Levels of Immunoglobulin E 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 one 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 to clinical disease variability, underlying the distinct nature of AR from AR+ conjunctivitis or AR+ asthma, is not known. OBJECTIVE: The aim of this study was to evaluate phenotypical differences between mono- and poly-sensitized patients with AR and to quantify their symptomatic variability. METHODS: 565 patients with a confirmed diagnosis of AR were included in this cross-sectional study. 155 were mono-sensitized and 410 poly-sensitized. Interactions between sensitization levels and reporting of different symptoms of AR and co-morbidities, disease duration and impact, were assessed. Furthermore, patients were stratified into mono- oligo- and poly-sensitized to assess whether the effect of sensitization on phenotype was ranked. RESULTS: Poly-sensitized patients reported significantly more often itchy eyes (p=0.001) and had higher number of ocular (p=0.005), itch-related (p=0.036) and total symptoms (p=0.007) than mono-sensitized patients. In addition, polysensitized adults and children more often reported wheeze (p=0.015) and throat-clearing (p=0.04), respectively. Polysensitization was associated with more burdensome AR according to VAS (p=0.005). Increasing sensitization level was reflected in more itchy eyes, number of ocular, itch-related and total number of symptoms, as well as disease burden. CONCLUSION: With increasing number of sensitizations, AR patients experience an increased diversity of symptoms. Multimorbidity-related symptoms increase with sensitization rank, suggesting organ-specific thresholds.

Endotyping Eosinophilic Inflammation in COPD with ELAVL1, ZfP36 and HNRNPD mRNA Genes.

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by progressive airflow obstruction, influenced by genetic and environmental factors. Eosinophils have been implicated in COPD pathogenesis, prompting the categorization into eosinophilic and non-eosinophilic endotypes. This study explores the association between eosinophilic inflammation and mRNA expression of ELAVL1, ZfP36, and HNRNPD genes, which encode HuR, TTP and AUF-1 proteins, respectively. Additionally, it investigates the expression of IL-9 and IL-33 in COPD patients with distinct eosinophilic profiles. Understanding these molecular associations could offer insights into COPD heterogeneity and provide potential therapeutic targets. Methods: We investigated 50 COPD patients, of whom 21 had eosinophilic inflammation and 29 had non-eosinophilic inflammation. Epidemiological data, comorbidities, and pulmonary function tests were recorded. Peripheral blood mononuclear cells were isolated for mRNA analysis of ELAVL1, ZfP36, and HNRNPD genes and serum cytokines (IL-9, IL-33) were measured using ELISA kits. Results: The study comprised 50 participants, with 66% being male and a mean age of 68 years (SD: 8.9 years). Analysis of ELAVL1 gene expression revealed a 0.45-fold increase in non-eosinophilic and a 3.93-fold increase in eosinophilic inflammation (p = 0.11). For the ZfP36 gene, expression was 6.19-fold higher in non-eosinophilic and 119.4-fold higher in eosinophilic groups (p = 0.07). Similarly, HNRNPD gene expression was 0.23-fold higher in non-eosinophilic and 0.72-fold higher in eosinophilic inflammation (p = 0.06). Furthermore, serum levels of IL-9 showed no statistically significant difference between the eosinophilic and non-eosinophilic group (58.03 pg/mL vs. 52.55 pg/mL, p = 0.98). Additionally, there was no significant difference in IL-33 serum levels between COPD patients with eosinophilic inflammation and those with non-eosinophilic inflammation (39.61 pg/mL vs. 37.94 pg/mL, p = 0.72). Conclusions: The data suggest a notable trend, lacking statistical significance, towards higher mRNA expression for the ZfP36 and HNRNPD genes for COPD patients with eosinophilic inflammation compared to those with non-eosinophilic inflammation.

Exploring Mechanisms in COPD: Time for Biomarker Reappraisal?

Chronic obstructive pulmonary disease (COPD) is a widespread condition often overlooked in diagnosis [...].

Patients Hospitalized for COVID-19 in the Periods of Delta and Omicron Variant Dominance in Greece: Determinants of Severity and Mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a pandemic since 2020, and depending on the SARS-CoV-2 mutation, different pandemic waves have been observed. The aim of this study was to compare the baseline characteristics of patients in two phases of the pandemic and evaluate possible predictors of mortality. METHODS: This is a retrospective multicenter observational study that included patients with COVID-19 in 4 different centers in Greece. Patients were divided into two groups depending on the period during which they were infected during the Delta and Omicron variant predominance. RESULTS: A total of 979 patients (433 Delta, 546 Omicron) were included in the study (median age 67 years (54, 81); 452 [46.2%] female). Compared to the Omicron period, the patients during the Delta period were younger (median age [IQR] 65 [51, 77] vs. 70 [55, 83] years, p < 0.001) and required a longer duration of hospitalization (8 [6, 13] vs. 7 [5, 12] days, p = 0.001), had higher procalcitonin levels (ng/mL): 0.08 [0.05, 0.17] vs. 0.06 [0.02, 0.16], p = 0.005, ferritin levels (ng/mL): 301 [159, 644] vs. 239 [128, 473], p = 0.002, C- reactive protein levels (mg/L): 40.4 [16.7, 98.5] vs. 31.8 [11.9, 81.7], p = 0.003, and lactate dehydrogenase levels (U/L): 277 [221, 375] vs. 255 [205, 329], p < 0.001. The Charlson Comorbidity Index was lower (3 [0, 5] vs. 4 [1, 6], p < 0.001), and the extent of disease on computed tomography (CT) was greater during the Delta wave (p < 0.001). No evidence of a difference in risk of death or admission to the intensive care unit was found between the two groups. Age, cardiovascular events, acute kidney injury during hospitalization, extent of disease on chest CT, D-dimer, and neutrophil/lymphocyte ratio values were identified as independent predictors of mortality for patients in the Delta period. Cardiovascular events and acute liver injury during hospitalization and the PaO2/FiO2 ratio on admission were identified as independent predictors of mortality for patients in the Omicron period. CONCLUSIONS: In the Omicron wave, patients were older with a higher number of comorbidities, but patients with the Delta variant had more severe disease and a longer duration of hospitalization.

Severe Asthma in the Era of Biologics: Continuous Challenges.

Asthma is a heterogenous disease characterized by different phenotypes and endotypes [...].

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.

Cardiovascular Diseases in COPD: From Diagnosis and Prevalence to Therapy.

Chronic obstructive pulmonary disease (COPD) is considered one of the leading causes of mortality. Cardiovascular comorbidities are diagnosed often in COPD patients, not only because of the common risk factors these two diseases share, but also because of the systemic inflammation which characterizes COPD and has deleterious effects in the cardiovascular system. The comorbid cardiovascular diseases in COPD result in several difficulties in the holistic treatment of these patients and affect outcomes such as morbidity and mortality. Several studies have reported that mortality from cardiovascular causes is common among COPD patients, while the risk for acute cardiovascular events increases during COPD exacerbations and remains high for a long time even after recovery. In this review, we focus on the prevalence of cardiovascular comorbidities in COPD patients, presenting the evidence regarding the interaction of the pathophysiological pathways which characterize each disease. Furthermore, we summarize information regarding the effects of cardiovascular treatment on COPD outcomes and vice versa. Finally, we present the current evidence regarding the impact of cardiovascular comorbidities on exacerbations, quality of life and survival of COPD patients.

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.

Eosinopenia as a Prognostic Biomarker for Noninvasive Ventilation Use in COPD Exacerbations.

BACKGROUND: In recent years, blood eosinophils have been evaluated as a surrogate biomarker for eosinophilic airway inflammation and as a prognostic indicator of the outcomes of hospitalized COPD subjects. During an exacerbation of COPD, eosinopenia has been proposed as a prognostic marker of adverse outcomes. OBJECTIVES: The aim of the present post hoc analysis was to elucidate the effectiveness of blood eosinophils for predicting the need of NIV in subjects with COPD exacerbation. METHODS: Consecutive subjects admitted to a hospital for COPD exacerbation were included in the analysis. The eosinophil count from the first complete blood count was used to designate the eosinophil groups. The relationship between the clinical characteristics and blood eosinophil counts, as dichotomized using 150 cells/µL, was evaluated. Results Subjects with blood eosinophil number < 150 k/µL had a more severe disease on admission compared to subjects with ≥150 k/µL, regarding pH 7.400 (7.36, 7.44) vs. 7.42 (7.38, 7.45), p = 0.008, PO2/FiO2 levels 238.1 (189.8, 278.6) vs. 276.2 (238.2, 305.6), p < 0.001, CRP (mg/L) levels 7.3 (3.1, 19.9) vs. 3.5 (0.7, 7.8), p < 0.001 and required a longer hospital stay (days) 10.0 (8.0, 14.0) vs. 5.0 (3.0, 7.0) p < 0.001 respectively. The number of blood eosinophils correlated with the levels of CRP upon admission (p < 0.001, r = -0.334), with arterial pH upon admission (p < 0.030, r = 0.121), with PO2/FiO2 (p < 0.001, r = -0.248), and with duration of hospital stay (p < 0.001, r = -0.589). In the multinomial logistic regression analysis, blood eosinophil count < 150 k/µL was an independent predictor of the use of NIV during hospital stay. CONCLUSION: During COPD exacerbation, low blood eosinophil levels upon admission are related to more severe disease and can be used as a predictor of the need of NIV. Further prospective studies are needed to identify the use of blood eosinophil levels as a predictor of unfavorable outcomes.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Global initiative for chronic obstructive lung disease (GOLD) recommendations: strengths and concerns for future needs.

Chronic obstructive pulmonary disease (COPD) is already the third leading cause of death worldwide and simultaneously a major cause of morbidity and mortality. Global initiative for Chronic Obstructive Lung Disease (also known as GOLD) committee, has been created in 1997 to increase the awareness regarding the burden of COPD. GOLD recommendations have been contributing to diagnosis, managementz, and therapy of COPD since 2001. Through these years, by reviewing published articles, GOLD aimed to provide state-of-the-art information not only for pulmonologists, but also for non-respiratory physicians, and to encourage research on COPD. From 2011, GOLD annual reports have changed the way of COPD evaluation from based entirely on spirometric parameters to more clinical indices, such as the assessment of symptoms and dyspnea alongside with exacerbations. Moreover, according to recent developments in pathophysiology of COPD, there is a trend in identifying new preclinical stages, contributing to prevention and early COPD treatment. In the field of therapeutic algorithms, changes turn to a more personalized approach. However, it is not clear in what extent this personalized disease management would be feasible and the real challenge for current recommendations is to include more patient characteristics such as comorbidities and multidimensional scores in disease evaluation.

Greek Guidelines for the Management of COPD, a Proposal of a Holistic Approach Based on the needs of the Greek Community.

Despite that COPD remains one of the most common respiratory diseases worldwide, it can be managed effectively with certain treatments and, more importantly, be prevented by the early implementation of various measures. The pathology and pathophysiology of this disease continue to be studied, with new pharmacological and invasive therapies emerging. In this consensus paper, the Working Group of the Hellenic Thoracic Society aimed to consolidate the up-to-date information and new advances in the treatment of COPD. Local and international data on its prevalence are presented, with revised strategies on the diagnostic approach and the evaluation of risk assessment and disease severity classification. Emphasis is placed on the management and therapy of patients with COPD, covering both common principles, specialized modalities, and algorithms to distinguish between home care and the need for hospitalization. Although pharmacological treatment is commonly recognized in COPD, an integrative approach of pulmonary rehabilitation, physical activity, patient education, and self-assessment should be encountered for a comprehensive treatment, prevention of exacerbations, and increased quality of life in patients.

Pulmonary hemorrhage in patients receiving anti-platelets- a case series and a suggested therapeutic algorithm.

Antiplatelet therapy including aspirin and thienopyridine agents (such as clopidogrel, prasugrel and ticagrelor) are often used in patients with coronary disease. Pulmonary hemorrhage due to antiplatelet therapy although very rare, when excessive, is a life-threatening event. So far, there is lack of specific guidelines for the management of these patients. We report a case series of 5 patients receiving antiplatelet therapy who were admitted to the hospital due to pulmonary hemorrhage related to antiplatelet therapy. We also propose an algorithm on the management of these patients taking into consideration the balance between thrombotic and bleeding risk and the severity of the hemorrhage.

IL-26 in the Lung and Its Role in COPD Inflammation.

IL-26 is a cytokine expressed by infiltrating pro-inflammatory IL-17-producing T cells in the tissues of patients with chronic lung inflammation. IL-26 induces the chemotactic response of human neutrophils to bacteria and other inflammatory stimuli. In recent years, the innovative properties of IL-26 have been described. Studies have shown that, as DNA is released from damaged cells, it binds to IL-26, which plays the role of a carrier molecule for extracellular DNA, further contributing to its binding to the site of inflammation. This mechanism of action indicates that IL-26 may serve both as a driver as well as a stimulus of the inflammatory process, leading to the installation of a noxious amplification loop and, eventually, persistent inflammation. IL-26 also demonstrates direct antimicrobial effects derived from its capability to create pores and disrupt bacterial membranes, as indicated by the presence of membrane blebs on the surface of the bacteria and cytosolic leakage pores in bacterial walls, produced in response to microbial stimuli in human airways by several different immune and structural cells. Surprisingly, while this particular cytokine induces the gathering of neutrophils in areas of infection, it also exhibits inhibitory and pro-inflammatory effects on airway epithelial and immune cells. These remarkable effects underline the necessity of a better understating of its biological behavior and its role in the pathophysiology and disease burden in several smoking-related airway inflammatory disorders, such as Chronic Obstructive Pulmonary Disease (COPD) and chronic bronchitis. In this review, we aim to discuss the current role of IL-26 in the lung, with an emphasis on systemic inflammation in patients suffering from COPD and chronic bronchitis.

Sestrin 2 levels are associated with emphysematous phenotype of COPD.

Sestrins (Sesns) are a family of highly conserved stress-inducible proteins and various stresses have been shown to strongly up-regulate them. Sestrin 2 (Sesn2) deficiency has been shown to partially suppress pulmonary emphysema. The aim of this study was to evaluate Sesn2 levels in COPD patients and its possible associations with the presence of emphysema and blood eosinophils. All patients underwent lung function testing and high-resolution computed tomography (HRCT) of the chest. The presence of emphysematous lesions in >15% of the pulmonary parenchyma was considered as significant emphysema. Sixty-seven patients were included in the study. 40/67 patients were characterized as having significant emphysema. Patients with significant emphysema had higher levels of Sesn2 (ng/ml) [median (IQR) 6.7 (2.7,10.3 vs 1.09 (0.9,1.9), p<0.001)] and significantly lower % and absolute blood eosinophil counts (cells/µL) compared to patients without emphysema [1 (0, 2) vs 4 (2, 4) p<0.001 and 62 (0, 110) vs 248 (180, 300), p<0.001 respectively]. Sesn2 presented a significant positive correlation to the score of emphysema in HRCT (rs = 0.87, p<0.001) and similar positive but weaker correlation to FRC (rs = 0.27, p = 0.024). Negative correlations were observed between Sesn2 and either the % of blood eosinophils and/or the absolute blood eosinophil count (rs = -0.79, p<0.001, and rs = -0.78, p<0.001 respectively). Sesn2 levels above 1.87 ng/ml showed a high diagnostic performance for the presence of significant emphysema in HRCT with an AUC 0.93, 95% CI (0.85,0.98), p<0.001. Sesn2 could serve as a potential biomarker of emphysema.