Continuous Positive Airway Pressure but Not GLP1-mediated Weight Loss Improves Early Cardiovascular Disease in Obstructive Sleep Apnea: A Randomized Proof-of-Concept Study.

Rationale: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) is uncertain. However, most randomized controlled trials have focused on the role of CPAP in secondary prevention, although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. Objectives: The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it with a glucagon-like peptide (GLP)-1-mediated weight loss regimen in patients with OSA. Methods: We performed a randomized proof-of-concept study comparing CPAP, a GLP1-mediated weight-loss regimen (liraglutide [Lir]), and both in combination for 24 weeks in 30 consecutive patients with OSA (apnea-hypopnea index >15 events/h; body mass index 30-40 kg/m2; and no history of diabetes, heart failure, or unstable CV disease). In addition to extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) for the measurement of aortic wall inflammation (target-to-background ratio) and coronary computed tomography angiography for semiautomated coronary plaque analysis. Results: Baseline characteristics were similar between groups. CPAP alone and in combination resulted in greater reduction in apnea-hypopnea index than Lir alone (mean difference, -45 and -43 events/h, respectively, vs. -12 events/h; P < 0.05). Both Lir and combination treatment led to significant weight loss, but only CPAP alone resulted in significant decrease in vascular inflammation (aortic wall target-to-background ratio from 2.03 ± 0.34 to 1.84 ± 0.43; P = 0.010), associated with an improvement in endothelial function and a decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as a marker of unstable plaque also decreased with CPAP (from 571 ± 490 to 334 ± 185 mm3) and with combination therapy (from 401 ± 145 to 278 ± 126 mm3) but not with Lir. Conclusions: These data suggest that CPAP therapy, but not GLP1-mediated weight loss, improves vascular inflammation and reduces unstable plaque volume in patients with OSA. Further large randomized controlled studies are warranted to assess the benefit of CPAP therapy in modifying early CV disease. Clinical trial registered with www.clinicaltrials.gov (NCT04186494).

Cardiovascular manifestations in obstructive sleep apnea: current evidence and potential mechanisms.

Obstructive sleep apnea (OSA) is an increasingly prevalent health concern characterized by repeated episodes of pharyngeal collapse during sleep. It is frequently associated with daytime sleepiness and impaired functional capacity, but it is also linked to cardiovascular disease by a growing body of epidemiological, clinical, and translational research. The severity of OSA is traditionally evaluated by the apnea­hypopnea index (AHI), but the value of this marker as a predictor of cardiovascular outcomes is limited. Thus, there is an increasing focus on alternative classification methods such as the hypoxic burden, other polysomnographic traits, and phenotypic subgroups based on clinical symptoms. There is a need to identify subgroups of patients with OSA who will benefit most from treatment, as recent large randomized controlled trials in selected populations have failed to show benefit in reducing overall cardiovascular mortality. Obstructive sleep apnea adversely affects cardiovascular structure and function by several distinct mechanisms such as intermittent hypoxia, sleep fragmentation, and intrathoracic pressure swings. These mechanisms lead to sympathetic activation, inflammation, and oxidative stress, which may result in the clinical consequences of OSA such as hypertension, coronary artery disease, heart failure, and cerebrovascular disease. This review focuses on the epidemiology and potential mechanisms of cardiovascular diseases in OSA. Furthermore, we will briefly discuss the role of personalized medicine, alternative treatment options, and precise phenotyping to optimize treatment of this complex condition and its associated cardiovascular risk.

Transbronchial lung cryobiopsy (TBLC) in the diagnosis of interstitial lung disease: experience of first 100 cases performed under conscious sedation with flexible bronchoscope.

BACKGROUND: Diagnosing the aetiology of interstitial lung disease (ILD) may require histology via a surgical lung biopsy (SLB). SLB is associated with significant complications. Transbronchial lung cryobiopsy (TBLC) can provide large, adequate biopsies with fewer complications offering a potential alternative to SLB. AIMS: This study evaluated the safety, diagnostic yield and impact of TBLC on diagnostic certainty in the multidisciplinary diagnosis (MDD) of ILD within routine clinical practice. METHODS: A retrospective study of all TBLC performed in a tertiary institute from March 2014 to December 2016 was performed. Procedures were performed using a flexible bronchoscope and cryoprobe without fluoroscopic guidance. RESULTS: One hundred procedures were performed on 85 patients. A total of 272 cryobiopsies were obtained with a mean biopsy diameter of 5.9 ± 3.2 mm. Ninety-seven percent contained alveolated lung tissue. Diagnosis based against MDD gold standard was confirmed using TBLC in 67.1% of patients and in 72/100 procedures. Three patients proceeded to SLB. The addition of histological information changed the clinic-radiological diagnosis in twelve patients. The most common diagnosis based on clinical-radiologic-pathologic correlation at MDD was idiopathic pulmonary fibrosis (IPF) (51.2%) and hypersensitivity pneumonitis (15.9%). Moderate bleeding occurred in 18% of cases and five patients (5%) developed pneumothorax requiring intervention. Eleven patients required admission, with a mean length of stay of 1.3 ± 0.9 days. CONCLUSION: TBLC aids the diagnosis of ILD in the appropriate patient and may be an acceptable alternative to SLB with fewer complications. Further work on standardizing the procedure is required.

Lymphangioleiomyomatosis: a clinical review.

Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease. There are two main types of LAM: sporadic, and LAM associated with the tuberous sclerosis complex (TSC), which is caused by mutations in the TSC1 and TSC2 genes. LAM is characterised by cystic lung disease resulting in progressive dyspnoea, renal angiomyolipomas and lymphatic complications. Pneumothorax occurs frequently (70%) and definitive management with pleurodesis is recommended as the risk of recurrence is high. Characteristic thin-walled cysts are seen on computed tomography and the presence of elevated serum levels of a vascular endothelial growth factor-D has good diagnostic specificity. Currently, no single clinical or serological factor has been shown to predict prognosis. However, over the past decade, significant advances in our understanding of the pathophysiology of LAM has led to improved recognition of this rare disease and identification of treatment options. Mechanistic target of rapamycin inhibitors slow the rate of lung function decline and can resolve chylous effusion and regress angiomyolipomas. Life expectancy in patients with LAM is favourable, with a mean transplant-free survival >20 years from the time of diagnosis. Continued advances in understanding the molecular basis of LAM will lead to improved therapeutic targets and the development of more robust prognostic indicators. EDUCATIONAL AIMS: To illustrate the clinical features, common presentations and radiological features of LAMTo outline the diagnostic approach to LAM, including the role of VEGF-DTo review the current prognostic indicators in LAM, and outline the impact of lung function, hormonal status, VEGF-D and clinical presentation on outcomeTo inform clinicians on the management options for LAM both pharmacological and nonpharmacological.

Technologic advances in the assessment and management of obstructive sleep apnoea beyond the apnoea-hypopnoea index: a narrative review.

Obstructive sleep apnoea (OSA) is a growing and serious worldwide health problem with significant health and socioeconomic consequences. Current diagnostic testing strategies are limited by cost, access to resources and over reliance on one measure, namely the apnoea-hypopnoea frequency per hour (AHI). Recent evidence supports moving away from the AHI as the principle measure of OSA severity towards a more personalised approach to OSA diagnosis and treatment that includes phenotypic and biological traits. Novel advances in technology include the use of signals such as heart rate variability (HRV), oximetry and peripheral arterial tonometry (PAT) as alternative or additional measures. Ubiquitous use of smartphones and developments in wearable technology have also led to increased availability of applications and devices to facilitate home screening of at-risk populations, although current evidence indicates relatively poor accuracy in comparison with the traditional gold standard polysomnography (PSG). In this review, we evaluate the current strategies for diagnosing OSA in the context of their limitations, potential physiological targets as alternatives to AHI and the role of novel technology in OSA. We also evaluate the current evidence for using newer technologies in OSA diagnosis, the physiological targets such as smartphone applications and wearable technology. Future developments in OSA diagnosis and assessment will likely focus increasingly on systemic effects of sleep disordered breathing (SDB) such as changes in nocturnal oxygen and blood pressure (BP); and may also include other factors such as circulating biomarkers. These developments will likely require a re-evaluation of the diagnostic and grading criteria for clinically significant OSA.

Obstetric and perinatal outcomes of twin pregnancies conceived following IVF/ICSI treatment compared with spontaneously conceived twin pregnancies.

OBJECTIVE: Twin pregnancy is associated with increased obstetric and perinatal risk. There are conflicting reports on whether assisted conception (ART) further increases these risks. The aim of this study is to assess the obstetric and perinatal outcomes of twin pregnancies according to mode of conception. STUDY DESIGN: A retrospective study of all viable dichorionic-diamniotic (DCDA) twin pregnancies (n=539) delivered at Cork University Maternity Hospital, Ireland between 2009 and 2012, divided according to spontaneous conception (SC) and ART conception, specifically IVF or ICSI. RESULTS: The ART conceived group were on average 4 years older (36.8±4.23 vs 32.3±4.93 years) and more frequently nulliparous (73.7%; n=126 vs 36.1%; n=133) than their SC counterparts (p<0.001). There was no significant difference in maternal antenatal complications. ART twins were twice as likely to be delivered by caesarean section (CS) (OR 2.35; 95% CI 1.76-3.14). There was no significant difference in the rates of preterm birth or NICU admission according to mode of conception. ART conceived twins were almost twice as likely to be delivered moderately preterm (32-33(+6)) (OR 1.98, 95% CI 1.21-3.23) and were more likely to have RDS and neonatal hypoglycaemia CONCLUSIONS: Twin pregnancy, irrespective of mode of conception, carries an increased risk of morbidity and mortality for both mother and babies and therefore couples should be counselled regarding the increased risk of iatrogenic twinning associated with double embryo transfer. However, for those that do conceive twins, they can be advised that assisted conception conveys no significant disadvantage over naturally conceived twin pregnancies.