Rationale: Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and computed tomography (CT) scan parameters at the time of infection would be associated with abnormal gas exchange at short term follow-up.Methods: We studied subjects who were hospitalized for COVID-19 pneumonia and then discharged. Those with pre-existing lung disease (except asthma) or reduced diffusing capacity for carbon monoxide (DLCO) prior to COVID-19 infection were excluded. Information on serum inflammatory biomarkers, CT scan, and clinical characteristics were collected in the index hospitalization. Pulmonary function tests and 6-minute walk tests were assessed at 2-3 months after discharge. CT images at the time of hospitalization were evaluated by Functional Respiratory Imaging (FRI;FLUIDDA, Inc., Antwerp, Belgium) with 3D reconstruction of the lungs and pulmonary vasculature to analyze pulmonary blood volume. Blood volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5-10), and ≥10mm (BV10) in cross-sectional area were analyzed. Additionally, the amount of inflammation on CT (ground-glass opacities) was quantified. We divided subjects into those with a DLCO <80% predicted and those with a DLCO ≥80% predicted based on follow-up pulmonary function tests. Results: 38 subjects were included in our cohort. Pulmonary function tests were performed 76.5±35.1 days after the first day of hospitalization. The results are summarized in the Table. 31 out of 38 (81.5%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, and smoking status. Peak D-dimer, LDH, and ferritin levels were greater in the DLCO<80% group. Spirometric measures and lung volumes were similar between groups. Inflammation was not different between groups, but BV5-10 and BV10 measures were higher in the DLCO<80% group. BV5-10 was associated with DLCO<80% in multivariable logistic regression with demographics, smoking status, lung volumes, and hemoglobin as covariates (OR 1.29, 95% CI 1.01, 1.64).Conclusions: Higher peak D-dimer levels at the time of hospitalization and abnormalities in pulmonary blood volumes are associated with a reduced DLCO at follow-up. These findings suggest that pulmonary vascular and coagulation abnormalities during hospitalization with COVID-19 might have long-lasting effects on pulmonary function. Further study regarding the influence of pulmonary blood volumes and measures of abnormal coagulation on short term COVID-19 outcomes is warranted.

Rationale: Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory illness resulting from infection by SARS-CoV2. COVID-19 in its severe state results in respiratory failure requiring mechanical ventilation. Usual reasons for mechanical ventilation are a combination of hypoxemia and ventilatory failure resulting in hypercapnia. It has been shown in acute respiratory distress syndrome (ARDS) that dead space fraction predicts mortality. In the wake of COVID-19, there has been postulation that the respiratory failure resulting from this disease might be different from ARDS. In this study, we propose that the dead space fraction can predict mortality in patients with COVID- 19 respiratory failure requiring mechanical ventilation.Methods: This is a retrospective study in which 42 mechanically ventilated patients' dead space at day 0, day 1, and day 3 were calculated. Dead space was estimated using Penn State estimates, rearranged Weir, and alveolar ventilation equation as was validated by Beitler et al. The two cohorts (alive and deceased) were compared using Chi-squared tests for categorical variables and 2-sample t-tests for continuous variables.Results: Of the 42 mechanically ventilated patients, majority (n=25, 60%) died. The demographics of the two cohorts were similar except for older age (68 vs. 56.47) and the presence of CKD (32% vs. 0%) which are both statistically higher in the deceased cohort. Dead space ventilation on day 3 of mechanical ventilation was found to predict 28-day mortality with a p-value of 0.045. The mean dead space on day 3 was statistically significantly different in the deceased cohort in contrast to the alive cohort (60.64 vs. 50.82). Fluid balance at day 3, D-dimer at day 0, and 1, Ferritin at day 0,1, and 3, Lactate dehydrogenase at day 0,1, and 3, were higher in the deceased cohort. Absolute lymphocyte count on day 3 was lower in the deceased group.Conclusion: Our study shows that higher dead space fraction is associated with higher 28-day mortality as has been previously shown in prior ARDS study. This study strengthens the data supporting dead space as a predictor of mortality in mechanically ventilated patients. It also raises several questions regarding the reason for elevated inflammatory markers as is seen here. Are these elevated inflammatory markers signals of progressive vasculopathy induced by the viral infection? Or are they elevated as a result of cytokine storm-like reaction in response to the act of intubation? These are questions we hope to answer as we continue further analysis of this patient population.

Abstract Introduction Positional OSA (non-supine apnea-hypopnea index [AHI] < 5 events/hr) is present in 30% of patients with OSA. We demonstrated that in patients with OSA- COPD overlap syndrome the AHI inversely correlated with the degree of gas trapping, suggesting a stabilizing effect on the upper airway. We hypothesized that sleep position would be less important, resulting in a lower prevalence of positional OSA. Methods Patients underwent a polysomnogram that demonstrated OSA (AHI > 5 events/hr). To confirm COPD, patients had spirometry performed and a chest computed tomography for measurements of percent gas trapping. Results Sixteen patients [6 (38%) males, 55±7 years/old, FEV1 1.2±0.5 L, FEV1 % Predicted 45±19%, FVC 2.3±0.8 L, FVC % Predicted 69±20%, FEV1/FVC 51±12%, BMI 33±9 kg/m2)] were diagnosed with OSA (AHI 15±12 events/hour). Four patients (25%) had positional OSA (AHI 13±6 events/hr, non-supine AHI 1±1 event/hr) compared to 12 patients who were non-positional [AHI 16±13 events/hr (p=0.95)]. There was no difference in age [52±8 and 56±7 yrs (p=0.3)] or severity of obstruction in those with and without positional OSA [FEV1 1.4±4 L and 1.1±0.5 L, (p=0.3), FEV1 % predicted 50±17% and 44±20%, (p=0.7), FVC 2.9±0.8 L and 2.1±0.8 L (p=0.1), FVC % predicted 78±21% and 66±20%, (p=0.3), and FEV1/FVC 50±11% and 51±12%, (p=0.8), respectively]. However, patients with positional OSA were less heavy than those with non-positional OSA [BMI 23±3 and 37±8 kg/m2, respectively (p=0.005)]. Finally, there was no difference in the CT-Derived % Gas Trapping in those with and without positional OSA [48±37% and 36±25%, (p=0.6), respectively]. Conclusion The prevalence of positional OSA in patients with OSA-COPD overlap is similar to OSA patients without COPD. Despite the presence of obstructive disease and gas trapping that may affect upper airway stability, other factors including body position and BMI remain important determinants for developing OSA in patients with COPD. Support R01-HL089856, R01-HL089897

Approximately 30% of patient with obstructive sleep apnea (OSA) have positional OSA [non-supine apnea-hypopnea index (AHI) < 5 events/hr]. However, the prevalence is based on variable definitions for hypopneas related to the degree of oxygen desaturation. In addition, use of a home sleep apnea test (HSAT) to identify positional OSA is limited. We hypothesized that in patients evaluated with an HSAT, using a definition for hypopneas based on 4% compared to 3% oxygen desaturation will significantly decrease the percentage diagnosed with positional OSA. Fourteen patients with positional OSA based on a non-supine respiratory event index (REI) < 5 events/hr were included. The initial diagnosis was determined based on a hypopnea definition of ≥ 3% oxygen desaturation. The studies were reanalyzed using a hypopnea definition of ≥ 4% oxygen desaturation. Fourteen patients [9 (64%) males, 46±14 yrs, BMI 31±6 kg/m2, ESS 7±5, REI 9±3 events/hr, mean SaO2 94±2%, lowest SaO2 81±6%, %TST SaO2 < 90% 4±6%] were identified with positional OSA (supine REI 16±7 events/hr, non-supine REI 3±1 events/hr) using a hypopneas definition of ≥ 3% oxygen desaturation. When reanalyzed using a hypopnea ≥ 4% oxygen desaturation there was a significant decrease in the REI to 7±2 events/hr (p<0.001). Three patients (21%) no longer were considered to have OSA. These patients were younger (32±14 vs. 50±11yrs, p=0.03) and had less severe OSA (REI 6±1 vs. 9±3 events/hr (p=0.04), but there was no difference in BMI (32±11 vs. 31±5 kg/m2, p=0.9) or mean and lowest SaO2 (96±0.4 vs. 94±2%, p=0.13, and 82±8 vs. 81±6%, p=0.9, respectively). In patients with mild positional OSA, using a hypopnea definition of at least 4% vs. 3% oxygen desaturation on a HSAT will have a significant effect on the overall REI and often exclude patients who would otherwise be treated for OSA. None.

Abstract Introduction Recently, the measurement of the hypoxic burden and apnea-hypopnea duration has been shown to correlate with mortality in patients with obstructive sleep apnea (OSA). We hypothesized that in patients with mild positional OSA (apnea-hypopnea index [AHI] < 5 events/hr in the non-supine position) the hypoxic burden would be increased and apnea-hypopnea duration shortened and similar to patients with non-positional OSA. Methods Fourteen patients with positional OSA and 24 patients non-positional OSA with similar severity of OSA based on the respiratory event index (REI) were included. All patients had a home sleep apnea test for suspected OSA. The hypoxic burden was calculated by the multiplication of REI and the mean area under the desaturation curves. Results Thirty-eight patients [12 (35%) males, 50±12 yrs, BMI 35±7 kg/m2, Epworth Sleepiness Scale (ESS) 11±8, REI 10±3 events/hr, apnea-hypopnea duration 19±4 sec, mean SaO2 94±2%, lowest SaO2 79±8%, % total sleep time (TST) SaO2 < 90% 11±16%, hypoxic burden 30±17 %min/hr] completed the study. Fourteen patients [9 (64%) males, 46±14 yrs, BMI 31±6 kg/m2, ESS 7±5, REI 9±3 events/hr, mean SaO2 94±2%, lowest SaO2 81±6%, %TST SaO2 < 90% 4±6%] had positional OSA (supine REI 16±7 events/hr, non-supine REI 3±1 events/hr) and 24 patients had non-positional OSA [3 (13%) males, 52±10 yrs, BMI 38±7 kg/m2, ESS 12±9, REI 10±3 events/hr, mean SaO2 94±2%, lowest SaO2 77±9%, %TST SaO2 < 90% 14±19%]. The hypoxic burden was elevated in both the positional and non-positional OSA patients with no difference between the groups (26±19 %min/hr and 32±15 %min/hr, respectively, p=0.13). The apnea-hypopnea duration was similar in positional and non-positional OSA patients (20±3 sec and 18±4 sec, respectively, p=0.08 sec). Conclusion In patients with mild positional OSA the hypoxic burden, which has been associated with cardiovascular mortality, is elevated and similar to patients with non-positional OSA. Support None

The American Academy of Sleep Medicine defines an optimal continuous positive airway pressure (CPAP) titration as a pressure that results in a respiratory disturbance index (RDI) < 5 events/hr maintained for at least 15 minutes with supine REM sleep. Many patients achieve an RDI < 5 events/hr for 15 minutes but do not have REM supine sleep at the recommended pressure. In these cases, patients are prescribed the perceived best CPAP pressure or placed on auto-titrating CPAP. It is unclear which treatment is superior. We conducted a retrospective analysis of patients who presented for a CPAP titration or split night study between 6/1/17–8/1/17. The lowest pressure (optCPAP) that reduced the RDI to < 5 events/hr was determined. Studies were optimal if 15 minutes of supine and REM sleep was recorded at optCPAP and suboptimal if these criteria were not met. Treatment modalities for all studies (auto or fixed pressure) were determined and compliance and residual RDI obtained from smart card data. Treatment failure was defined as a residual RDI >5 at 1 month with less than 5% of nights spent with a large leak. A total of 209 patients presented for a CPAP titration or split night study. In 172(82%), an optCPAP was determined. There were 102 (61%) optimal studies and 67(39%) suboptimal studies. There was no statistically significant difference in Age, BMI, severity of OSA or Epworth score. Patients with suboptimal studies were predominately female (75% vs 57%,p=0.02) with lower sleep efficiencies (78% vs 83%,p<0.001). One hundred and one patients (59%) had compliance data at 1 month, of which 41 were suboptimal. Seventeen suboptimal patients received Auto-titrating CPAP and 24 patients a fixed pressure. There was no significant difference in treatment failures between fixed and auto-titrating CPAP (16% Vs 17%) even when compared to failures in the optimal group (15%). Both fixed pressure and auto-titrating CPAP are equally effective at normalizing RDI at 1 month and are acceptable for suboptimal titration studies. None.

In chronic obstructive pulmonary disease (COPD) patients without associated obstructive sleep apnea (OSA) quantitative measurements of sleep quality appear to be related to the severity of obstructive airways disease and nocturnal oxygenation. However, the determinants of sleep quality in patients with COPD-OSA overlap syndrome are unknown. We hypothesize that both parameters of airflow obstruction and severity of OSA contribute to the sleep quality in COPD-OSA overlap syndrome. Participants were derived from the COPDGene project. The study included patients who underwent a full night polysomnogram (PSG) and where diagnosed with OSA (AHI≥ 5 events/hr). To confirm the presence of COPD, and prior to the PSG, patients had spirometry performed, and obtained a chest computed tomography (CT) for measurements of percent emphysema and gas trapping. Twenty-one patients [10 (48%) males, 57 ± 8 years/old, FEV1 1.2 ± 0.5 L, FEV1 %Predicted 45 ± 19%, FVC 2.3 ± 0.7 L, FVC %Predicted 68 ± 20%, FEV1/FVC 50 ± 11%, BMI 34 ± 9 kg/m2)] were diagnosed with OSA (apnea-hypopnea index [AHI] 16 ± 12 events/hour). The total sleep time (TST) was 286 ± 86 minutes with a sleep efficiency (SE) of 67 ± 23%.The Arousal index (AI) was 26 ± 27 arousals/hr. The mean SaO2 was 93 ± 3% with the lowest SaO2 of 82 ± 7%. The % TST with an SaO2 < 90% was 17 ± 29%. There was a significant inverse correlation between the AHI and TST (r=-0.78, p<0.001), and AHI and SE (r=-0.71, p<0.001) as well as the AHI and AI (r=-0.84, p<0.001). There was also a significant inverse correlation between the BMI and SE (r=-0.49, p=0.03). In addition, there was significant inverse correlation between % TST with an SaO2 < 90% and TST (r=-0.46, p=0.04).There was no correlation between TST, SE, or AI and FEV1 %Pred, FVC %Pred, CT-Derived % Emphysema, or CT-Derived % Gas Trapping. In patients with COPD-OSA overlap syndrome,sleep quality, as measured by TST, SE, and AI appears to be mostly influenced by the severity of the patient’s OSA rather than the severity of their obstructive airways disease. R01-HL089856, R01-HL089897.

Positional obstructive sleep apnea (OSA) is reported to be quite prevalent, accounting for more than 25% of all patients with OSA. Prior research has suggested that positional OSA patients may actually demonstrate a learning effect to avoid sleeping on their back during the night. The aim of our study is to more closely evaluate this relationship between disease severity and avoidance of the supine position in those patients with positional OSA. We hypothesized that those patients with the most severe disease while supine would be those that tended to avoid this position during sleep. We evaluated 38 patients (25 men, aged 49 ± 12 years, body mass index 31 ± 5 kg/ m2) diagnosed with positional OSA on a baseline polysomnogram study (overall apnea-hypopnea index [AHI] of 13 ± 5 events/hour, supine AHI 31 ± 19 events/hr, non-supine AHI 2 ± 1 events/hr) that was performed for suspected OSA. There was a significant correlation noted between the overall AHI during the night and the % total sleep time (TST) supine (R = 0.498, p = 0.002). However, there was a significant inverse correlation noted between the supine AHI and the % TST supine (R = -0.605, p = 0.0001). In addition, there was a significant correlation noted for supine AHI and the %TST spent non-supine (R = 0.605, p = 0.0001). The relationship between AHI and %TST supine was similar in male as compared to female patients (R = -0.665, p = 0.012, R = -0.662, p = 0.0002, respectively). In patients with positional OSA, those with more severe disease spend the least amount of time in the supine position, suggesting there may be a learning effect. These finding appear to be similar in both male and female patients with positional OSA. None

While age, BMI and disease severity (apnea-hypopnea index [AHI]) have all been shown to be important factors in predicting the presence of positional obstructive sleep apnea (OSA) and the effectiveness of therapy, no prior study has looked at the influence of gender. The aim of the study is to compare the effectiveness of positional therapy in male and female patients with positional OSA. We hypothesized that therapy would be equally effective in the 2 groups. Thirteen male (aged 51 ± 13 years, BMI 31 ± 6 kg/ m2) and 25 female (aged 48 ± 12 years, BMI 30 ± 5 kg/ m2) patients were included. All of the patients had positional OSA (non-supine AHI < 5 events/hr) on a baseline polysomnogram. Patients then underwent a treatment night polysomnogram using the Zzoma® Positional Device. The baseline AHI in male patients (AHI 11 ± 4, supine AHI 27 ± 16, non-supine AHI 3 ± 1 events/hr) was similar to that in female patients (AHI 13 ± 6, supine AHI 33 ± 20, non-supine AHI 2 ± 2 events/hr) (p = 0.22). When compared to baseline, there was a similar decrease in the AHI with positional therapy in the male (AHI 2 ± 2 events/hr, p<0.0001) as compared to the female (AHI 3 ± 2 events/hr, p<0.0001) patients (p = 0.91). When compared to baseline, there was no change in total sleep time or sleep efficiency in the male (335 ± 59 to 300 ± 68 min, p = 0.13, and 82 ± 9 to 78 ± 15 %, p = 0.37, respectively) and female (337 ± 54 to 331 ± 47 min, p = 0.28 and 87 ± 12 to 87 ± 11, p = 0.91, respectively) patients. There was a similar non-significant increase in the lowest oxygen saturation during the night in the male (85 ± 5 to 87 ± 4 %, p = 0.32) and female (86 ± 4 to 89 ± 4 %) patients. Positional therapy appears to be equally effective at normalizing sleep disordered breathing in male and female patients with positional OSA. None.

RATIONALE:The presence of obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD) is referred to as the OSA-COPD overlap syndrome. While lung inflation has been shown to be an important factor in determining upper airway stability, its role in determining OSA severity in smokers, including those with emphysema, has not been evaluated.OBJECTIVES:To evaluate the importance of lung inflation on OSA severity (apnea-hypopnea index [AHI]) in smokers with suspected OSA.METHODS:Fifty-one smokers (18 males; mean [±SD] age, 59 ± 9 yr; body mass index [BMI], 32 ± 9 kg/m(2)) who were part of the Genetic Epidemiology of COPD (COPDGene) project were studied. Patients underwent a full-night polysomnography for suspected OSA. Other testing included spirometry and volumetric chest computed tomography (CT) for quantitative measurement of CT-derived percent emphysema and CT-derived percent gas trapping.MEASUREMENTS AND MAIN RESULTS:For the group overall, there was evidence of obstructive airway disease by spirometry (FEV1, 1.4 ± 0.5 L, 58 ± 14% predicted) and emphysema by quantitative CT (CT-derived percent emphysema, 11 ± 13%; CT-derived percent gas trapping, 31.6 ± 24.1%). Twenty-nine (57%) of the patients had OSA (AHI, 18 ± 12 events/h). Patients with OSA had a higher BMI but were younger than those without OSA (BMI, 35 ± 9 kg/m(2) vs. 29 ± 7 kg/m(2), respectively [P = 0.007]; age, 56 ± 8 yr vs. 62 ± 9 yr, respectively [P = 0.01]). There was an inverse correlation between the AHI and the CT-derived percent emphysema and CT-derived percent gas trapping, both for the entire group (r = -0.41 [P < 0.01] and r = -0.44 [P < 0.01], respectively) and when just those patients with OSA were evaluated (r = -0.43 [P = 0.04] and r = -0.49 [P = 0.03], respectively). Multiple linear regression revealed that, in addition to CT-derived percent emphysema and CT-derived percent gas trapping, sex and BMI were important in determining the AHI in these patients.CONCLUSIONS:In smokers with OSA, increased gas trapping and emphysema as assessed by CT are associated with a decreased AHI. Along with sex and BMI, these measurements may be important in determining the severity of OSA in patients with COPD and may offer a protective mechanism in patients with more advanced disease.