ENaC gene variants and their involvement in Covid­19 severity.

Epidemiological studies report the association of diverse cardiovascular conditions with coronavirus disease 2019 (COVID-19), but the causality has remained to be established. Specific genetic factors and the extent to which they can explain variation in susceptibility or severity are largely elusive. The present study aimed to evaluate the link between 32 cardio-metabolic traits and COVID-19. A total of 60 participants were enrolled, who were categorized into the following 4 groups: A control group with no COVID-19 or any other underlying pathologies, a group of patients with a certain form of dyslipidemia and predisposition to atherosclerotic disease, a COVID-19 group with mild or no symptoms and a COVID-19 group with severe symptomatology hospitalized at the Intensive Care Unit of Sotiria Hospital (Athens, Greece). Demographic, clinical and laboratory data were recorded and genetic material was isolated, followed by simultaneous analysis of the genes related to dyslipidemia using a custom-made next-generation sequencing panel. In the COVID-19 group with mild or absent symptoms, the variant c.112C>T:p.P38S was detected in the sodium channel epithelial 1 subunit α (SCNN1A) gene, with a major allele frequency (Maf) of <0.01. In the COVID-19 group with severe symptoms, the variant c.786G>A:p.T262T was detected in the SCNN1B gene, which encodes for the ß-subunit of the epithelial sodium channel ENaC, with a Maf <0.01. None of the two rare variants were detected in the control or dyslipidemia groups. In conclusion, the current study suggests that ENaC variants are likely associated with genetic susceptibility to COVID-19, supporting the rationale for the risk and protective genetic factors for the morbidity and mortality of COVID-19.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, ß was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, ß was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting.

BACKGROUND: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. RESULTS: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. CONCLUSIONS: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion.

Exercise Intolerance Is Associated with Cardiovascular Dysfunction in Long COVID-19 Syndrome.

Background/Objectives: Cardiorespiratory complications are commonly reported among patients with long COVID-19 syndrome. However, their effects on exercise capacity remain inconclusive. We investigated the impact of long COVID-19 on exercise tolerance combining cardiopulmonary exercise testing (CPET) with resting echocardiographic data. Methods: Forty-two patients (55 ± 13 years), 149 ± 92 days post-hospital discharge, and ten healthy age-matched participants underwent resting echocardiography and an incremental CPET to the limit of tolerance. Left ventricular global longitudinal strain (LV-GLS) and the left ventricular ejection fraction (LVEF) were calculated to assess left ventricular systolic function. The E/e' ratio was estimated as a surrogate of left ventricular end-diastolic filling pressures. Tricuspid annular systolic velocity (SRV) was used to assess right ventricular systolic performance. Through tricuspid regurgitation velocity and inferior vena cava diameter, end-respiratory variations in systolic pulmonary artery pressure (PASP) were estimated. Peak work rate (WRpeak) and peak oxygen uptake (VO2peak) were measured via a ramp incremental symptom-limited CPET. Results: Compared to healthy participants, patients had a significantly (p < 0.05) lower LVEF (59 ± 4% versus 49 ± 5%) and greater left ventricular end-diastolic diameter (48 ± 2 versus 54 ± 5 cm). In patients, there was a significant association of E/e' with WRpeak (r = -0.325) and VO2peak (r = -0.341). SRV was significantly associated with WRpeak (r = 0.432) and VO2peak (r = 0.556). LV-GLS and PASP were significantly correlated with VO2peak (r = -0.358 and r = -0.345, respectively). Conclusions: In patients with long COVID-19 syndrome, exercise intolerance is associated with left ventricular diastolic performance, left ventricular end-diastolic pressure, PASP and SRV. These findings highlight the interrelationship of exercise intolerance with left and right ventricular performance in long COVID-19 syndrome.

The Effects of Exercise Training on Functional Capacity and Quality of Life in Patients with Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation. The purpose of this systematic review is to evaluate the effectiveness of exercise training on functional capacity and quality of life (QoL) in patients with RA. We performed a search in four databases, selecting clinical trials that included community or outpatient exercise training programs in patients with RA. The primary outcome was functional capacity assessed by peak VO2 or the 6 min walking test, and the secondary outcome was QoL assessed by questionnaires. Seven studies were finally included, identifying a total number of 448 patients. The results of the present systematic review show a statistically significant increase in peak VO2 after exercise training in four out of seven studies. In fact, the improvement was significantly higher in two out of these four studies compared to the controls. Six out of seven studies provided data on the patients' QoL, with five of them managing to show statistically significant improvement after exercise training, especially in pain, fatigue, vitality, and symptoms of anxiety and depression. This systematic review demonstrates the beneficial effects of exercise training on functional capacity and QoL in patients with RA.

Restoration of Pulmonary Compliance after Laparoscopic Gynecologic Surgery Using a Recruitment Maneuver.

BACKGROUND/OBJECTIVES: This study aimed to investigate the hypothesis that an alveolar recruitment maneuver can restore lung compliance to initial values after laparoscopic gynecological surgery. METHODS: A total of 31 patients who underwent laparoscopic gynecological surgery were enrolled. Protective mechanical ventilation was applied, and the radial artery was catheterized in all patients. An alveolar recruitment maneuver (incremental and decremental positive end-expiratory pressure) was applied ten minutes after the release of pneumoperitoneum. The respiratory mechanics and blood gas results were recorded at eight different time points: after induction of anesthesia (T1), in the lithotomy position (T2), in the Trendelenburg position (T3), 10 and 90 min after insufflation of carbon dioxide (T4 and T5), in the supine position (T6), after desufflation (T7), and 10 min after an alveolar recruitment maneuver at the end of surgery (T8). RESULTS: Pneumoperitoneum and the Trendelenburg position caused a decline of 15 units in compliance (T7 vs. T1; p < 0.05) compared to baseline. After the alveolar recruitment maneuver, compliance increased by 17.5% compared with the mean value of compliance at time T1 (T8 vs. T1; p < 0.05). The recruitment maneuver had favorable results in patients with low initial compliance (41.5 mL/cmH2O, IQR: 9.75 mL/cmH2O), high Body Mass Index 30.32 kg/m2 (IQR: 1.05 kg/m2), and high initial plateau airway pressure (16.5 cmH2O, IQR: 0.75 cmH2O). CONCLUSIONS: Lung compliance does not return to initial values after performing laparoscopic gynecological procedures. However, after the release of pneumoperitoneum, an alveolar recruitment maneuver is beneficial as it improves compliance and gas exchange.

Strong ion gap and anion gap corrected for albumin and lactate in patients with sepsis in the intensive care unit.

INTRODUCTION: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis. MATERIALS AND METHODS: The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AGcl]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AGcl], [SIG] and inorganic [SIG] ([SIGi]) on admission. RESULTS: There was a strong correlation linking [AGcl] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AGcl] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AGcl] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIGi] AUC: 0.581, 95% CI [0.457, 0.705], [AGcl] AUC: 0.529, 95% CI [0.401, 0.656]. CONCLUSION: [AGcl] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.

Exploring the Impact of Airway Microbiome on Asthma Morbidity: A Focus on the "Constructing a 'Eubiosis Reinstatement Therapy' for Asthma-CURE" Project.

The asthma pandemic imposes a huge burden on patients and health systems in both developed and developing countries. Despite available treatments, symptom control is generally suboptimal, and hospitalizations and deaths remain at unacceptably high levels. A pivotal aspect of asthma that warrants further exploration is the influence of the respiratory microbiome and virome in modulating disease activity. A plethora of studies report that the respiratory microbiome is characteristically dysbiotic in asthma. In addition, our data suggest that dysbiosis is also observed on the respiratory virome, partly characterized by the reduced abundance of bacteriophages (phages). Even though phages can naturally infect and control their bacterial prey, phage therapy has been grossly neglected in the Western world, although more recently it is more widely used as a novel tool against bacterial infections. However, it has never been used for tackling microbiome dysbiosis in human non-communicable diseases. This review provides an up-to-date understanding of the microbiome and virome's role within the airways in relation to asthma morbidity. It also advances the rationale and hypothesis for the CURE project. Specifically, the CURE project suggests that managing the respiratory microbiome through phage therapy is viable and may result in restoring eubiosis within the asthmatic airway. This entails controlling immune dysregulation and the clinical manifestation of the disease. To accomplish this goal, it is crucial to predict the effects of introducing specific phage mixtures into the intricate ecology of the airways and devise suitable interventions.

Intensive Care Unit Mortality Trends during the First Two Years of the COVID-19 Pandemic in Greece: A Multi-Center Retrospective Study.

Data on COVID-19 mortality among patients in intensive care units (ICUs) from Eastern and/or Southern European countries, including Greece, are limited. The purpose of this study was to evaluate the ICU mortality trends among critically ill COVID-19 patients during the first two years of the pandemic in Greece and to further investigate if certain patients' clinical characteristics contributed to this outcome. We conducted a multi-center retrospective observational study among five large university hospitals in Greece, between February 2020 and January 2022. All adult critically ill patients with confirmed COVID-19 disease who required ICU admission for at least 24 h were eligible. In total, 1462 patients (66.35% males) were included in this study. The mean age of this cohort was 64.9 (±13.27) years old. The 28-day mortality rate was 35.99% (n = 528), while the overall in-hospital mortality was 50.96% (n = 745). Cox regression analysis demonstrated that older age (≥65 years old), a body mass index within the normal range, and a delay in ICU admission from symptom onset, as well as worse baseline clinical severity scores upon ICU admission, were associated with a greater risk of death. Mortality of critically ill COVID-19 patients was high during the first two years of the pandemic in Greece but comparable to other countries. Risk factors for death presented in this study are not different from those that have already been described for COVID-19 in other studies.

Levels of IgE sensitization drive symptom thresholds in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a common respiratory disease encompassing a variety of phenotypes. Patients can be sensitized to 1 or more allergens. There are indications that polysensitization is associated with more severe disease. However, the extent to which the level of sensitization is associated with clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: To evaluate phenotypical differences between monosensitized and polysensitized patients with AR and to quantify their symptomatic variability. METHODS: A total of 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. Of those, 155 were monosensitized and 410 were polysensitized. Interactions between sensitization levels and the reporting of different symptoms of AR and co-morbidities, disease duration, and impact were assessed. Furthermore, patients were stratified into monosensitized, oligosensitized, and polysensitized to assess whether the effect of sensitization on the phenotype was ranked. RESULTS: Polysensitized patients reported itchy eyes significantly more often (P = .001) and had a higher number of ocular (P = .005), itch-related (P = .036), and total symptoms (P = .007) than monosensitized patients. In addition, polysensitized adults and children more often reported wheeze (P = .015) and throat-clearing (P = .04), respectively. Polysensitization was associated with more burdensome AR based on a visual analog scale (P = .005). Increased sensitization level was reflected in more itchy eyes, a higher number of ocular, itch-related, and total number of symptoms, and disease burden. CONCLUSION: With an increasing number of sensitizations, patients with AR experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

Small airways in asthma: From inflammation and pathophysiology to treatment response.

Small airways are characterized as those with an inner diameter less than 2 mm and constitute a major site of pathology and inflammation in asthma disease. It is estimated that small airways dysfunction may occur before the emergence of noticeable symptoms, spirometric abnormalities and imaging findings, thus characterizing them as "the quiet or silent zone" of the lungs. Despite their importance, measuring and quantifying small airways dysfunction presents a considerable challenge due to their inaccessibility in usual functional measurements, primarily due to their size and peripheral localization. Several pulmonary function tests have been proposed for the assessment of the small airways, including impulse oscillometry, nitrogen washout, body plethysmography, as well as imaging methods. Nevertheless, none of these methods has been established as the definitive "gold standard," thus, a combination of them should be used for an effective assessment of the small airways. Widely used asthma treatments seem to also affect several parameters of the small airways. Emerging biologic treatments show promising results in reducing small airways inflammation and remodelling, providing evidence for potential alterations in the disease's progression and outcomes. These novel therapies have implications not only in the clinical aspects of asthma but also in its inflammatory and functional aspects.

COVID-19 vaccination acceptance, safety and side-effects in European patients with severe asthma.

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma. Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021. Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients. Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated.

Defining response to therapy with biologics in severe asthma: from global evaluation to super response and remission.

INTRODUCTION: In recent years, monoclonal antibodies targeting Type-2 inflammatory pathways have been developed for severe asthma treatment. However, even when patients are carefully selected, the response to treatment varies. AREAS COVERED: Different studies have evaluated response to therapy with biologics such as exacerbation reduction, symptom improvement, pulmonary function increase, improvement in QoL, or decrease of oral corticosteroids, showing that all patients do not respond to all disease aspects and leading to an extensive debate regarding the definition of response. EXPERT OPINION: Assessing response to therapy is of great importance, but since there is no uniform definition of treatment response, the recognition of patients who really benefit from these therapies remains an unmet need. In the same context, identifying non-responding patients in which biologic therapy should be switched or substituted by alternative treatment options is of paramount importance. In this review, we present the road trip of the definition of therapeutic response to biologics in severe asthmatics by presenting the current relevant medical literature. We also present the suggested predictors of response, with an emphasis on the so-called super-responders. Finally, we discuss the recent insights regarding asthma remission as a feasible treatment goal and provide a simple algorithm for the evaluation of response.

Modified SCOPE (mSCOPE) Score as a Tool to Predict Mortality in COVID-19 Critically Ill Patients.

INTRODUCTION: Efficient clinical scores predicting the outcome of severe COVID-19 pneumonia may play a pivotal role in patients' management. The aim of this study was to assess the modified Severe COvid Prediction Estimate score (mSCOPE) index as a predictor of mortality in patients admitted to the ICU due to severe COVID-19 pneumonia. MATERIALS AND METHODS: In this retrospective observational study, 268 critically ill COVID-19 patients were included. Demographic and laboratory characteristics, comorbidities, disease severity, and outcome were retrieved from the electronical medical files. The mSCOPE was also calculated. RESULTS: An amount of 70 (26.1%) of patients died in the ICU. These patients had higher mSCOPE score compared to patients who survived (p < 0.001). mSCOPE correlated to disease severity (p < 0.001) and to the number and severity of comorbidities (p < 0.001). Furthermore, mSCOPE significantly correlated with days on mechanical ventilation (p < 0.001) and days of ICU stay (p = 0.003). mSCOPE was found to be an independent predictor of mortality (HR:1.219, 95% CI: 1.010-1.471, p = 0.039), with a value ≥ 6 predicting poor outcome with a sensitivity (95%CI) 88.6%, specificity 29.7%, a positive predictive value of 31.5%, and a negative predictive value of 87.7%. CONCLUSION: mSCOPE score could be proved useful in patients' risk stratification, guiding clinical interventions in patients with severe COVID-19.

Prevalence and Characteristics of Self-Reported Adult Asthma in Cyprus: A Population-Based Observational Study.

Purpose: To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. Patients and Methods: This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. Results: The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). Conclusion: This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.

Does the Addition of Strength Training to a High-Intensity Interval Training Program Benefit More the Patients with Chronic Heart Failure.

Background: Aerobic exercise, either continuous or high intensity interval training (HIIT), induces important benefits in chronic heart failure (CHF) patients. Resistance training has been also shown to be beneficial in CHF. However, data regarding combined aerobic exercise and muscle strength training is still limited. The aim of this study was to investigate whether adding strength training to a HIIT protocol within a cardiac rehabilitation (CR) program has a cumulative beneficial effect on the functional capacity (FC) and quality of life (QoL) in patients with CHF. Methods: Forty-four consecutive patients [35 males, ejection fraction (EF) < 50%] with CHF under medication enrolled in a 36-session CR program and were randomized in two exercise groups; HIIT (HIIT group) or HIIT combined with strength training (high intensity interval training combined with strength training (COM) group). All patients underwent baseline and endpoint outcome measures of a symptom-limited maximal cardiopulmonary exercise testing (CPET), 1 repetition maximum (1RM) test, muscular endurance test, echocardiography, and Minnesota Living with Heart Failure Questionnaire (MLWHFQ). Results: Most of the CPET indices, EF, 1RM test, muscular endurance and QoL were improved after the CR program in each exercise training group (p < 0.05). However, COM group demonstrated a further improvement in chest muscle testing and workload at anaerobic threshold (AT) compared to HIIT group. Conclusions: An exercise-based CR program, consisted of either HIIT or HIIT combined with strength training, improves FC and QoL of patients with CHF. However, the addition of strength training to HIIT seems to have further beneficial effects on chest muscle strength and endurance, as well as workload at AT. Clinical Trial Registration: The study was registered in ClinicalTrials.gov with number NCT02387411.

Sleep Apnea and Cardiovascular Risk in Patients with Prediabetes and Type 2 Diabetes.

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Daily Physical Activity in Asthma and the Effect of Mepolizumab Therapy.

For the various asthma-specific beneficial effects of physical activity, daily physical activity (DPA) and the potential of asthma therapies on DPA require better characterization. Hence, we aimed to determine (a) the DPA of asthma patients, and (b) the effect of add-on mepolizumab on the DPA of severe asthma patients. Methods: Adult outpatients with mild-to-moderate or severe asthma had accelerometer assessment of DPA. Severe asthma patients who were commenced on mepolizumab had their DPA reassessed after 12 months. Results: For the total cohort (n = 36), daily step count, time in moderate-to-vigorous physical activity (MVPA), MVPA volume and Movement Intensity (MI) were 7806 ± 3823 steps, 123 (interquartile range, 63) min, 657 ± 255 MET·min and 1.96 (0.45) m/s2, respectively. All patients met at least one recommendation for DPA but less than half met recommendations for vigorous DPA. Patients on mepolizumab therapy increased daily step count (646 steps; 9%), time in MVPA (20 min; 21%), MVPA volume (87 MET·min; 17%) and MI (0.11 m/s2; 6%) for the same amount of moving time; lung function, asthma control and health-related quality of life also improved. Conclusions: Analysis of the first national data on DPA in asthma and novel comparison against current applicable guidelines and identified beneficial thresholds showed borderline levels of DPA with room for improvement especially for severe asthma patients. In a non-sedentary cohort of severe asthma patients, mepolizumab conferred significant and meaningful improvements in DPA.