Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain. METHODS: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population. RESULTS: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1). CONCLUSIONS: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).

Reliability of Home Nocturnal Oximetry in the Diagnosis of Overlap Syndrome in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and sleep apnea are common conditions and often coexist. The proper diagnosis of sleep apnea may affect the management and outcome of patients with COPD. OBJECTIVE: To determine the accuracy of home nocturnal oximetry to distinguish between nocturnal oxygen desaturation related to COPD alone or to sleep apnea in patients with moderate-to-severe COPD who have significant nocturnal hypoxemia with cyclical changes in saturation. METHODS: This study involved a comparison of home nocturnal oximetry and laboratory-based polysomnography (PSG) in patients with moderate-to-severe COPD considered for inclusion in a trial of nocturnal oxygen therapy. All of the patients had significant nocturnal oxygen desaturation (defined as ≥30% of the recording time with a transcutaneous arterial oxygen saturation <90%) with cyclical changes in saturation suggestive of sleep apnea. RESULTS: PSG was obtained in 90 patients; 45 patients (mean age = 68 years, SD = 8; 71% men; mean forced expiratory volume in 1 s [FEV1] = 50.6% predicted value, SD = 18.6%; data from 41 patients) fulfilled the criteria for sleep apnea (mean apnea-hypopnea index = 32.6 events/h, SD = 19.9) and 45 patients (mean age = 69 years, SD = 8; 87% men; mean FEV1 predicted value 44.6%, SD = 15%) did not (mean apnea-hypopnea index = 5.5 events/h, SD = 3.8). None of the patients' characteristics (including demographic, anthropometric, and physiologic measures) predicted the diagnosis of sleep apnea according to PSG results. CONCLUSION: The diagnosis of sleep apnea in patients with moderate to severe COPD cannot rely on nocturnal oximetry alone, even when typical cyclical changes in saturation are seen on oximetry tracing. When suspecting an overlap syndrome, a full-night, in-laboratory PSG should be obtained.

Effect of continuous positive airway pressure on blood pressure and metabolic profile in women with sleep apnoea.

Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04 mmHg, 95% CI -4.02- -0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54 mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90 mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12 weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment.

Continuous Positive Airway Pressure Improves Quality of Life in Women with Obstructive Sleep Apnea. A Randomized Controlled Trial.

RATIONALE: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. OBJECTIVES: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. METHODS: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). CONCLUSIONS: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).

Catheter directed therapy in high-risk pulmonary embolism: Analysis of 9 cases. / Terapia dirigida por catéter en embolia pulmonar de alto riesgo: análisis de 9 casos.

BACKGROUND: Mechanical thrombectomy is a useful technique in patients with high-risk pulmonary embolism. It is indicated as an alternative to systemic fibrinolysis when it is contraindicated or as an adjuvant therapy when it fails. OBJECTIVE: To describe clinical characteristics, evolution and survival of patients with high-risk pulmonary embolism who have undergone mechanical thrombectomy. METHOD: Single-center retrospective descriptive study of consecutive patients who underwent mechanical thrombectomy. Demographic, clinical and survival variables were analyzed. RESULTS: 9 patients were included (56% men, 44% women). All patients had pulmonary artery pressure assessed using a Swan-Ganz catheter before thrombectomy. The median pulmonary artery pressure before the procedure was 46mmHg (51-38mmHg). Systemic fibrinolysis was also performed in 5 cases, in 2 of them in the setting of cardiorespiratory arrest, without hemorrhagic complications. No patient died during hospitalization. Survival one month after the procedure was 100%. CONCLUSIONS: In our series, mechanical thrombectomy is a useful technique as an alternative to systemic fibrinolysis or as an adjuvant therapy to it.

Influence of Chronotypes in Respiratory Pathology.

The circadian rhythm of sleep occurs in a cyclical 24-h pattern that is adjusted by the influence of several main synchronizers or "zeitgebers". The most powerful synchronizer is the light-dark alternation, but also, socio-economic factors play a role, such as social and work relationships. Circadian rhythm regulation plays a crucial role in human health. This disruption of circadian rhythm can lead to increased incidence of diseases: diabetes, obesity, cancer, neurodegenerative diseases, increased risk of cardiovascular disease and stroke. Polygenic variations and environmental factors influence the circadian rhythm of each person. This is known as chronotype, which manifests itself as the degree of morning of evening preferences of each individual. There are indications to establish an association between individual chronotype preferences and the behavior of respiratory diseases.

El ritmo circadiano del sueño ocurre en un patrón cíclico de 24 horas que se ajusta por la influencia de varios sincronizadores principales o zeitgebers. El sincronizador más poderoso es la alternancia luz-oscuridad, además de los factores socioeconómicos, las relaciones sociales y las laborales. La regulación del ritmo circadiano juega un papel crucial en la salud humana. Esta interrupción del ritmo circadiano puede conducir a una mayor incidencia de enfermedades: diabetes, obesidad, cáncer, enfermedades neurodegenerativas, mayor riesgo de enfermedad cardiovascular e ictus.Las variaciones poligénicas y los factores ambientales influyen en el ritmo circadiano de cada persona. Esto se conoce como cronotipo, que se manifiesta como el grado de preferencias matutinas o vespertinas de cada individuo. Existen indicios para establecer una asociación entre las preferencias individuales de cronotipo y el comportamiento de las enfermedades respiratorias.

Short-Term Oxygen Therapy Outcomes in COPD.

Rationale: Short-term oxygen therapy (STOT) is often prescribed to allow patients with chronic obstructive pulmonary disease (COPD) to be discharged safely from hospital following an acute illness. This practice is widely accepted without being based on evidence. Purpose: Our objective was to describe the characteristics and outcomes of patients with COPD who received STOT. Patients and Methods: The study was a secondary analysis of the INOX trial, a 4-year randomised trial of nocturnal oxygen in COPD. The trial indicated that nocturnal oxygen has no significant effect on survival or progression to LTOT, allowing our merging of patients who received nocturnal oxygen and those who received placebo into a single cohort to study the predictors and outcomes of STOT regardless of the treatment received during the trial. Results: Among the 243 participants in the trial, 60 required STOT on at least one occasion during follow-up. Patients requiring STOT had more severe dyspnoea and lung function impairment, and lower PaO2 at baseline than those who did not. STOT was associated with subsequent LTOT requirement (hazard ratio [HR]: 4.59; 95% confidence interval [CI]: 2.98-7.07) and mortality (HR: 1.93; 95% CI: 1.15-3.24). The association between STOT and mortality was confounded by age, disease severity and comorbidities. Periods of STOT of more than one month and/or repeated prescriptions of STOT increased the probability of progression to LTOT (OR: 5.07; 95% CI: 1.48-18.8). Conclusion: Following an acute respiratory illness in COPD, persistent hypoxaemia requiring STOT is a marker of disease progression towards the requirement for LTOT.

Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study).

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with cardiovascular events (CVEs), although recent randomized controlled trials have not demonstrated that long-term continuous positive airway pressure (CPAP) prevents CVEs. Our objective was to determine the effect of CPAP on older adults with moderate OSA regarding CVE reduction. METHODS: An observational and multicenter study of a cohort of older adults (> 70 years of age) diagnosed with moderate OSA (apnea-hypopnea index 15.0-29.9 events/h) was conducted. Two groups were formed: (1) CPAP treatment and (2) standard of care. The primary endpoint was CVE occurrence after OSA diagnosis. Association with CPAP treatment was assessed by propensity score matching and inverse weighting probability. Secondary endpoints were incidence of CVE separately and time to first CVE. RESULTS: A total of 614 patients were included. After matching, 236 older adults (111 men, mean age 75.9 ± 4.7 years) with a follow-up of 47 months (interquartile range: 29.6-64.0 months) were considered for primary and secondary endpoint evaluations. Forty-one patients presented at least 1 CVE (17.4%): 20 were in the standard-of-care group (16.9%) and 21 were in the CPAP group (17.8%), with a relative risk of 1.05 (95% confidence interval [CI], 0.60-1.83; P = .43) for CPAP treatment. Inverse probability weighting of the initial 614 patients determined an adjusted relative risk of 1.24 (95% CI, 0.79-1.96; P = .35) for CPAP treatment. No statistical differences were found in secondary endpoint analyses. CONCLUSIONS: CPAP should not be prescribed to reduce CVE probability in older adults with moderate OSA. CITATION: López-Padilla D, Terán-Tinedo J, Cerezo-Lajas A, et al. Moderate obstructive sleep apnea and cardiovascular outcomes in older adults: a propensity score-matched multicenter study (CPAGE-MODE study). J Clin Sleep Med. 2022;18(2):553-561.

High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.

INTRODUCTION: High-flow nasal cannula oxygen therapy (HFNC) has been shown to be a useful therapy in the treatment of patients with Acute Respiratory Distress Syndrome (ARDS), but its efficacy is still unknown in patients with COVID-19. Our objective is to describe its utility as therapy for the treatment of ARDS caused by SARS-CoV-2. METHODS: A retrospective, observational study was performed at a single centre, evaluating patients with ARDS secondary to COVID-19 treated with HFNC. The main outcome was the intubation rate at day 30, which defined failure of therapy. We also analysed the role of the ROX index to predict the need for intubation. RESULTS: In the study period, 196 patients with bilateral pneumonia were admitted to our pulmonology unit, 40 of whom were treated with HFNC due to the presence of ARDS. The intubation rate at day 30 was 52.5%, and overall mortality was 22.5%. After initiating HFNC, the SpO2/FiO2 ratio was significantly better in the group that did not require intubation (113.4±6.6 vs 93.7±6.7, p=0.020), as was the ROX index (5.0±1.6 vs 4.0±1.0, p=0.018). A ROX index less than 4.94 measured 2 to 6 h after the start of therapy was associated with increased risk of intubation (HR 4.03 [95% CI 1.18 - 13.7]; p=0.026). CONCLUSION: High-flow therapy is a useful treatment in ARDS in order to avoid intubation or as a bridge therapy, and no increased mortality was observed secondary to the delay in intubation. After initiating HFNC, a ROX index below 4.94 predicts the need for intubation.

Continuous Positive Airway Pressure Treatment Does not Reduce Uric Acid Levels in OSA Women.

OBJECTIVES: Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. METHODS: We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥4h/night and those with UA levels ≥6mg/dl. RESULTS: Women had a mean (SD) age of 57.1 (10.1) years, median (first-third quartile) body mass index of 33.7 (29.0-38.5) mg/kg2 and AHI of 32.0 (22.6-48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA≥6mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference -0.03mg/dl, 95%CI -0.20 to 0.13; p=0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4h/night, or the subgroup of women with hyperuricemia. CONCLUSIONS: Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA.

[Sleep-apnea syndrome, mechanical ventilation and critical care in Archivos de Bronconeumología (December 2009-December 2010)]. / El síndrome de apnea del sueño, la ventilación mecánica y los cuidados críticos en Archivos de Bronconeumología (diciembre 2009-diciembre 2010).

The present study aims to review all the major articles on respiratory sleep disorders, mechanical ventilation, and respiratory critical care published in the last year in Archivos de bronconeumología. Between December 2009 and November 2010, 15 studies on these topics were published in Archivos de bronconeumología. Ten of these studies dealt with respiratory sleep disorders, consisting of six original articles, one special article, one review article, one letter to the editor and one supplement on chronic obstructive pulmonary disease and its association with sleep apneas. Five articles were published on non-invasive mechanical ventilation: one editorial, one special article, one article in a supplement and two original articles. As in previous years, there was a marked difference in the number of articles published on non-invasive mechanical ventilation and sleep-apnea syndrome, with a greater number of articles being published on the latter. Although some articles highlight the importance of the place where ventilation is commenced, no study specifically dealing with intermediate care units was published in Archivos de bronconeumología in 2010. This absence could be interpreted as a result of the low implantation of this type of unit in Spain, contrasting with the high activity undertaken in this field by pneumology services.