Effect of Continuous Positive Airway Pressure on Incident Frailty in Elderly Patients with Obstructive Sleep Apnea: A Study Based on Propensity Score Matching.

Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model.

BACKGROUND: Multiple organ dysfunction syndrome in the elderly (MODSE) is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models. METHODS: Twenty-four-month old rats (elderly) received intravenous injection of lipopolysaccharide (LPS) to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats. RESULTS: All rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats ((43.4 ± 8.4)%) than in young rats ((24.2 ± 3.0)%). LPS injection also enhanced tumor necrosis factor a (TNF-a) concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-a level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 (TLR4) expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung. CONCLUSION: Lung is the first and most seriously injured organ in rat model of MODSE and it may play an "initiating" role in the development of MODSE.

[Apoptosis of pulmonary alveolar macrophages in aged and adult rats: a comparative study].

OBJECTIVE: To investigate the role of alveolar macrophages (AM) in the initiation of multiple organ failure in the elderly (MOFE). METHODS: Three-month-old (adult) and 24-month-old (aged) males SD rats were used as experimental animals. Zymosan 0.5 g/kg was used to establish animal model of MOFE, normal saline were used among the control rats. The rats were divided into 4 groups: aged model group, aged control group, adult model group, and adult control group. Twenty-four hours after the establishment of model, 6 surviving rats from each group were killed. The trachea, bronthi, and lungs were isolated and lavaged with normal saline. One minute later the bronchi-alveolar lavage fluid (BALF) was re-extracted. Cells were collected from the fluid and put into 24-well cell culture plate. The alveolar macrophages (AMs) adhered to the wall were collected, suspended again, cultured, re-collected, centrifuged, and isolated. Apoptosis of the enriched AM was measured by propidium staining and flow cytometry. Fluo-3.AM staining and flow cytometry were used to detect the intracellular free calcium. Mitochondrial membrane electric potential was detected by rhodamine 123 staining with flow cytometry. RESULTS: The apoptotic rate (APO) of AM in the aged rat models was 43.4% +/- 8.4%, significantly higher than that of adult model rats (24.2% +/- 3.0%, P < 0.01). Compared with the controls, the intracellular calcium increased, but mitochondrial Dgr;Psim decreased in the 2 model groups. CONCLUSION: The AM APO% of aged MOFE model increases. It may be one of the causes of difficulty to control the inflammation in the lung with MOFE and easiness to induce MOFE in elderly when their lungs are infected or injured. Changes of intracellular calcium and mitochondrial Dgr;Psim may play pivotal roles in apoptosis of AM.