Arterial Stiffness in Patients with Sarcoidosis and Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) and sarcoidosis have both been implied to be risk factors for increased arterial stiffness. However, it is unclear whether an elevated apnea–hypopnea index (AHI) in sarcoidosis patients increases arterial stiffness and thus the cardiovascular risk. Methods: We performed non-invasive applanation tonometry in 57 adults with sarcoidosis. The participants underwent SphygmoCor to assess arterial stiffness using an aortic augmentation index with a heart rate of 75/min (AIx) and level-3 respiratory polygraphy. An AHI of ≥5/h, ≥15/h, and ≥30/h defined mild, moderate, and severe OSA, respectively. Multivariate regression analysis was used to investigate the association between AIx and AHI, adjusted for prespecified risk factors for AIx. Results: 23 (40%) sarcoidosis patients had at least mild OSA (AHI ≥ 5), while 7 (12%) patients showed AHI ≥ 15/h. AHI was significantly associated with AIx (coef. (95%CI) of 0.31 (0.09/0.52), p = 0.006) even after adjustment for known risk factors of arterial stiffness. While severe OSA was positively associated with increased AIx, mild and moderate OSA were not associated with increased AIx after adjusting for known risk factors. Conclusions: Increased AHI is independently associated with increased arterial stiffness in sarcoidosis patients. Further investigations are needed to underline the association between OSA severity and the magnitude of arterial stiffness

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis

INTRODUCTION: Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction. METHODS: In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline. RESULTS: 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = –0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90–1.06, p = 0.64 over a period of 382.97 patient-years). CONCLUSION: Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors

The effect of longitudinal sleep monitoring on clinician agreement in obstructive sleep apnea diagnosis: The ELSA study

There is strong evidence for clinically relevant night‐to‐night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in‐laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea–hypopnea index in the respiratory polygraphy was  100 per year compared with 0–29 patients per year (Coef. [95% confidence interval] −0.63 [−1.22/−0.04] and −0.61 [−1.07/−0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty

Mortality Related to Chronic Obstructive Pulmonary Disease during the COVID-19 Pandemic: An Analysis of Multiple Causes of Death through Different Epidemic Waves in Veneto, Italy

Mortality related to chronic obstructive pulmonary disease (COPD) during the COVID-19 pandemic is possibly underestimated by sparse available data. The study aimed to assess the impact of the pandemic on COPD-related mortality by means of time series analyses of causes of death data. We analyzed the death certificates of residents in Veneto (Italy) aged ≥40 years from 2008 to 2020. The age-standardized rates were computed for COPD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple cause of death-MCOD). The annual percent change (APC) in the rates was estimated for the pre-pandemic period. Excess COPD-related mortality in 2020 was estimated by means of Seasonal Autoregressive Integrated Moving Average models. Overall, COPD was mentioned in 7.2% (43,780) of all deaths. From 2008 to 2019, the APC for COPD-related mortality was -4.9% (95% CI -5.5%, -4.2%) in men and -3.1% in women (95% CI -3.8%, -2.5%). In 2020 compared to the 2018-2019 average, the number of deaths from COPD (UCOD) declined by 8%, while COPD-related deaths (MCOD) increased by 14% (95% CI 10-18%), with peaks corresponding to the COVID-19 epidemic waves. Time series analyses confirmed that in 2020, COPD-related mortality increased by 16%. Patients with COPD experienced significant excess mortality during the first year of the pandemic. The decline in COPD mortality as the UCOD is explained by COVID-19 acting as a competing cause, highlighting how an MCOD approach is needed

Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61 +/- 10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal;however, no statistically significant changes of the renin-angiotensin-aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic-pituitary-adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425

Severe Obstructive Sleep Apnea Disrupts Vigilance-State-Dependent Metabolism

The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood. The aim of this secondary analysis was to translate recent findings in healthy subjects on vigilance-state-dependent metabolism into the context of OSA patients and answer the question of how symptomatic OSA influences metabolism and whether these changes might explain metabolic and cardiovascular consequences of OSA. Patients with suspected OSA were assigned according to their oxygen desaturation index (ODI) and Epworth Sleepiness Scale (ESS) score into symptomatic OSA and controls. Vigilance-state-dependent breath metabolites assessed by high-resolution mass spectrometry were used to test for a difference in both groups. In total, 44 patients were eligible, of whom 18 (40.9%) were assigned to the symptomatic OSA group. Symptomatic OSA patients with a median [25%, 75% quartiles] ODI of 40.5 [35.0, 58.8] events/h and an ESS of 14.0 [11.2, 15.8] showed moderate to strong evidence for differences in 18 vigilance-state-dependent breath compounds compared to controls. These identified metabolites are part of major metabolic pathways in carbohydrate, amino acid, and lipid metabolism. Thus, beyond hypoxia per se, we hypothesize that disturbed sleep in OSA patients persists as disturbed sleep-dependent metabolite levels during daytime

Augmentation Index in Patients with Thoracic Aortic Aneurysm: A Matched Case-Control Study

Thoracic aortic aneurysms (TAA) may be associated with complications such as rupture and dissection, which can lead to a fatal outcome. Increased central arterial stiffness has been proposed to be present in patients with TAA compared to unmatched controls. We aimed to assess whether wall properties in patients with TAA are also altered when compared to a matched control group. Applanation tonometry was performed in 74 adults with TAA and 74 sex, age, weight, height, and left ventricular ejection fraction matched controls. Subsequently analysis of the pulse wave was done using the SphygmoCor System. For comparing the two groups, AIx was adjusted to a heart rate of 75/min (AIx@75). 148 1-to-1 matched participants were included in the final model. There was no significant difference in the Alx@75 between the TAA group and the matched control group [mean (SD) of 24.7 (11.2) % and 22.8 (11.2) %, p = 0.240]. Adjusted for known cardiovascular risk factors, there was no association between TAA and AIx@75. Patients with TAA showed comparable arterial wall properties to cardiovascular risk factor matched controls. Since higher arterial stiffness is associated with TAA progression, it remains to be investigated if increased central arterial stiffness is a relevant factor of TAA emergence. Keywords: thoracic aortic aneurysm; augmentation index; arterial stiffnes

Prevalence of Obstructive Sleep Apnea in Joint Hypermobility Syndrome: A Systematic Review and Meta-Analysis

STUDY OBJECTIVES: Because of associated abnormalities affecting connective tissue in various organs including airways, hypermobility syndrome has been associated with high risk for the development sleep apnea. Ehlers-Danlos syndrome (EDS) and Marfan syndrome (MFS) represent the most common hypermobility syndromes; therefore, the purpose of this review was to examine the prevalence of obstructive sleep apnea (OSA) in these populations. METHODS: All publications and poster presentations written in English found through August 2018 that describe the prevalence of sleep apnea among people with EDS or MFS were included. RESULTS: A total of 13 studies were identified, 7 for EDS and 6 for MFS. A combined random prevalence rate of OSA across both populations was 48.9% (95% confidence interval 38.3-59.6), with a slightly higher rate of 59.7% (39.7-77.0) for MFS versus 39.4% (28.8-51.1) for EDS. However, a high degree of heterogeneity across studies was found in both groups (EDS group: Q = 28.6 and I2 = 79.0; MFS group: Q = 37.1 and I2 = 86.5). When directly compared to the general population, patients with EDS/MFS were on average six times more likely (odds ratio 6.28 [95% confidence interval 3.31-11.93], P < 0.001, Z = 5.61) to have a diagnosis of OSA. CONCLUSIONS: OSA is a previously underestimated EDS/MFS-related complication. The high prevalence of OSA might be the result of bony and soft-tissue abnormalities associated with these hypermobility syndromes. Untreated OSA is thought to worsen cardiovascular complications especially among those with MFS. Further research is needed to better delineate whether the prevalence of OSA is moderated by factors such as sex, body mass index, bony structure, and disorder subtype