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Purpose: OSAS is a syndrome that often presents clinically differently between men and women. The aim of this study was to assess the clinical presentation, nocturnal home sleep cardiorespiratory monitoring and therapeutic adherence to CPAP in both sexes to identify the most frequent patterns., Methods: Data from the first visit, the nocturnal home sleep cardiorespiratory monitoring and follow-up visit of 74 OSA patients were collected. Exclusion criteria included other respiratory and/or neuromuscular diseases (including Obesity hypoventilation syndrome) and other non-respiratory sleep disorders., Results: Men were older and had a higher supine AHI and ODI compared to women. In addition, BMI and age correlated positively with AHI in males. Women had a higher hypopneas frequency and better therapeutic adherence to CPAP., Conclusions: Men were associated with a higher AHI when sleeping in the supine position and this may be useful to look for new therapeutic options in combination with or as an alternative to CPAP. BMI correlated positively with AHI in men and this should be considered to stimulate weight loss as the main treatment to reduce the number of apneas/hypopneas, as men also had less therapeutic adherence to CPAP in our study. Females presented a significantly higher frequency of hypopneas than men, as well as a lower number of desaturation events per hour (ODI): these differences in the nocturnal home sleep cardiorespiratory monitoring could reflect different pathophysiological mechanisms of OSAS onset between the two sexes, which should be investigated in future scientific studies., (© 2024. The Author(s).)

Transbronchial lung cryobiopsy (TBCB) is a reliable method for obtaining histopathological findings in interstitial lung diseases. TBCB is traditionally performed during rigid bronchoscopy, positioning an endobronchial balloon blocker to facilitate bleeding management. Therefore, it can be challenging to implement in Centers without access to anesthesiologic support or dedicated beds for endoscopic procedures. We present a series of 11 patients who underwent 12 TBCBs using a flexible bronchoscope and a 5 Fr endobronchial blocker passing through an uncuffed endotracheal tube, under moderate sedation and spontaneous breathing. All procedures were carried out in an endoscopy suite, using fluoroscopy guidance but without requiring anesthesiologic assistance. TBCB was feasible in all cases, and it demonstrated similar or improved diagnostic yield (90.1%) and safety compared to rigid bronchoscopy. In 1 case, it was successfully repeated due to an inconclusive histological definition at the first attempt. The size of the samples was consistent with the literature, as it was the incidence of pneumothorax (16.6%). Four cases of moderate bleeding and 4 cases of severe bleeding were managed without further complications. To our knowledge, this is the first description of a technique allowing to perform TBCB through an artificial airway without need for either rigid bronchoscopy or general anesthesia. We believe this technique could make TBCB faster, cost-effective, and feasible even in resource-limited settings without compromising on safety. However, further studies are needed to validate these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma., Methods: A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%., Results: Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference (p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant., Conclusions: This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor., (© 2022. The Author(s).)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking., Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction ( P aO 2 / F IO 2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14., Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO 2 / F IO 2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points., Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia., Competing Interests: Conflict of interest: F. Salton, P. Confalonieri, S. Centanni, M. Mondoni, N. Petrosillo, D. Lacedonia, A. Voza, N. Carpenè, M. Montico, N. Reccardini, G.U. Meduri, B. Ruaro and M. Confalonieri have no conflicts of interest to disclose. P. Bonfanti received personal fees from ViiV Healthcare, Gilead, Janssen, Merck and Pfizer, not related to this work. G. Lapadula received personal fees from ViiV Healthcare and Pfizer, not related to this work., (Copyright ©The authors 2023.)

Introduction: The treatment of choice for obstructive sleep apnea syndrome (OSAS) is continuous positive airway pressure (CPAP). However, CPAP is usually poorly tolerated and mandibular advancement devices (MADs) are an alternative innovative therapeutic approach. Uncertainty still remains as to the most suitable candidates for MAD. Herein, it is hypothesized that the presence of low arousal threshold (low ArTH) could be predictive of MAD treatment failure. Methods: A total of 32 consecutive patients, with OSAS of any severity, who preferred an alternate therapy to CPAP, were treated with a tailored MAD aimed at obtaining 50% of their maximal mandibular advancement. Treatment response after 6 months of therapy was defined as AHI < 5 events per hour or a reduction of AHI ≥ 50% from baseline. Low ArTH was predicted based on the following polysomnography features, as previously shown by Edwards et al.: an AHI of 82.5% and a hypopnea fraction of total respiratory events of >58.3%. Results: There were 25 (78.1%) responders (p-value < 0.01) at 6 months. Thirteen patients (40.6%) in the non-severe group reached AHI lower than 5 events per hour. MAD treatment significantly reduced the median AHI in all patients from a median value of 22.5 to 6.5 (74.7% of reduction, p-value < 0.001). The mandibular advancement device reduced AHI, whatever the disease severity. A significant higher reduction of Delta AHI, after 6 months of treatment, was found for patients without low ArTH. Conclusions: Low ArTH at baseline was associated with a poorer response to MAD treatment and a lower AHI reduction at 6 months. A non-invasive assessment of Low ArTH can be performed through the Edwards’ score, which could help to identify an endotype with a lower predicted response to oral appliances in a clinical setting.

Obstructive sleep apnea syndrome (OSAS) is characterized by symptoms and signs of more than 5 apneas per hour (AHI) at polysomnography or 15 or more apneas per hour without symptoms. In this review, the focus will be a subgroup of patients: adult non-obese subjects with OSA and their specific features. In non-obese OSA patients (patients with BMI < 30 kg/m 2 ), there are specific polysomnographic features which reflect specific pathophysiological traits. Previous authors identified an anatomical factor (cranial anatomical factors, retrognatia, etc.) in OSA non-obese. We have hypothesized that in this subgroup of patients, there could be a non-anatomical pathological prevalent trait. Little evidence exists regarding the role of low arousal threshold. This factor could explain the difficulty in treating OSA in non-obese patients and emphasizes the importance of a specific therapeutic approach for each patient., (© 2021. The Author(s).)

Laser speckle contrast analysis (LASCA) is a non-contact technique able to quantify peripheral blood perfusion (PBP) over large skin areas. LASCA has been used to study hand PBP in several clinical conditions. These include systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) and LASCA showed that PBP was significantly lower in these conditions than in healthy subjects (HS). Moreover, it has been demonstrated that LASCA is a safe technique also able to monitor digital ulcer perfusion and their evolution in SSc patients, during systemic and local treatment. The use of LASCA, coupled with reactivity tests is commonplace in the field of microvascular function research. Post-occlusive hyperemia reactivity (POHR) and local thermal hyperemia, associated with laser techniques are reliable tests in the evaluation of perfusion in SSc patients. Other studies used laser speckled techniques, together with acetylcholine and sodium nitroprusside iontophoresis, as specific tests of endothelium function. In conclusion, LASCA is a safe, non-contact reliable instrument for the quantification of PBP at skin level and can also be associated with reactivity tests to monitor disease progression and response to treatment in different connective tissue diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruaro, Bruni, Wade, Baratella, Confalonieri, Antonaglia, Geri, Biolo, Confalonieri and Salton.)

Hydroxyurea is a cytotoxic agent widely used in the treatment of myeloproliferative disorders. It is considered a-well-tolerated anti-neoplastic drug, with a dose-related bone marrow suppression as main adverse effect. This report describes a patient with essential thrombocythemia who developed an interstitial pneumonitis and respiratory failure within 4 years from be- ginning therapy with hydroxyurea (HU). After discontinuing of HU. both clinical and radiological resolution of pneumonitis occurred. In conclusion, HU-induced pulmonary toxicity is a potentially life-threatening side effect. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea syndrome (OSAS) has emerged as a risk factor for cardiovascular disease. A prothrombotic state may affect coagulation and participate in the atherosclerotic process in subjects with OSAS. These alterations in coagulation seem to involve the plasminogen activation system. We evaluated the imbalances of the plasminogen activation system related to OSAS, and we assessed the effects of CPAP on the plasminogen activation system., Methods: Thirty-nine subjects were submitted to a home-based cardiorespiratory sleep study, and 14 healthy subjects (apnea-hypopnea index < 5) were used as controls. Serum levels of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and active transforming growth factor-β (TGF-β) were measured. These molecules were reassessed in only 17 of the subjects after 1 month of CPAP., Results: PAI-1 and tPA were significantly higher in the subjects with OSAS compared with the controls, whereas TGF-β and uPA levels were lower. PAI-1 showed a significant positive correlation with the apnea-hypopnea index, percentage of time spent at O2 saturation < 90%, and oxygen desaturation index, whereas TGF-β was inversely related to all 3 of these parameters. After the CPAP therapy, PAI-1 significantly decreased, whereas TGF-β showed a significant increase, although the values did not reach those of the controls. uPA and tPA did not show significant differences after the treatment., Conclusions: Our results suggest an imbalance of fibrinolysis related to OSAS and an improvement of the prothrombotic state after the CPAP treatment., (Copyright © 2015 by Daedalus Enterprises.)

Community-acquired pneumonia (CAP) has a significant impact on public health in terms of short-term and long-term morbidity and mortality. Irrespective of microbiological etiology, the host's inability to fully downregulate systemic inflammation is the dominant pathogenetic process contributing to acute and long-term morbidity and mortality in CAP. Glucocorticoids are the natural regulators of inflammation, and their production increases during infection. There is consistent evidence that downregulation of systemic inflammation with prolonged low-dose glucocorticoid treatment in patients with severe sepsis and acute respiratory distress syndrome improves cardiovascular and pulmonary organ physiology. A recent meta-analysis of pooled controlled small trials (n = 970) of patients admitted with CAP found improved short-term mortality in the subgroup with severe CAP and/or receiving >5 days of glucocorticoid treatment. We have expanded on this meta-analysis by including patients with CAP recruited in trials investigating prolonged low-dose glucocorticoid treatment in septic shock and/or early acute respiratory distress syndrome (n = 1,206). Our findings confirm a survival advantage for severe CAP (RR 0.66, 95% confidence interval 0.51-0.84; p = .001). A large randomized trial is in progress to confirm the aggregate findings of these small trials and to evaluate the long-term effect of this low-cost treatment.

Plasminogen activator inhibitor-1 (PAI-1) has a significant role in fibrinolysis, atherogenesis, cellular senescence, and chronic inflammation. OSA (obstructive sleep apnea) leads to increased PAI-1 levels and the development of cardiovascular disease (CVD). The aim of this study was to determine the effects of CPAP therapy on coagulation parameters and PAI-1 in patients with severe OSA. This prospective, controlled study enrolled 57 patients who were newly diagnosed with severe OSA, 37 of whom had had good CPAP adherence after 6 months of therapy (usage of the device for at least 4 h per night), and their data were analyzed. The analysis showed a statistically significant increase in D-dimer values before CPAP therapy (415 (316.5–537.5)) vs. after therapy (499 (327–652)), p = 0.0282, and a decrease in fibrinogen values (3.665 ± 0.752 before CPAP therapy vs. 3.365 ± 0.771 after therapy, p = 0.0075)). PAI-1 concentration values before and after CPAP therapy did not differ significantly (17.35 ± 7.01 ng/mL before CPAP therapy vs. 17.42 ± 6.99 ng/mL after therapy, p = 0.9367). This study shows a tendency for fibrinolytic capacity to improve in patients with OSA after CPAP therapy, although PAI-1 levels did not differ significantly. [ABSTRACT FROM AUTHOR]

People with obstructive sleep apnea (OSA) are a heterogeneous group. While many succeed in the treatment of their OSA, many others struggle with therapy. Herein, we discuss how anatomical and physiological factors that cause sleep apnea (OSA traits) impact treatment response and may offer an avenue for more precise care. These OSA traits, including anatomical (upper-airway collapsibility) and physiological (loop gain, airway muscle responsiveness, and arousal threshold) factors, may help determine who can succeed with continuous positive airway pressure, oral appliances, hypoglossal nerve stimulation, or pharmacotherapy. In the future, identifying OSA traits before initiating treatment may help guide the selection of the most effective and tolerable therapy modalities for each individual. [ABSTRACT FROM AUTHOR]

Objective: The immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD). Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, "Leave-one-out" analyses, and tests for adherence to the assumption of normal distribution. Results: The random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051- 1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031- 1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution. Conclusion: This investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Asthma and obstructive sleep apnea are highly prevalent conditions with a high cost burden. In addition to shared risk factors, existing data suggest a bidirectional relationship between asthma and OSA, where each condition can impact the other. Patients with asthma often complain of sleep fragmentation, nocturnal asthma symptoms, daytime sleepiness, and snoring. The prevalence of OSA increases with asthma severity, as evidenced by multiple large studies. Asthma may lower the threshold for arousal in OSA, resulting in the hypopnea with arousal phenotype. Epidemiologic studies in adults have shown that OSA is associated with worse asthma severity, increased frequency of exacerbation, and poor quality of life. The current literature assessing the relationship among OSA, asthma, and CPAP therapy is heavily dependent on observational studies. There is a need for randomized controlled trials to minimize the interference of confounding shared risk factors. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas longterm lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography. [ABSTRACT FROM AUTHOR]

Introduction: Many scales are designed to screen for obstructive sleep apnoea‐hypopnoea syndrome (OSAHS); however, there is a lack of an efficiently and easily diagnostic tool, especially for Chinese. Therefore, we conduct a cross‐sectional study in China to develop and validate an efficient and simple clinical diagnostic model to help screen patients at risk of OSAHS. Methods: This study based on 782 high‐risk patients (aged >18 years) admitted to the Sleep Medicine department of the Sixth Affiliated Hospital, Sun Yat‐sen University from 2015 to 2021. Totally 34 potential predictors were evaluated. We divided all patients into training and validation dataset to develop diagnostic model. The univariable and multivariable logistic regression model were used to build model and nomogram was finally built. Results: Among 602 high‐risk patients with median age of 46 (37, 56) years, 23.26% were women. After selecting using the univariate logistic model, 15 factors were identified. We further used the stepwise method to build the final model with five factors: age, BMI, total bilirubin levels, high Berlin score, and symptom of morning dry mouth or mouth breathing. The AUC was 0.780 (0.711, 0.848), with sensitivity of 0.848 (0.811, 0.885), specificity of 0.629 (0.509, 0.749), accuracy of 0.816 (0.779, 0.853). The discrimination ability had been verified in the validation dataset. Finally, we established a nomogram model base on the above final model. Conclusion: We developed and validated a predictive model with five easily acquire factors to diagnose OSAHS patient in high‐risk population with well discriminant ability. Accordingly, we finally build the nomogram model. [ABSTRACT FROM AUTHOR]

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Obstructive sleep apnea (OSA) is a common respiratory disorder. Multiple organs, especially the central nervous system (CNS), are damaged, and dysfunctional when intermittent hypoxia (IH) occurs during sleep for a long time. The quality of life of individuals with OSA is significantly impacted by cognitive decline, which also escalates the financial strain on their families. Consequently, the development of novel therapies becomes imperative. IH induces oxidative stress, endoplasmic reticulum stress, iron deposition, and neuroinflammation in neurons. Synaptic dysfunction, reactive gliosis, apoptosis, neuroinflammation, and inhibition of neurogenesis can lead to learning and long-term memory impairment. In addition to nerve injury, the role of IH in neuroprotection was also explored. While causing neuron damage, IH activates the neuronal self-repairing mechanism by regulating antioxidant capacity and preventing toxic protein deposition. By stimulating the proliferation and differentiation of neural stem cells (NSCs), IH has the potential to enhance the ratio of neonatal neurons and counteract the decline in neuron numbers. This review emphasizes the perspectives and opportunities for the neuroprotective effects of IH and informs novel insights and therapeutic strategies in OSA., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Vitamin D deficiency has been associated with the occurrence of obstructive sleep apnea syndrome (OSAS). Megalin (LRP2) and cubilin (CUBN) are implicated in vitamin D metabolism, whereas LRP2 and CUBN polymorphisms have been previously associated with variable serum vitamin D levels. The present study aimed to evaluate the role of LRP2 rs2228171 c.8614C > T and CUBN rs1801222 c.758A > G polymorphisms in OSAS susceptibility, independently or in synergy with vitamin D levels., Methods: Vitamin D serum concentration of consecutive individuals was measured. PCR-RFLP was used for LRP2 rs2228171 and CUBN rs1801222 genotyping., Results: A total of 176 individuals was enrolled, including 144 patients with OSAS and 32 controls. Frequency of LRP2 rs2228171 c.8614 T and CUBN rs1801222 c.758G alleles was estimated at 22.4% and 79.8%, respectively. LRP2 and CUBN polymorphisms were not associated with OSAS occurrence (rs2228171Τ allele: 22.9% in OSAS group vs. 20.3% in controls, p = 0.651; rs1801222A allele 19.4% in OSAS group vs. 23.4% in controls, p = 0.471). Frequency of CUBN rs1801222A allele carriers was increased in patients with moderate or severe OSAS compared to mild OSAS (p = 0.028). Patients with OSAS homozygous for LRP2 CC and CUBN GG genotypes had lower vitamin D serum concentration compared to controls carrying the same genotype (18.0 vs 27.0 ng/mL, p = 0.006 and 19.0 vs 27.5 ng/mL, p = 0.007, respectively)., Conclusion: CUBN rs1801222 polymorphism may affect OSAS severity. Among other factors, low vitamin D concentration is associated with OSAS occurrence, irrespectively of LRP2 and CUBN polymorphisms., (© 2023. The Author(s).)

Adult lungs present high cellular plasticity against stress and injury, mobilizing stem/progenitor populations from conducting airways to maintain tissue homeostasis and gas exchange in alveolar spaces. With aging, pulmonary functional and structural deterioration occurs, mainly in pathological conditions, which is associated with impaired stem cell activity and increased senescence in mice. However, the impact of these processes underlying lung physiopathology in relation to aging has not been explored in humans. In this work, we analyzed stem cell (SOX2, p63, KRT5), senescence (p16INK4A, p21CIP, Lamin B1) and proliferative (Ki67) markers in lung samples from young and aged individuals, with and without pulmonary pathology. We identified a reduction in SOX2+ cells but not p63+ and KRT5+ basal cells in small airways with aging. In alveoli, we revealed the presence of triple SOX2+, p63+ and KRT5+ cells specifically in aged individuals diagnosed with pulmonary pathologies. Notably, p63+ and KRT5+ basal stem cells displayed colocalization with p16INK4A and p21CIP, as well as with low Lamin B1 staining in alveoli. Further studies revealed that senescence and proliferation markers were mutually exclusive in stem cells with a higher percentage colocalizing with senescence markers. These results provide new evidence of the activity of p63+/KRT5+ stem cells on human lung regeneration and point out that regeneration machinery in human lung is activated under stress due to aging, but fails to repair in pathological cases, as stem cells would likely become senescent. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) with a low arousal threshold (low-ArTH) phenotype can cause minor respiratory events that exacerbate sleep fragmentation. Although anthropometric features may affect the risk of low-ArTH OSA, the associations and underlying mechanisms require further investigation. This study investigated the relationships of body fat and water distribution with polysomnography parameters by using data from a sleep center database. The derived data were classified as those for low-ArTH in accordance with criteria that considered oximetry and the frequency and type fraction of respiratory events and analyzed using mean comparison and regression approaches. The low-ArTH group members (n = 1850) were significantly older and had a higher visceral fat level, body fat percentage, trunk-to-limb fat ratio, and extracellular-to-intracellular (E–I) water ratio compared with the non-OSA group members (n = 368). Significant associations of body fat percentage (odds ratio [OR]: 1.58, 95% confident interval [CI]: 1.08 to 2.3, p < 0.05), trunk-to-limb fat ratio (OR: 1.22, 95% CI: 1.04 to 1.43, p < 0.05), and E–I water ratio (OR: 1.32, 95% CI: 1.08 to 1.62, p < 0.01) with the risk of low-ArTH OSA were noted after adjustments for sex, age, and body mass index. These observations suggest that increased truncal adiposity and extracellular water are associated with a higher risk of low-ArTH OSA. [ABSTRACT FROM AUTHOR]

Background: There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa. Methods: We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger's test for bias analysis. Results: 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763–0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16–1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49–7.64). Conclusion: OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to examine the effects of continuous positive airway pressure (CPAP) treatment on inflammation parameters in patients with obstructive sleep apnea syndrome (OSAS). Methods: Patients aged 18 to 65 years who underwent polysomnography (PSG) in the sleep clinic between January 1, 2019, and December 31, 2019, were included in the study. Patients with severe OSAS initiated treatment with CPAP. Patients and control subjects were assessed for levels of periostin, TNF-alpha, TGF-beta, and IL-6. Patients were re-evaluated 3 months later. Comparisons for the serum markers were made between controls and patients of different severity of OSAS. Comparisons of serum markers were also made between baseline and 3 month follow-up. Results: A total of 92 patients were enrolled in the study, including 25 controls (apnea-hypopnea index or AHI < 5/h), 39 patents with mild to moderate OSAS who did not receive CPAP, and 28 patients with severe OSAS receiving CPAP treatment. When all three groups were compared, levels of periostin, TNF-alpha, TGF-beta, and IL-6, as inflammatory markers, were higher in the OSAS group, though not at a statistically significant level. In patients with severe OSAS, there were statistically significant decreases in the TGF-beta 1, TNF-alpha, and IL-6 values between baseline values and the same measures taken after 3 months of CPAP treatment. Periostin values also decreased after treatment, but this decrease was not at a significant level. Conclusion: Inflammatory parameters of patients with OSAS were significantly higher compared with healthy participants. Regression of inflammation was detected after CPAP treatment. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade. [ABSTRACT FROM AUTHOR]

Simple Summary: Obstructive sleep apnoea (OSA) is an underdiagnosed disorder from which many patients are suffering, and may lead to severe complications. The adipose tissue near the upper airways is essential in upper-airway collapses and OSA severity. The present investigation aimed to determine the correlations between upper-airway adipose tissue MRI parameters and OSA, using artificial intelligence to analyse the pathophysiology of OSA and predict obstruction location. Including anthropometric and MRI adipose tissue parameters, OSA and upper-airway obstruction can be predicted with high precision. Artificial intelligence can effectively be used in OSA diagnostics as it can analyse non-linear correlations; thus, it can be helpful for undiagnosed OSA cases. This study aimed to analyse the thickness of the adipose tissue (AT) around the upper airways with anthropometric parameters in the prediction and pathogenesis of OSA and obstruction of the upper airways using artificial intelligence. One hundred patients were enrolled in this prospective investigation, who were divided into control (non-OSA) and mild, moderately severe, and severe OSA according to polysomnography. All participants underwent drug-induced sleep endoscopy, anthropometric measurements, and neck MRI. The statistical analyses were based on artificial intelligence. The midsagittal SAT, the parapharyngeal fat, and the midsagittal tongue fat were significantly correlated with BMI; however, no correlation with AHI was observed. Upper-airway obstruction was correctly categorised in 80% in the case of the soft palate, including parapharyngeal AT, sex, and neck circumference parameters. Oropharyngeal obstruction was correctly predicted in 77% using BMI, parapharyngeal AT, and abdominal circumferences, while tongue-based obstruction was correctly predicted in 79% using BMI. OSA could be predicted with 99% precision using anthropometric parameters and AT values from the MRI. Age, neck circumference, midsagittal and parapharyngeal tongue fat values, and BMI were the most vital parameters in the prediction. Basic anthropometric parameters and AT values based on MRI are helpful in predicting OSA and obstruction location using artificial intelligence. [ABSTRACT FROM AUTHOR]

Simple Summary: Although several methods are used to diagnose obstructive sleep apnoea (OSA), the disorder is still underdiagnosed, leading to public healthcare problems. The main aim of the present study was to analyse the role of artificial intelligence in OSA diagnostics and obstruction localisation and, moreover, the role of subcutaneous adipose tissue in OSA pathophysiology. The significance of the present investigation is that using US in OSA diagnostics and obstruction location, an additional opportunity besides standard procedures (i.e., drug-induced sleep endoscopy or polygraphy) is presented, which is vital due to the high number of undiagnosed cases. Applying the algorithm, including artificial intelligence, the presence of obstructions and its localisation, can be determined with high precision. This can be essential in therapy planning or preoperative patient preparation. Introduction: Our aim was to investigate the applicability of artificial intelligence in predicting obstructive sleep apnoea (OSA) and upper airway obstruction using ultrasound (US) measurements of subcutaneous adipose tissues (SAT) in the regions of the neck, chest and abdomen. Methods: One hundred patients were divided into mild (32), moderately severe-severe (32) OSA and non-OSA (36), according to the results of the polysomnography. These patients were examined using anthropometric measurements and US of SAT and drug-induced sleep endoscopy. Results: Using SAT US and anthropometric parameters, oropharyngeal obstruction could be predicted in 64% and tongue-based obstruction in 72%. In predicting oropharyngeal obstruction, BMI, abdominal and hip circumferences, submental SAT and SAT above the second intercostal space on the left were identified as essential parameters. Furthermore, tongue-based obstruction was predicted mainly by height, SAT measured 2 cm above the umbilicus and submental SAT. The OSA prediction was successful in 97% using the parameters mentioned above. Moreover, other parameters, such as US-based SAT, with SAT measured 2 cm above the umbilicus and both-sided SAT above the second intercostal spaces as the most important ones. Discussion: Based on our results, several categories of OSA can be predicted using artificial intelligence with high precision by using SAT and anthropometric parameters. [ABSTRACT FROM AUTHOR]

Background and Objectives: Apnea hypopnea index is the most important criterion in determining the severity of obstructive sleep apnea (OSA), while the percentage of the total number of times which oxygen saturation is measured below 90% during polysomnography (CT90%) is important in determining the severity of hypoxemia. As hypoxemia increases, inflammation will also increase in OSA. Inflammation in the respiratory tract may affect phonation. We aimed to determine the effects of the degree of OSA and CT90% on phonation. Materials and Methods: The patients were between the ages of 18–60 years and were divided into four groups: normal, mild, moderate, and severe OSA. Patients were asked to say the vowels /α:/ and /i:/ for 5 s for voice recording. Maximum phonation time (MPT) was recorded. Using the Praat voice analysis program, Jitter%, Shimmer%, harmonics-to-noise ratio (HNR), and f0 values were obtained. Results: Seventy-two patients were included. Vowel sound /α:/; there was a significant difference for Jitter%, Shimmer%, and HNR measurements between the 1st and the 4th group (p < 0.001, p < 0.001, and p < 0.001, respectively) and a correlation between CT90% and Shimmer% and HNR values (p < 0.001 and p < 0.021, respectively). Vowel sound /i:/; there was a significant difference in f0 values between the 1st group and 2nd and 4th groups (p < 0.028 and p < 0.015, respectively), and for Jitter%, Shimmer%, and HNR measurements between the 1st and 4th group (p < 0.04, p < 0.000, and p < 0.000, respectively), and a correlation between CT90% and Shimmer% and HNR values (p < 0.016 and p < 0.003, respectively). The difference was significant in MPT between the 1st group and 3rd and 4th groups (p < 0.03 and p < 0.003, respectively). Conclusions: Glottic phonation can be affected, especially in patients whose AHI scores are ≥15. Voice quality can decrease as the degree of OSA increases. The increase in CT90% can be associated with the worsening of voice and can be used as a predictor in the evaluation of voice disorders in the future. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Nursing in Practice is the property of Journal of Clinical Nursing in Practice (Editorial Board, Shanghai Jiao Tong University Press) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea is a chronic and prevalent condition that is associated with endothelial dysfunction, atherosclerosis, and imposes excess overall cardiovascular risk and mortality. Despite its high prevalence and the susceptibility of CVD patients to OSA-mediated stressors, OSA is still under-recognized and untreated in cardiovascular practice. Moreover, conventional OSA treatments have yielded either controversial or disappointing results in terms of protection against CVD, prompting the need for the identification of additional mechanisms and associated adjuvant therapies. Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator (tPA) and urinary-type plasminogen activator (uPA), is a key regulator of fibrinolysis and cell migration. Indeed, elevated PAI-1 expression is associated with major cardiovascular adverse events that have been attributed to its antifibrinolytic activity. However, extensive evidence indicates that PAI-1 can induce endothelial dysfunction and atherosclerosis through complex interactions within the vasculature in an antifibrinolytic-independent matter. Elevated PAI-1 levels have been reported in OSA patients. However, the impact of PAI-1 on OSA-induced CVD has not been addressed to date. Here, we provide a comprehensive review on the mechanisms by which OSA and its most detrimental perturbation, intermittent hypoxia (IH), can enhance the transcription of PAI-1. We also propose causal pathways by which PAI-1 can promote atherosclerosis in OSA, thereby identifying PAI-1 as a potential therapeutic target in OSA-induced CVD. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a common sleep disorder with multiple comorbidities including hypertension, diabetes, and cardiovascular disorders. Detected based on an overnight sleep study is called polysomnography (PSG); OSA still remains undiagnosed in majority of the population mainly attributed to lack of awareness. To overcome the limitations posed by PSG such as patient discomfort and overnight hospitalization, newer technologies are being explored. In addition, challenges associated with current management of OSA using continuous positive airway pressure (CPAP), etc. presents several pitfalls. Conventional and modern detection/management techniques including PSG, CPAP, smart wearable/pillows, bio-motion sensors, etc., have both pros and cons. To fulfill the limitations in OSA diagnostics, there is an imperative need for new technology for screening of symptomatic and more importantly asymptomatic OSA patients to reduce the risk of several associated life-threatening comorbidities. In this line, molecular marker-based diagnostics have shown great promises. A detailed overview is presented on the OSA management and diagnostic approaches and recent advances in the molecular screening methods. The potentials of biomarker-based detection and its limitations are also portrayed and a comparison between the standard, current modern approaches, and promising futuristic technologies for OSA diagnostics and management is set forth. ABBREVIATIONS AHI: Apnea hypopnea index; AI: artificial intelligence; CAM: Cell adhesion molecules; CPAP: Continuous Positive Airway Pressure; COVID-19: Coronavirus Disease 2019; CVD: Cardiovascular disease; ELISA: Enzyme linked immunosorbent assay; HSAT: Home sleep apnea testing; IR-UWB: Impulse radio-ultra wideband; MMA: maxillomandibular advancement; PSG: Polysomnography; OSA: Obstructive sleep apnea; SOD: Superoxide dismutase; QD: Quantum dot [ABSTRACT FROM AUTHOR]

As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal‐like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal‐like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air‐liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS‐CoV‐2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs. [ABSTRACT FROM AUTHOR]

Summary : Proteomic‐based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep‐disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease‐related proteins in a population‐based cohort of women. In the community‐based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek® Inflammation panel and Olink Proseek® Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women. p‐Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea−hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement−apnea−hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea−hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement−apnea−hypopnea index ≥ 30) was associated with decreased levels of two anti‐inflammatory proteins; Sirt2 (q‐value.016) and LAP‐TGF‐β1 (q‐value.016). There was also a negative association between rapid eye movement−apnea−hypopnea index of ≥ 30 and Axin1 (q‐value.095), a protein thought to facilitate TGF‐β‐signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP‐TGF‐β1 and Axin1, anti‐inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index. [ABSTRACT FROM AUTHOR]

Introduction: Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA.Methods: Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities.Results: Plasma survivin levels were lower in OSA in the evening (27.6 ± 89.9 vs. 108.3 ± 161.2 pg/ml, p < 0.01) and in the morning (17.4 ± 48.6 vs. 36.4 ± 69.2 pg/ml, p = 0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea-hypopnoea index (r = − 0.45) or oxygen desaturation index (r = − 0.40, both p < 0.01); however, when adjusting to BMI, these became insignificant (p > 0.05). Low plasma survivin concentrations were associated with high BMI (r = − 0.35), high CRP (r = − 0.31), low HDL cholesterol (r = 0.24) and high triglyceride levels (r = − 0.24, all p < 0.05).Conclusion: Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail. [ABSTRACT FROM AUTHOR]

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