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The article presents a study which investigates the effects of buccal air leaks and glottal aperture in the measurement of respiratory resistance using the forced oscillation technique (FOT). Topics discussed include an overview of the clinical procedures used by researchers to acquire the relevant data for the study, the use of the GraphPad Prism 5.03 statistical software in the analysis, and the study confirming glottal narrowing by direct rhinolaryngoscopy.

A protective role of vascular endothelial growth factor (VEGF) on right heart function has been reported only in animal studies of pulmonary hypertension. Twenty patients with idiopathic pulmonary hypertension and fifteen healthy volunteers were involved. Plasma VEGF levels were compared to right heart parameters. Plasma VEGF levels tended to be higher in patients (82/0-345/pg/ml) than in controls (48/0-141/pg/ml, p = 0.08) with a significant correlation between VEGF concentration and tricuspid annular plane systolic excursion (TAPSE; p = 0.03, r = 0.48). This is the first study to report a positive association between elevated plasma VEGF levels and right heart function in humans. [ABSTRACT FROM AUTHOR]

The article discusses case study of a 63-year old man with a chronic nonproductive cough of 8 years, in which gabapentin has been eventually found as a potential treatment for cough syncope. Topics discussed include symptoms and diagonosis of the patient, several treatment trials given to patient to manage his underlying cough and associated syncope, and effects of gabapentin in improving quality of life of the patient.

Obstructive sleep apnoea (OSA) is associated with increased insulin resistance. Triglyceride-glucose index (TyG) is a simple marker of insulin resistance; however, it has been investigated only by two studies in OSA. The aim of this study was to evaluate TyG in non-diabetic, non-obese patients with OSA. A total of 132 patients with OSA and 49 non-OSA control subjects were included. Following a diagnostic sleep test, fasting blood was taken for the analysis of the lipid profile and glucose concentrations. TyG was calculated as ln(triglyceride [mg/dL] × glucose [mg/dL]/2). Comparison analyses between OSA and control groups were adjusted for age, gender, body mass index (BMI) and smoking. TyG was higher in men (p < 0.01) and in ever-smokers (p = 0.02) and it was related to BMI (ρ = 0.33), cigarette pack-years (ρ = 0.17), apnoea–hypopnoea index (ρ = 0.38), oxygen desaturation index (ρ = 0.40), percentage of total sleep time spent with oxygen saturation below 90% (ρ = 0.34), and minimal oxygen saturation (ρ = −0.29; all p < 0.05). TyG values were significantly higher in OSA (p = 0.02) following adjustment for covariates. OSA is independently associated with higher TyG values which are related to disease severity in non-obese, non-diabetic subjects. However, the value of TyG in clinical practice should be evaluated in follow-up studies in patients with OSA. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with "hypoxic stress" (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies. [ABSTRACT FROM AUTHOR]

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31–0.88/ng/mL vs. 0.31/0.31–0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11–59.25/ng/mL vs. 46.83/25.41–89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = − 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA. [ABSTRACT FROM AUTHOR]

Work-related asthma has become a highly prevalent occupational lung disorder. Our study aims to evaluate occupational exposure as a predictor for asthma exacerbation. We performed a retrospective evaluation of 584 consecutive patients diagnosed and treated for asthma between October 2017 and December 2019 in four clinics from Western Romania. We evaluated the enrolled patients for their asthma control level by employing the Asthma Control Test (ACT < 20 represents uncontrolled asthma), the medical record of asthma exacerbations, occupational exposure, and lung function (i.e. spirometry). Then, we used statistical and data mining methods to explore the most important predictors for asthma exacerbations. We identified essential predictors by calculating the odds ratios (OR) for the exacerbation in a logistic regression model. The average age was 45.42 ± 11.74 years (19–85 years), and 422 (72.26%) participants were females. 42.97% of participants had exacerbations in the past year, and 31.16% had a history of occupational exposure. In a multivariate model analysis adjusted for age and gender, the most important predictors for exacerbation were uncontrolled asthma (OR 4.79, p <.001), occupational exposure (OR 4.65, p <.001), and lung function impairment (FEV1 < 80%) (OR 1.15, p =.011). The ensemble machine learning experiments on combined patient features harnessed by our data mining approach reveal that the best predictor is professional exposure, followed by ACT. Machine learning ensemble methods and statistical analysis concordantly indicate that occupational exposure and ACT < 20 are strong predictors for asthma exacerbation. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors.Methods: Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied.Results: The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index.Conclusion: OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence for the interrelation between health status and religious beliefs. Our aim was to evaluate the level of religiosity in patients hospitalized for COVID-19 and to assess the link between religiosity and measurable health outcomes. This was an observational, single-center study which included patients with moderate-to-severe forms of COVID-19. A total of 112 patients were enrolled in the study, of whom 77 were highly religious (CRS-15 score ≥ 4) and 35 non-highly religious (CRS-15 score < 4). There was no difference in demographics or prevalence of comorbidities between the two groups. Furthermore, we found no difference between groups in radiological extension of lung lesions, length of hospital stays, or ICU need; however, in-hospital mortality rate was significantly lower in highly religious group (1% vs. 14%, p = 0.005). Serum ferritin level at admission was significantly lower (p = 0.03) and prevalence of post-COVID-19 pulmonary sequelae significantly higher in highly religious group (p = 0.02). [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder that may lead to gas exchange abnormalities, including hypercapnia. Chronic hypercapnia is an independent risk factor of mortality in COPD, leading to epithelial dysfunction and impaired lung immunity. Moreover, chronic hypercapnia affects the cardiovascular physiology, increases the risk of cardiovascular morbidity and mortality, and promotes muscle wasting and musculoskeletal abnormalities. Noninvasive ventilation is a widely used technique to remove carbon dioxide, and several studies have investigated its role in COPD. In the present review, we aim to summarize the causes and effects of chronic hypercapnia in COPD. Furthermore, we discuss the use of domiciliary noninvasive ventilation as a treatment option for hypercapnia while highlighting the controversies within the evidence. Finally, we provide some insightful clinical recommendations and draw attention to possible future research areas. [ABSTRACT FROM AUTHOR]

Daytime sleepiness is a cardinal symptom of obstructive sleep apnoea (OSA) and a well-recognised side effect of beta-blockers, therefore patients with OSA under this treatment may have worse sleepiness. However, the interaction between daytime sleepiness and beta-blockers use has not been thoroughly investigated in patients with OSA before. We analysed the data of 2183 individuals (1852 patients with OSA and 331 snorer controls) from 3 countries (Greece, Hungary and Moldova). Medical history, including medication usage and the Epworth Sleepiness Scale (ESS) were recorded. Patients and controls were divided into somnolent (ESS ≥ 11) and non-somnolent (ESS < 11) groups, and the association between-blocker use with the somnolent group was investigated with multivariate logistic regression analysis adjusted for confounders. Sensitivity analyses were performed in each cohort, in the severity subgroups, in patients who did not take statins and in those who had polysomnography as a diagnostic test. There was no relationship between beta-blocker usage and the somnolent OSA (p = 0.24) or control (p = 0.64) groups. These results were similar in sensitivity analyses (all p > 0.05). ESS was related to BMI (ρ = 0.25), total sleep time (ρ = 0.07), AHI (ρ = 0.32), oxygen desaturation index (ρ = 0.33) and minimum oxygen saturation (ρ = – 0.32, all p < 0.05) in OSA, and was higher in patients with hypertension, diabetes and cerebro/cardiovascular disease and those who took statins (all p < 0.05). In general, beta-blockers are not associated with increased daytime sleepiness in OSA. Thus, the diagnosis of OSA should not discourage initiation of beta-blocker treatment, if it is clinically indicated. [ABSTRACT FROM AUTHOR]

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland‐Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0–3.5/ vs. 0/0–1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain. [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]

Purpose: Obstructive sleep apnoea (OSA) is a prevalent disorder, characterised by collapse of the upper airways during sleep. The impact of sleep-disordered breathing on pulmonary function indices is however currently not well described. The aim of the study was to evaluate diurnal change in lung function indices in a cohort of patients with OSA and relate pulmonary function changes to disease severity. Methods: 42 patients with OSA and 73 healthy control subjects participated in the study. Asthma and COPD were excluded in all volunteers following a clinical and spirometric assessment. Spirometry was then performed in all subjects in the evening and the morning following a polysomnography study. Results: There was no difference in evening or morning FEV or FVC between patients and control subjects ( p > 0.05). Neither FEV nor FVC changed in control subjects overnight ( p > 0.05). In contrast, FEV significantly increased from evening (2.18/1.54-4.46/L) to morning measurement (2.26/1.42-4.63/L) in OSA without any change in FVC. The FEV increase in OSA was related to male gender, obesity and the lack of treatment with statins or β-blockers (all p < 0.05). A tendency for a direct correlation was apparent between overnight FEV change and RDI ( p = 0.05, r = 0.30). Conclusions: Diurnal variations in spirometric indices occur in patients with OSA and FEV appears to increase in subjects with OSA overnight. These changes occur in the absence of change in FVC and are directly related to the severity of OSA. These findings dictate a need to consider time of lung function measurement. [ABSTRACT FROM AUTHOR]

Background: Obstructive Sleep Apnea (OSA) is a prevalent disorder characterized by repetitive upper airway obstructions during sleep, leading to intermittent hypoxia and sleep fragmentation. Current treatments, particularly Continuous Positive Airway Pressure (CPAP), face adherence challenges, necessitating novel therapeutic approaches. Methods : This review explores the potential of Glucagon-like Peptide-1 receptor agonists (GLP-1RA), commonly used for type 2 diabetes and obesity, in managing OSA. GLP-1RA promotes weight loss, enhances insulin sensitivity, and exhibits anti-inflammatory and neuroprotective properties, potentially addressing key pathophysiological aspects of OSA. Results : Emerging evidence suggests that these agents may reduce OSA severity by decreasing upper airway fat deposition and improving respiratory control. Clinical trials have demonstrated significant reductions in the Apnea-Hypopnea Index (AHI) and improvements in sleep quality with GLP-1 therapy. Conclusions: Future research should focus on elucidating the mechanisms underlying GLP-1 effects on OSAS, optimizing combination therapies, and identifying patient subgroups that may benefit the most. Integrating GLP-1RA into OSAS management could revolutionize treatment by addressing both the metabolic and respiratory components of the disorder, ultimately enhancing patient outcomes.

Background : There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods : As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results : Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0-5.0/ to 2.8/0.71-4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0-7.0/ to 3.5/1.2-5.5/) or opioids (3.0/2.0-6.0/ to 3.0/0.8-5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant ( p = 0.12). Opioids were not associated with adverse outcomes. Conclusions : Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV.

Depression and periodic limb movement disease are both common disorders which frequently co-exist. Furthermore, antidepressants are known to cause and worsen periodic limb movements in sleep, which can worsen the quality of sleep and subsequently daytime symptoms. However, the effect of antidepressants on periodic limb movements is not uniform and depends on their mechanism of action. In this review we summarise the knowledge on the mechanism of periodic limb movements in sleep, and how changes in the concentration of neurotransmitters can contribute to them. We comprehensively evaluate the literature on antidepressants induced periodic limb movement in sleep. Based on this, we suggest clinical implications and further focus on research., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background : Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnoea (OSA). Maintaining adherence to CPAP in the long term is a clinical problem, and numerous factors have been identified that impact adherence. Although fully remote diagnostic and CPAP services were frequently utilised during the COVID-19 pandemic for patients with OSA, long-term adherence data have not been published. The aim of this service evaluation project was to describe the long-term adherence to CPAP. We also analysed factors that are associated with it. Methods : two-hundred and eighty patients diagnosed with OSA and set up on CPAP remotely during the first wave of the COVID-19 pandemic as part of routine clinical practice were analysed. Results : One-hundred and seven patients (38%) were fully adherent to CPAP at 24 months, determined by at least 4 h of usage on at least 70% of the days. Of the factors analysed, body mass index, disease severity, driving status and the presence of depression were related to long-term adherence (all p < 0.05). Conclusions : with the likelihood of future pandemics similar to COVID-19, our data provide evidence that fully remote pathways for management of patients with OSA can be designed and be sustainable with good long-term adherence.

Periodic limb movements during sleep and obstructive sleep apnea are both associated with increased sympathetic tone, and have been proposed as risk factors for heart diseases and, in particular, cardiovascular disease. As sympathetic system activation may lead to dyslipidaemia, periodic limb movements during sleep could be an additional risk factor for cardiovascular disease in patients with obstructive sleep apnea. The aim of the study was to determine whether the presence of periodic limb movements during sleep affects serum lipid levels in obstructive sleep apnea. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non- high-density lipoprotein cholesterol and triglyceride levels were investigated in 4138 patients with obstructive sleep apnea in the European Sleep Apnea Database (ESADA) cohort, divided into those with periodic limb movements during sleep index ≥ 15 per hr (n = 628) and controls (n = 3510). ANCOVA adjusted for age, sex, body mass index, apnea-hypopnea index, alcohol intake, smoking status, diabetes, insomnia and study site was used to assess differences in lipids between periodic limb movements during sleep and controls. Patients with periodic limb movements during sleep (24% female, 54.4 ± 12.1 years, body mass index 31.9 ± 5.8 kg m -2 , apnea-hypopnea index 36.7 ± 25.4 per hr) had higher triglyceride (1.81 ± 1.04 versus 1.69 ± 0.90 mmol L -1 , p = 0.002) and lower high-density lipoprotein cholesterol (1.19 ± 0.34 versus 1.24 ± 0.37 mmol L -1 , p = 0.002) levels, whilst there was no difference in either total cholesterol (4.98 ± 1.10 versus 4.94 ± 1.07 mmol L -1 ), low-density lipoprotein cholesterol (3.04 ± 0.96 versus 2.98 ± 0.98 mmol L -1 ) or non- high-density lipoprotein cholesterol (3.78 ± 1.10 versus 3.70 ± 1.05 mmol L -1 ) concentrations (all p > 0.05). The results remained unchanged after most sensitivity analyses. Patients with obstructive sleep apnea with periodic limb movements during sleep had more prevalent cardiovascular disease (11% versus 6%, p < 0.01). Periodic limb movements during sleep in obstructive sleep apnea is associated with dyslipidaemia independently of important confounders. Our results highlight periodic limb movements during sleep as an additional risk factor for cardiovascular disease in obstructive sleep apnea., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore, they are prone to chest infections, such as pneumonia or bronchitis. Acute exacerbations of COPD are major events that accelerate disease progression, contributing to its symptoms' burden, morbidity, and mortality. Both pneumonia and acute exacerbations in COPD are caused by bacteria against which there are effective vaccinations. Although the number of randomised controlled studies on bacterial vaccinations in COPD is limited, national and international guidelines endorse specific vaccinations in patients with COPD. This review will summarise the different types of vaccinations that prevent pneumonia and COPD exacerbations. We also discuss the results of early phase studies. We will mainly focus on Streptococcus pneumoniae , as this bacterium was predominantly investigated in COPD. However, we also review studies investigating vaccinations against Haemophilus influenzae , Moraxella catarrhalis , and Bordetella pertussis .

We aimed to conduct a state-of-the-art review of the current literature and offer further insights into the methodological aspects concerning induced sputum. The increasing popularity of sputum induction as a non-invasive and cost-effective method for obtaining lower airway secretions from patients who cannot produce sputum naturally has led to extensive research and applications in respiratory conditions like asthma and COPD. This technique allows for analysis of the cellular and biochemical components of the sputum to take place, providing insights into airway inflammation, immune cells, and help in predicting treatment response. Furthermore, induced sputum enables various analyses, including microRNA and gene expression studies and immunophenotyping. The procedure is generally safe and well tolerated, even in patients with airflow limitations; however, monitoring lung function is essential, especially in those with airway hyperresponsiveness. Optimal saline solution concentration and inhalation duration have been investigated, recommending a 15-20 min induction with hypertonic saline. Expectoration involves coughing at the end of each inhalation time. Careful handling during sputum processing is necessary for obtaining accurate results in cell cytology, immunocytochemistry, and in situ hybridization. Overall, induced sputum offers significant advantages as a preferred alternative for large-scale and repeated airway sampling, despite some technical demands and limitations.

Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Many lines of evidence suggest that the disturbances in circadian rhythm are responsible for the development of CVDs; however, circadian misalignment is not yet a treatable trait in clinical practice. The circadian rhythm is controlled by the central clock located in the suprachiasmatic nucleus and clock genes (molecular clock) located in all cells. Dyslipidaemia and vascular inflammation are two hallmarks of atherosclerosis and numerous experimental studies conclude that they are under direct influence by both central and molecular clocks. This review will summarise the results of experimental studies on lipid metabolism, vascular inflammation and circadian rhythm, and translate them into the pathophysiology of atherosclerosis and cardiovascular disease. We discuss the effect of time-respected administration of medications in cardiovascular medicine. We review the evidence on the effect of bright light and melatonin on cardiovascular health, lipid metabolism and vascular inflammation. Finally, we suggest an agenda for future research and recommend on clinical practice.

The asthmatic inflammatory process results in the generation of volatile organic compounds (VOCs), which are subsequently secreted by the airways. The study of these elements through gas chromatography-mass spectrometry (GC-MS), which can identify individual molecules with a discriminatory capacity of over 85%, and electronic-Nose (e-NOSE), which is able to perform a quick onboard pattern-recognition analysis of VOCs, has allowed new prospects for non-invasive analysis of the disease in an "omics" approach. In this review, we aim to collect and compare the progress made in VOCs analysis using the two methods and their instrumental characteristics. Studies have described the potential of GC-MS and e-NOSE in a multitude of relevant aspects of the disease in both children and adults, as well as differential diagnosis between asthma and other conditions such as wheezing, cystic fibrosis, COPD, allergic rhinitis and last but not least, the accuracy of these methods compared to other diagnostic tools such as lung function, FeNO and eosinophil count. Due to significant limitations of both methods, it is still necessary to improve and standardize techniques. Currently, e-NOSE appears to be the most promising aid in clinical practice, whereas GC-MS, as the gold standard for the structural analysis of molecules, remains an essential tool in terms of research for further studies on the pathophysiologic pathways of the asthmatic inflammatory process. In conclusion, the study of VOCs through GC-MS and e-NOSE appears to hold promise for the non-invasive diagnosis, assessment, and monitoring of asthma, as well as for further research studies on the disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the evaluation of response to biologics after 4 months of treatment., Method: Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts., Results: Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics., Conclusions: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.

The human body contains a very complex and dynamic ecosystem of bacteria. The bacteriome interacts with the host bi-directionally, and changes in either factor impact the entire system. It has long been known that chronic airway diseases are associated with disturbances in the lung bacteriome. However, less is known about the role of gut bacteriome in the most common respiratory diseases. Here, we aim to summarise the evidence concerning the role of the intestinal bacteriome in the pathogenesis and disease course of bronchial asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea. Furthermore, we discuss the consequences of an altered gut bacteriome on the most common comorbidities of these lung diseases. Lastly, we also reflect on the therapeutic potential of influencing the gut microbiome to improve disease outcomes.

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia.

Purpose: Obstructive sleep apnoea (OSA) is a recognised risk factor for cardiovascular disease. However, it is difficult to evaluate the risk of cardiovascular disease in patients with OSA due to multiple shared risk factors. Composite lipid indices, such as atherogenic index of plasma (AIP), visceral adiposity index (VAI) and lipid accumulation product (LAP) have been shown to predict cardiovascular disease better than their individual lipid components. This study aimed to evaluate these indices in patients with OSA., Patients and Methods: Six hundred sixty-seven (667) patients with OSA and 139 non-OSA control volunteers participated in the study. Fasting serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) levels were measured, and AIP, LAP and VAI were calculated following cardiorespiratory polygraphy. The relationship between lipid parameters, OSA and its comorbidities was evaluated using receiver operating curve (ROC) analysis., Results: We found a significant difference in all lipid parameters between OSA patients and controls. Comparing ROCs, LAP was significantly more strongly associated with OSA compared to all the other parameters. The optimal cut-off value for LAP to detect OSA was 76.4, with a sensitivity of 63% and a specificity of 76%. In addition, LAP was the best parameter to predict hypertension and diabetes in patients with OSA, and it was predictive for ischaemic heart disease together with HDL-C., Conclusion: Our results support the use of LAP in clinical practice when evaluating cardiovascular risk in patients with OSA. However, the optimal cut-off value should be determined in large-scale follow-up studies., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Bikov et al.)

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use., Competing Interests: Conflict of interest: A.G. Mathioudakis reports grants from Boehringer Ingelheim, outside the submitted work. Conflict of interest: F. Abroug has nothing to disclose. Conflict of interest: A. Agusti reports grants and personal fees for advisory board work and lectures from GSK, Menarini, Chiesi and AZ, outside the submitted work. Conflict of interest: S. Ananth has nothing to disclose. Conflict of interest: P. Bakke reports personal fees for lectures from AstraZeneca, Novartis and GlaxoSmithKline, outside the submitted work. Conflict of interest: K. Bartziokas has nothing to disclose. Conflict of interest: B. Beghe has nothing to disclose. Conflict of interest: A. Bikov has nothing to disclose. Conflict of interest: T. Bradbury reports receiving an academic scholarship funded by GlaxoSmithKline outside the submitted work. Conflict of interest: G. Brusselle reports personal fees for advisory board work and lectures from Astra Zeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Teva, outside the submitted work. Conflict of interest: C. Cadus reports personal fees from Mundipharma and AstraZeneca outside the submitted work. Conflict of interest: C. Coleman is an employee of the European Lung Foundation. Conflict of interest: M. Contoli reports board membership, payment for lectures, grants for research and travel expenses reimbursement from Chiesi, AstraZeneca and GlaxoSmithKline, board membership, consultancy, payment for lectures, grants for research and travel expenses reimbursement from Boehringer Ingelheim, board membership, consultancy and travel expenses reimbursement from Alk-Abello, board membership, payment for lectures, travel expenses reimbursement from Novartis and Zambon, grants from University of Ferrara, Italy, outside the submitted work. Conflict of interest: A. Corlateanu has nothing to disclose. Conflict of interest: O. Corlateanu has nothing to disclose. Conflict of interest: G.J. Criner reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Mereo, AstraZeneca, Pulmonx, Pneumrx, Olympus, Broncus, Lungpacer, Nuvaira, ResMed, Respironics and Patara, personal fees from Verona, BTG, EOLO and NGM, grants from Alung, Fisher Paykel and Galapagos, outside the submitted work. Conflict of interest: B. Csoma has nothing to disclose. Conflict of interest: A. Emelyanov has nothing to disclose. Conflict of interest: R. Faner reports grants and other (advisory board) from GSK, grants from Menarini and AstraZeneca, other (lecture fee) from Chiesi, outside the submitted work. Conflict of interest: G. Fernandez Romero has nothing to disclose. Conflict of interest: Z. Hammouda has nothing to disclose. Conflict of interest: P. Horváth has nothing to disclose. Conflict of interest: A. Huerta Garcia has nothing to disclose. Conflict of interest: M. Jacobs has nothing to disclose. Conflict of interest: C. Jenkins reports personal fees for advisory board work and educational content from AstraZeneca and Boehringer Ingelheim, grants and personal fees for advisory board work and educational content from GlaxoSmithKline, personal fees for consultancy, advisory board work and educational content from Novartis, outside the submitted work. Conflict of interest: G. Joos reports grants, personal fees for lectures and advisory board work, and non-financial support from AstraZeneca and GlaxoSmithKline, grants from Chiesi, personal fees for lectures from Novartis and Lapharcon, outside the submitted work; all fees were paid to his department. Conflict of interest: O. Kharevich has nothing to disclose. Conflict of interest: K. Kostikas was an employee and shareholder of Novartis Pharma AG until 2018; he has received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Sanofi Genzyme and WebMD; his department has received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir; and he is a member of the GOLD Assembly. Conflict of interest: E. Lapteva has nothing to disclose. Conflict of interest: Z. Lazar has nothing to disclose. Conflict of interest: J.D. Leuppi is supported by grants from the Swiss National Science Foundation (SNF 160072 and 185592) as well as by Swiss Personalised Health Network (SPHN 2018DR108); and has also received unrestricted grants from AstraZeneca AG Switzerland, Boehringer Ingelheim GmbH Switzerland, GSK AG Switzerland, and Novartis AG Switzerland. Conflict of interest: C. Liddle has nothing to disclose. Conflict of interest: J. Linnell has nothing to disclose. Conflict of interest: A. López-Giraldo has nothing to disclose. Conflict of interest: V.M. McDonald reports grants and personal fees from GSK and AZ, personal fees from Novartis, outside the submitted work. Conflict of interest: R. Nielsen reports grants from GlaxoSmithKline Norway and Boehringer Ingelheim, grants and personal fees from AstraZeneca, outside the submitted work. Conflict of interest: A. Papi report grants, personal fees, non-financial support, and other interests at AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma and Teva; personal fees and non-financial support from Menarini, Novartis and Zambon; and grants from Sanofi. Conflict of interest: I. Saraiva has nothing to disclose. Conflict of interest: G. Sergeeva has nothing to disclose. Conflict of interest: A. Sioutkou has nothing to disclose. Conflict of interest: P. Sivapalan reports personal fees for lectures from Boehringer Ingelheim, AstraZeneca and GSK, outside the submitted work. Conflict of interest: E. Stovold has nothing to disclose. Conflict of interest: H. Wang has nothing to disclose. Conflict of interest: F. Wen has nothing to disclose. Conflict of interest: J. Yorke has nothing to disclose. Conflict of interest: P.R. Williamson reports personal fees from European Respiratory Society, during the conduct of the study. Conflict of interest: J. Vestbo reports personal fees for consultancy and lectures from AstraZeneca, Chiesi and Novartis, grants and personal fees for consultancy and lectures from Boehringer Ingelheim, personal fees for consultancy from GSK, outside the submitted work; and the author's son works for Chiesi. Conflict of interest: J-U. Jensen has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Obstructive sleep apnoea (OSA) and asthma are two common respiratory disorders in children and adults. Apart from common risk factors, such as obesity, gastroesophageal reflux disease and allergic rhinitis, emerging evidence suggest that the two diseases may complicate the clinical course of each other. On one hand, OSA modifies asthmatic airway inflammation and is associated with poor asthma control. On the other hand, asthma and its medications increase the collapsibility of the upper airways contributing to the development and worsening of OSA. The overnight respiratory symptoms of OSA and asthma are often similar, and an inpatient polysomnography is often necessary for a proper diagnosis, especially in children. Continuous positive pressure, the gold standard treatment for OSA can improve asthma control in patients suffering from both diseases. However, there is limited evidence how anti-asthma medications act in the same patients. Nevertheless, adenotonsillectomy seems to be effective in children with concomitant asthma and OSA. This review summarises the evidence for the bidirectional link between asthma and OSA, focuses on diagnostic and therapeutic challenges and highlights the need for further research., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD), a very common disease, is the third leading cause of death worldwide. Due to the significant heterogeneity of clinical phenotypes of COPD there is no single method suitable for predicting patients' health status and outcomes, and therefore multidimensional indices, assessing different components of the disease, were developed and are recommended for clinical practice by international guidelines. Several indices have been widely accepted: BODE and its modifications, ADO, DOSE, CODEX, COTE. They differ in their composition and aim, while they are more accurate and better validated in specific settings and populations. We review the characteristics, strengths and limitations of these indices, and we discuss their role in routine management of patients with COPD, as well as in specific clinical scenarios, such as resuscitation and ceiling of care, or decisions to offer more invasive treatments. This analysis may help clinicians to use those indexes in a more practical and appropriate way., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The survivin protein contributes to the development and progression of tumors. Protein expression and mRNA levels correlate with clinicopathological parameters and survival of cancer patients. Our purpose was to evaluate whether circulating survivin levels have any diagnostic or predictive value in lung cancer. 118 patients with advanced stage lung cancer participated in our study. 53 suffered from adenocarcinoma (ADC), 33 from squamous cell carcinoma (SqCC), and 32 from small cell lung cancer (SCLC). We also enrolled 21 control subjects. Blood samples were collected before and after two cycles of chemotherapy. We measured survivin concentrations with ELISA. Non-parametric tests were used for analysis. We did not find significant difference in survivin levels between patients and control subjects (17.19/0-829.74/vs. 49.13/0-165.92/pg/ml; p = 0.07). We found lower survivin concentrations in patients with SqCC (0/0-171.24/pg/ml) than in those with ADC (24.94/0-626.46 pg/ml) and SCLC (45.51/0-829.74/pg/ml) (ADC vs. SqCC p < 0.0001, ADC vs. SCLC p = 0.0405, SqCC vs. SCLC p < 0.0001). Survivin levels were higher in stage IV patients than in patients without distant metastases ( p = 0.0061), and concentrations were progressively higher with increasing number of metastatic organ sites ( p = 0.04). We observed a decrease in survivin levels in ADC patients after platinum plus pemetrexed chemotherapy (26.22/0-626.46/pg/ml before vs. 0/0-114.36/pg/ml after; p = 0.01). Neither progression-free nor overall survival correlated with survivin levels at baseline. Our data imply that survivin may be involved in the development of metastases and it might be used as a biomarker of disease progression. However, circulating survivin concentrations do not predict survival of patients with lung cancer., 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 Puskas, Bikov, Horvath, Lazar, Kunos, Nagy, Pinter and Galffy.)

The anti-aging factor, klotho has been identified as a tumor suppressor in various human cancers, including lung cancer. In vitro studies provided evidence that klotho expression influences the characteristics of lung cancer cells, however, in vivo results are lacking. The aim of our study was to evaluate whether circulating klotho protein might serve as a potential biomarker of lung cancer. Blood samples were taken from 45 newly diagnosed lung cancer patients (31 NSCLC, 14 SCLC) and 43 control subjects. Plasma klotho concentration was measured using ELISA. No difference in plasma klotho values was detected between patients and control subjects (366.3 (257.9-486.8) vs. 383.5 (304.6-489.7) pg/ml respectively (median (IQR)); p > 0.05). Plasma klotho levels in patients with distant metastasis did not differ from less advanced stage disease (354.2 (306.9-433.3 vs. 328.5 (242.5-419.7) pg/ml, p > 0.05). In contrast, analyzed with one-way ANOVA, significant difference (p = 0.04) was found between the examined histological types of lung cancer: adenocarcinoma (353 (329.4-438.5) pg/ml), squamous cell carcinoma (308 (209.6-348.1) pg/ml) and small cell lung cancer (388.8 (289.9-495.4) pg/ml). However, Tukey's post hoc test did not reveal significant difference between any pairs of histological groups. There was no difference between any histological subtype and health either. Our results suggest that circulating klotho protein cannot be considered as a biomarker for lung cancer. Further studies are warranted in order to examine the relationship between klotho expression in lung tissue and circulating levels of the protein, and to explore its mechanism of action in lung cancer.

Purpose: Obstructive sleep apnoea (OSA) represents a risk for dyslipidaemia. Obstructive respiratory events during rapid eye movement (REM) sleep are more strongly related to the development of hypertension and diabetes than in non-REM. However, the relationship between sleep phases and serum lipid profile is unclear. We aimed to analyse the relationship between obstructive respiratory events in REM and non-REM sleep as well as serum lipid profile., Methods: Polysomnography was performed in 94 adult subjects who did not take any lipid-modifying medications. Fasting venous blood sample was taken the following morning for total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, lipoprotein(a), apoprotein A1 (ApoA1) and for apoprotein B (ApoB) measurements. Lipid profiles were correlated with apnoea-hypopnoea index (AHI) during REM (AHI REM ) and non-REM (AHI NREM ) stages in all subjects. In addition, lipid profiles were compared between REM-dependent OSA patients (AHI REM  ≥ 5/h, but AHI NREM  < 5/h) and control subjects (both AHI REM and AHI NREM  < 5/h)., Results: AHI REM correlated only with triglyceride concentrations (p = 0.04, Spearman's rho, ρ = 0.21). In contrast, there was a significant association between AHI NREM and triglyceride (p = 0.02, ρ = 0.23), ApoB (p = 0.03, ρ = 0.21), HDL-C (p < 0.01, ρ = - 0.32) as well as ApoA1 levels (p = 0.04, ρ = - 0.21). However, these correlations were not present after adjustment for BMI (all p > 0.05). There was no difference in the lipid profile of REM-dependent OSA subjects and healthy controls (p > 0.05)., Conclusions: Altered serum lipid profile is equally associated with a disturbed REM and non-REM sleep in OSA. Obesity must be considered as a strong covariate when interpreting lipid data in sleep apnoea.

Obstructive sleep apnea (OSA) is a prevalent disorder that affects not only the upper airways but also the intrathoracic airways. In this review, we summarize the results of studies on lung function and airway inflammation. We provide evidence that the alterations in intrathoracic airways observed in OSA are not purely consequences of mechanical trauma and oxidative stress during apneic events but have a causal role in the structural changes associated with OSA and increasing severity of this disorder., (Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Accelerated airway inflammation may play a crucial role in the pathophysiology of obstructive sleep apnoea (OSA); however this phenomenon has been investigated only in a limited number of studies. The analysis of exhaled breath represents a promising, non-invasive tool to evaluate airway inflammation in this context. The knowledge on exhaled biomarkers in OSA has been growing with an emerging number of methodological studies which help to interpret exhaled breath data. This article not only summarises the results of studies on exhaled breath condensate (EBC) biomarkers, exhaled volatile compounds and exhaled monoxides in OSA, but also aims to critically review methodological limitations and provide some guideline for further research., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables., Methods: Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer., Results: No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history., Conclusions: Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer.