Relapsing Eosinophilia in a Severe Allergic Asthma Patient on Biological Therapy.

Background: Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease management. However, correct phenotyping and monitoring of severe asthma patients is key to the success of targeted biologic therapy. Materials and Methods: We present the case of a 63-year-old female, never a smoker, diagnosed with asthma at the age of 45 and associated persistent mild rhinitis, without other notable comorbidities. She was prescribed medium-dose ICS/LABA, administered inconstantly in the first years after the diagnosis, with poor overall control of the disease. After several exacerbation episodes, treatment compliance improved, but the control of the disease remained poor despite adding an antileukotriene. In January 2019, she presented an exacerbation episode requiring treatment with oral corticosteroids (OCS) and she was afterwards put on high-dose ICS/LABA and continued the antileukotriene. She was referred for a skin allergy test, which revealed mild sensitization to Dermatophagoides pteronyssinus and farinae, with a total IgE level of 48.3 IU/mL. The blood eosinophil level was 270 cells/mm3. The lung function was variable, going from mild impairment to severe fixed obstruction during exacerbations. Despite optimized inhaled treatment, good adherence and inhaler technique, and allergen avoidance strategies, asthma control was not achieved, and she continued to experience severe episodes of exacerbation requiring OCS. Results: In October 2019, she was initiated on biologic therapy with omalizumab, which allowed asthma control to be achieved and maintained for 18 months, with preserved lung function, good symptom control, no exacerbations and slightly elevated blood eosinophil level (340-360 cells/mm3). In April 2021, she started experiencing exacerbation episodes requiring OCS (three episodes within 6 months), with a progressive increase in blood eosinophil level (up to 710 cells/mm3), and progressive deterioration of asthma control and lung function, despite continuation of previous therapy. A specific IgE test against Aspergillus was negative, and total IgE level was 122.4 IU/mL. In December 2021, the patient was switched from omalizumab to benralizumab. Asthma control was again achieved, lung function improved significantly and the patient did not experience any other exacerbation episodes up until today, which allowed for a reduction in ICS dose. Intriguingly, a relapsing eosinophilia was also noted under anti-IL5-R treatment prior to the dose administration, but with preserved asthma control. Conclusions: This case underscores the pivotal role of meticulous phenotyping in severe asthma management on one side, and careful monitoring of patient evolution and possible side effects of treatment on the other side. By showcasing how diverse inflammatory pathways can coexist within a single patient and impact treatment outcomes, it highlights the necessity of tailored biologic therapy for sustained control.

Severe Asthma or Chronic Obstructive Pulmonary Disease with Eosinophilic Inflammation? From Uncertainty to Remission under Anti IL-5R Therapy.

Background and Objectives: Severe adult-onset eosinophilic asthma and COPD with eosinophilic inflammation are two entities with a similar clinical course and are sometimes difficult to differentiate in clinical practice, especially in patients with a history of smoking. Anti-IL-5 or -IL-5R biological therapy has been shown to be highly effective in severe eosinophilic asthma but has not demonstrated significant benefit in patients with COPD with the eosinophilic phenotype. Our aim was to illustrate this issue in the form of a case report. Materials and Methods: We present the case of a 67-year-old patient who is a former smoker with late-onset severe uncontrolled asthma (ACT score < 15) who experienced frequent exacerbations requiring treatment with systemic corticosteroids. The patient's lung function gradually worsened to a nadir FEV1 = 18%, despite a high dose of ICS in combination with a LABA and intermittent courses of OCS, with negative allergic skin-tests, but with high blood eosinophils level. Biological treatment with an anti-IL5R monoclonal antibody (benralizumab) was initiated, despite the difficulty in the differential diagnosis between asthma and COPD with eosinophilic inflammation. Results: The patient's evolution was favorable; clinical remission was effectively achieved with significant improvement in lung function (FEV1 > 100%), but with persistence of residual mild fixed airway obstructive dysfunction (FEV1/FVC < 0.7). The therapeutic response has been maintained to date. Conclusions: Benralizumab was shown to be very effective in a patient with late-onset severe eosinophilic asthma presenting features of chronic obstructive disease-habitual exposure to tobacco and inhaled noxious substances, and persistent airflow limitation on spirometry.

The Controversy of Using Insufficient Great Saphenous Veins in Coronary Artery Bypass Grafting: A Comparative Morphological Analysis of Healthy and Insufficient Veins Related to the Possibility of Using Them as a Graft.

BACKGROUND: Despite advancements in coronary artery bypass grafting (CABG), the optimal choice of graft material remains a subject of investigation. This study aimed to comprehensively analyze the morphological characteristics of varicose veins, exploring their potential utilization in CABG compared to healthy veins. METHODS: The study included 178 patients, categorized into two groups based on healthy and varicose veins. Morphological parameters, including maximum venous diameter, wall thickness, and specific changes in tunica intima (TI), tunica media (TM), and tunica adventitia (TA), were analyzed through microscopic evaluation. RESULTS: Varicose veins exhibited a significantly larger maximum venous diameter (p = 0.0001) and increased wall thickness (p = 0.0001) compared to healthy veins. Although varicose veins showed thickening in TI and TM, the differences were not statistically significant. Notably, disorganized smooth muscle bundles were more prevalent in varicose veins (p = 0.001), suggesting potential wall weakness. The absence of vasa vasorum in TA was significantly higher in varicose veins (p = 0.050), influencing vascularization considerations. CONCLUSIONS: The comparative morphological microscopic analysis of the specimens of healthy and varicose veins reveals significant differences between the groups, which make the conclusion of this study to plead for avoiding the use of varicose veins as a graft.

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.

Bed partner perception of CPAP therapy on relationship satisfaction and intimacy-A European perspective from the ESADA network.

Obstructive sleep apnea increases morbidity and mortality risks. The most common treatment is continuous positive airway pressure, with nasal mask usage being important, but not always optimal. While most research on treatment adherence focuses on the patient, the bed partner's involvement may be detrimental. Our study aim is to obtain a European-wide picture of the bed partner's attitude and support towards continuous positive airway pressure therapy, including effects on relationship satisfaction and intimacy. The English translation of a German bed partner questionnaire, assessing relationship satisfaction and three major components (general attitude, perceived mask looks, intimacy effects) was distributed within the European Sleep Apnea Database Network and translated in participating countries' local language. Data were collected for 2 years. In total, 10 European countries (13 sleep centres) participated with 1546 questionnaires. Overall, 91% of bed partners had a positive attitude towards continuous positive airway pressure therapy, 86% perceived mask looks not negative, 64% stated no negative intimacy effects. More specifically, 71% mentioned improved sleep quality, 68% supported nightly device usage. For 41% of bed partners, relationship satisfaction increased (no change for 47%). These results were significantly more pronounced in Eastern/Southern Europe compared with Middle Europe, especially regarding intimacy effects. However, increased continuous positive airway pressure therapy length affected attitude negatively. These results provide necessary information to improve treatment strategies by including educational couple-focused approaches. Among others, we revealed that negative intimacy effects are not considered a barrier to continuous positive airway pressure adherence. These results may inspire more research identifying regional gaps with need for treatment adjustments.

Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication.

Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT). Methods and results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0 kg/m2, apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9 h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7 mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8 mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders. Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA.

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.

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.

Post-Severe-COVID-19 Cardiopulmonary Rehabilitation: A Comprehensive Study on Patient Features and Recovery Dynamics in Correlation with Workout Intensity.

The aftermath of severe COVID-19 frequently involves considerable cardiopulmonary damage, necessitating rehabilitation. This study aimed to evaluate the impact of COVID-19 on cardiopulmonary health and assess the effectiveness of various rehabilitative interventions. Conducted between September 2021 and September 2022, this prospective study included patients who had been diagnosed with severe COVID-19 and admitted at the "Victor Babes" Infectious Diseases and Pulmonology Hospital, Timisoara, Romania. The patients were stratified into low- and high-intensity rehabilitation groups. The rehabilitation protocols were individually tailored, and the patient recovery was closely monitored over a 3-month period. Our cohort comprised 84 patients, with a mean age of 56.3 years for the low-intensity group (n = 42) and 53.1 years for the high-intensity group (n = 42). Both groups showed significant improvements in the lung injury area, need for oxygen supplementation, ejection fraction, systolic pulmonary artery pressure, and forced vital capacity. Additionally, considerable enhancements were observed in maximal voluntary ventilation, FEV1, FEV1/FVC ratio, peak expiratory flow, and forced expiratory flow at 25-75%. The work intensity also demonstrated substantial improvements from the initial testing to the 3-month mark in both groups. This study provides evidence that personalized, targeted rehabilitation strategies can improve long-term cardiopulmonary health in patients recovering from severe COVID-19, proving both low-intensity and high-intensity training as sufficient to improve heart and lung function if performed correctly and over a relatively short duration of 3 months. The study findings underscore the importance of implementing comprehensive cardiopulmonary rehabilitation protocols in the care of post-COVID-19 patients and highlight the value of stratified rehabilitation intensity based on individual patient dynamics and recovery features.

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.

Clinical characteristics and positive airway pressure adherence among elderly European sleep apnoea patients from the ESADA cohort.

Background: The prevalence of obstructive sleep apnoea (OSA) is growing as the population is ageing. However, data on the clinical characteristics of elderly patients with OSA and their adherence to positive airway pressure (PAP) treatment are scarce. Methods: Data from 23 418 30-79-year-old OSA patients prospectively collected into the ESADA database during 2007-2019 were analysed. Information on PAP use (h·day-1) in association with a first follow-up visit was available for 6547 patients. The data was analysed according to 10-year age groups. Results: The oldest age group was less obese, less sleepy and had a lower apnoea-hypopnoea index (AHI) compared with middle-aged patients. The insomnia phenotype of OSA was more prevalent in the oldest age group than in the middle-aged group (36%, 95% CI 34-38 versus 26%, 95% CI 24-27, p<0.001). The 70-79-year-old group adhered to PAP therapy equally well as the younger age groups with a mean PAP use of 5.59 h·day-1 (95% CI 5.44-5.75). PAP adherence did not differ between clinical phenotypes based on subjective daytime sleepiness and sleep complaints suggestive of insomnia in the oldest age group. A higher score on the Clinical Global Impression Severity (CGI-S) scale predicted poorer PAP adherence. Conclusion: The elderly patient group was less obese, less sleepy, had more insomnia symptoms and less severe OSA, but were rated to be more ill compared with the middle-aged patients. Elderly patients with OSA adhered to PAP therapy equally well as middle-aged patients. Low global functioning (measured by CGI-S) in the elderly patient predicted poorer PAP adherence.

Fractional Dynamics Foster Deep Learning of COPD Stage Prediction.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Current COPD diagnosis (i.e., spirometry) could be unreliable because the test depends on an adequate effort from the tester and testee. Moreover, the early diagnosis of COPD is challenging. The authors address COPD detection by constructing two novel physiological signals datasets (4432 records from 54 patients in the WestRo COPD dataset and 13824 medical records from 534 patients in the WestRo Porti COPD dataset). The authors demonstrate their complex coupled fractal dynamical characteristics and perform a fractional-order dynamics deep learning analysis to diagnose COPD. The authors found that the fractional-order dynamical modeling can extract distinguishing signatures from the physiological signals across patients with all COPD stages-from stage 0 (healthy) to stage 4 (very severe). They use the fractional signatures to develop and train a deep neural network that predicts COPD stages based on the input features (such as thorax breathing effort, respiratory rate, or oxygen saturation). The authors show that the fractional dynamic deep learning model (FDDLM) achieves a COPD prediction accuracy of 98.66% and can serve as a robust alternative to spirometry. The FDDLM also has high accuracy when validated on a dataset with different physiological signals.

Baseline clusters and the response to positive airway pressure treatment in obstructive sleep apnoea patients: longitudinal data from the European Sleep Apnea Database cohort.

Introduction: The European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment. Method: Prospective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up. Results: At baseline, 20 164 patients were assigned (mean age 54.1±12.2 years, 73% male, median apnoea-hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1-49.3) events·h-1, and ESS 9.8±5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134-465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, -5.0 and -5.1 units, respectively (all p<0.01), limited reduction in clusters 2 (obese males with systemic hypertension) and 5 (elderly multimorbid obese males, -4.2 (p<0.05) and -3.7 (p<0.001), respectively). Residual sleepiness in cluster 5 was particularly evident at long-term follow-up (p<0.05). Conclusion: OSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.

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.

Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

NMDA Autoimmune Encephalitis and Severe Persistent Hypokalemia in a Pregnant Woman.

Introduction: For more than a decade, NMDAR autoimmune encephalitis has been studied and treated as a neurological condition, and good results have been achieve through immune therapies. Apart from being well represented in the CNS, NMDA receptors are currently known of and being studied in multiple non-neuronal cells with potential clinical significance. The association of NMDAR autoimmune encephalitis with pregnancy is rare, and hypokalemia is not mentioned. Methods: We present the case of a 30-year-old woman with NMDAR autoimmune encephalitis in her 17th week of pregnancy associated with persistent hypokalemia that had no apparent cause and resisted Kalium chloride supplementation. A diagnostic work-up including clinical, laboratory, and imagistic examinations, was performed. The case was monitored between May and September 2016 at Neurology, SCJUT. Results: Severe hypokalemia with normal serum sodium levels persisted throughout the course of clinical manifestation of anti-NMDAR autoimmune encephalitis. Conclusions: NMDAR autoimmune encephalitis is under-diagnosed in its atypical clinical variants, and this disease's association with hypokalemia is not mentioned in the literature. Still, it is of clinical importance because it attests to the implications of other organs/systems in the general autoimmune process of NMDAR encephalitis, and it might change the way we address certain psychiatric disorders by searching underlying organic conditions.

Manifesto on united airways diseases (UAD): an Interasma (global asthma association - GAA) document.

OBJECTIVE: The large amount of evidence and the renewed interest in upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD). METHODS: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members. RESULTS: The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refers to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life. CONCLUSIONS: Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and home based continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.

Asthma and obstructive sleep apnoea in adults and children - an up-to-date review.

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.