2009 before, and the corresponding 6 months in 2010, after the intervention. We collected demographics, ED, MICU, and hospital duration of stay, duration of mechanical ventilation, Acute Physiology and Chronic Health Evaluation (APACHE) scores, and mortality from electronic medical records. Linear models compared duration of stay differences; logistic regression compared in-hospital mortality. T-tests assessed APACHE score changes before and after the policy change. Analyses were adjusted for age and sex. RESULTS: We included 498 patients, average age 66 years (±18), 52% male. Hospital duration of stay decreased 18% from 6.8 to 5.6 days (unadjusted p = 0.029). MICU duration of stay decreased from 3.5 to 3.3 days (unadjusted p = 0.34) and ED duration of stay from arrival to physical transfer decreased 40 min (375 to 324 min; unadjusted p = 0.006). Mortality and APACHE scores were unchanged. CONCLUSIONS: A streamlined admission intervention from the ED to the MICU was associated with decreased ED and hospital duration of stay without altering mortality.