Home Noninvasive Ventilation in COPD.

Evidence is increasing that long-term noninvasive ventilation (LTNIV) can improve outcomes in individuals with severe, hypercapnic COPD. Although the evidence remains unclear in some aspects, LTNIV seems to be able to improve patient-related and physiologic outcomes like dyspnea, FEV1 and partial pressure of carbon dioxide (Pco2) and also to reduce rehospitalizations and mortality. Efficacy generally is associated with reduction in Pco2. To achieve this, an adequate interface (mask) is essential, as are appropriate ventilation settings that target the specific respiratory physiologic features of COPD. This will ensure comfort, synchrony, and adherence that will result in physiologic improvements. This article briefly reviews the newest evidence and current guidelines on LTNIV in severe COPD. It describes an actual patient who benefitted from the therapy. Finally, it provides strategies for initiating and optimizing this LTNIV in COPD, discussing high-pressure noninvasive ventilation, optimization of triggering, and control of inspiratory time. As demand increases, clinicians will need to be familiar with this therapy to reap its benefits, because inadequately adjusted LTNIV will not be tolerated or effective.

Pathogenesis of sleep disordered breathing in the setting of opioid use: A multiple mediation analysis using physiology.

STUDY OBJECTIVES: Opioid medications are commonly used and are known to impact both breathing and sleep, and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing pathogenesis are not established. METHODS: Patients who underwent clinically-indicated polysomnography confirming sleep-disordered breathing (SDB) (AHI≥5/hr) were included. Each patient using opioids was matched by sex, age, and BMI to three control individuals not using opioids. Physiology known to influence SDB pathogenesis were determined from validated polysomnography-based signal analysis. PSG and physiology paramters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics. RESULTS: 178 individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs 1.7 events/hr; p=0.001) and worsened hypoxemia (5 vs 3% sleep with SpO2<88%; p=0.013), with similar overall AHI. Use of opioids was associated with higher loop gain, a lower respiratory rate and higher respiratory rate variability. Higher loop gain and increased respiratory rate variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia. CONCLUSIONS: Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate deleterious respiratory consequences of chronic opioid use.

Effect of obesity on sleep apnea pathogenesis differs in women versus men: multiple mediation analyses in the retrospective SNOOzzzE cohort.

There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m2]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.124), a reduction in circulatory delay (ßstandardized = 0.063), and an increase in arousal threshold (ßstandardized = 0.029; Pboot-strapped,all < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (ßstandardized = 0.05) and circulatory delay (ßstandardized = 0.037; Pboot-strapped,all < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex.NEW & NOTEWORTHY Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).

Apnea-Specific Pulse-Rate Response is Associated With Early Subclinical Atherosclerosis in Obstructive Sleep Apnea.

INTRODUCTION: In patients with obstructive sleep apnea (OSA), novel metrics such as hypoxic burden (HB) and sleep apnea-specific pulse-rate response (ΔHR) may better correlate with cardiovascular diseases (CVD) than the apnea-hypopnea index (AHI). This manuscript aims to assess the correlation between ΔHR and HB with subclinical atherosclerosis in patients with OSA, testing the hypothesis that elevated ΔHR and HB are associated with subclinical atherosclerosis development. METHODS: In a prospective study, individuals aged 20-65 years with suspected OSA without known comorbidities were consecutively recruited and defined as OSA (AHI≥5events/h) or healthy controls. Using bilateral carotid ultrasonography, common carotid intima-media thickness (CIMT) was assessed and the identification of at least one atheromatous plaque defined the presence of subclinical atherosclerosis. ΔHR, and HB were derived from pulse-oximetry. RESULTS: We studied 296 patients of age 45±10 years old, of whom 28% were women, and with a BMI of 30.3±5.3kg/m2. Overall, 245 had OSA and 51 were healthy controls. After controlling for confounding variables higher ΔHR but not HB, was associated with higher CIMT (p=0.006) and higher time spent with oxygen saturation below 90% (T90) was associated with an increase in carotid atheroma plaques (p=0.032). When stratifying OSA based on HB tertiles, we observed that within tertile 2 of HB, an increase in ΔHR was associated with larger CIMT (p=0.017). CONCLUSION: A higher ΔHR is associated with an increase in CIMT among adult patients with OSA. This study suggests that ΔHR could be a biomarker of risk for CVD in patients with OSA.