Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial.

Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.Objectives: In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.Methods: At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV.Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.Conclusions: In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

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.

Cost-effectiveness of positive airway pressure modalities in obesity hypoventilation syndrome with severe obstructive sleep apnoea.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is treated with either non-invasive ventilation (NIV) or CPAP, but there are no long-term cost-effectiveness studies comparing the two treatment modalities. OBJECTIVES: We performed a large, multicentre, randomised, open-label controlled study to determine the comparative long-term cost and effectiveness of NIV versus CPAP in patients with OHS with severe obstructive sleep apnoea (OSA) using hospitalisation days as the primary outcome measure. METHODS: Hospital resource utilisation and within trial costs were evaluated against the difference in effectiveness based on the primary outcome (hospitalisation days/year, transformed and non-transformed in monetary term). Costs and effectiveness were estimated from a log-normal distribution using a Bayesian approach. A secondary analysis by adherence subgroups was performed. RESULTS: In total, 363 patients were selected, 215 were randomised and 202 were available for the analysis. The median (IQR) follow-up was 3.01 (2.91-3.14) years for NIV group and 3.00 (2.92-3.17) years for CPAP. The mean (SD) Bayesian estimated hospital days was 2.13 (0.73) for CPAP and 1.89 (0.78) for NIV. The mean (SD) Bayesian estimated cost per patient/year in the NIV arm, excluding hospitalisation costs, was €2075.98 (91.6), which was higher than the cost in the CPAP arm of €1219.06 (52.3); mean difference €857.6 (105.5). CPAP was more cost-effective than NIV (99.5% probability) because longer hospital stay in the CPAP arm was compensated for by its lower costs. Similar findings were observed in the high and low adherence subgroups. CONCLUSION: CPAP is more cost-effective than NIV; therefore, CPAP should be the preferred treatment for patients with OHS with severe OSA. TRIAL REGISTRATION NUMBER: NCT01405976.

Predictors of respiratory complications in patients with C5-T5 spinal cord injuries.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: Describing the respiratory complications and their predictive factors in patients with acute traumatic spinal cord injuries at C5-T5 level during the initial hospitalization. SETTING: Hospital Vall d'Hebron, Barcelona. METHODS: Data from patients admitted in a reference unit with acute traumatic injuries involving levels C5-T5. Respiratory complications were defined as: acute respiratory failure, respiratory infection, atelectasis, non-hemothorax pleural effusion, pulmonary embolism or haemoptysis. Candidate predictors of these complications were demographic data, comorbidity, smoking, history of respiratory disease, the spinal cord injury characteristics (level and ASIA Impairment Scale) and thoracic trauma. A logistic regression model was created to determine associations between potential predictors and respiratory complications. RESULTS: We studied 174 patients with an age of 47.9 (19.7) years, mostly men (87%), with low comorbidity. Coexistent thoracic trauma was found in 24 (19%) patients with cervical and 35 (75%) with thoracic injuries (p < 0.001). Respiratory complications were frequent (53%) and were associated to longer hospital stay: 83.1 (61.3) and 45.3 (28.1) days in patients with and without respiratory complications (p < 0.001). The strongest predictors of respiratory complications were: previous respiratory disease (OR 5.4, 95% CI: 1.5-19.2), complete motor function impairment (AIS A-B) (OR 4.7, 95% CI: 2.4-9.5) and concurrent chest trauma (OR 3.73, 95% CI: 1.8-7.9). CONCLUSIONS: Respiratory complications are common in traumatic spinal cord injuries between C5-T5. We identified previous respiratory disease, complete motor function impairment and the coexistence of thoracic trauma as predictors of respiratory complications. Identification of patients at risk might help clinicians to implement preventive strategies.

Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

BACKGROUND: Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear. METHODS: Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5 nM insulin-induced pAKT/AKT expression changes by western blotting. RESULTS: When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n = 24; p < 0.001), while no such changes occur in untreated patients (n = 8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naive murine adipocytes, without altering pre-adipocyte differentiation. CONCLUSIONS: Using in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome. Pickwick Study.

RATIONALE: The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in patients with OHS, information regarding efficacy is limited. OBJECTIVES: We performed a large, multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure. METHODS: Sequentially screened patients with OHS with severe sleep apnea were randomized into the above-mentioned groups for a 2-month follow up. Arterial blood gas parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, 6-minute-walk distance, dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed. MEASUREMENTS AND MAIN RESULTS: In total, 351 patients were selected, and 221 were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control group but not relative to the CPAP group. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, some health-related quality-of-life assessments, the spirometry, and 6-minute-walk distance results improved more with NIV than with CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP. CONCLUSIONS: NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

Gender differences in outcomes of ambulatory and hospitalized patient with obesity hypoventilation syndrome.

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 PaCO2 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.

Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Forced vital capacity (FVC) less than 50% of predicted is one of the main parameters used for Non-Invasive Ventilation (NIV) initiation in Amyotrophic Lateral Sclerosis (ALS). Recent studies suggest that higher values of FVC could be considered as a threshold. The aim of this study is to evaluate whether early use of NIV improves the prognosis of ALS patients compared with standard initiation. METHODS: This is a randomized, parallel, multicenter, open-label, controlled clinical trial, with recruitment at the ALS outpatient multidisciplinary units of six Spanish hospitals. Patients were included when their FVC reached the 75% threshold and were randomized by computer, stratifying by center in an allocation ratio of 1:1 to Early NIV (FVC below 75%) or Standard NIV (FVC below 50%) initiation. The primary outcome was time to death or tracheostomy.Trial registration number ClinicalTrials.gov: NCT01641965. RESULTS: Between May 2012 and June 2014, 42 patients were randomized to two groups, 20 to Early NIV and 22 to Standard NIV initiation. We found differences in survival in favor of the intervention group: an incidence of mortality (2.68 [1.87-5.50] vs. 3.33 [1.34-4.80] person-months) and a median survival (25.2 vs. 19.4 months), although without reaching statistical significance (p = 0.267). CONCLUSIONS: This trial did not reach the primary endpoint of survival; nevertheless, it is the first Randomized Controlled Trial (RCT) to demonstrate the benefits of early NIV in slowing the decline of respiratory muscle strength and reducing adverse events. Although not all the results reached statistical significance, all the analyzed data favor early NIV. In addition, this study demonstrates good tolerance and compliance with early NIV without quality of sleep impairment. These data reinforce the early respiratory evaluation of ALS patients and NIV initiation with an FVC of around 75%.

Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients.

STUDY OBJECTIVES: To investigate the association between moderate or severe obstructive sleep apnea treated with home continuous positive airway pressure (CPAP) and severe coronavirus disease 2019 (COVID-19). METHODS: Retrospective study of patients admitted for COVID-19. Patients with obstructive sleep apnea treated with home CPAP were identified and for each of them we selected 5 patients admitted consecutively in the following hours. The main outcome of the study was the development of severe COVID-19, defined as 1) death or 2) a composite outcome of death or the presence of severe hypoxemic respiratory failure at or during admission. The association between CPAP-treated obstructive sleep apnea and these outcomes was estimated by logistic regression analysis after applying inverse probability of treatment weighting using a propensity score-weighting approach. RESULTS: Of the 2,059 patients admitted, 81 (3.9%) were receiving treatment with home CPAP. Among the 486 patients included in the study, 19% died and 39% presented the composite outcome. The logistic regression analysis did not show an association of CPAP treatment either with death (odds ratio [OR]: 0.684; 95% confidence interval [CI]: 0.332-1.409; P = .303) or with the composite outcome (OR: 0.779; 95% CI: 0.418-1.452; P = .432). Death was associated with age (OR: 1.116; 95% CI: 1.08-1.152; P < .001) and number of comorbidities (OR: 1.318; 95% CI: 1.065-1.631; P = .012), and the composite outcome was associated with male sex (OR: 2.067; 95% CI: 1.19-3.589; P = .01) and number of comorbidities (OR: 1.241; 95% CI: 1.039-1.484; P = .018). CONCLUSIONS: In hospitalized patients with COVID-19, prior obstructive sleep apnea treated with home CPAP is not independently associated with worse outcomes. CITATION: Sampol J, Sáez M, Martí S, et al. Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients. J Clin Sleep Med. 2022;18(7):1857-1864.

Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study.

STUDY OBJECTIVES: In patients treated with noninvasive ventilation, sleep-related breathing changes can modify patient-ventilator interactions, which could reduce its effectiveness. The aim of this prospective observational study was to determine the impact of sleep/wake state on leaks, upper airway obstructive events, and asynchronies in patients treated by long-term noninvasive ventilation. METHODS: Stable patients adapted to noninvasive ventilation were considered for nocturnal polysomnography. Unintentional leaks, upper airway obstructive events, and asynchronies were compared between sleep and awake periods. RESULTS: Twenty-eight patients were enrolled. Underlying diagnoses were neuromuscular disease (n = 11), chest wall disease (n = 8), and obesity-hypoventilation (n = 9). Leaks were more frequent in sleep than in awake periods, with a median of 10% (interquartile range [IQR], 0%-75%) vs 1% (IQR, 0%-9%) of time (P < .001), respectively. During sleep, asynchronies with and without associated leak affected 27% of breaths (IQR, 16%-39%) compared with non-leak-related asynchronies that were recorded in 8% (IQR, 3%-25%) of breaths (P < .001). Asynchronies affecting more than 10% of total breaths were more frequent in sleep (25 patients, 89%) than in awake time (8 patients, 29%; P = .25). Eleven patients (39%) presented with 5 or more upper airway obstructive events without reduction in ventilatory drive per hour of sleep. CONCLUSIONS: In patients adapted to home noninvasive ventilation, leaks, asynchronies, and upper airway obstructive events are frequent during the night and are concentrated in sleep periods. Asynchronies are often associated with leaks. These findings may have clinical implications considering that in patients with low sleep efficiency respiratory events could be underestimated if sleep is not evaluated. CITATION: Martí S, Ferré A, Sampol G, et al. Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study. J Clin Sleep Med. 2022;18(1):225-233.

Cluster Analysis of Home Mechanical Ventilation in COPD Patients: A Picture of the Real World and Its Impact on Mortality.

BACKGROUND: Treatment of chronic hypercapnic failure in COPD patients with home noninvasive ventilation (HNIV) remains unclear. AIM: To create a curated cohort of all COPD patients on HNIV in Catalonia, perform a cluster analysis, and evaluate mortality evolution. STUDY DESIGN AND METHODS: This study was a multicenter, observational study including all COPD patients on HNIV on 1st January of 2018. Patients were selected through the Catalan Health Service, and administrative and clinical data were obtained in the previous four years. Principal component analysis of mixed data and hierarchical clustering were performed to identify clusters of patients. Mortality was evaluated from 1 January 2018 until 31 December 2020. RESULTS: A total of 247 patients were enrolled. They were mostly male (78.1%), with a median (SD) age of 70.4 (9.4) years old. In 60%, 55% and 29% of patients, obesity, sleep apnea and heart failure coexisted, respectively. Cluster analysis identified four well-differentiated groups labeled for their clinical characteristics: (1) obese smokers, (2) very severe COPD, (3) sleep apnea and (4) older comorbid males. Patients belonging to Clusters (2) and (4) had a worse prognosis than patients in Clusters (1) and (3). INTERPRETATION: A high heterogeneity in the prescription of HNIV was demonstrated. Cluster analysis identifies four different groups, of which only one had COPD as the main cause of ventilation, while the other three clusters showed a predominance of other comorbidities. This leads to different survival outcomes, including an overlapping phenotype of obesity-related disease and sleep apnea with better survival.

Higher mortality and intubation rate in COVID-19 patients treated with noninvasive ventilation compared with high-flow oxygen or CPAP.

The effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.2%), CPAP (133, 36.2%) or NIV (79, 21.5%). The main outcome was intubation or death at 28 days after respiratory support initiation. After adjusting for relevant covariates and taking patients treated with HFNC as reference, treatment with NIV showed a higher risk of intubation or death (hazard ratio 2.01; 95% confidence interval 1.32-3.08), while treatment with CPAP did not show differences (0.97; 0.63-1.50). In the context of the pandemic and outside the intensive care unit setting, noninvasive ventilation for the treatment of moderate to severe hypoxemic acute respiratory failure secondary to COVID-19 resulted in higher mortality or intubation rate at 28 days than high-flow oxygen or CPAP. This finding may help physicians to choose the best noninvasive respiratory support treatment in these patients.Clinicaltrials.gov identifier: NCT04668196.

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome.

STUDY OBJECTIVES: Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS. METHODS: In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a P value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea. RESULTS: Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO2 and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98; P = .003 for PaO2, and 1.07; 95% confidence interval 1.03 to 1.12; P = .001 for body mass index). In separate analyses, body mass index and PaO2 were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype. CONCLUSIONS: This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976. CITATION: Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome. J Clin Sleep Med. 2022;18(4):983-992.

Effectiveness of CPAP vs. Noninvasive Ventilation Based on Disease Severity in Obesity Hypoventilation Syndrome and Concomitant Severe Obstructive Sleep Apnea.

RATIONALE: Obesity hypoventilation syndrome (OHS) with concomitant severe obstructive sleep apnea (OSA) is treated with CPAP or noninvasive ventilation (NIV) during sleep. NIV is costlier, but may be advantageous because it provides ventilatory support. However, there are no long-term trials comparing these treatment modalities based on OHS severity. OBJECTIVE: To determine if CPAP have similar effectiveness when compared to NIV according to OHS severity subgroups. METHODS: Post hoc analysis of the Pickwick randomized clinical trial in which 215 ambulatory patients with untreated OHS and concomitant severe OSA, defined as apnoea-hypopnea index (AHI)≥30events/h, were allocated to NIV or CPAP. In the present analysis, the Pickwick cohort was divided in severity subgroups based on the degree of baseline daytime hypercapnia (PaCO2 of 45-49.9 or ≥50mmHg). Repeated measures of PaCO2 and PaO2 during the subsequent 3 years were compared between CPAP and NIV in the two severity subgroups. Statistical analysis was performed using linear mixed-effects model. RESULTS: 204 patients, 97 in the NIV group and 107 in the CPAP group were analyzed. The longitudinal improvements of PaCO2 and PaO2 were similar between CPAP and NIV based on the PaCO2 severity subgroups. CONCLUSION: In ambulatory patients with OHS and concomitant severe OSA who were treated with NIV or CPAP, long-term NIV therapy was similar to CPAP in improving awake hypercapnia, regardless of the severity of baseline hypercapnia. Therefore, in this patient population, the decision to prescribe CPAP or NIV cannot be solely based on the presenting level of PaCO2.

Predicting nocturnal hypoventilation in hypercapnic chronic obstructive pulmonary disease patients undergoing long-term oxygen therapy.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients are very sensitive to changes in pulmonary mechanics and central ventilation control during sleep and may develop significant gas exchange alterations with increased hypoxemia and hypercapnia. Oxygen therapy improves nocturnal desaturation but can worsen hypoventilation. OBJECTIVES: To analyze the prevalence of nocturnal hypoventilation (NHV) in hypercapnic COPD patients and to determine predictive factors for this phenomenon. METHODS: This was a prospective multicenter study which enrolled 80 clinically stable COPD patients with hypercapnic respiratory failure who fulfilled the conventional criteria for long-term oxygen therapy (LTOT). All patients had undergone pulmonary function testing, blood gas analysis, and respiratory polygraphy. Arterial blood gas samples were obtained while patients were awake and during sleep. NHV was considered when an increase in PaCO2 >10 mm Hg was observed in any nocturnal arterial blood gas sample as compared to the awake levels. RESULTS: Seventeen patients (21%) developed NHV. NHV was associated with the values of BMI, hemoglobin, hematocrits, DLCO, and PaO2 reached after oxygen administration. In the logistic regression analysis BMI (OR 1.26, 95% CI 1.068-1.481; p = 0.006) and the diurnal increase of PaO2 after O2 (OR 0.89, 95% CI 0.807-0.972; p = 0.010) were the variables that best discriminated with a sensitivity of 82% and a specificity of 78%. CONCLUSIONS: NHV is a relatively common finding in stable hypercapnic COPD patients undergoing LTOT and it is related to a higher BMI and lower PaO2 after oxygen administration.

Sleep hypoventilation due to increased nocturnal oxygen flow in hypercapnic COPD patients.

UNLABELLED: This study shows the risks and benefits of increasing the nocturnal oxygen flow in hypercapnic COPD patients undergoing LTOT, as recommended by some COPD treatment guidelines to avoid nocturnal desaturation. BACKGROUND AND OBJECTIVE: Several COPD treatment guidelines recommend increasing oxygen flow during sleep to avoid nocturnal desaturation. However, such an increase could have deleterious clinical and gas exchange effects. The objective of this study was to evaluate short-term gas exchange alterations produced by increasing the nocturnal oxygen flow rate. METHODS: Thirty-eight COPD patients with chronic hypercapnic respiratory failure were evaluated. In a cross-over study, patients were randomly assigned to receive the daytime oxygen flow rate on one night and an additional litre on the alternate night. Nocturnal pulse oximetry and arterial blood gases at awakening were measured, in each patient, on two consecutive days. RESULTS: The administration of 1 L more oxygen during the night resulted in improved parameters of nocturnal oxygenation (oxygen pulse oximetry saturation-SpO2; percentage of sleep time spent at SpO2<90%-CT90; PaO2 at awakening). Nevertheless, such an increase in oxygen flow during the night was also associated with greater hypercapnia and acidosis (p<0.05) the next morning. CONCLUSIONS: The increase of oxygen flow in severe COPD patients with established daytime hypercapnia improved nocturnal oxygenation but it also led to greater hypercapnia and respiratory acidosis at awakening in a considerable proportion of these patients.

Noninvasive home mechanical ventilation in elderly patients.

STUDY OBJECTIVE: To determine the short- and long-term benefits of noninvasive home mechanical ventilation (NIHMV) in patients aged 65 and older who were eligible for this treatment. DESIGN AND SETTING: This retrospective, comparative, longitudinal study was carried out in a tertiary care hospital in Barcelona (Spain). PATIENTS AND METHODS: The study included all patients in whom NIHMV with a nasal mask was established in the period from 1998 to 2001. Patients were divided into 3 groups according to age: group 1 (n = 10) > or =75; group 2 (n = 40) 65-74, and group 3 (n = 41) <65 years old. Clinical characteristics, pulmonary function results, and arterial blood gas findings were assessed in all patients before starting ventilation and after 6 months. MEASUREMENTS AND RESULTS: Statistically significant improvements in PaO(2) (13.4, 10, and 15.3 mm Hg for groups 1-3) and PaCO(2) (-17.6, -9.6 and -12.8 mm Hg for groups 1-3) were found at 6 months (p < 0.001 in all cases). There were no significant differences between the groups in blood gas parameters and treatment compliance. The incidence of related adverse events was not statistically different between the study groups (40%, 35% and 32% for groups 1-3; p = 0.859). CONCLUSIONS: NIHMV is effective in all patients for whom it is indicated, regardless of their age.

Facial fractures: classification and highlights for a useful report.

In patients with facial trauma, multidetector computed tomography is the first-choice imaging test because it can detect and characterize even small fractures and their associated complications quickly and accurately. It has helped clinical management and surgical planning, so radiologists must communicate their findings to surgeons effectively. In Le Fort fractures, there is a breach between the pterygoid plates and the posterior maxilla. These fractures are classified in three basic patterns that can be combined and associated with various complications. Conceptualized when low-speed trauma was predominant, the Le Fort classification system has become less relevant giving more importance on maxillary occlusion-bearing segments. The classification of naso-orbito-ethmoid depends on the extent of injury to the attachment of the medial canthal tendon, with possible complications like nasofrontal duct disruption. Displaced fractures of the zygomaticomaxillary complex often widen the angle of the lateral orbital wall, resulting in increased orbital volume and sometimes in enophthalmos. Severe comminution or angulation can lead to wide surgical exposure. In orbital fractures, entrapment of the inferior rectus muscles can lead to diplopia, so it is important to assess its positioning and morphology. Orbital fractures can also result in injuries to the globe or infraorbital nerve. Frontal sinus fractures that extend through the posterior sinus wall can create a communication with the anterior cranial fossa resulting in leakage of cerebrospinal fluid, intracranial bleeding. It is essential to categorize fracture patterns and highlight features that may affect fracture management in radiology reports of facial trauma.

Long-term Noninvasive Ventilation in Obesity Hypoventilation Syndrome Without Severe OSA: The Pickwick Randomized Controlled Trial.

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 Paco2, 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.