Real-Life Clinical Outcomes of Benralizumab Treatment in Patients with Uncontrolled Severe Asthma and Coexisting Chronic Rhinosinusitis with Nasal Polyposis.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p < 0.001), steroid cycles by 84% (p < 0.001), emergencies visit by 83% p < 0.001) and admissions by 76% (p < 0.001), improving all the scales for asthma control, (p < 0.001). In terms of lung function, differences were observed in FVC% (p < 0.001), FEV1% (p < 0.001), and FEV1/FVC% (69.5 ± 10 vs. 74 ± 10, p < 0.001). In relation to CRSwNP, differences were observed in SNOT-22 (54.66 ± 17 vs. 20.24 ± 9, p < 0.001), VAS obstruction (7.91 ± 1 vs. 1.36 ± 1, p < 0. 001), VAS drip (7.76 ± 1 vs. 1.38 ± 1, p < 0.001), VAS anosmia (7.66 ± 1 vs. 1.38 ± 1, p < 0.001) and VAS facial pressure (7.91 ± 1 vs. 1.22 ± 1, p < 0.001). The mean FEOS score after treatment was 73 ± 14. A complete response/super response was achieved in 33 patients (57%), good response in 16 (28%) and partial response in 9 (15%). Conclusions: The administration of benralizumab to patients with uncontrolled severe asthma associated with CRSwNP has been demonstrated to improve nasal symptoms, asthma control and lung function. This resulted in a reduction in the need for oral steroids, maintenance and rescue medication, emergency room visits, and hospital admissions, with 57% of patients achieving the clinical remission criteria.

Analysis of Patients Admitted for Asthma Exacerbation in a Tertiary Hospital in Spain.

OBJECTIVES: To analyze the characteristics of adult patients admitted for asthma exacerbation and determine optimization, treatment adherence, and follow-up in clinics. METHODS: Patients ≥ 18 years old admitted from May 2021 to June 2023 with a primary diagnosis of asthma exacerbation were included. Patients with a secondary diagnosis of asthma exacerbation and those without a confirmed diagnosis were excluded. RESULTS: A total of 186 patients were analyzed, 63% were female, with a mean age of 49 ± 34 years, mean body mass index (BMI) of 26.4 ± 5 kg/m2, mean immunoglobulin E level of 132 ± 235 IU/mL (range: 25-2041), mean eosinophils count of 180 ± 443, and length of stay of 8.6 ± 5 days. Comparing patients with one admission to those with multiple admissions, differences were observed in age (39 ± 15 vs. 58 ± 20, p < 0.0001), BMI (25.2 ± 3 vs. 27.4 ± 4, p < 0.0003), comorbidity (15% vs. 60%, p < 0.0001), and length of stay (4.5 ± 2 vs. 11 ± 3, p < 0.0001). Of the patients, 15% had undiagnosed asthma, 28% had known asthma without maintenance therapy, 23% were managed by primary care, and 34% were followed by pneumology. The mean Test of Adherence to Inhalers (TAI) score was 42.5 ± 8 points, with 70% showing erratic non-adherence, 46% showing deliberate non-adherence, and 21% showing unconscious non-adherence. CONCLUSIONS: The young population represents a significant percentage of admissions for asthma exacerbation due to poor follow-up in pulmonology clinics, inadequate treatment optimization, and low adherence. This study adds that it is necessary to improve the approach to asthma in primary care to optimize treatment, reduce under-diagnosis, and avoid hospital admissions.

Real-world clinical remission of severe asthma with benralizumab in Spanish adults with severe asthma.

OBJECTIVE: Patients with severe eosinophilic asthma experience high risk of exacerbations and reduced quality of life. Benralizumab, a monoclonal antibody binding to IL-5 receptor α subunit, is an approved drug for its treatment. The objective was to describe clinical remission after benralizumab prescription in routine clinical practice. METHODS: Retrospective multicenter study with data from four hospitals in Valencian Community (Spain) with asthma units between 2019 and 2020. Data was gathered at baseline and after 12 months. We considered clinical remission after 1 year if the patient remained without exacerbations and use of systemic corticosteroids and with good clinical control and normal lung function. RESULTS: Data from 139 patients was gathered. At the 12-month follow-up, 44.1% were in clinical remission, since 84.0%, 77.5%, 51.0% and 95.5% of patients did not experience exacerbations, had total asthma control test score of ≥20, prebronchodilator FEV1 of ≥80% and did not use systemic corticosteroids. A significant reduction of long-acting muscarinic antagonists (p = 0.0001), leukotriene receptor antagonists (p = 0.0326), oral corticosteroids (p < 0.0001) and short-acting beta agonists (p = 0.0499) was observed. Baseline factors with greatest individual influence on clinical remission were employment situation, tobacco use, comorbidity number, eosinophil value, number of exacerbations, FEV1, emergency visit number, and ACT, MiniAQLQ and TAI scores. Final analysis of multiple logistic regression indicated that having baseline FEV1 value below 80% increases remission chance 9.7 times a year compared to FEV1 >80%. CONCLUSION: Clinical remission after treatment with benralizumab is achievable in a high percentage of patients with severe asthma eosinophilia not controlled in real life.

Biliothorax in a patient with unresectable cholangiocarcinoma.

Biliothorax is a rare but serious condition, as the presence of bile is damaging and can lead to empyema. Here, we report a case of a 51-year-old man recently diagnosed with unresectable cholangiocarcinoma, admitted to the hospital for malignant obstructive jaundice. After interventional management of biliary obstruction, the patient developed a significant right pleural effusion compatible with biliothorax, successfully managed with pleural drainage and antibiotic therapy. Resolution was possible with a conservative approach: biliary decompression, chest tube drainage and antibiotics.

Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

BACKGROUND: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored. RESEARCH QUESTION: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma? STUDY DESIGN AND METHODS: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome. RESULTS: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90). INTERPRETATION: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA.

Features of Obstructive Sleep Apnea in Children with and without Comorbidities.

BACKGROUND: To compare the clinical and polysomnographic features of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy (Group A) and comorbidities (Group B). METHODS: A five-year prospective study using nocturnal polysomnography before and after treatment. RESULTS: We included 168 patients: 121 in Group A and 47 in Group B, with differences in age (6.5 ± 3 vs. 8.6 ± 4 years; p < 0.001), body mass index (BMI) (18 ± 4 vs. 20 ± 7 kg/m2; p < 0.05), neck circumference (28 ± 4 vs. 30 ± 5 cm; p < 0.05), and obesity (17% vs. 30%; p < 0.05). Group B patients were more likely to have facial anomalies (p < 0.001), macroglossia (p < 0.01), dolichocephaly (p < 0.01), micrognathia (p < 0.001), and prognathism (p < 0.05). Adenotonsillectomy was performed in 103 Group A patients (85%) and 28 Group B patients (60%) (p < 0.001). In B, 13 children (28%) received treatment with continuous positive airway pressure (CPAP) and 2 (4%) with bilevel positive airway pressure (BiPAP), compared with 7 in Group A (6%) (p < 0.001). Maxillofacial surgery was more common in Group B (p < 0.01). Clinical and polysomnography parameters improved significantly in both groups after therapeutic intervention, though Group A showed better results. CONCLUSIONS: Obesity and facial anomalies are more frequent in childhood OSA patients with comorbidities, who often require combination therapy, such as ventilation and surgery.

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with a recurrent cardiovascular event (CVE) risk in patients with a first acute coronary syndrome (ACS). However, the pathological pathways by which OSA promotes this deleterious role are unknown. We aim to explore the proteomic profile associated with OSA that promote the recurrent CVE risk in severe OSA patients with ACS without previous cardiovascular diseases. METHODS: This post-hoc analysis from the ISAACC study (NCT01335087) included 86 patients admitted for ACS. Patients underwent respiratory polygraphy for the first 24-72 h to OSA diagnosis. We analyzed of 276 cardiovascular and inflammatory related proteins in baseline fasting plasma samples using proximity expression assay technology (Olink®, Sweden). Protein levels were compared between severe OSA patients with/without recurrent CVEs during follow-up. Random forest was conducted to select relevant proteins and generate a predictive model of recurrent CVE. RESULTS: We included 86 patients (median age: 61 years, median BMI: 29.4 kg/m2 and 86 % males) admitted for ACS with severe OSA (56 without recurrent CVE/30 with recurrent CVE). The plasma levels of 38 proteins were differentially expressed between groups. Additionally, 12 proteins had a significant association with respiratory polygraphy parameters. Three proteins discriminate with an AUC of 0.81 (95 % CI of 0.71-0.9) between severe OSA patients with and without recurrent CVE. These proteins were implicated in cell proliferation, communication and apoptosis, and regulation/response to the inflammatory and immune systems. CONCLUSION: In ACS patients with severe OSA, a proteomic profile was associated with recurrent CVEs. This proteomic profile was correlated with specific OSA parameters from respiratory polygraphy. Proteomic profiling may provide an new direction for patient risk stratification and clinical management.

Respiratory Polygraphy Patterns and Risk of Recurrent Cardiovascular Events in Patients With Acute Coronary Syndrome.

Introduction: Obstructive sleep apnea (OSA) severity is based on the apnea-hypopnea index (AHI). The AHI is a simplistic measure that is inadequate for capturing disease severity and its consequences in cardiovascular diseases (CVDs). Deleterious effects of OSA have been suggested to influence the prognosis of specific endotypes of patients with acute coronary syndrome (ACS). We aim to identify respiratory polygraphy (RP) patterns that contribute to identifying the risk of recurrent cardiovascular events in patients with ACS. Methods: Post hoc analysis of the ISAACC study, including 723 patients admitted for a first ACS (NCT01335087) in which RP was performed. To identify specific RP patterns, a principal component analysis (PCA) was performed using six RP parameters: AHI, oxygen desaturation index, mean and minimum oxygen saturation (SaO2), average duration of events and percentage of time with SaO2 < 90%. An independent HypnoLaus population-based cohort was used to validate the RP components. Results: From the ISAACC study, PCA showed that two RP components accounted for 70% of the variance in the RP data. These components were validated in the HypnoLaus cohort, with two similar RP components that explained 71.3% of the variance in the RP data. The first component (component 1) was mainly characterized by low mean SaO2 and obstructive respiratory events with severe desaturation, and the second component (component 2) was characterized by high mean SaO2 and long-duration obstructive respiratory events without severe desaturation. In the ISAACC cohort, component 2 was associated with an increased risk of recurrent cardiovascular events in the third tertile with an adjusted hazard ratio (95% CI) of 2.44 (1.07 to 5.56; p-value = 0.03) compared to first tertile. For component 1, no significant association was found for the risk of recurrent cardiovascular events. Conclusion: A RP component, mainly characterized by intermittent hypoxemia, is associated with a high risk of recurrent cardiovascular events in patients without previous CVD who have suffered a first ACS.

Long-Term Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Treatment on Blood Pressure in Patients with Acute Coronary Syndrome: A Clinical Trial.

Rationale: Obstructive sleep apnea (OSA) is prevalent in patients with acute coronary syndrome (ACS) and is a cause of secondary hypertension. Objectives: To explore the long-term effects of OSA and continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in patients with ACS. Methods: Post hoc analysis of the ISAACC study (Continuous Positive Airway Pressure in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea; NCT01335087) included 1,803 patients admitted for ACS. Patients with OSA (apnea-hypopnea index [AHI], ⩾15 events/h) were randomly assigned to receive either CPAP or usual care and were seen in follow-up for 1-5 years. Office BP was determined at each visit. Results: We included 596 patients without OSA, 978 patients in the usual care or poor CPAP adherence group, and 229 patients in the good CPAP adherence group. At baseline, 52% of the patients were diagnosed with hypertension. Median (25th to 75th percentile) age and body mass index were 59 (52.0 to 67.0) years and 28.2 (25.6 to 31.2) kg/m2, respectively. After a median (25th to 75th percentile) follow-up of 41.2 (18.3 to 59.6) months, BP changes were similar in the OSA and non-OSA groups. However, we observed an increase in BP in the third tertile of the AHI (AHI, >40 events/h), with a maximum difference in mean BP of +3.3 mm Hg at 30 months. Patients with OSA with good CPAP adherence (⩾4 h/night) reduced mean BP after 18 months compared with patients with usual care/poor CPAP adherence, with a maximum mean difference (95% confidence interval) of -4.7 (-6.7 to -2.7) mm Hg. In patients with severe OSA, we observed a maximum mean difference of -7.1 (-10.3 to -3.8) mm Hg. Conclusions: In patients with ACS, severe OSA is associated with a long-term increase in BP, which is reduced by good CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT01335087).

Spanish COPD Guidelines (GesEPOC 2021): Non-pharmacological Treatment Update. / Actualización 2021 de la Guía Española de la EPOC (GesEPOC). Tratamiento no farmacológico.

In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included.

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.

Spanish COPD Guideline (GesEPOC) Update: Comorbidities, Self-Management and Palliative Care. / Actualización de la Guía Española de la EPOC (GesEPOC): comorbilidades, automanejo y cuidados paliativos.

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD.

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.