Assessment of bronchodilator responsiveness to salbutamol or ipratropium using different criteria in treatment-naïve patients with asthma and COPD.

Background: The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing. Aims: We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+. Methods: Symptomatic, treatment-naïve patients with expiratory airflow limitation (n = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis. Results: We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6-94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p < 0.01; 2021: 64% vs. 41%, p = 0.001). 2005-BDR+ and 2021-BDR+ to SABA were associated with decreasing pre-BD FEV1% predicted and the presence of cough. More patients with asthma were in the SABA+ group compared to the SAMA+ group (2005: 71% vs. 53%, Fischer exact p = 0.04; 2021: 77% vs. 52%, p = 0.02). Conclusions: Fewer patients show BDR+ according to the 2021 criteria in comparison with the 2005 recommendations, and protocols for BDR testing may consider the assessment of response to both SABA and SAMA after 30 minutes.

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.

Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.

Cytokines can modulate vascular remodelling and the adaptation of the right ventricle in pre-capillary pulmonary hypertension (PH). However, detailed data on the circulating levels of cytokines in patients are limited. We measured blood cytokine concentration in 39 treatment-naïve patients (pulmonary arterial hypertension: N = 16, chronic thromboembolic PH: N = 15, PH due to lung disease: N = 8) and 12 control subjects using enzyme-linked immunoassays. Apelin concentration >1,261 ng/mL identified patients with PH (66% sensitivity and 82% specificity), and in patients it was related to systolic pulmonary arterial pressure (PAP) (r = 0.33, P = 0.04), right atrial pressure (r = 0.38, P = 0.02), cardiac index (r = -0.34, P = 0.04), and right ventricular stroke work index (r = -0.47, P = 0.003). IL22RA2 concentration correlated with mean PAP (r = -0.32, P = 0.04) and serum N-terminal pro B-type natriuretic peptide level (r = -0.42, P = 0.01). VEGF concentration increased in patients upon clinical improvement (N = 16, P = 0.02). Circulating apelin is a novel biomarker of pre-capillary PH. Apelin and IL22RA2 levels are related to right ventricular function upon diagnosis of PH.

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.

Combined Pulmonary Fibrosis and Emphysema: Comparative Evidence on a Complex Condition.

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical syndrome characterized by upper lobe emphysema and lower lobe fibrosis manifested by exercise hypoxemia, normal lung volumes, and severe reduction of diffusion capacity of carbon monoxide. It has varying prevalence worldwide with a male predominance, and with smoking history of more than 40 pack-years being a common risk factor. The unique imaging features of CPFE emphasize its distinct entity, aiding in the timely detection of pulmonary hypertension and lung cancer, both of which are common complications. High-resolution computed tomography (HRCT) is an important diagnostic and prognostic tool, while lung cancer is an independent factor that alters the prognosis in CPFE patients. Treatment options for CPFE are limited, but smoking cessation, usual treatments of pulmonary fibrosis and emphysema, and avoidance of environmental exposures are encouraged.

Modeling of pulmonary deposition of agents of open and fixed dose triple combination therapies through two different low-resistance inhalers in COPD: a pilot study.

Introduction: Inhalation therapy is a cornerstone of treating patients with chronic obstructive pulmonary disease (COPD). Inhaler devices might influence the effectiveness of inhalation therapy. We aimed to model and compare the deposition of acting agents of an open and a fixed dose combination (FDC) triple therapy and examine their repeatability. Methods: We recruited control subjects (Controls, n = 17) and patients with stable COPD (S-COPD, n = 13) and those during an acute exacerbation (AE-COPD, n = 12). Standard spirometry was followed by through-device inhalation maneuvers using a pressurized metered dose inhaler (pMDI) and a soft mist inhaler (SMI) to calculate deposition of fixed dose and open triple combination therapies by numerical modeling. Through-device inspiratory vital capacity (IVCd) and peak inspiratory flow (PIFd), as well as inhalation time (tin) and breath hold time (tbh) were used to calculate pulmonary (PD) and extrathoracic deposition (ETD) values. Deposition was calculated from two different inhalation maneuvers. Results: There was no difference in forced expiratory volume in 1 s (FEV1) between patients (S-COPD: 42 ± 5% vs. AE-COPD: 35 ± 5% predicted). Spiriva® Respimat® showed significantly higher PD and lower ETD values in all COPD patients and Controls compared with the two pMDIs. For Foster® pMDI and Trimbow® pMDI similar PD were observed in Controls, while ETD between Controls and AE-COPD patients did significantly differ. There was no difference between COPD groups regarding the repeatability of calculated deposition values. Ranking the different inhalers by differences between the two deposition values calculated from separate maneuvers, Respimat® produced the smallest inter-measurement differences for PD. Discussion: Our study is the first to model and compare PD using pMDIs and an SMI as triple combination in COPD. In conclusion, switching from FDC to open triple therapy in cases when adherence to devices is maintanined may contribute to better therapeutic effectiveness in individual cases using low resistance inhalers.

Mucolytics for acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis.

This meta-analysis explored the safety and effectiveness of mucolytics as an add-on treatment for chronic obstructive pulmonary disease (COPD) exacerbations. Based on a pre-registered protocol and following Cochrane methods, we systematically searched for relevant randomised or quasi-randomised controlled trials (RCTs). We used the Risk of Bias v2 tool for appraising the studies and performed random-effect meta-analyses when appropriate. We assessed certainty of evidence using GRADE. This meta-analysis included 24 RCTs involving 2192 patients with COPD exacerbations, entailing at least some concerns of methodological bias. We demonstrated with moderate certainty that mucolytics increase the rate of treatment success (relative risk 1.37, 95% CI 1.08-1.73, n=383), while they also exert benefits on overall symptom scores (standardised mean difference 0.86, 95% CI 0.63-1.09, n=316), presence of cough at follow-up (relative risk 1.93, 95% CI 1.15-3.23) and ease of expectoration (relative risk 2.94, 95% CI 1.68-5.12). Furthermore, low or very low certainty evidence suggests mucolytics may also reduce future risk of exacerbations and improve health-related quality of life, but do not impact on breathlessness, length of hospital stay, indication for higher level of care or serious adverse events. Overall, mucolytics could be considered for COPD exacerbation management. These findings should be validated in further, rigorous RCTs.

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.

ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Assessing Treatment Success or Failure as an Outcome in Randomised Clinical Trials of COPD Exacerbations. A Meta-Epidemiological Study.

A recently published ERS core outcome set recommends that all trials of COPD exacerbation management should assess the treatment success (or "cure" of the exacerbation), defined as a dichotomous measure of the overall outcome of an exacerbation. This methodological systematic review describes and compares the instruments that were used to assess treatment success or failure in 54 such RCTs, published between 2006-2020. Twenty-three RCTs used composite measures consisting of several undesirable outcomes of an exacerbation, together defining an overall unfavourable outcome, to define treatment failure. Thirty-four RCTs used descriptive instruments that used qualitative or semi-quantitative descriptions to define cure, marked improvement, improvement of the exacerbation, or treatment failure. Treatment success and failure rates among patients receiving guidelines-directed treatments at different settings and timepoints are described and could be used to inform power calculations in future trials. Descriptive instruments appeared more sensitive to treatment effects compared to composite instruments. Further methodological studies are needed to optimise the evaluation of treatment success/failure. In the meantime, based on the findings of this systematic review, the ERS core outcome set recommends that cure should be defined as sufficient improvement of the signs and symptoms of the exacerbation such that no additional systemic treatments are required.

Measurements of upper and lower airway nitric oxide in healthy adults.

Introduction.Nasal nitric oxide (NO) measurement can be a useful tool for monitoring upper airway diseases. However, there is a considerable lack of validation data.Aims.To evaluate the repeatability and intra-subject variations of nasal NO output (nVNO) in healthy adults and to study its correlation with lower airway NO parameters.Methods.nVNOwas measured in healthy non-smokers at baseline (N= 31, age: 28 ± 6 years), after 1 h (N= 15), 1 d (N= 15), 1 week (N= 17), and compared using the Bland-Altman method. At baseline, lower airway NO parameters (FENO, flux of NO in the conducting airways and alveolar NO concentration) were also measured and correlated tonVNO(Spearman correlation). Multivariate regression analysis was used to assess the factors influencingnVNO.Results.Baseline mediannVNOwas 465 (interquartile range (IQR) = 404-536) nL min-1. The mean differences between the baseline and repeated measurements were not significant (p> 0.05). The coefficient of repeatability (mean: 118, IQR = 88-181 nL min-1) and coefficient of variation (mean: 9.1%) were low. We found no correlation betweennVNOand lower airway NO parameters (p> 0.05). Sex (ß= -0.52,p= 0.02) and body weight (ß= -0.65,p= 0.03) influencednVNO(model:p= 0.04,R2= 0.31).Conclusion.nasal NO output has good repeatability in healthy adults. The NO productions of lower and upper airways are not related in health, but nasal NO output seems to be affected by sex and body weight.

Right ventricular adaptation in pulmonary arterial hypertension / Jobb kamrai adaptáció pulmonalis artériás hypertoniában

Összefoglaló. Pulmonalis artériás hypertoniában (PAH) a tüdoartériák falának átépülése az elsodleges patofiziológiai eltérés, amely a pulmonalis vascularis rezisztencia (PVR) és a pulmonalis nyomás progresszív emelkedéséhez vezet. Ez a nyomásemelkedés a jobb szívfélben az afterload fokozódásához vezet, ami hosszú távon jobbkamra-diszfunkciót és jobbszívfél-elégtelenséget okoz. Az egyre növekvo PVR mellett kialakuló cardialis adaptáció pontos patomechanizmusa nem ismert, de egyes betegek esetén nagyon eltéro lehet az adaptáció mértéke és kialakulásának üteme. A kialakuló myocardium-hypertrophia és -dilatáció mértéke nagyban függ a PAH etiológiájától, de emellett egyéb tényezok - mint az életkor, a neurohumoralis aktiváció mértéke, genetikai és epigenetikai faktorok - is jelentosen befolyásolják. Minél kevésbé képes a jobb kamra megtartani funkcióját az egyre növekvo ellenállással szemben, annál gyorsabban alakul ki a jobbszívfél-elégtelenség, és annál rosszabbak a beteg életkilátásai. Ezen folyamatok jobb megismerése klinikai jelentoséggel bír, mivel a jobb kamrai adaptáció elosegítése javíthatja a betegség kimenetelét. Orv Hetil. 2021; 162(37): 1485-1493. Summary. Remodeling of the pulmonary artery wall is the primary pathophysiological abnormality in pulmonary arterial hypertension leading to a progressive increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure. The elevation of pressure increases the afterload in the right heart, causing right ventricular dysfunction and right heart failure in the long term. The exact pathomechanism of cardiac adaptation with increasing PVR is unknown, but the degree and rate of adaptation may be very different in patients suffering from pulmonary hypertension. The development of myocardial hypertrophy and dilatation is highly dependent on the etiology of pulmonary hypertension, but is also significantly influenced by other factors such as age, degree of neurohumoral activation, and genetic and epigenetic factors. Right heart failure develops and life expectancy shortens if the right ventricle is unable to maintain its function in the face of increasing resistance. Orv Hetil. 2021; 162(37): 1485-1493.

Circulating Survivin Protein Levels in Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

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

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea.

Intermittent hypoxia in obstructive sleep apnoea (OSA) is related to inflammation and metabolic abnormalities. Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) is involved in anti-inflammatory and metabolic processes. However, its ligand, calreticulin (CALR) promotes pro-inflammatory responses and apoptosis. Our aim was to analyse the levels of these biomarkers in OSA. We recruited 46 patients with OSA and 30 control subjects. Inpatient sleep study was performed and fasting plasma samples were collected. Triglyceride glucose index (TyG) and atherogenic index of plasma (AIP) were calculated. Plasma sLRP-1 levels were significantly lower in the OSA group compared to the controls (1.67 (0.90-2.11) mg/L vs. 1.99 (1.53-3.51) mg/L; p = 0.04) after adjustment for age, gender, BMI and lipid profile. Plasma sLRP-1 concentrations were inversely related to age (r = -0.29), BMI (r = -0.35), cigarette pack years (r = -0.31), LDL-C (r = -0.34) and triglyceride levels (r = -0.27), TyG (r = -0.37) and AIP (r = -0.27) as well as to the oxygen desaturation index (ODI, r = -0.24; all p < 0.05). BMI (p = 0.01) and ODI (p = 0.04) were independent predictors for low sLRP-1 levels. CALR did not differ significantly between the two groups (0.23 (0.17-0.34) ng/mL vs. 0.24 (0.20-0.36) ng/mL p = 0.76). We detected lower sLRP-1 levels in subjects with OSA which could contribute to metabolic abnormalities associated with this disease.

Circulating levels of clusterin and complement factor H in patients with obstructive sleep apnea.

Aim: Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. Materials & methods: We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. Results: There was no difference in CFH levels between patients (1099.4/784.6-1570.5/µg/ml) and controls (1051.4/652.0-1615.1/µg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2-763.2/µg/ml vs 276.1/131.0-424.3/µg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Conclusion: Increase in clusterin levels may be protective in OSA by blocking the MAC formation.

Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses.

BACKGROUND AND OBJECTIVE: The relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up. METHODS: Patients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses. RESULTS: We did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL-1, n=51, median (interquartile range): 21 (10-36) weeks) and non-eosinophilic groups (n=101, 17 (9-36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL-1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission. CONCLUSIONS: Our data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

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

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.