Long-Term Adherence to Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnoea Set Up in a Complete Remote Pathway: A Single-Centre Service Evaluation Project.

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.

Platelet count and platelet-to-lymphocyte ratio at the onset of a severe COPD exacerbation are unrelated to the time till the next moderate or severe relapse.

PURPOSE: Acute exacerbations (AE) are severe complications of chronic obstructive pulmonary disease (COPD); however, the need for biomarkers which predict them is still unmet. High platelet count (PLC) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in patients with COPD. We investigated if PLC and PLR at the onset of a severe AE could predict the time of the next relapse. METHODS: In a prospective observational cohort study, data of 152 patients hospitalized with AECOPD were collected, and patients were divided into PLC-low (<239 â€‹× â€‹109/L, n â€‹= â€‹51), PLC-medium (239-297 â€‹× â€‹109/L, n â€‹= â€‹51) and PLC-high (>297 â€‹× â€‹109/L, n â€‹= â€‹50) or PLR-low (<147, N â€‹= â€‹51), PLR-medium (147-295, n â€‹= â€‹51) and PLR high (>295, n â€‹= â€‹50) groups based on PLC and PLR tertiles using admission laboratory results. Clinical characteristics and the time to the next severe or moderate AE within 52 weeks were compared among subgroups using log-rank test. RESULTS: PLC and PLR tertiles did not differ in clinical characteristics or the time till the next AE (p â€‹> â€‹0.05). PLC and PLR showed a direct weak correlation to neutrophil count (Pearson r â€‹= â€‹0.26, p â€‹< â€‹0.01 and r â€‹= â€‹0.20, p â€‹= â€‹0.01) and PLC also demonstrated a weak relationship to white blood cell counts (Pearson r â€‹= â€‹0.29, p â€‹< â€‹0.001). However, PLR presented an inverse relationship to monocyte and eosinophil counts (r â€‹= â€‹-0.32, p â€‹< â€‹0.001 and r â€‹= â€‹-0.17, p â€‹= â€‹0.03). CONCLUSION: PLC and PLR do not predict the time till the next relapse; however, they may reflect on neutrophilic inflammatory response during an exacerbation of COPD.

Bacterial Vaccinations in Patients with Chronic Obstructive Pulmonary Disease.

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.

The relationship between periodic limb movement during sleep and dyslipidaemia in patients with obstructive sleep apnea.

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.

Multivariate analysis and data mining help predict asthma exacerbations.

BACKGROUND: Work-related asthma has become a highly prevalent occupational lung disorder. OBJECTIVE: Our study aims to evaluate occupational exposure as a predictor for asthma exacerbation. METHOD: 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. RESULTS: 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. CONCLUSIONS: Machine learning ensemble methods and statistical analysis concordantly indicate that occupational exposure and ACT < 20 are strong predictors for asthma exacerbation.

Methodological Aspects of Induced Sputum.

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.

The Role of the Circadian Rhythm in Dyslipidaemia and Vascular Inflammation Leading to Atherosclerosis.

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.

Analysis of possible risk factors for the severity of paediatric obstructive sleep apnoea syndrome.

PURPOSE: This study aimed to determine the effect of body mass index (BMI) percentile, asthma, sex, and age on the paediatric obstructive sleep apnoea (OSA) severity. Furthermore, to determine the possible predictive role of the BMI percentile and age in severe OSA. METHODS: This retrospective study included 921 children aged 2-18 years diagnosed with OSA by polysomnography. Analysis of Covariance (ANCOVA), Spearman's correlation, Receiver Operating Characteristics (ROC) analyses were performed and area under the curve (AUC) was determined. RESULTS: We observed a significant association between a higher BMI percentile and the severity of OSA (p < 0.001, ρ = 0.15). The correlation also was significant under (p = 0.007, ρ = 0.11) and over 7 (p = 0.0002, ρ = 0.23) years of age. There was no association between the severity of OSA and the presence of asthma (p = 0.9) or sex (p = 0.891), respectively. Age was significantly related to OSA severity (p = 0.01, ρ = 0.08). Although both the BMI percentile (0.59 AUC [0.54-0.65]) and age (0.58 AUC [0.52-0.63]) predicted severe OSA, according to the sensitivity and specificity values of the ROC curve, the association presents a slight clinical relevance. CONCLUSIONS: OSA severity is determined by the BMI percentile and age in children; however, these factors are unsuitable for predicting severe OSA in clinical practice. Based on our results, obesity is also a significant risk factor for OSA in younger children. Our study highlights that older, overweight, and obese children have a higher risk for severe OSA.

Exhaled volatile organic compounds for diagnosis and monitoring of asthma.

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.

Time Spent with Saturation below 80% versus 90% in Patients with Obstructive Sleep Apnoea.

BACKGROUND: Nocturnal hypoxaemia measured as the percentage of total sleep time spent with saturation below 90% (TST90%) may better predict cardiovascular consequences of obstructive sleep apnoea (OSA) than the number of obstructive respiratory events measured with the apnoea-hypopnea index (AHI). Deeper hypoxaemia may potentially induce more severe pathophysiological consequences. However, the additional value of the percentage of total sleep time spent with saturation below 80% (TST80%) to TST90% is not fully explored. METHODS: Comprehensive medical history was taken and fasting lipid and C-reactive protein levels were measured in 797 volunteers participating in two cohort studies in Hungary and Romania. Sleep parameters, including AHI, TST90% and TST80%, were recorded following a polysomnography (PSG, n = 598) or an inpatient cardiorespiratory polygraphy (n = 199). The performance of TST80% to predict cardiovascular risk was compared with TST90% using linear and logistic regression analyses as well receiver operating characteristics curves. Sensitivity analyses were performed in patients who had PSG, separately. RESULTS: Both parameters are significantly related to cardiovascular risk factors; however, TST80% did not show better predictive value for cardiovascular risk than TST90%. On the other hand, patients with more severe hypoxaemia reported more excessive daytime sleepiness. CONCLUSIONS: TST80% has limited additional clinical value compared to TST90% when evaluating cardiovascular risk in patients with OSA.

Criteria to evaluate efficacy of biologics in asthma: a Global Asthma Association survey.

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 link between the sphingolipid rheostat and obstructive sleep apnea.

Chronic inflammation induced by hypoxia during sleep is an important mechanism of microvascular damage in OSA patients. In this study, we investigated the role of the sphingosine rheostat, which has diverse inflammatory effects. Thirty-seven healthy subjects and 31 patients with OSA were recruited. We collected data on demographics and comorbidities. Plasma sphingosine-1-phosphate and ceramide antibody concentrations were measured by ELISA. The results were compared between the OSA and control groups, and the correlations between these measurements and markers of disease severity and comorbidities were explored. Ceramide antibody levels were significantly elevated in OSA patients (892.17 ng/ml) vs. controls (209.55 ng/ml). S1P levels were also significantly higher in patients with OSA (1760.0 pg/ml) than in controls (290.35 pg/ml, p < 0.001). The ceramide antibody concentration showed correlations with BMI (ρ = 0.25, p = 0.04), CRP (ρ = 0.36, p = 0.005), AHI (ρ = 0.43, p < 0.001), ODI (ρ = 0.43, p < 0.001), TST90% (ρ = 0.35, p = 0.004) and the lowest oxygen saturation (ρ =  0.37, p = 0.001) in the whole study population but not when patients with OSA were analyzed separately. The elevated ceramide antibody and sphingosine-1-phosphate concentrations in patients suffering from OSA suggests their involvement in the pathomechanism of OSA and its comorbidities.

En Route to Personalised Medicine in Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is a common disorder that can cause night- and daytime symptoms and impair driving and work performance [...].

The Role of Gut Bacteriome in Asthma, Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnoea.

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 and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia.

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.

Comparison of Composite Lipid Indices in Patients with Obstructive Sleep Apnoea.

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.

A Rounded Approach to the Management and Treatment of Obstructive Lung Diseases.

Obstructive lung diseases are characterized by obstruction to airflow, inflamed and easily collapsible airways, and difficulties in exhaling, with a socio-economic burden in terms of medical visits and hospitalizations [...].

Peripheral blood and bronchoalveolar leukocyte profile in lung transplant recipients and their changes according to immunosuppressive regimen: A single-center experience.

BACKGROUND: After lung transplantation (LuTX), lower respiratory tract infections (LRTI) and acute cellular rejection (ACR) are associated with changes in peripheral blood and bronchoalveolar lavage fluid mononuclear cell profile (PBMC and BALIC). PBMC is also influenced by immunosuppressive regimen and its changes with postoperative time. First-year PBMC and BALIC changes were evaluated in this study with rabbit anti-thymocyte globulin (ATG) and alemtuzumab (AL) induction therapy. METHODS: In total, 64 LuTX recipients were included, 53 of them received AL and 11 ATG as induction therapy. PBMC and BALIC were examined routinely and in cases suspicious of infection and/or rejection. A PBMC- and BALIC-based algorithm for infection and rejection prediction was also tested. RESULTS: In the AL group, peripheral blood lymphocyte and basophil cell numbers were significantly reduced, while the neutrophil cell number elevation during LRTI was significantly higher compared to the control. Early postoperative measurements showed a lower BALIC lymphocyte count. The algorithm had 17% sensitivity and 94% specificity for ACR in all patients and 33% sensitivity and 95% specificity for ACR with coexisting LRTI. CONCLUSION: BALIC is not significantly influenced by the immunosuppressive regimen. PBMC- and BALIC-based algorithm may improve the differential diagnosis of ACR.

Hypercapnia in COPD: Causes, Consequences, and Therapy.

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.

Postoperative respiratory complications in children with obstructive sleep apnoea syndrome.

Objective: We aimed to prospectively assess the effect of comorbidities on the occurrence of postoperative respiratory complications (PoRCs) after adenotonsillectomy in children with obstructive sleep apnoea syndrome (OSA) and whether otherwise healthy children need a higher level of postoperative monitoring. Methods: 577 children who had OSA and underwent adenotonsillectomy were enrolled. The effects of demographics, comorbidities and OSA on PoRCs were investigated with logistic regression analysis. Results: The PoRC rate was 4.3%. Postoperative oxygen desaturations were more marked in patients with comorbidities (p = 0.005). The presence of comorbidity increased the risk of PoRCs (odds ratio 4.234/3.226-5.241, 95% confidence intervals, p < 0.001). There was no difference in apnoea-hypopnoea index (AHI) values between comorbid patients with and without PoRCs [8.2 (3.8-50.2) vs 14.3 (11.7-23.3)]. (p = 0.37). In the group of patients without comorbidities, PoRCs were associated with a higher AHI [14.7 (3.4-51.3) vs 3.9 (2.0- 8.0), p < 0.001]. Conclusions: Comorbidities are more closely linked with PoRCs than OSA severity. In patients without comorbidity, PoRCs are associated with OSA severity and usually occur within the first 2 hours after the intervention.