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Background Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P Interpretation According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations.Consecutive patients40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (50, 50-149 and ≥150 cells/μL). Patients received standard care and were followed up for a year.A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaOHigher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.

Background and objectives: Administration of inhaled medication for asthma and COPD is often difficult and incorrect device use is associated with unfavorable outcomes. We aimed to evaluate device ...

Systemic inflammation may be the common denominator between COPD and type 2 diabetes and may explain the correlation in both diseases' development and progress. The aim of this prospective observational study is to examine the prognostic value of glycated hemoglobin levels (HbA1c) and HbA1c-adjusted glycemic variables (glycemic gap, stress hyperglycemia ratio και modified stress hyperglycemia ratio) in an acute exacerbation of COPD (AECOPD) as well as in COPD disease's morbidity and mortality during the following year. We evaluated patients hospitalized only for COPD exacerbations. Levels of HbA1c and HbA1c-adjusted glycemic variables were recorded upon admission. The study outcomes included duration of hospital stay, need for mechanical ventilation and exacerbation outcome. All subjects were followed up for one year. A total of 156 patients were included in the study (74.4% men, age [mean ±

Pharmacological medications used for the treatment of COPD patients have increased significantly. Long-acting bronchodilators have been recognized as the mainstay of the treatment of stable COPD, while ICS are usually added in patients with COPD who experience exacerbations, despite bronchodilator treatment. In the latest years, several studies have been published showing the beneficial effect of adding ICS on dual bronchodilation in patients suffering from more severe disease comparing triple therapy with several therapeutic regiments including dual bronchodilation and providing a message that this triple therapy might be more appropriate for COPD patients. However, not all COPD patients have a desirable response to ICS treatment while long-term ICS use in COPD is associated with several side effects. In this report, we aimed to provide a review of the current knowledge on the importance of dual bronchodilation on COPD patients and to compare its use with triple therapy, by covering a wide spectrum of topics. Finally, we propose an algorithm on performing treatment step up from dual bronchodilation to triple therapy and step down from triple to double bronchodilation considering the current evidence.

In Sarcoidosis joints-muscles-bones (JMBs) localizations are of the least common. 18F-FDG-PET/CT imaging revolutionized detection of JMBs involvement by adding metabolic activity information and al...

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases worldwide. Although different guidelines regarding therapeutic algorithms exist, the most widely adopted approach is the one suggested by the Global Initiative in Chronic Obstructive Lung Disease in which patients are stratified according to their dyspnea severity and their exacerbation history during the previous year. This combined assessment of COPD, which takes into consideration all aforementioned characteristics of COPD patients as well as the number of blood eosinophils, results in a proposed therapeutic algorithm which is complex and hard to memorize. This complexity is probable one of the causes that most health care professionals are not adherent to the guidelines when treating COPD patients. Here, we propose a simplified therapeutic algorithm for the treatment of COPD patients taking into consideration the current evidence on the use of bronchodilators and inhaled corticosteroids.

Introduction The pathogenesis of Chronic obstructive pulmonary disease (COPD) is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. Areas covered COPD has been traditionally associated with neutrophilic inflammation of the bronchi, but in the last decade studies have demonstrated that eosinophils may also migrate into the lower airways of patients with COPD and their increased numbers can be noticed during exacerbations as well as stable disease. In this review, we present clinical characteristics of eosinophilic COPD, as well as the role of eosinophils as a biomarker-guided therapy in COPD. A systematic research using database of Pubmed up to February of 2021 was performed. The terms we searched were: eosinophilic inflammation, COPD, COPD phenotypes, COPD exacerbations, corticosteroids in COPD, monoclonal antibodies in COPD. Expert opinion Blood eosinophil levels show strong potential as a prognostic and theragnostic biomarker in the clinical management of COPD being at the moment the most reliable biomarker. The lack of a certain cut-off value of blood eosinophils as guidance for treatment with ICS and biologic therapies and the uncertainty regarding the stability of eosinophilia and eosinophilic phenotype through the course of COPD remain as unmet dilemmas and problems.

To the editorWe have recently proposed a simplified approach of pharmacological treatment of stable COPD that has been previously published in this journal [1]. The most widely adopted approach reg...

Background Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Introduction: The age of asthma onset is often implicated in clinical manifestation, diagnosis, and management of the disease.Aim: To define demographic, clinical and functional features and inflam...

David B Price,1,2 Sen Yang,1 Simon Wan Yau Ming,1 Antony Hardjojo,1 Claudia Cabrera,3,4 Andriana I Papaioannou,5 Stelios Loukides,5 Vicky Kritikos,6 Sinthia Z Bosnic-Anticevich,6 Victoria Carter,7 Paul M Dorinsky8 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Global Medical Affairs, AstraZeneca R and D, Mölndal, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 52nd Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Attikon General Hospital, Athens, Greece; 6Woolcock Institute of Medical Research, Quality Use of Respiratory Medicines Group, School of Medical Sciences, University of Sydney, Glebe, Australia; 7Optimum Patient Care, Cambridge, UK; 8Pearl – a member of the AstraZeneca Group, Durham, NC, USABackground: Peak inspiratory flow (PIF) as generated through the resistance of a dry powder inhaler (DPI) device is a critical patient-dependent maneuver impacting the success of DPI medication delivery. Despite its importance, it is not routinely measured in clinical practice. Little is currently known about the relationship, if any, between PIF through DPI devices, routine spirometry and disease outcomes.Aim: The aim of this study was to identify potential predictors of PIF for different DPIs from spirometric parameters and patient characteristics and explore the association between PIF and follow-up events.Patients and methods: A retrospective observational study at discharge among patients hospitalized for a COPD exacerbation at Attikon hospital, Athens, Greece. Spirometry was performed using an Easy on-PC™ spirometer. PIF was measured through four DPI resistances using the In-Check™ DIAL. Regression analyses were used to investigate the association between PIF through resistances and spirometric parameters obtained at discharge, comorbidities and demographic parameters.Results: Forty-seven COPD patients (mean [±SD], age 71[±9] years, 72% males, 51% current smokers) were included in this study. Overall, 85% and 15% were classified as GOLD (2017) groups D and C, respectively. Most prevalent comorbidities were hypertension (70%) and cardiovascular disease (53%). In the final regression model, higher PIF was significantly associated with the following: higher FEV1 and% predicted peak expiratory flow (PEF) for Turbohaler® (R-squared value 0.374); higher FEV1 and diagnosis of gastroesophageal reflux disease (GERD) for Aerolizer® (R-squared value 0.209) and higher FEV1, younger age and diagnosis of ischemic heart disease (IHD) for Diskus® (R-squared value 0.350). However, R-squared values for all three devices were weak (

Background: The efficacy and safety of omalizumab in patients with severe allergic asthma have been established in both randomized controlled trials and real-life studies. Objective: To evaluate the sustained effectiveness and safety of long-term treatment with omalizumab in a real-world setting. Methods: In this retrospective study, we included patients treated with omalizumab for at least 8 years in four asthma clinics in Greece. Pulmonary function, asthma control, oral corticosteroids (OCS) dose, and exacerbations were recorded before treatment, 6 months later, and annually thereafter. Adverse events were also recorded. Results: Forty-five patients (66.7% women), mean ± standard deviation (SD) age 55.3 ± 12.2 years, were included. The duration of treatment with omalizumab was 10.6 ± 1.2 years. The annual exacerbation rate decreased from 4.1 before omalizumab initiation to 1.1 after 1 year of treatment and remained low up to the 8th year of treatment (p < 0.001). From the 19 patients who were receiving OCS at baseline, 21.1% patients discontinued after 6 months, 47.4% were still on OCS after 4 years of therapy, and 31.6% were on OCS after 8 years. With regard to the OCS dose, 36.8% of the patients reduced the dose ≥ 50% after 6 months and 68.4% achieved 50% reduction after 2 years. The mean daily OCS dose before omalizumab initiation was 7.8 mg of prednisolone or the equivalent, reduced to 4.7 mg/day after 6 months, which reached 1.6 mg/day after 8 years (p < 0.001). Treatment with omalizumab resulted in significant improvements of asthma control and lung function. No severe adverse events were reported. Conclusion: In this real-life study, omalizumab resulted in significant and sustained improvements in asthma exacerbations, asthma control, and lung function, and had a steroid sparing effect and a good safety profile.

Introduction: MAB is a sensitive biomarker of cardiovascular risk, that is directly associated with cardiovascular events and mortality. Recent studies have evaluated the presence of MAB in patients with stable COPD or hospitalised for AECOPD. Objectives: To assess the impact of MAB in patients admitted for AECOPD and to detect possible associations of MAB with AECOPD outcomes and various COPD functional parameters. Methods: We evaluated prospectively 153 consequent patients, admitted for AECOPD in respiratory medicine departments of two University hospitals (Ioannina and Attikon). Upon admission demographic, clinical and laboratory values and COPD severity were assessed. Patients were evaluated monthly for one year, recording new AECOPD and death from any cause. Results: Patients with documented MAB (urine albumin/creatinine ratio g30 μg/mg) on admission had worse lung function (FEV1%) [median (IQR) 34 (25-44)% vs. 61 (53-74)%, pl0.001], higher mMRC [3 (2-3) vs. 1 (1-2), pl0.001], lower 6MWT [170 (139-243) vs. 360 (320-420), pl0.001] and more hospitalisation days [9 (6-11) vs. 4 (3-6), pl0.001]. MAB was also correlated with GOLD 2020 COPD stages (pl0.001). In multivariate regression analysis, significant predictors of hospitalisation duration were MAB [HR (95%CI) 2.034 (0.855-3.213)], FEV1 [-4.324 (-7.067- -3.135)] and presence of atrial fibrillation [0.988 (0.042-1.934)]. Twelve-month follow-up revealed that patients with MAB experienced more AECOPDs [3 (1.5-4.5) vs. 1 (0-3), pl0.001] and hospitalisations for AECOPD [1 (0-2) vs. 0 (0-1), pl0.001]. Conclusions: The presence of MAB upon admission for AECOPD was associated with the presence of more severe COPD and prolonged hospitalisation, as well as with higher rates of AECOPD and hospitalisations for AECOPD at 1-year follow-up.

Objectives: Serum uric acid (UA) and arterial lactate acid (LA) are markers of oxidative stress and tissue hypoxia that are present in patients with obstructive sleep apnea syndrome (OSAS). The aim...

Introduction: Efficacy and safety of omalizumab in patients with severe allergic asthma has been established in both randomized controlled trials and real-life studies Aim: To evaluate the sustained effectiveness and safety of long-term treatment with omalizumab in a real-world setting Methods: In this retrospective study, we included patients treated with omalizumab for at least 8 years, in 4 asthma clinics in Greece. Pulmonary function, asthma control, OCS dose and exacerbations were recorded before treatment, 6months later and annually thereafter. Adverse events were also recorded Results: 45 patients(66.7% women), mean age 55.3±12.2years, were included. Duration of treatment with omalizumab was 11.0±1.2years. Annual exacerbation rate decreased from 4.1 before omalizumab initiation to 0.8 after one year of treatment and remained low up to the 8th year of treatment(p Conclusions: In this real-life study omalizumab resulted in significant and sustained improvements in asthma exacerbations, asthma control and lung function, had a steroid sparing effect and a good safety profile

Background: Telomere-related genes (TRG) mutations are detected in 30% of familial pulmonary fibrosis (FPF) and are also associated with personal/familial extra-pulmonary disease suggestive of short telomere syndrome (STS). Aim: to evaluate the prevalence of TRG mutations in a national cohort of interstitial lung disease (ILD) with suspected genetic predisposition in Greece and to define patients’ characteristics and impact on outcome.Methods: Genetic diagnoses made between December 2014-September 2019 in patients with FPF, pulmonary fibrosis at young age or personal and/or family extra-pulmonary disease suggestive of STS were analyzed. Results: 150 ILD patients, 73% male, age-at-diagnosis 67 years old, 33% non-smokers, 75% with definite/probable UIP or CPFE, 93% with dyspnea/cough, FVC% pred 75%, DLCO% pred 49% were tested; FPF was 65%, 19% young age, 21% personal and 17% family extra-pulmonary disease suggestive of STS; 21% were tested for more than 1 indication. TRG pathogenic variations were detected in 19 (13%): 13 in a familial, 3 in young age and 3 in extra-pulmonary disease suggestive of STS context as follows: TERT, TERC, RTEL1, PARN, NOP10, NHP2 in 8,5,2,2,1 and 1 respectively. No difference was detected in epidemiological-clinical-radiologic-functional characteristics between patients without and with mutations apart from age-at-diagnosis [69 vs 62 years, p

Introduction: Μepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed one year of therapy with mepolizumab. Material and Method: This study is a prospective multi-centre, non-interventional 2 -year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. Results: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3±2.3 to 1.3±1.8; p Conclusions: We have shown that in patients with severe eosinophilic asthma, one year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of oral corticosteroids, and improvements of asthma control and lung function.

Background: Incorrect use of inhaler devices is associated with unfavorable outcomes Aim: To evaluate device use errors in asthma and COPD patients treated in outpatient clinics of 3 tertiary hospitals and one private practice office in Greece Methods: Demographics and medical history were recorded. Patients demonstrated the use of their prescribed device and use was evaluated according to predefined steps Results: 607 patients (50.2%male, mean age 60.2years) performed 663 demonstrations (56 patients were using 2 different types of devices). 49.8% were treated for asthma and 50.2% for COPD. 79.5% were using DPIs. Errors were documented in 41.2%, were associated with the type of device, p Conclusion: Device use errors are common and associated with unfavorable outcomes. Trained patients were more likely to use the device correctly. Patients should be encouraged to demonstrate the use of their devices during medical visits in everyday clinical practice

Introduction: Alpha1-antitrypsin (A1AT) deficiency is an autosomal co-dominant disease related to SERPINA-1 gene mutations predisposing to pulmonary emphysema and/or liver disease. Aim: to examine the genotype and phenotype of a Greek cohort of A1AT-deficiency patients. Methods: This multicenter study enrolled A1AT-deficiency patients under augmentation treatment from 8 centers in Greece. Results: 23 adult patients, 61% male, 17.4% non-smokers, diagnosed at a median age (IQR) of 47(42-58) years with A1AT levels of 0.24 (0.04-0.4) g/L were identified. Indications for A1AT measurement were severe obstructive pulmonary disease at the age Conclusion: In contrast with the literature, where Z and S are the most common A1AT-deficiency alleles, the present study reveals extremely rare deleterious variants in Greek A1AT-deficiency patients under augmentation treatment. Further examination of phenotype-genotype associations and outcome is expected to unveil their clinical significance in the future.

During the lockdown, IPF patients experienced lower than expected COVID-19, suggesting that simple measures for the winter months, such as face masking, clean hands, physical distancing could be adopted as promising advances in non-pharmacological therapyhttps://bit.ly/2ISi2EV

Introduction: Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. Methods: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. Results: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. Conclusions: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.

Introduction: Since the discovery of eosinophils in the sputum of asthmatic patients, several studies have offered evidence on their prominent role in the pathology and severity of asthma. Blood eosinophils, are a useful biomarker for therapy selection in severe asthma patients. IL-5 plays crucial role on maturation, activation, recruitment, and survival of eosinophils and constitutes an important therapeutic target for patients with severe uncontrolled eosinophilic asthma.Areas covered: This review focuses on the similarities and differences on mechanisms of action, efficacy, and safety, of two subcutaneously(SC) administered agents, the anti-interleukin(IL)-5 monoclonal antibody mepolizumab and the IL-5 receptor-α(IL-5Rα)-directed cytolytic monoclonal antibody benralizumab. All information used was collected from PubMed using keywords such as severe asthma, eosinophils, IL-5, airway inflammation, asthma exacerbations, mepolizumab, benralizumab, anti-IL5, and anti-IL5R either as single terms or in several combinations.Expert opinion: Both mepolizumab and benralizumab are promising for the treatment of severe eosinophilic asthma resulting in asthma control improvement and exacerbations reduction and can serve as steroid-sparing agents. However, since no head-to-head comparisons exist, it is unknown whether their different mechanisms of action might be related to different efficacy in specific patients' sub-phenotypes. Long-term clinical observations will provide real-world evidence regarding their lasting effectiveness and safety.

Asthma is a common disease, and although its clinical manifestations may be similar among patients, recent research discoveries have shown that it consists of several distinct clinical clusters or phenotypes, each with different underlying molecular pathways yielding different treatment responses. Based on these observations, an alternative approach - known as 'precision medicine' - has been proposed for the management of patients with severe asthma. Precision medicine advocates identification of treatable traits, linking them to therapeutic approaches targeting genetic, immunological, environmental, and/or lifestyle factors in individual patients. The main "goal" of this personalised approach is to enable choosing a treatment which will be more likely to produce a beneficial response in the individual patient rather than a 'one size fits all' approach. The aim of the present review is to discuss different ways of phenotyping asthma and to provide a rationale for treatment algorithms based on principles of precision medicine.

Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2 ± 9.1 vs. 43.9 ± 16.9 ng/ml, p = 0.037, and 24.3 ± 2.8 vs. 39.3 ± 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5 ± 31.6 vs. 31.4 ± 32.3 ng/ml, p = 0.052 and 64.8 ± 32.6 vs. 32.8 ± 25.6 ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients.

Background: Osteopontin (OPN) is involved in cancer development and metastasis. Increased sputum OPN was detected in chronic obstructive pulmonary disease (COPD). Methods: We evaluated serum OPN levels in patients with lung cancer (LC) and/or COPD and aimed to determine OPN prognostic performance in 1-year mortality in LC and also its diagnostic performance in LC among COPD patients. We recruited 167 LC patients, 85 with concomitant COPD. 28 COPD patients served as control group. Results: OPN levels were higher in LC compared to COPD alone (P=0.017) and higher in COPD and LC compared to COPD alone (P=0.031). No difference was observed in OPN levels between LC and COPD vs . LC without COPD (P=0.171). Serum OPN ≥50.3 ng/mL was an independent predictor of 1-year mortality in LC. Conclusions: OPN levels ≥35 ng/mL could predict the presence of LC among COPD patients. In patients with LC and/or COPD, LC is the major determinant for serum OPN. Serum OPN might be a promising prognostic biomarker of LC and a diagnostic biomarker of LC among COPD patients.

Sputum and blood eosinophils are proposed as candidate biomarkers for the identification of chronic obstructive pulmonary disease (COPD) patients at risk for exacerbation and treatment response. In this study, we evaluated the associations of eosinophils with the presence of emphysema in COPD patients. Induced sputum and blood eosinophil measurements were performed in consecutive COPD patients. Patients underwent lung function testing and high resolution computed tomography (HRCT) of the chest and the presence of emphysema was quantified. Patients with emphysematous lesions in ≥15% of the pulmonary parenchyma were considered having significant emphysema. Ninety-eight patients were included in the study. Patients with significant emphysema had lower blood eosinophil counts compared to patients without emphysema [median (IQR) 34.6 (0.0, 63.0) vs. 169.0 (110.0, 260.0) cells/µL, p < 0.001]; similar results were observed for the percentage (%) of blood eosinophils, but no difference was observed for sputum eosinophils. The differences were evident in frequent and non-frequent exacerbators and irrespective of the use of inhaled corticosteroids (ICS). Patients with significant emphysema in HRCT present lower levels of blood eosinophils and these differences were present irrespective of the frequent exacerbator history or the use of ICS. Blood eosinophils may not represent a clinically relevant biomarker in the presence of emphysema.

Introduction Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases. Objectives We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. Methods We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. Results We enrolled 40 subjects (21 men, mean age 63.5 yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic-eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL-8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL-13. Sputum IL-8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r = 0.799), the extent of bronchiectasis in HRCT (r = 0.765) and post-bronchodilator FEV 1 (r = −0.416). Sputum IL-13 levels correlated with sputum eosinophils (r = 0.656) and bronchodilator reversibility (r = 0.441). Neutrophilic bronchiectasis exhibited comparable IL-8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL-13 levels compared to asthma. Conclusions Sputum cell counts and IL-8 and IL-13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non-invasively assessing inflammation in non-cystic fibrosis bronchiectasis.

Background According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma. Methods A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded. Results Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P

Serum periostin has been proposed as a surrogate biomarker of Th2 inflammatory response in patients with asthma, but its predictive role in hospitalized patients with COPD has not been evaluated. The aim of the present observational prospective cohort study was to evaluate the possible role of serum periostin as predictor of outcome in COPD patients hospitalized for AECOPD. Serum periostin was measured on admission and at discharge in patients admitted to the hospital for a COPD exacerbation. Patients were followed-up for 1year for future exacerbations, hospitalizations and mortality. 155 consecutive patients admitted to the hospital for AECOPD were included to the study. Periostin levels on admission were elevated compared to discharge [34.7 (25.2-52.2) vs. 25.9 (17.4-41.0) ng/mL, p=0.003], but serum periostin levels did not differ between patients with or without prolonged hospitalization, or those who required non-invasive ventilation, intubation, or died during hospitalization. Frequent exacerbators had higher serum periostin levels at the time of discharge compared to non-frequent exacerbators [37.9 (26.6, 64.5) vs. 23.9 (16.2, 37.9), p

Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks, late responders when improvement was achieved between 16 and 32 weeks and non responders when they did not show any improvement after 32 weeks of therapy. 41 patients were included in the study. 28 patients were characterized as responders while 13 patients were considered as non-responders. Among responders, 25 were early responders and 3 were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC=0.718) and IL-13 in sputum supernatant (AUC=0.709). Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.

Massive Hemoptysis and pulmonary embolism are two very severe and potentially fatal pulmonary emergencies requiring completely different treatments. We present the case of a 45-year old male transmitted to our Hospital for massive hemoptysis who at the same time was found to suffer from pulmonary embolism. Hemoptysis was treated with bronchial artery embolization which resulted in cessation of haemorrhage and allowed the administration of anticoagulant therapy a few days later. This case report gives an answer on how to manage a real therapeutic conundrum which is the coexistence of a massive hemoptysis and a concomitant pulmonary embolism.

Objectives: In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18F-FDG PET/CT defines...

Objectives: In sarcoidosis progressive pulmonary disease affects prognosis. Pulmonary disease activity estimated by classic means poorly predicts severity and progressiveness. 18F-fluoro-2-deoxyglu...

International audience; Previous studies have shown that the co-existence of bone marrow failure and pulmonary fibrosis in a single patient or in a family is suggestive of telomere related genes (TRG) germline mutations. This study presents the genetic background, clinical characteristics, and outcome of a group of five Greek patients co-affected with IPF and MDS. Four out of five patients developed an IPF acute exacerbation that was not reversible. We failed to detect any mutation in the TERT, TERC, DKC1, TINF2, RTEL1, PARN, NAF1, ACD, NHP2 and NOP10 genes in any patient. Moreover, telomere length was normal in the two patients tested. This could suggest that although the co-occurence of IPF and MDS are suggestive of TRG mutation in patients

Introduction Growing evidence suggests a role of vitamin D in various cancers but the significance of vitamin D in malignant pleural disease remains unexplored. We sought to investigate the concentration and diagnostic role of 25-hydroxyvitamin D (25(OH)D) in malignant pleural effusions. Materials and Methods Prospective study of consecutive treatment-naive patients with a new diagnosis of pleural effusion. Results Seventy-eight patients were studied, 45 of whom had malignant pleural effusions. Concentration of 25(OH)D in pleural fluid was significantly higher than serum in both malignant (15.2 ng/mL (9.7, 25.6) versus 10.2 ng/mL (6.4, 17.7), P

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. Patients with this condition experience severe dyspnea and impaired gas exchange with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT imaging, showing the coexistence of emphysema and pulmonary fibrosis both in varying extent and locations within the lung parenchyma. Individual genetic background seem to predispose to the development of the disease. The risk of the development of pulmonary hypertension in patients with CPFE is high and related to poor prognosis. CPFE patients also present a high risk of lung cancer. Mortality is significant in patients with CPFE and median survival is reported between 2.1 and 8.5 years. Currently, no specific recommendations are available regarding the management of patients with CPFE. In this review we provide information on the existing knowledge on CPFE regarding the pathophysiology, clinical manifestations, imaging, complications, possible therapeutic interventions and prognosis of the disease.

Introduction: COPD and impaired glycemic control are characterized by systemic inflammation. Etiologic correlation between them is under investigation. Objective: The aim of this study is to examine the prognostic value of HbA1c levels in an acute exacerbation of COPD (AECOPD) as well as in COPD disease9s morbidity and mortality during the following year. Methods: Levels of HbA1c were recorded in patients admitted to the hospital for an AECOPD. Values above 6.5 % were considered high. All subjects were followed up for one year, their vital status and new AECOPD events were recorded. The study outcomes included duration of hospital stay, need for mechanical ventilation, time to next AECOPD and death. Results: Thirty-seven patients optimally treated were included. HbA1c was high in 7 (18.9%) patients. There was no difference in the duration of hospital stay between patients with low an high HbA1c levels (p=0.149). Though 57% of patients with high levels of HbA1c required mechanical ventilation vs 13% of patients with low HbA1c levels (p=0.012). In the follow up year no significant difference was observed in the time of the next AECOPD, the time of the next hospitalization for AECOPD and one-year mortality between the two study groups (p=0.258, p=0.929, p=0.076 respectively, Log Rank test). Conclusion: Preliminary data indicate that HbA1c levels >6.5% could be used as a prognostic biomarker of an exacerbation9s severity and could possibly be extended to to predicting one year mortality. Increased HbA1c levels are likely to reflect an increased inflammatory state which amplifies the risk of COPD disease9s adverse effects.

Physical inactivity is very common in patients with COPD. Improvement in daily physical activity has been documented in COPD patients following the completion of a pulmonary rehabilitation (PR) program, however, the predicting factors of daily physical activity have not been thoroughly studied. Therefore, we set out to investigate the predictors of daily physical activity in COPD patients undergoing PR. We studied 76 Caucasian, ambulatory COPD patients. Patients had: age, years=66±8, FEV1, %pred=49±19, FVC, %pred=80±19, FEV1/FVC, %=47±13, and DLco, %pred=56±20. Patients had 3.2±2.4 exacerbations in the year before. All patients underwent a hospital based comprehensive PR program. The duration of the program was 8-weeks with a frequency of 3 sessions per week. Daily physical activity measurements were performed by using a patient activity monitor validated for COPD. At baseline, vector magnitude units (VMU) were 420 (318, 589) and following completion of the PR, VMU were 444 (304, 629). The difference in VMU prior and following PR was related with the following baseline measurements: age (r=-0.294, p=0.010), 6MWT (r=0.254, p=0.027), PaO2 (r=0.289, p=0.016), St George’s Respiratory Questionnaire (r=-0.263, p=0.023), and the number of exacerbations the year before (r=-0.294, p=0.010). Following multivariate analysis, the PaO2 and the number of exacerbations the year before were the strongest predictors of the difference in VMU prior and following PR (r=0.392, p=0.026). In conclusion, the magnitude of changes in daily physical activity in COPD patients following the completion of PR program is influenced by the degree of hypoxemia and the number of exacerbations the year before.

A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute, Stepwise approach for the treatment of severe asthma http://ow.ly/rLPl30i0TyZ

We are presenting a case of acrometastasis in a male patient with lung adenocarcinoma. Acrometastases accumulate for 0.1% of all metastatic bone lesions and can be the first manifestation of cancer in approximately 10% of cases. The main clinical manifestations are tenderness, intermittent pain, functional impairment, erythema, heat and swelling of the affected part. Lung cancer is the main primary malignancy which causes acrometastases. Although the lesions can be recognized in X-rays or CT scans, the gold standard for the diagnosis is MRI scan in which the full extension of the tumor can be evaluated. The diagnosis is usually confirmed by fine-needle biopsy of the affected bone. In the presence of acrometastases, prognosis is very poor and palliative treatment is usually recommended. This case shows that patients at risk for lung cancer should be screened intensively when they develop persistent digital symptoms.

Background Guidelines suggest that patients hospitalized for acute COPD exacerbations (AECOPD) are treated with short acting bronchodilators. Long acting bronchodilators, offer longer symptom relief but since they are usually administered via Dry Powder Inhalers (DPIs) it is considered that during AECOPD patients would not be able to achieve appropriate inspiratory flow (IF) to receive appropriate drug doses. The aim of the present study was to evaluate whether patients admitted to the hospital for AECOPD, are able to achieve the necessary IF using different DPIs. Methods IF was measured daily in patients admitted for AECOPD with a portable IF meter (In-Check Oral inhaler assessment kit), containing a series of adapters that simulate the resistance of 4 DPIs [Turbuhaler (T), Breezhaler/Aerolizer (B/F), Discus (A/A/D) and Handinhaler (HH)]. Dyspnea, spirometry and arterial blood gases were also recorded daily. Results 44 consecutive patients were included in the study. The majority of patients were able to achieve an IF over 30 L/min with all four device resistances. This minimum required IF was achieved in 90.9%, 100%, 95.5% and 81.8% of patients on admission and in 100%, 100%, 97.7%, and 95.5% of patients on discharge for T, B/F, A/A/D and HH respectively. No functional characteristic was able to predict the achievement of this minimum necessary IF. Conclusion Most patients hospitalized for AECOPD, are able to receive treatment with long acting bronchodilators administered via DPIs. The possible beneficial effects of such an intervention should be tested in further studies.

BACKGROUND: Hospital admissions for COPD exacerbations account for 70% of total costs of COPD treatment, and the duration of hospital stay is directly related to this cost. The aim of this study was to investigate possible associations of demographic, clinical, laboratory, and functional parameters with stay of subjects admitted for COPD exacerbations and to provide a score for the prediction of the need for prolonged hospitalization. METHODS: We included 164 consecutive subjects admitted to 2 respiratory medicine departments of 2 tertiary hospitals for a COPD exacerbation, and we evaluated laboratory, clinical, and functional parameters possibly related to the duration of hospital stay. RESULTS: Seven parameters evaluated on subject admission (Antonisen type of exacerbation, number of Exacerbations in the previous year, Charlson index of comorbidities, Oxygenation, Partial pressure of PaCO2 in arterial blood gases, Dyspnea according to the Borg dyspnea scale, and history of chronic respiratory Failure) were able to predict stay and were included in a simple score named AECOPD-F. The area under the curve of the score for the prediction of prolonged hospital stay is 0.960, and a cutoff point > 3 predicts prolonged stay with a sensitivity of 84.5% and a specificity of 92.5% (95% CI 0.917–0.984). The AECOPD-F score was validated in a second group of 88 subjects admitted to the hospital for a COPD exacerbation. In the validation group, subjects with a score > 3 required prolonged stay compared with those with a score < 3 (8.0 [6.0–10.0] vs 6.5 [4.0–9.0] d, respectively, P .007). CONCLUSION: The AECOPD-F score could accurately predict stay in hospitalized COPD subjects. The implementation of this score in clinical practice could be useful in the discharge planning of such subjects. Key words: COPD exacerbation; duration of hospital stay; predictors of outcomes; dyspnea; comorbidities. [Respir Care 2014;59(11):1–. © 2014 Daedalus Enterprises]

Depression is a frequent comorbidity in COPD patients and is associated with greater physical impairment, increased health-care utilization, and worse outcomes. The presence of depressive symptoms in the partners of COPD patients has not been evaluated. We evaluated the partners of 230 consecutive COPD patients included in a prospective study. Depressive symptoms were evaluated using Beck’s Depression Inventory (BDI) on the first day of admission for COPD exacerbation. Patients were followed-up for 1 year. Significant depressive symptoms were present in 39.6 % of the COPD patients and in 40.9 % of their partners. Beck scores were higher in the partners of patients with severe airflow obstruction and in those with ≥2 exacerbations and ≥1 hospitalizations for COPD exacerbation during the 1-year follow-up. The BDI score of the patients’ partners was significantly correlated with the BDI score of the COPD patients (r s = 0.422). In multivariate analysis, depressive symptoms in the COPD patients were an independent predictor of depressive symptoms in their partners (OR 4.136, 95 % CI 1.991–8.594; p