MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

[Traditional Chinese medicine and active ingredients regulate M1/M2 macrophage polarization balance to treat chronic obstructive pulmonary disease: a review].

Chronic obstructive pulmonary disease(COPD) is a progressive lung dysfunction(disease) caused by long-term inhalation of toxic particles, especially smoking. The continued exposure to harmful substances triggers an abnormal inflammatory response, which causes permanent damage to the respiratory system, ultimately leading to irreversible pathological changes. Lung macrophages(LMs) are key innate immune effectors involved in the recognition, phagocytosis, and clearance of pathogens, as well as in the processing of inhaled hazardous particulate matter(e. g., cigarette smoke and particulate matter). LMs are polarized toward the M1 or M2 phenotype in response to the activation of inflammatory mediators to exert pro-/anti-inflammatory effects, respectively, thus being involved in the pulmonary parenchymal damage(emphysema) and repair(airway remodeling) throughout the process of COPD.In addition, they are responsible for phagocytosis and clearance of apoptotic or necrotic tissue cells, which helps to maintain the stability of the microenvironment in the lungs of COPD patients. Modern studies have revealed that macrophage polarization plays a pivotal role in the pathogenesis and development of COPD and is considered a potential target for treating COPD because of its ability to reduce airway inflammation, inhibit tissue remodeling, and combat oxidative stress. In recent years, traditional Chinese medicine(TCM) and its active ingredients have become a hot area in the treatment of COPD by targeting the balance of M1/M2 macrophage polarization. TCM and its active ingredients can intervene in the inflammatory response to promote the repair of the lung tissue in the patients with COPD. This paper reviews the research achievements of TCM and its active ingredients in this field in recent years,aiming to provide a scientific basis and strong support for the precise diagnosis and treatment of COPD.

[Effect of Polygonati Rhizoma aqueous extract on chronic obstructive pulmonary disease in rats].

This study aimed to investigate the effects and potential mechanism of Polygonati Rhizoma aqueous extract on chronic obstructive pulmonary disease(COPD) in rats. Forty-eight Sprague-Dawley rats were randomly assigned to the normal, model,Yupingfeng Granules(1. 5 g·kg~(-1)), and low-, medium-, and high-dose(0. 25, 0. 5, and 1 g·kg~(-1), respectively) Polygonati Rhizoma aqueous extract groups. The rat model of COPD was established by cigarette smoke inhalation for 8 weeks, and then the modeled rats received corresponding treatment for 4 weeks. The grip strength and fecal moisture content were measured, and the lung index was calculated. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α in the lung tissue. Hematoxylin-eosin(HE) staining and Masson staining were performed to assess the pathological changes in the lung tissue. Flow cytometry was used to analyze T lymphocytes and their subpopulations in the peripheral blood, and the immunofluorescence assay and Western blot were employed to measure the protein levels of Toll-like receptor 4(TLR4), phosphorylated nuclear factor-kappaB(p-NF-κB), NF-κB, phosphorylated inhibitory kappa B-α(p-IκBα), IκBα, IL-6,and TNF-α in the lung tissue. The results indicated that the treatment with Polygonati Rhizoma aqueous extract significantly reduced the fecal moisture content, enhanced the grip strength, and inhibited inflammatory infiltration and fibrosis in the lung tissue. The treatment increased the Th/Tc ratio and Th cell proportion and decreased the Tc cell proportion in the peripheral blood. Furthermore,the treatment down-regulated the expression levels of TLR4, IL-6, and TNF-α and the p-NF-κB/NF-κB and p-IκBα/IκBα ratios in the lung tissue. In conclusion, Polygonati Rhizoma aqueous extract can ameliorate lung tissue damage in the rat model of COPD by inhibiting the TLR4/NF-κB signaling pathway and the production of inflammatory mediators.

Reasonable Risk Ratio of Palate Surgery: A New Critical Analysis.

OBJECTIVE.: A new critical complication risk analysis, the reasonable risk ratio (RRR or R3) for palate surgeries in obstructive sleep apnea patients. METHODS.: Analysis from published meta-analyses, systematic reviews on success rates, and complications encountered for 3 palate surgeries, expansion sphincter pharyngoplasty (ESP), barbed repositioning pharyngoplasty (BRP) and modified uvulopalatopharyngoplasty (mUPPP), over 20 years. The RRR is derived from a ratio of the percentage of each respective complication over the success rate of that particular surgical procedure. The benchmark RRR of tonsillectomy is set at 0.035 to 0.078. An RRR below this benchmark value is more favorable as tonsillectomy is a widely accepted ENT procedure with risks to benefit well accepted. RESULTS.: The RRR for foreign body (FB) sensation (BRP) ranged from 0.03 to 0.23 (mean RRR of 0.14), FB sensation (ESP) 0.01, FB sensation (mUPPP) ranged from 0.33 to 0.55 (mean RRR of 0.44). The RRR for swallowing difficulties (BRP) ranged from 0.04 to 0.23 (mean RRR of 0.11), mUPPP, was 0.37; no reported swallowing difficulties with the ESP. The RRR for velopharyngeal insufficiency (VPI) (BRP) ranged from 0.009 to 0.18 (mean RRR of 0.07), and RRR VPI (mUPPP) was 0.14. The RRR (BRP) for dry throat was 0.06 and the mUPPP was 0.35, with no reported VPI or dry throat for ESP. The overall RRR for the BRP was 0.09, ESP was 0.01 and mUPPP was 0.29. CONCLUSION.: RRR provides a summarized data-driven, statistical guide to aid decision-making, and helps in patient counseling. BRP and ESP have been shown to have less complications compared to mUPPP.Level of evidence: IV.

Neurite Orientation Dispersion and Density Imaging (NODDI) reveals white matter microstructural changes in Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) patients with cognitive impairment.

PURPOSE: This study aimed to assess changes in white matter microstructure among patients undergoing obstructive sleep apnea hypopnea syndrome (OSAHS) complicated by cognitive impairment through neurite orientation dispersion and density imaging (NODDI), and evaluate the relationship to cognitive impairment as well as the diagnostic performance in early intervention. METHODS: Totally 23 OSAHS patients, 43 OSAHS patients complicated by cognitive impairment, and 15 healthy controls were enrolled in OSA, OSACI and HC groups of this work. NODDI toolbox and FMRIB's Software Library (FSL) were used to calculate neurite density index (NDI), Fractional anisotropy (FA), volume fraction of isotropic water molecules (Viso), and orientation dispersion index (ODI). Tract-based spatial statistics (TBSS) were carried out to examine the above metrics with one-way ANOVA. This study explored the correlations of the above metrics with mini-mental state examination (MMSE), and montreal cognitive assessment (MoCA) scores. Furthermore, receiver operating characteristic (ROC) curves were plotted. Meanwhile, area under curve (AUC) values were calculated to evaluate the diagnostic performance of the above metrics. RESULTS: NDI, ODI, Viso, and FA were significantly different among different brain white matter regions, among which, difference in NDI showed the greatest statistical significance. In comparison with HC group, OSA group had reduced NDI and ODI, whereas elevated Viso levels. Conversely, compared to the OSA group, the OSACI group displayed a slight increase in NDI and ODI values, which remained lower than HC group, viso values continued to rise. Post-hoc analysis highlighted significant differences in these metrics, except for FA, which showed no notable changes or correlations with neuropsychological tests. ROC analysis confirmed the diagnostic efficacy of NDI, ODI, and Viso with AUCs of 0.6908, 0.6626, and 0.6363, respectively, whereas FA's AUC of 0.5042, indicating insufficient diagnostic efficacy. CONCLUSIONS: This study confirmed that NODDI effectively reveals microstructural changes in white matter of OSAHS patients with cognitive impairment, providing neuroimaging evidence for early clinical diagnosis and intervention.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Exposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown. METHODS: The cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models. RESULTS: Each 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively. CONCLUSION: Blood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

A case of rare obstructive jaundice induced by concealed displacement of T-tube.

We present the case of a 32-year-old woman who was ultimately diagnosed with obstructive jaundice. She exhibited persist jaundice, liver dysfunction with normal drainage of T-tube (400-500 ml per day), and normal stools. Prior to her admission to our department, she had undergone a cholecystectomy and T-tube placement following common bile duct exploration for cholelithiasis. Although her serum bilirubin levels initially decreased post-surgery, it rose sharply after T-tube cholangiography. The diagnosis remained unclear until we performed endoscopic retrograde cholangiopancreatography (ERCP), which revealed that the obstructive jaundice was induced by improper T-tube placement. There were few such presentations reported before, and it's particularly unusual to encounter jaundice following T-tube placement. Moreover, diagnosing and treating this condition can be challenging when T-tube drainage appears normal. Thus, our case report provides a unique contribution to the literature on obstructive jaundice.

Causal effects of obstructive sleep apnea on chronic kidney disease and renal function: a bidirectional Mendelian randomization study.

Background: Observational studies have suggested an association between obstructive sleep apnea (OSA), chronic kidney disease (CKD), and renal function, and vice versa. However, the results from these studies are inconsistent. It remains unclear whether there are causal relationships and in which direction they might exist. Methods: We used a two-sample Mendelian randomization (MR) method to investigate the bidirectional causal relation between OSA and 7 renal function phenotypes [creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), rapid progress to CKD, rapid decline of eGFR, urinary albumin to creatinine ratio (UACR) and CKD]. The genome-wide association study (GWAS) summary statistics of OSA were retrieved from FinnGen Consortium. The CKDGen consortium and UK Biobank provided GWAS summary data for renal function phenotypes. Participants in the GWAS were predominantly of European ancestry. Five MR methods, including inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were used to investigate the causal relationship. The IVW result was considered the primary outcome. Then, Cochran's Q test and MR-Egger were used to detect heterogeneity and pleiotropy. The leave-one-out analysis was used for testing the stability of MR results. RadialMR was used to identify outliers. Bonferroni correction was applied to test the strength of the causal relationships (p < 3.571 × 10-3). Results: We failed to find any significant causal effect of OSA on renal function phenotypes. Conversely, when we examined the effects of renal function phenotypes on OSA, after removing outliers, we found a significant association between BUN and OSA using IVW method (OR: 2.079, 95% CI: 1.516-2.853; p = 5.72 × 10-6). Conclusion: This MR study found no causal effect of OSA on renal function in Europeans. However, genetically predicted increased BUN is associated with OSA development. These findings indicate that the relationship between OSA and renal function remains elusive and requires further investigation.

Prevalence, mortality and risk factors for self-reported COPD among smokers and never smokers, NHANES 1999-2018.

INTRODUCTION: Cigarette smoke is the main risk factor for chronic obstructive pulmonary disease (COPD), but 25% to 50% of cases occur in non-smokers. In the US, limited recent national data compare COPD prevalence between smokers and never smokers. Furthermore, our study seeks to explore the prevalence and mortality of self-reported COPD among smokers (including current smokers and ex-smokers) and never smokers in the US from 1999 to 2018, and to identify the risk factors and differences. METHODS: This cross-sectional analysis used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Age-standardized prevalence of self-reported COPD among current smokers, ex-smokers, and never smokers was calculated using sample weights and 2010 US Census estimates. Risk factors were evaluated through weighted logistic regression models. Subsequently, participants who enrolled in the study cohort were followed until 31 December 2019, to determine all-cause mortality rates. RESULTS: Between 1999 and 2018, the weighted prevalence of COPD among current smokers, ex-smokers, and never smokers in the U.S. was 12.6%, 9.6%, and 4.1%, respectively. The mortality rates observed were 21.1% among current smokers with COPD, 29% among ex-smokers with COPD, and 12% among never smokers with COPD. Over this period, among the general population in the U.S., the proportion of current smokers has declined, the proportion of never smokers has increased, and the proportion of ex-smokers has remained relatively stable. From 1999 to 2018, COPD prevalence rose from 13.7% to 21.9% among current smokers, stayed at 10.1% among ex-smokers, and dropped from 4.9% to 3.3% among never smokers. Independent risk factors for COPD across all groups included being female, older, and lower income. In particular, US citizens and non-Hispanic Whites (among ex-smokers and never smokers) were at higher risk compared to their counterparts. CONCLUSIONS: The prevalence and all-cause mortality of COPD among current smokers and ex-smokers remain elevated. Although the prevalence of COPD among never smokers is gradually declining, it continues to be significant, thereby maintaining a substantial burden of disease. Furthermore, common independent risk factors for COPD across current smokers, ex-smokers, and never smokers include female gender, advanced age, lower income, and deviations from normal body weight whether overweight or underweight.

Impact of sleep disturbance on longitudinal cognitive performance in patients with transient ischemic attack or mild stroke.

INTRODUCTION: Sleep disturbances including obstructive sleep apnea (OSA) and poor sleep quality are common after stroke, while its association with cognitive changes following transient ischemic attack (TIA) or mild stroke remains unclear. We aim to determine whether sleep duration, OSA parameters, or nocturnal hypoxemia is associated with a greater cognitive decline after stroke. METHODS: We prospectively followed-up patients with acute TIA/mild stroke [National Institute Health Stroke Scale (NIHSS) < 7] who underwent baseline sleep questionnaire [Pittsburgh Sleep Quality Index (PSQI)], and serial cognitive assessments [Montreal Cognitive Assessment (MoCA) 5-min, Stroop Test] at baseline and one-year. We also evaluated apnea-hypopnea index (AHI) and nocturnal hypoxemia by Home Sleep Apnea Test (HSAT) at one-year. Primary outcome was one-year change in MoCA 5-min score. RESULTS: One hundred and five patients with TIA/mild stroke (mean age 63 years, 65 % male) were included. Baseline short sleep (< 6 hour/night) and AHI ≥ 20/hour at one-year were independently associated with a decline in the MoCA 5-min total score after covariates adjustment [short sleep: ß = -2.36 95 % confidence interval (CI) (-4.13, -0.59), p = 0.009; AHI ≥ 20/hour: ß = -1.79 (-3.26, -0.32), p = 0.017; remained significant after multiple comparisons correction]. A lower mean MinSpO2 was associated with a decline in executive function [Stroop interference index: ß = 0.29 (0.04, 0.53), p = 0.021], but not with MoCA 5-min score at one-year. Moderation analysis indicated AHI ≥ 20/hour was associated with a pronounced decline in executive function only in men. CONCLUSIONS: Short sleep after stroke onset, AHI ≥ 20/hour and nocturnal hypoxemia at one-year contributed to an impaired cognitive trajectory at one-year following stroke in patients with TIA/mild stroke.

The association between obstructive sleep apnea and osteoporosis: A systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is a sleep disorder with well-known metabolic consequences. The relationship between OSA and bone health, especially osteoporosis, remains poorly understood. Given that both OSA and osteoporosis are highly prevalent chronic conditions with significant public health implications, this study aims to investigate the association of OSA with bone health and osteoporosis. A systematic search of PubMed, Embase and Cochrane Library was conducted from inception to November 22, 2022. Fifteen studies comprising 158,273 individuals were included. The presence of OSA correlated negatively with bone mineral density on meta-analysis (pooled correlation = -0.30; 95 % CI, -0.42 to -0.17; N = 8). Individuals with OSA had poorer bone mineral density scores (mean difference = -0.58, 95 % CI, -1.15 to -0.01; N = 8), and significantly higher risk of developing osteoporosis (adjusted odds ratio = 2.18; 95 % CI, 1.14 to 4.16; N = 4). Notably, both body mass index (BMI) and age were not significant effect modulators in the correlation of OSA and bone density. These findings suggest that OSA is associated with diminished bone health, and it is severity-dependent. Further studies are required to determine if treatment of OSA may have the potential to mitigate these risks.

Effects of Expiratory Muscle Strength Training on Oropharyngeal Swallow Physiology in Persons with Obstructive Sleep Apnea (OSA): A Preliminary Study.

Despite the high estimated prevalence of dysphagia in OSA, there is a paucity of evidence supporting behavioral interventions for treatment. The purpose of this study was to assess the impact of expiratory muscle strength training (EMST) on validated, standardized metrics of swallow and airway clearance capacity functions in moderate-to-severe OSA. 10 participants with OSA (mean age = 65.2 years) completed four weeks of EMST training employing a prospective single-arm, double-baseline interventional design. The Modified Barium Swallow Impairment Profile (MBSImP) Component and Composite (Oral Total [OT] and Pharyngeal Total [PT]) scores measured swallow physiology. Airway clearance capacity measures included maximum expiratory pressure (MEP) and peak cough flow (PCF). A historical normative database was used for OSA patient comparison of swallowing metrics. A total of 234 swallows were analyzed. At baseline, impairments in lingual control, oral residue and esophageal clearance were observed. However, no significant differences in the MBSImP Composite (OT/PT) scores were observed between the OSA and healthy referent group. After EMST intervention, there were no significant differences in pre- to post-intervention Composite (OT/PT) scores. However, large effect size was observed for MEP (p < 0.001, d = 3.0), and non-significant, but moderate effect size was observed in PCF (p = 0.19, d = 0.44). Study findings further quantify swallowing in moderate-to-severe OSA and provide preliminary evidence supporting the impact of EMST on airway clearance capacity.

One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy.

Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world use of mavacamten in 50 patients with oHCM at a tertiary care referral center. In both our highlighted case and in our aggregate data, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and New York Heart Association symptom class. Moreover, in our center's experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: we note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Moreover, our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.

The Association Between Respiratory Functions, Pain Tolerance and Body Awareness in Obstructive Lung Diseases.

PURPOSE: There are only a limited number of studies in the literature evaluating body awareness, pain perception, and the relationship between clinical parameters and respiratory functions in patients with obstructive lung disease (OLD) and compared with healthy individuals. Therefore, this study aimed to evaluate respiratory functions, pain tolerance, and body awareness in patients with OLD and compare these findings with those of healthy individuals. METHODS: The study included 33 patients and 30 healthy individuals. The respiratory function (spirometer), respiratory muscle strength (mouth pressure device), endurance (threshold loading device), pain level and tolerance (short-form McGill Pain Questionnaire and algometer), posture, and body awareness (Body Awareness Questionnaire-BAQ) were evaluated. RESULTS: The pain threshold and tolerance of the biceps, triceps, trapezius, and quadriceps muscles were significantly lower and BAQ scores were higher in patients with OLD compared with healthy individuals (p < .05). There was a significant relationship between FEV1 (%) and pain tolerance of the triceps (r = 0.371, p = .047) and gastrocnemius muscles (r = 0.419, p = .024); FVC (%) and pain threshold of the gastrocnemius (r = 0.413, p = .023), triceps muscles (r = 0.394, p = .034), and pain tolerance of the gastrocnemius muscle (r = 0.549, p = .002). CONCLUSIONS: Patients with OLD have a marked increase in pain perception and body awareness levels and a decrease in pain threshold and tolerance compared with healthy controls. Future studies should assess the effectiveness of pain management interventions as a part of pulmonary rehabilitation for patients with chronic respiratory diseases. CLINICAL IMPLICATIONS: Pain management is important for planning pulmonary rehabilitation programmes.

Knowledge and Attitude of General Dentists, Senior Dental Students, and Orthodontic Residents Toward Obstructive Sleep Apnea.

OBJECTIVE: The main objective of this study was to compare the knowledge and attitude of general dentists, senior dental students, and orthodontic residents toward obstructive sleep apnea (OSA). MATERIALS AND METHODS: A questionnaire was designed and administered among 73 senior dental students, 84 general dentists, and 50 orthodontic residents. The questionnaire asked for demographic information of the participants and assessed their knowledge and attitude toward OSA. The validity and reliability of the questionnaire were confirmed by experts. Data were analyzed by the Kruskal-Wallis and Bonferroni tests using SPSS (α = 0.05). RESULTS: The mean knowledge scores of general dentists and senior dental students were significantly lower than those of orthodontic residents (p < 0.001). However, there was no significant difference in the knowledge score of senior dental students and general dentists (p = 1). The mean knowledge score was significantly higher in dentists with 1-3 years of professional clinical experience (p = 0.02). The knowledge score was the highest in dentists working in private clinics followed by private offices and public clinics. The mean attitude score was the highest in orthodontic residents followed by general dentists and dental students. There was no significant difference in attitude based on the attended university, age, or time of graduation. CONCLUSION: According to the results, general dentists had insufficient knowledge about OSA, which could result in under-diagnosis or misdiagnosis of patients with OSA. This finding highlights the need for further education and training for dentists to properly identify and refer OSA patients to orthodontists or sleep specialists.

Type V collagen-induced nasal tolerance prevents lung damage in an experimental model: new evidence of autoimmunity to collagen V in COPD.

Background: Chronic obstructive pulmonary disease (COPD) has been linked to immune responses to lung-associated self-antigens. Exposure to cigarette smoke (CS), the main cause of COPD, causes chronic lung inflammation, resulting in pulmonary matrix (ECM) damage. This tissue breakdown exposes collagen V (Col V), an antigen typically hidden from the immune system, which could trigger an autoimmune response. Col V autoimmunity has been linked to several lung diseases, and the induction of immune tolerance can mitigate some of these diseases. Evidence suggests that autoimmunity to Col V might also occur in COPD; thus, immunotolerance to Col V could be a novel therapeutic approach. Objective: The role of autoimmunity against collagen V in COPD development was investigated by analyzing the effects of Col V-induced tolerance on the inflammatory response and lung remodeling in a murine model of CS-induced COPD. Methods: Male C57BL/6 mice were divided into three groups: one exposed to CS for four weeks, one previously tolerated for Col V and exposed to CS for four weeks, and one kept in clean air for the same period. Then, we proceeded with lung functional and structural evaluation, assessing inflammatory cells in bronchoalveolar lavage fluid (BALF) and inflammatory markers in the lung parenchyma, inflammatory cytokines in lung and spleen homogenates, and T-cell phenotyping in the spleen. Results: CS exposure altered the structure of elastic and collagen fibers and increased the pro-inflammatory immune response, indicating the presence of COPD. Col V tolerance inhibited the onset of emphysema and prevented structural changes in lung ECM fibers by promoting an immunosuppressive microenvironment in the lung and inducing Treg cell differentiation. Conclusion: Induction of nasal tolerance to Col V can prevent inflammatory responses and lung remodeling in experimental COPD, suggesting that autoimmunity to Col V plays a role in COPD development.

A systematic review of the methodology for examining the relationship between obstructive sleep apnea and type two diabetes mellitus.

Background: The association between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) has been explored in various studies, revealing inconsistent correlations that impact therapeutic effectiveness. This heterogeneity in findings requires further exploration to understand what may be driving this. Therefore, this study focuses on systematically reviewing the data, classification of variables, and analytical approach to understand if and how this may be contributing to the mixed findings. This review aims to provide insights that can enhance the generalisability of future research findings. Methods: A comprehensive electronic search was conducted, including EMBASE, MEDLINE, PsycINFO, CINAHL, Web of Science Core Collection, Scopus and specialised sleep journals. The included studies were observational studies published in English from 2011 onwards, involving adults above 18 years with OSA and T2DM or prediabetes, and included a control group. Exclusions were pregnant women, interventional studies, randomised trials, systematic reviews, conference abstracts, case studies and studies without a control group or only with descriptive analysis. Results: We reviewed 23 studies that met the inclusion criteria. Among cohort studies, 54% did not report attrition rates, and 52% did not detail methods for handling missing data in all studies. Nine studies (39%) predominantly included male participants. Objective measures were prevalent in assessing OSA, with 11 using home portable sleep monitors and four employing clinic polysomnography, though only three validated home sleep monitors. The apnea-hypopnea index was commonly used to define OSA severity, with six studies adapting the American Academy of Sleep Medicine criteria. Two studies utilised validated self-report questionnaires for OSA symptoms. T2DM diagnosis methods varied, with 17 studies using blood samples, two relying only on self-reporting, and four confirmed diagnosis via medical records. Conclusions: The variability in sample characteristics, data quality, and variable coding may contribute to the mixed finding. This review identifies gaps in using the standardised measures, reporting attrition rates, handling missing data, and including both sexes. Addressing these issues is crucial to enhancing future research generalisability. Standardising diagnostic criteria, considering clinical and sociodemographic factors, and ensuring inclusivity in study populations are essential for advancing understanding and treatment strategies for OSA and T2DM. Protocol registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023397547.

Smoking cessation program preferences of individuals with chronic obstructive pulmonary disease: a qualitative study.

AIM: To explore the views of tobacco-smoking chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) patients on telehealth-based cessation programs and the role of e-cigarettes as an aid to quit smoking. BACKGROUND: Tobacco smoking accelerates the progression of COPD. Traditional smoking cessation programs often do not entirely address the unique needs of COPD patients, leading to suboptimal effectiveness for this population. This research is aimed at describing the attitudes and preferences of COPD and ACO patients toward innovative, telehealth-based smoking cessation strategies and the potential application of e-cigarettes as a quitting aid. METHODS: A qualitative exploratory approach was adopted in this study, employing both focus groups and individual interviews with English-speaking adults with diagnosed COPD or ACO. Participants included both current smokers (≥ 5 cigarettes/day) and recent ex-smokers (who quit < 12 months ago). Data were systematically coded with iterative reliability checks and subjected to thematic analysis to extract key themes. FINDINGS: A total of 24 individuals participated in this study. The emergent themes were the perceived structure and elements of a successful smoking cessation program, the possible integration of telehealth with digital technologies, and the strategic use of e-cigarettes for smoking reduction or cessation. The participants stressed the importance of both social and professional support in facilitating smoking cessation, expressing a high value for insights provided by ex-smokers serving as mentors. A preference was observed for group settings; however, the need for individualized plans was also highlighted, considering the diverse motivations individuals had to quit smoking. The participants perceived online program delivery as potentially beneficial as it could provide immediate access to support during cravings or withdrawals and was accessible to remote users. Opinions on e-cigarettes were mixed; some participants saw them as a less harmful alternative to conventional smoking, while others were skeptical of their efficacy and safety and called for further research.

Obstructive Sleep Apnea and Cerebral Small Vessel disease in Community-based Older People: An ASPREE Imaging Substudy.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) may increase risk of dementia. A potential pathway for this risk is through cerebral small vessel disease (CSVD). In the context of an existing randomized trial of aspirin for primary prevention, we aimed to investigate OSA's impact on CSVD imaging measures and explore whether aspirin effects these measures over 3 years that differ in the presence or absence of OSA. METHODS: A sub-study of the ASPirin in Reducing Events in the Elderly randomized placebo-controlled trial of low-dose aspirin. Community-dwelling participants aged 70 years and above, without cognitive impairment, cardiovascular disease or known OSA completed an unattended limited-channel sleep study that calculated the oxygen desaturation index and apnea-hypopnea index. At baseline and 3 years later, volumes of white matter hyperintensities (WMH) and silent brain infarctions (SBI) were measured on 1.5 Tesla brain magnetic resonance imaging, and retinal vessel calibers were calculated from retinal vascular imaging. RESULTS: Mild and moderate/severe OSA was detected in 48.9% and 29.9%, respectively, of the 311 participants, who had a mean age of 73.7 years (SD 3.4 years), 38.6% female. OSA of any severity did not associate with WMH volumes, SBI, nor with retinal vessel calibers at baseline, nor with change in these measures in the 277 participants with repeated measures acquired after 3 years. OSA of any severity did not interact with aspirin on change in these measures over 3 years. CONCLUSION: In healthy older adults undiagnosed OSA was not associated with retinal vascular calibers and neuroimaging measures of CSVD.

Age-Related Clinical and Polysomnographic Features of Severe Obstructive Sleep Apnea in Infants.

OBJECTIVE: To use clinical and polysomnographic (PSG) parameters to define the features of severe OSA in infants including PSG parameters, risk factors, and interventions. METHODS: Retrospective comparison of PSG features in 207 infants (<12 months) referred for sleep-disordered breathing. Stepwise multivariate logistic regression was used to define risk factors for severe OSA including sleep stage-specific PSG parameters. Oxygenation was assessed as % of time with SpO2 < 90% nadir with apneic events and frequency of SpO2 desaturations (>3%) calculated as stage-specific O2 desaturation indexes. RESULTS: We found that 43% of the infants had an OAHI ≥10/h (90/207) with 152 analyzed due to lack of follow-up. Age is the strongest predictor for severe OSA with infants at or less than 3 months of age with 6.22 higher risk of severe OSA (95% CI, 3.16-12.27). Age-stratified analyses showed that infants ≤3 months had significantly higher total and OSA sleep stage-specific apnea hypopnea (OAHI) indexes (REM and NREM), hypopnea indexes (HI), obstructive apnea indexes (OI), arousal indexes, and more severe hypoxemia, both sustained and intermittent. The top risk factor in infants ≤3 months was craniofacial abnormality, which occurred in 57.9% of cases. No intervention was the most common management for each group (61.1% in ≤3 months and 56.6% in 4-12 months). The most common procedures in infants ≤3 months were mandibular distraction osteogenesis (MDO) and supraglottoplasty (SGP) while adenoidectomy was the most common in the 4- to 12- month group. CONCLUSION: Diagnosis ≤3 months is the strongest predictor for severe OSA, demonstrated across PSG parameters. No surgical intervention is the most common management. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.