Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

Prevalence and Characteristics of Patients with Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease: Overlap Syndrome.

Overlap syndrome (OVS) is a distinct clinical entity that seems to result in potential cardiovascular consequences. We aimed to estimate the prevalence and risk factors for OVS in OSA patients and analyze clinical and PSG characteristics associated with OVS. In this cross-sectional study, 2616 patients evaluated for OSA underwent type-1 polysomnography (PSG). They were grouped as pure OSA (AHI > 15/h) and OVS patients. Demographics, PSG data, pulmonary function tests and arterial blood gases (ABGs) were compared between groups after adjustments for confounders. OSA was diagnosed in 2108 out of 2616 patients. Of those, 398 (19%) had OVS. Independent predictors of OVS were older age [OR: 5.386 (4.153-6.987)], current/former smoking [OR: 11.577 (7.232-18.532)], BMI [OR: 2.901 (2.082-4.044)] and ABG measurements [PaCO2 ≥ 45 OR: 4.648 (3.078-7.019), PO2 [OR: 0.934 (0.920-0.949)], HCO3- [OR: 1.196 (1.133-1.263), all p < 0.001]. OVS was also associated with prevalent hypertension [OR: 1.345 (1.030-1.758), p = 0.03] and cardiovascular disease [OR: 1.617 (1.229-2.126), p < 0.001], depressive symptoms [OR: 1.741 (1.230-2.465), p = 0.002] and nocturia [OR: 1.944 (1.378-2.742), p < 0.001], as well as with indices of OSA severity. Disturbances in sleep architecture were more prominent in OVS expressed by lower %N3 and REM% and higher arousal index. Our data suggest that OVS is prevalent among OSA patients, with distinct clinical and PSG characteristics. These characteristics could be utilized as predictive factors for early identification and further evaluation of these patients towards desirable patient-reported outcomes.

Sleepiness and Vitamin D Levels in Patients with Obstructive Sleep Apnea.

STUDY OBJECTIVES: The aim of this cross-sectional study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of the Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). METHODS: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS > 10) and those without EDS (ESS < 10). All patients underwent night polysomnography. Measurement of serum 25(OH)D vitamin was performed using a radioimmunoassay. RESULTS: In total, 217 patients with OSA (197 males and 20 females) were included. Patients with EDS had higher AHI (p < 0.001) values and lower mean serum 25(OH)D levels, compared with those of non-somnolent patients [17.4 (12.2-25.7) versus 21.1 (15.3-28.8) ng/mL, respectively, p = 0.005]. In patients with EDS, serum 25(OH)D levels correlated with average oxyhemoglobin saturation during sleep (r = 0.194, p = 0.043), and negatively with ESS score (r = -0.285, p = 0.003), AHΙ (r = -0.197, p = 0.040) and arousal index (r = -0.256, p = 0.019). Binary regression analysis identified Vit D serum levels (ß = -0.045, OR: 0.956, 95% CI: 0.916-0.997, p = 0.035), total sleep time (ß = 0.011, OR: 1.011, 95% CI: 1.002-1.021, p = 0.016) and AHI (ß = 0.022, OR: 1.022, 95% CI: 1.003-1.043, p = 0.026) as independent predictors of EDS in patients with OSA. In patients with EDS, multiple regression analysis indicated that ESS score was negatively associated with Vit D serum levels (ß = -0.135, p = 0.014) and minimum oxyhemoglobin saturation during sleep (ß = -0.137, p = 0.043). CONCLUSIONS: In the present study, EDS in patients with OSA is associated with low levels of Vitamin D, while sleep hypoxia may play a role in this process.

Unraveling the Link between Ιnsulin Resistance and Bronchial Asthma.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Pulmonary Function Tests Post-Stroke. Correlation between Lung Function, Severity of Stroke, and Improvement after Respiratory Muscle Training.

Stroke is a significant cause of mortality and chronic morbidity caused by cardiovascular disease. Respiratory muscles can be affected in stroke survivors, leading to stroke complications, such as respiratory infections. Respiratory function can be assessed using pulmonary function tests (PFTs). Data regarding PFTs in stroke survivors are limited. We reviewed the correlation between PFTs and stroke severity or degree of disability. Furthermore, we reviewed the PFT change in stroke patients undergoing a respiratory muscle training program. We searched PubMed until September 2023 using inclusion and exclusion criteria in order to identify studies reporting PFTs post-stroke and their change after a respiratory muscle training program. Outcomes included lung function parameters (FEV1, FVC, PEF, MIP and MEP) were measured in acute or chronic stroke survivors. We identified 22 studies of stroke patients, who had undergone PFTs and 24 randomised controlled trials in stroke patients having PFTs after respiratory muscle training. The number of patients included was limited and studies were characterised by great heterogeneity regarding the studied population and the applied intervention. In general, PFTs were significantly reduced compared to healthy controls and predicted normal values and associated with stroke severity. Furthermore, we found that respiratory muscle training was associated with significant improvement in various PFT parameters and functional stroke parameters. PFTs are associated with stroke severity and are improved after respiratory muscle training.

Risk factors for the in­hospital and 1­year mortality of elderly patients hospitalized due to COVID­19­related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high.

Challenging subjective excessive daytime sleepiness as an insomnia symptom: a retrospective study.

Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT-I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre-post evaluation of the ESS in a sub-sample of patients with ID who underwent CBT-I. Component 2 of the Insomnia Severity Index and Profile of Mood States-Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT-I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.

A Questionnaire-Based Cross-Sectional Study of Insomnia among Middle-Aged Adults from Greece's Northeastern Fringe, Thrace.

Background, aim: Insomnia constitutes a common and very debilitating disorder in modern societies. A better understanding of the etiologies and risk factors, modifiable or not, of insomnia is essential for a swifter diagnosis and a more appropriate treatment, mitigating its toll on individuals and society. To this purpose, the present study assessed the prevalence of insomnia in a randomly-selected adult population and its relation with a diverse range of socio-demographic characteristics and medical conditions. Methods:A sample of 771 participants aged 24 to 89 years (mean age 58±13 years; 42.7% women) was randomly selected from the general population of Thrace, a prefecture in Northeastern Greece with special cultural considerations, using a two-stage stratified sampling scheme. The Greek version of the Athens Insomnia Scale (AIS) was utilized to evaluate the presence of insomnia. Moreover, the Berlin Questionnaire for Obstructive Sleep Apnea and the Epworth Sleepiness Scale for Excessive Daytime Sleepiness were also utilized. Results:A total of 141 study participants (18.3%) were found to suffer from insomnia. Impaired sleep maintenance was reported as the most frequent symptom (62%). The following independent statistically significant risk factors emerged (p-value <0.05): BMI ≥35 (aOR=2.91), divorced or widowed individuals (aOR=2.23), female gender (aOR=1.76), age >70 years (aOR=1.61), snoring (aOR=1.61), midday sleep (aOR=1.58) and presence of chronic disease (aOR=1.55). Conclusion:The prevalence of isomnia in Thrace aligns with similar studies conducted in Greece and internationally. A multitude of socio-demographic characteristics and diseases, especially chronic, predispose to insomnia.

Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.

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.

The Influence of CPAP Therapy on Basal Metabolic Rate and Physical Activity in Obese Patients with Obstructive Sleep Apnea.

BACKGROUND: Energy balance in Obstructive Sleep Apnea (OSA), a disease closely related to obesity, is disturbed, and physical activity levels are impaired. The role of Continuous Positive Airway Pressure treatment (CPAP) in alleviating the disruptions mentioned above is questioned. The objective of this study is to explore changes in energy expenditure (EE) and physical activity (PA) in obese patients with OSA after CPAP treatment. METHODS: An assessment of Basal Metabolic Rate (BMR) via indirect calorimetry (IC) was performed on 24 obese patients (male in the majority (87.5%), mean age of 52.4 ± 9.8 years), newly diagnosed with moderate-severe OSA by polysomnography, at 4-time points: at baseline, at CPAP titration, at the 1-month and the 3-month follow up. Physical activity levels were subjectively estimated using the International Questionnaire of Physical Activity (IPAQ) before and after 3 months of adherent CPAP application. RESULTS: BMR significantly decreased after CPAP treatment (1926 ± 537.8 kcal/d at baseline, 1790 ± 493.7 kcal/d at CPAP initiation, 1680.3 ± 600.8 kcal/d at 1 month, and 1581.3 ± 478.9 kcal/d at 3 months follow up (p < 0.001)). No significant changes in IPAQ were observed over time: baseline median IPAQ: 3894 (1487.5-11,755.5) total MET·min·wk-1, 3-month median IPAQ: 3900 (1512-11,824.5) total MET·min·wk-1. CONCLUSIONS: CPAP has an appreciable time effect on the BMR of obese patients with moderate-severe OSA. However, this change is not accompanied by a significant increase in physical activity levels.

Is COPD the Determinant Factor for Myocardial Injury and Cardiac Wall Stress in OSA Patients?

Background and Objectives: Evidence shows that COPD-OSA overlap syndrome (OS) is more frequently accompanied by cardiovascular disease (CVD) in comparison to either disease alone. The aim of the study was to explore whether patients with OS have a higher burden of subclinical myocardial injury and wall stress compared with OSA patients. Materials and Methods: Consecutive patients, without established CVD, underwent polysomnography and pulmonary function testing, due to suspected sleep-disordered breathing. An equal number of patients with OS (n = 53, with an apnea hypopnea index (AHI) > 5/h and FEV1/FVC < 0.7) and patients with OSA (n = 53, AHI > 5/h and FEV1/FVC > 0.7) were included in the study. The detection of asymptomatic myocardial injury and wall stress was performed via the assessment of serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), respectively. Results: OS patients were older (p < 0.001) and had worse hypoxemic parameters, namely average oxyhemoglobin saturation (SpO2) (p = 0.002) and time spent with SpO2 < 90% (p = 0.003) during sleep as well as daytime pO2 (p < 0.001), than patients with OSA. No difference was observed between groups in terms of Epworth Sleepiness Scale (p = 0.432) and AHI (p = 0.587). Both levels of hs-cTnT (14.2 (9.1-20.2) vs. 6.5 (5.6-8.7) pg/mL, p < 0.001) and NT-proBNP (93.1 (37.9-182.5) vs. 19.2 (8.3-35.4) pg/mL, p < 0.001) were increased in OS compared to OSA patients. Upon multivariate linear regression analysis, levels of NT-proBNP and hs-cTnT correlated with age and average SpO2 during sleep. Conclusions: Our study demonstrated higher levels of hs-cTnT and NT-proBNP in OS patients, indicating an increased probability of subclinical myocardial injury and wall stress, compared with OSA individuals.

A Clinical Approach of Allergic Rhinitis in Children.

Allergic rhinitis is an important disease with a global footprint and a growing prevalence, affecting children and adults. Although it is commonly under-diagnosed and under-treated, it causes important social and economic effects (diminished quality of life, poor academic performance, escalated medical visits, heightened medication usage, and effects in other chronic conditions, e.g., asthma). It is characterized by distinctive, easily identifiable symptoms (sneezing, nasal discharge, nasal congestion, nasal-eye-palatal itching) and indirect accompanying indicators (fatigue and decreased school performance). The classification of allergic rhinitis hinges upon its nature and chronic distribution (seasonal or perennial) and its intensity, which spans from mild to moderate and severe. The diagnostic process primarily relies upon recognizing key clinical indicators, evaluating historical records, and considering risk factors. It is supported by abnormal laboratory findings, like in vitro allergen-specific IgE tests (enzyme immunoassay-EIA, chemiluminense immunoassay-CLIA) or in vivo skin prick tests for specific allergens. In the differential diagnosis, other chronic diseases manifesting with chronic rhinitis should be excluded (e.g., rhinosinusitis, chronic non-allergic rhinitis, rhinitis triggered by medications). The treatment of allergic rhinitis in children is mainly chronic and is focused on allergen exposure prevention, drug therapy, and immunotherapy in severe cases. Locally administered intranasal corticosteroids are the cornerstone of therapy. They are safe, effective, and have a favorable safety profile even during long-term use. Choosing a suitable intranasal corticosteroid drug with low systemic bioavailability makes long-term treatment even safer. Combinations of intranasal corticosteroids and H1 antihistamines are available in several countries and are widely used in more severe cases and the presence of year-round symptoms. Adding newer-generation oral H1-antihistamines broadens the available therapeutic inventory without significant effects compared to using previous-generation, once widely available, H1-antihistamines. Treatment of allergic rhinitis is complex and multi-dimensional, requiring an effective approach by a specialized group of specialized pediatricians, and is severely affected by the concurrent presence or development of other diseases in the spectrum of allergic diseases (conjunctivitis, asthma).

Epithelial alarmins: a new target to treat chronic respiratory diseases.

INTRODUCTION: In response to injury, epithelial cells release alarmins including thymic stromal lymphopoietin (TSLP), high mobility group-box-1 (HMGB1), interleukin (IL)-33 and -25 that can initiate innate immune responses. These alarmins are recognized as activators of T2-immune responses characteristic for asthma, but recent evidence highlighted their role in non-T2 inflammation, airway remodeling, and pulmonary fibrosis making them an attractive therapeutic target for chronic respiratory diseases (CRD). AREAS COVERED: In this review, firstly we discuss the role of TSLP, IL-33, IL-25, and HMGB1 in the pathogenesis of asthma, COPD, idiopathic pulmonary fibrosis, and cystic fibrosis according to the published data. In the second part, we summarize the current evidence concerning the efficacy of the antialarmin therapies in CRD. Recent clinical trials showed that anti-TSLP and IL-33/R antibodies can improve severe asthma outcomes. Blocking the IL-33-mediated pathway decreased the exacerbation rate in COPD patients with more important benefit for former-smokers. EXPERT OPINION: Despite progress in the understanding of the alarmins' role in the pathogenesis of CRD, all their mechanisms of action are not yet identified. Blocking IL-33 and TSLP pathways offers an interesting option to treat severe asthma and COPD, but future investigations are needed to establish their place in the treatment strategies.

Predictors of COVID­19­associated mortality among hospitalized elderly patients with dementia.

The mortality of elderly patients with dementia hospitalized with coronavirus disease 2019 (COVID-19)-associated pneumonia is high. The mortality rate of these patients continues to be high following their discharge. However, data on the outcomes of these patients in all phases of the pandemic are limited. The aim of the present study was to examine the clinical characteristics and the in-hospital and 90-day mortality rates of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia during all phases of the pandemic. During the time period between February 15, 2021 to July 15, 2022, 105 elderly patients (≥65 years old) with dementia of various etiologies were hospitalized due to COVID-19-associated pneumonia. The patient characteristics and in-hospital outcomes within 90 days of admission were recorded. The mean age of the patients was 84.03±7.61 years and 60 (57.1%) patients were females. A total of 52 (49.5%) patients were hospitalized during the omicron variant period, 27 (25.7%) were fully vaccinated (three doses) and 38 (36.2%) patients succumbed during their hospitalization. In total, 52 (49.5%) patients succumbed within the first 90 days of admission. According to the univariate regression analysis, the omicron variant [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with a higher in-hospital mortality. In the multivariate regression analysis, only the absence of complete vaccination was an independent predictor of mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027). According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the lack of complete vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with 90-day mortality; in addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality rate. Based on the findings presented herein, the in-hospital and 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia is high. An older age and the lack of complete vaccination are independently associated with poor outcomes.

Niclosamide Attenuates Inflammation-Associated Profibrotic Responses in Human Subepithelial Lung Myofibroblasts.

Niclosamide is a commonly used helminthicidic drug for the treatment of human parasitosis by helminths. Recently, efforts have been focusing on repurposing this drug for the treatment of other diseases, such as idiopathic pulmonary fibrosis. Subepithelial lung myofibroblasts (SELMs) isolated from tissue biopsies of patients undergoing surgery for lung cancer were stimulated with TNF-α (50 ng/mL), IL-1α (5 ng/mL), added alone or in combination, and TGF-ß1 (5 ng/mL). After treatment with niclosamide at 30 nM and 100 nM concentrations, expression of collagen type I, collagen type III, and fibronectin was studied by total RNA isolation and qRT-PCR and protein collagen secretion with the use of Sircol collagen assay. The migration of SELMs was assessed by a wound-healing assay. Niclosamide had no effect on baseline SELM fibrotic factor expression. When stimulated with TGF-ß1, IL-1α, and/or TNF-α, SELM expression of collagen type I, type III, and fibronectin were upregulated, as was the secretion of total collagen in the culture medium. Treatment with niclosamide attenuated the effects of cytokine stimulation leading to a notable decrease in the mRNA expression of collagen type I, type III, and fibronectin in a concentration-dependent manner. SELM collagen secretion was also reduced by niclosamide at 100 nM concentration when examined at the protein level. Migration of both TGF-ß1 stimulated and unstimulated SELMs was also inhibited by niclosamide. In this study, we highlight the anti-fibrotic properties of niclosamide on SELMs under stimulation with pro-fibrotic and pro-inflammatory cytokines, thus proposing this compound as a possible new therapeutic agent against lung fibrosis.

Sleep and cardiometabolic comorbidities in the obstructive sleep apnoea-COPD overlap syndrome: data from the European Sleep Apnoea Database.

Aim: The impact of obstructive sleep apnoea (OSA)-COPD overlap syndrome (OVS) on sleep quality and cardiovascular outcomes has not been fully explored. We aimed to compare clinical and polysomnographic characteristics of patients with OVS versus patients with OSA, and to explore pathophysiological links between OVS and comorbidities. Study design and methods: This cross-sectional analysis initially included data from 5600 patients with OSA and lung function in the European Sleep Apnoea Database. Two subgroups of patients with OSA (n=1018) or OVS (n=509) were matched (2:1) based on sex, age, body mass index and apnoea-hypopnea index at baseline. Results: After matching, patients with OVS had more severe hypoxia, lower sleep efficiency and presented with higher prevalences of arterial hypertension, ischaemic heart disease and heart failure compared with patients with OSA. OVS was associated with a significant decrease in sleep efficiency (mean difference (ß) -3.0%, 95% CI -4.7 to -1.3) and in nocturnal mean peripheral oxyhaemoglobin saturation (SpO2) (ß -1.1%, 95% CI -1.5 to -0.7). Further analysis revealed that a decrease in forced expiratory volume in 1 s and arterial oxygen tension was related to a decrease in sleep efficiency and in mean nocturnal SpO2. A COPD diagnosis increased the odds of having heart failure by 1.75 (95% CI 1.15-2.67) and systemic hypertension by 1.36 (95% CI 1.07-1.73). Nocturnal hypoxia was strongly associated with comorbidities; the mean nocturnal SpO2 and T90 (increase in time below SpO2 of 90%) were associated with increased odds of systemic hypertension, diabetes and heart failure but the oxygen desaturation index was only related to hypertension and diabetes. Conclusion: Patients with OVS presented with more sleep-related hypoxia, a reduced sleep quality and a higher risk for heart failure and hypertension.

Acute Exacerbations of Interstitial Lung Diseases: Focus on Biomarkers.

Interstitial lung diseases (ILDs) are a large group of pulmonary disorders characterized histologically by the cardinal involvement of the pulmonary interstitium. The prototype of ILDs is idiopathic pulmonary fibrosis (IPF), an incurable disease characterized by progressive distortion and loss of normal lung architecture through unchecked collagen deposition. Acute exacerbations are dramatic events during the clinical course of ILDs, associated with high morbidity and mortality. Infections, microaspiration, and advanced lung disease might be involved in the pathogenesis of acute exacerbations. Despite clinical scores, the prediction of the onset and outcome of acute exacerbations is still inaccurate. Biomarkers are necessary to characterize acute exacerbations better. We review the evidence for alveolar epithelial cell, fibropoliferation, and immunity molecules as potential biomarkers for acute exacerbations of interstitial lung disease.