Lung adenocarcinoma discovered during the follow-up of lung-dominant connective tissue disease: a case report and literature review.

Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.

Clinical Features and Management of Lung Cancer During Pregnancy: A Narrative Review Based on Reported Cases.

This review aims to provide a summary of the clinical characteristics and outcomes of lung cancer during pregnancy. A comprehensive literature search yielded 93 cases of lung cancer during pregnancy from 1953 to 2022, with an average maternal age of ∼34 years old. The initial symptoms reported were often nonspecific, such as cough, dyspnea, and chest pain. Cancer-related treatments, including surgery, radiotherapy, chemotherapy, and tyrosine kinase inhibitors, have shown beneficial effects on maternal outcomes. A majority of the newborns were born without malformation or diseases, but extended follow-up remains necessary. Early diagnosis of lung cancer is imperative for reducing the risks of placental and fetal metastasis and enhancing overall survival.

Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma.

Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy's involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

Combined aspartate aminotransferase level and PE-SARD score predict 1-month bleeding risk in acute pulmonary embolism.

BACKGROUND: Anti-coagulation is the cornerstone management of acute pulmonary embolism (PE), which is a double-edged sword, as it increases the risk of bleeding. Thus, predicting bleeding risk is necessary. The liver produces most coagulation factors to maintain the coagulation balance. However, the association between liver dysfunction markers and bleeding risk has not been thoroughly investigated. METHODS: A single-center, retrospective analysis of patients with acute PE was performed. First, the authors studied the association between liver dysfunction indexes and the 1-month bleeding risk. Then, they investigated whether it is more effective to predict the bleeding risk using a new joint model, i.e., adding liver dysfunction indexes to the PE-SARD score, which is the first score to assess the bleeding risk of acute PE. RESULTS: Among 469 patients with acute PE, 34 patients (7.2%) had bleeding events within 1 month after the onset. The levels of aspartate aminotransferase (AST) were higher in the bleeding group compared with the non-bleeding group (36.0 [18.25-90.0] vs. 23.0 [18.0-31.0], p = 0.008). Compared with AST<40, the odds ratios of 80≤AST<120 and AST≥120 were significant (8.825 [2.449-31.804] and 8.023 [2.543-25.315] respectively, p<0.01), even when adjusted for nine confounding factors (p<0.05). The area under the curve of PE-SARD combined with AST was significantly higher than that of the PE-SARD score (p = 0.02). CONCLUSIONS: In PE patients, AST is an independent factor in predicting the 1-month bleeding risk, and a novel joint model that combines AST and PE-SARD score improved the predictive efficiency for the 1-month bleeding risk.

Diagnosis of obstructive sleep apnea using a bio-radar contact-free system compared with an established HST device in older adults.

GOAL AND AIMS: To compare a bio-radar contact-free monitoring device in diagnosing obstructive sleep apnea (OSA) in older people with an established home sleep apnea testing system (HST). FOCUS METHOD/TECHNOLOGY: A bio-radar contact-free monitoring device (OrbSense+). REFERENCE METHOD/TECHNOLOGY: An established HST, Alice NightOne. SAMPLE: Fifty-three out of 63 recruited subjects were included in the final analysis. Seventy-two percent were male (age 72 ± 9 years; body mass index 31.05 ± 5.56 kg/m2). DESIGN: An observational, prospective study. CORE ANALYTICS: Intraclass correlation coefficient (ICC), Bland-Altman analysis, and receiver operating characteristic analysis. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: None. CORE OUTCOMES: Both 45 (84.91%) were diagnosed with OSA by Alice NightOne (average respiratory event index = 21.23 events/h) and by OrbSense+ (average respiratory event index = 25.98 events/h). Respiratory event index and oxygen desaturation index obtained by Alice NightOne and OrbSense+ were highly correlated, with ICC of 0.93 and 0.88, respectively. The Bland-Altman plot comparing the means showed good agreement between the 2 diagnostic techniques. With more than 5 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ had a sensitivity of 100% and a specificity of 100% in diagnosis of OSA (P < .0001). With more than 15 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ was found to have a sensitivity of 100% and a specificity of 86.96% in diagnosis of OSA (P < .0001). IMPORTANT ADDITIONAL OUTCOMES: None. CORE CONCLUSION: The bio-radar sleep monitoring device is a reasonably accurate home sleep apnea test for use in older patients.

Rapid recovery of fat embolism syndrome with acute respiratory failure due to liposuction.

Liposuction is not a risk-free procedure and potentially fatal complications may occur, especially liposuction-induced fat embolism syndrome (FES). Here we report the case of a 29-year-old woman who developed FES suddenly during a liposuction operation in a cosmetic medical clinic. She was transferred to the hospital and achieved complete recovery within 11 days by comprehensive therapeutic strategies, including noninvasive ventilation (NIV), corticosteroids, albumin, diuretics and anticoagulation. Liposuction-induced FES is a life-threatening condition, which can be treated with complate recovery by comprehensive therapeutic strategies according to its pathophysiologic mechanism.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Moderate to severe OSA screening based on support vector machine of the Chinese population faciocervical measurements dataset: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) has received much attention as a risk factor for perioperative complications and 68.5% of OSA patients remain undiagnosed before surgery. Faciocervical characteristics may screen OSA for Asians due to smaller upper airways compared with Caucasians. Thus, our study aimed to explore a machine-learning model to screen moderate to severe OSA based on faciocervical and anthropometric measurements. DESIGN: A cross-sectional study. SETTING: Data were collected from the Shanghai Jiao Tong University School of Medicine affiliated Ruijin Hospital between February 2019 and August 2020. PARTICIPANTS: A total of 481 Chinese participants were included in the study. PRIMARY AND SECONDARY OUTCOME: (1) Identification of moderate to severe OSA with apnoea-hypopnoea index 15 events/hour and (2) Verification of the machine-learning model. RESULTS: Sex-Age-Body mass index (BMI)-maximum Interincisal distance-ratio of Height to thyrosternum distance-neck Circumference-waist Circumference (SABIHC2) model was set up. The SABIHC2 model could screen moderate to severe OSA with an area under the curve (AUC)=0.832, the sensitivity of 0.916 and specificity of 0.749, and performed better than the STOP-BANG (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference, and male gender) questionnaire, which showed AUC=0.631, the sensitivity of 0.487 and specificity of 0.772. Especially for asymptomatic patients (Epworth Sleepiness Scale <10), the SABIHC2 model demonstrated better predictive ability compared with the STOP-BANG questionnaire, with AUC (0.824 vs 0.530), sensitivity (0.892 vs 0.348) and specificity (0.755 vs 0.809). CONCLUSION: The SABIHC2 machine-learning model provides a simple and accurate assessment of moderate to severe OSA in the Chinese population, especially for those without significant daytime sleepiness.

A narrative review of exploring potential salivary biomarkers in respiratory diseases: still on its way.

Saliva is abundant with proteins, metabolites, DNA, and a diverse range of bacterial species. During the past two decades, saliva has emerged as a novel diagnostic and evaluation medium for several diseases. Collection of saliva samples is simple, minimally invasive, and convenient even in infants, children, and patients with anxious. Furthermore, with the development of hypersensitive techniques [e.g., microsensor arrays, enzyme-labeled immunosensors, nanoparticle-labeled immunosensors, capacitive or impedimetric immunosensors, magneto immunosensors, field effect transistor immunosensors, and surface enhanced Raman spectroscopy (SERS)], the sensitivity and accuracy of saliva diagnostic procedures have been improved. Nowadays, saliva has been used as a potential medium for several disease diagnosis and assessment, such as periodontitis, caries, cancers, diabetes mellitus, and cardiovascular diseases. Saliva has been used widely for studying microbiomics, genomics, transcriptomics, proteomics, and metabolomics of respiratory diseases, however, the use of salivary biomarkers for the diagnosis, prognosis, and monitoring of respiratory disease is still in its infancy. Herein, we review the progress of research on salivary biomarkers related to several respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pneumonia, tuberculosis (TB), Langerhans cell histiocytosis (LCH) and cystic fibrosis (CF). Furthermore, several limitations of saliva test such as the lack of standard protocol for saliva collection and reasonable reference values for saliva test are also mentioned in this review.

Burden of Sleep Disturbance During COVID-19 Pandemic: A Systematic Review.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%-84.7%, and 29.5-40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4-84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65-81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.

Model for Identifying High Carotid Body Chemosensitivity in Patients with Obstructive Sleep Apnea.

OBJECTIVE: The carotid body (CB) is a major peripheral respiratory chemoreceptor. In patients with obstructive sleep apnea (OSA), high CB chemosensitivity (CBC) is associated with refractory hypertension and insulin resistance and known to further aggravate OSA. Thus, the identification of high CB (hCBC) among OSA patients is of clinical significance, but detection methods are still limited. Therefore, this study aimed to explore the association of CBC with OSA severity and to develop a simplified model that can identify patients with hCBC. METHODS: In this cross-sectional study of subjects who underwent polysomnography (PSG), CBC was measured using the Dejours test. We defined hCBC as a decrease of >12% in respiratory rate (RR) after breathing of pure O2. The association of CBC with OSA severity was explored by logistic regression, and a model for identifying hCBC was constructed and confirmed using receiver operating characteristic analysis. RESULTS: Patients with OSA (n=142) and individuals without OSA (n=38) were enrolled. CBC was higher in patients with OSA than in those without OSA (% decrease in RR, 15.2%±13.3% vs 9.1%±7.5%, P<0.05). Apnea-hypopnea index (AHI), fraction of apnea-hypopnea events in rapid-eye-movement sleep (Fevents-in-REM), and longest time of apnea (LTA) were associated with hCBC independently (odds ratio [OR]=1.048, OR=1.082, and OR=1.024 respectively; all P<0.05). The model for identifying hCBC allocated a score to each criterion according to its OR values, ie, 1 (LTA >48.4 s), 2 (AHI >15.7 events/hour), and 3 (Fevents-in-REM >12.7%). A score of 3 or greater indicated hCBC with a sensitivity of 79.4% and specificity of 88.2%. CONCLUSION: High CBC is associated with the severity of OSA. A simplified scoring system based on clinical variables from PSG can be used to identify hCBC.

Bronchial Variation: Anatomical Abnormality May Predispose Chronic Obstructive Pulmonary Disease.

Noxious particulate matter in the air is a primary cause of chronic obstructive pulmonary disease (COPD). The bronchial tree acts to filter these materials in the air and preserve the integrity of the bronchi. Accumulating evidence has demonstrated that smoking and air pollutants are the most prominent risk factors of COPD. Bifurcations in the airway may act as deposition sites for the retention of inhaled particles, however, little is known concerning the impacts of abnormalities of the bronchial anatomy in the pathogenesis of COPD. Studies have reported significant associations between bronchial variations and the symptoms in COPD. In particular, it has been shown that bronchial variations in the central airway tree may contribute to the development of COPD. In this review, we identified three common types of bronchial variation that were used to formulate a unifying hypothesis to explain how bronchial variations contribute to the development of COPD. We also investigated the current evidence for the involvement of specific genes including fibroblast growth factor 10 (Fgf10) and bone morphogenetic protein 4 (Bmp4) in the formation of bronchial variation. Finally, we highlight novel assessment strategies and opportunities for future research of bronchial variations and genetic susceptibility in COPD and comorbidities. Our data strongly highlight the role of bronchial variations in the development, complications, and acute exacerbation of COPD.

Neutrophil-to-Lymphocyte Ratio Predicts Clinical Outcome of Severe Acute Exacerbation of COPD in Frequent Exacerbators.

PURPOSE: Frequent exacerbators are a specific phenotype of chronic obstructive pulmonary disease (COPD), whose clinical characteristics and prognostic biomarkers during severe acute exacerbation (AECOPD) have not yet been fully elucidated. The aim of this study was to investigate the clinical features of severe AECOPD in frequent exacerbators and explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcome in this phenotype during severe exacerbation. PATIENTS AND METHODS: A total of 604 patients with severe AECOPD were retrospectively included in the study. Subjects were defined as frequent exacerbators if they experienced two or more exacerbations in the past year. Clinical characteristics and worse outcome (ICU admission, or invasive ventilation, or in-hospital mortality) during severe AECOPD were compared between frequent exacerbators and non-frequent ones. Furthermore, the relationship between NLR and worse outcome in frequent exacerbators was analyzed using logistic regression and receiver operating characteristic (ROC). RESULTS: Among 604 patients with severe AECOPD, 282 (46.69%) were frequent exacerbators and 322 (53.31%) were non-frequent exacerbators. Compared with the non-frequent ones, frequent exacerbators presented higher levels of NLR (5.93 [IQR, 3.40-9.28] vs 4.41 [IQR, 2.74-6.80]; p<0.001), and more worse outcome incidence (58 [20.57%] vs 38 [11.80%]; p=0.003). Moreover, among the frequent exacerbators, NLR levels in the patients with worse outcome were much higher than in those without worse outcome (11.09 [IQR, 7.74-16.49] vs 5.28 [IQR, 2.93-7.93]; p<0.001). Increased NLR was significantly associated with a higher risk of worse outcome in frequent exacerbators (OR, 1.43; 95% CI, 1.28-1.64; p<0.001). Furthermore, ROC analysis revealed that a cut-off value of 10.23, NLR could predict worse outcome of severe AECOPD in frequent exacerbators (sensitivity 62.1%, specificity 92.0%, AUC 0.833). CONCLUSION: Frequent exacerbators exhibited an increased level of NLR and a higher proportion of worse outcome during severe AECOPD. NLR is expected to be a promising predictive biomarker for the prognosis of severe AECOPD in frequent exacerbators.

Impact of insomnia and obstructive sleep apnea on the risk of acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by worsening of patients' respiratory symptoms that requires a modification in medication. This event could accelerate disease progression and increase the risk of hospital admissions and mortality. Both insomnia and obstructive sleep apnea (OSA) are prevalent in patients with COPD, and are linked to increased susceptibility to AECOPD. Improper treatment of insomnia may increase the risk of adverse respiratory outcomes for patients with COPD, while effective continuous positive airway pressure (CPAP) treatment may reduce the risk of AECOPD and mortality in patients with overlap syndrome. Sleep disorders should be considered in clinical management for COPD.

Chronic intermittent hypoxia-induced mitochondrial dysfunction mediates endothelial injury via the TXNIP/NLRP3/IL-1ß signaling pathway.

Oxidative stress and inflammation induced by chronic intermittent hypoxia (CIH) are trigger factors of cardiovascular diseases in patients with obstructive sleep apnea (OSA). This study aimed to investigate the role of CIH-induced mitochondrial dysfunction in vascular endothelial injury both in vivo and in vitro. Human umbilical vein endothelial cells and Sprague Dawley rats were exposed to CIH. CIH promoted the production of intracellular reactive oxygen species, caused mitochondrial dysfunction, and induced cell apoptosis in human umbilical vein endothelial cells. RNA-Seq analysis revealed that the NOD-like receptor signaling pathway was involved in endothelial injury induced by CIH. TXNIP/NLRP3/IL-1ß pathway was found to be upregulated by CIH. Knock-down of TNXIP rescued the endothelial cells from CIH-induced apoptosis, indicating that activation of the TXNIP/NLRP3/IL-1ß pathway mediated the CIH-induced endothelial apoptosis. Administration of the mitochondria-targeted antioxidant mito-TEMPO improved mitochondrial function and suppressed upregulation of the TXNIP/NLRP3/IL-1ß pathway, thereby alleviating CIH-induced endothelial apoptosis. In vivo experiments confirmed the results, where mito-TEMPO was found to ameliorate endothelial injury in rat aortas exposed to CIH. The results imply that CIH-induced mitochondrial dysfunction mediates endothelial injury implication of TXNIP/NLRP3/IL-1ß signaling pathway.

Angiotensin-(1-7) Rescues Chronic Intermittent Hypoxia-Aggravated Transforming Growth Factor-ß-Mediated Airway Remodeling in Murine and Cellular Models of Asthma.

Renin-angiotensin system (RAS) is involved in TGF-ß-mediated epithelial-to-mesenchymal transition (EMT) and is responsible for airway remodeling in refractory asthma. Obstructive sleep apnea (OSA), which affects RAS activity, is a risk factor for refractory asthma. We aimed to investigate how chronic intermittent hypoxia (IH), the main pathophysiology of OSA, exacerbates asthma and whether Ang-(1-7) protects against chronic IH-induced airway remodeling in asthma. We exposed ovalbumin (OVA)-challenged asthma mice to chronic IH and observed that chronic IH aggravated airway inflammation and collagen deposit in OVA-challenged mice. Compared with the OVA group, the OVA + chronic IH group had a lower expression level of epithelial marker E-cadherin and higher expression levels of mesenchymal markers α-smooth muscle actin and collagen IV in airway epithelia, accompanied with activation of TGF-ß/Smad pathway. These changes were reversed by the administration of Ang-(1-7). Consistently, Ang-(1-7) mitigated chronic IH-induced activation of TGF-ß-mediated EMT in lipopolysaccharide-treated bronchial epithelial cells in a dose-dependent manner, which was blocked by Ang-(1-7)-specific Mas receptor antagonist A779. Taken together, Ang-(1-7) rescued chronic IH-aggravated TGF-ß-mediated EMT to suppress airway remodeling, implying that RAS activity is involved in the mechanisms of OSA-related airway dysfunction in asthma. SIGNIFICANCE STATEMENT: OSA is a risk factor for refractory asthma. In this study, we aimed to explore the mechanisms of how OSA exacerbates refractory asthma. We found that chronic IH induces TGF-ß-mediated EMT and aggravates airway collagen deposit. We also found that Ang-(1-7) erased the aggravation of TGF-ß-mediated EMT and epithelial fibrosis upon chronic IH exposure. These findings provided new insights that the ACE2/Ang-(1-7)/Mas axis might be considered as a potential therapeutic target for patients with asthma and OSA.

Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia.

PURPOSE: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure. METHODS: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting. RESULTS: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2. CONCLUSION: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.

The Association of Salivary Biomarkers With the Severity of Obstructive Sleep Apnea and Concomitant Hypertension.

BACKGROUND: We aimed to assess the association between salivary alpha-amylase and salivary cortisol, and obstructive sleep apnea (OSA) severity. METHODS: Fifty-eight adults with suspected OSA were divided into the following 4 groups based on the apnea hypopnea index (AHI): control (AHI <5 events/hour), mild OSA (5 events/hour < AHI ≤15 events/hour), moderate OSA (15 events/hour < AHI ≤30 events/hour) and severe OSA (AHI >30 events/hour) groups. Salivary samples were collected after overnight polysomnography. Correlations between the salivary biomarkers and polysomnography parameters were analyzed. RESULTS: Salivary alpha-amylase levels of the moderate and severe OSA groups were significantly higher than those of the control and mild OSA groups, and no association was found between salivary cortisol and OSA severity. The salivary alpha-amylase levels were positively correlated with the AHI (r = 0.538; P < 0.01) and microarousal index (r = 0.541, P < 0.01), and negatively correlated with the lowest pulse oxygen saturation (r = -0.375, P < 0.01). Salivary cortisol levels were significantly higher in patients with hypertension than in those without hypertension (10.01 ± 2.77 ng/mL vs. 5.52 ± 1.90 ng/mL, P < 0.05), and the salivary alpha-amylase levels were highest in the OSA concomitant hypertension group (32.81 ± 11.85 U/mL). Areas under the receiver operator characteristic analysis revealed that the cutoff values of salivary alpha-amylase for identifying moderate-severe OSA and OSA concomitant hypertension were 17.64 U/mL (sensitivity 85%, specificity 91%) and 25.35 U/mL (sensitivity 70%, specificity 94%), respectively. CONCLUSIONS: Salivary alpha-amylase is positively associated with the severity of OSA and OSA concomitant hypertension.