Stylianos Loukides

BackgroundAllergic 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.ObjectiveThe aim of this study was to evaluate phenotypical differences between mono- and poly-sensitized patients with AR and to quantify their symptomatic variability.Methods565 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 …

We recently treated in our clinic a 49-year-old patient with clinical and imaging findings compatible with pneumonia, who showed clinical improvement after intravenous antimicrobial therapy. We recommended a follow-up chest X-ray 6 weeks after hospital discharge, which showed persistent consolidation [Figure 1]. The diagnostic procedure revealed lung adenocarcinoma.

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 …

COPD is a major healthcare problem and cause of mortality worldwide. COPD patients at increased mortality risk are those that are more symptomatic, have lower lung function and lower DLCO, have decreased exercise capacity, belong to the emphysematous phenotype and those who have concomitant bronchiectasis. Also mortality risk seems to be greater in patients who experience COPD exacerbations and in those who suffer from concomitant cardiovascular and/or metabolic diseases. To predict the risk of death in COPD patients several composite scores have been created using different parameters. In the previous years, large studies (also called Mega-Trials) have evaluated the efficacy of different therapies on COPD mortality, but until recently only non-pharmaceutical interventions have proven to be effective. However, recent studies on fixed combinations of triple therapy (long-acting beta agonists, long …

PurposeA1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants.Aimto investigate genotype and clinical profile of Greeks with AATD.MethodsSymptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany.ResultsIncluded are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5–58.5) years, AAT-levels 0.20(0.08–0.26) g/L, FEV1(%predicted) 41.5(28.8–64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 …

Granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling is essential in both alveolar macrophage (AM) differentiation and activation of lung immune cells [1]. Differentiated AMs are crucial in both the elimination of alveolar microbes and surfactant clearance. The disruption of the GM-CSF axis in AMs leads to the development of pulmonary alveolar proteinosis (PAP) [1]. In the majority of patients, this relates to the presence of autoantibodies against GM-CSF (autoimmune (a)PAP) but there are multiple other causes [1–3]. GM-CSF-deficient animals may have impaired lung inflammatory response to commensal microbes and humans with PAP may occasionally develop opportunistic lung infections [4]. The mainstay of pharmacological treatment in aPAP is inhaled GM-CSF (iGM-CSF), which is off-label but increasingly used worldwide [5–9].

Background Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable. Methods The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy. Results Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also …

Chronic obstructive pulmonary disease (COPD) is a widespread condition often overlooked in diagnosis [1]. The intricate underlying mechanisms contribute to a wide range of clinical manifestations, posing challenges to accurate diagnosis and treatment. Given the diversity within COPD, the aim of this editorial was to identify markers that help to examine the distinct endotype and phenotype for each individual patient [1]. Systemic inflammation and oxidative stress contribute to COPD’s development [2]. Interestingly, serum albumin, which is an essential marker of malnutrition, possesses antioxidant properties as a negative acute-phase protein [2]. In patients with stable COPD, there is a notable reduction in serum albumin levels when compared to non-COPD counterparts [2]. This observation suggests an insufficiency in systemic anti-inflammatory and antioxidant defense mechanisms within the context of COPD [2], especially during exacerbations [3]. Moreover, not only serum albumin but also microalbuminuria, indicative of endothelial dysfunction, may serve as a pertinent inflammatory marker for potential systemic consequences of COPD as Romundstad et al.[4] posited the presence of a positive correlation between microalbuminuria and mortality in COPD individuals. Within COPD, mitochondria-derived reactive oxygen species (mtROS) are discharged from activated inflammatory cells or structural cells like epithelial, endothelial, or smooth muscle cells, signifying an adaptive response to the situation [3]. Furthermore, these reactive oxygen species (ROS) activate transcription factors such as nuclear factor-kappa B (NFkB). This leads to the …

Introduction: Monoclonal antibodies are the pillar of individualized treatment of severe asthma. However, there is often phenotypic overlap in patients with severe asthma, and these patients may be eligible for more than one of the available therapies and switching between treatments as to achieve the best clinical response.Objective: The clinical benefit of patients with severe asthma who, due to non-response, switched from omalizumab to mepolizumab.Materials-methods: This is the post-hoc analysis of the 2-year prospective, multicenter, non-interventional observational study, RELIght. 2 groups of patients were studied:(A)those who received and (B)those who did not receive omalizumab in the past, before starting treatment with mepolizumab.Results: Of the 169 patients, 60 (35.5%,19 men, median age 59[49.5,67.5]years) had received previous treatment with omalizumab. In Group(A) switching to mepolizumab …

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published the complete 2023 GOLD report, which can be freely downloaded from its web page (www. goldcopd. org) together with a “pocket guide” and “teaching slide set”(1). It contains important changes compared to earlier versions, and incorporates 387 new references (1). Here, we present an executive summary of this GOLD 2023 report (1) that summarizes aspects that a) are relevant from a clinicians perspective and b) updates evidence published since the prior executive summary in 2017.

Switching from omalizumab to mepolizumab in severe asthmatics: A post hoc analysis of the RELight study Switching from omalizumab to mepolizumab in severe asthmatics: A post hoc analysis of the RELight study Clin Exp Allergy. 2023 Dec 12. doi: 10.1111/cea.14436. Online ahead of print. Authors Maria Kallieri 1 , Andriana I Papaioannou 2 , Eleftherios Zervas 3 , Evangelia Fouka 4 , Konstantinos Porpodis 4 , Marija Hadji Mitrova 4 , Eleni Tzortzaki 5 , Michael Makris 6 , Maria Ntakoula 6 , Panagiotis Lyberopoulos 1 , Katerina Dimakou 7 , Sofia Koukidou 7 , Sevasti Ampelioti 7 , Anastasia Papaporfyriou 8 , Konstantinos Katsoulis 9 , Maria Kipourou 9 , Nikoletta Rovina 2 , Katerina Antoniou 10 , Stylianos Vittorakis 11 , Petros Bakakos 2 , Paschalis Steiropoulos 12 , Katerina Markopoulou 13 , Panteleimon Avarlis 14 , Ιlias C Papanikolaou 15 , Miltiadis Markatos 11 , Eleni Gaki 16 , Konstantinos Samitas 3 , …

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 …

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 …

Asthma is a heterogenous disease characterized by different phenotypes and endotypes. Severe asthma is a unique phenotype of the disease characterized by two major endotyping mechanisms—the high T2 process and the low T2 process. The definition of severe asthma is mainly based on the high requirements of treatment regimens. In the last 20 years, biologic agents have had a central role in targeting the previously refractory T2 high process, with many randomized controlled trials (RCTs) clearly verifying both safety and efficacy [1]. Despite their effectiveness in different aspects of disease assessment there are many challenges which need to be either addressed or resolved. These aspects are mainly attributed to the presence of co-morbidities, long-term effects of treatment, and baseline characteristics of the selected patients, as well as to additive treatment strategies. An important issue in severe asthma is the presence of bronchiectasis. In a recently published study, the presence of high blood eosinophilia in patients with severe asthma and bronchiectasis was mainly attributed to the different localization of bronchiectasis [2]. The above finding may indirectly reveal aspects of treatment interventions, such as an inflammatory profile sensitive to high T2 targeting interventions; however, simultaneously, a question arises: In a disease where neutrophils are mainly involved, how effective are treatments which eliminate the refractory high T2 process? In a population characterized by severe asthma with co-existing bronchiectasis, the presence of leukotriene receptor antagonists (LTRAs) in treatment strategies may influence both the T2 …

Background Molnupiravir (M) and Nirmatrelvir/Ritonavir (N/R) have been authorized for use in COVID-19 patients at high risk for severe disease. We aimed to evaluate the effectiveness of M and N/R in highly vulnerable SARS-CoV-2 patients using a retrospective cohort study design. Methods The study population consisted of SARS-CoV-2 infected non-hospitalized patients in Greece, aged 65 years or older, that received M between February 2 and March 25, 2022 and N/R between March 26 and July 20, 2022. The impact of each drug was determined via comparisons with age-matched control groups of SARS-CoV-2-positive patients who did not receive oral antiviral therapy, using as outcome (i) hospital admission with COVID-19 within 10 days after tested positive, and (ii) death from COVID-19 within 35 days from positive test. Results Overall, 4,240 M …

Introduction: Benralizumab is a humanized monoclonal antibody targeting the interleukin-5 receptor (IL-5a) that is expressed on eosinophils and inhibits eosinophilic inflammation. It is approved for the treatment of severe eosinophilic asthma.Aim: To evaluate the clinical experience, effectiveness and safety of benralizumab treatment to patients with severe eosinophilic asthma in Greece.Methods: A multicenter prospective observational study which was conducted in 19 different Pulmonary Centers in Greece. The recruitment period lasted 18 months and the follow-up period is 2 years.Preliminary results: 122 patients were eligible (70 women), with an average age of 56 years (min 30, max 82). 76 patients completed the 12month follow up. Significant improvement in ACT score (22±3.5 vs 15.9±4.4, p<0,01) and in FEV1 %pred (81.2±20 vs 72.4±22.2, p<0,01) was observed. There was 77,8% (p<0,001) reduction in …

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 …

IntroductionIn 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 coveredDifferent 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 opinionAssessing 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 …

Introduction-Aim: Chronic Obstructive Pulmonary Disease (COPD) is a common disease involving both the airways and lung parenchyma.RNA Binding Proteins, such as HuR(Human antigen R), TTP (Tristetraprolin), AUF-1 (AU-rich element-binding factor 1), have been reported to be differentially expressed in COPD depending on the level of eosinophilic inflammation. We aimed to investigate the association between eosinophilic inflammation and the levels of mRNA expression for the ELAVL1, ZΑP36 and HNRNPD genes, which encode the HuR, TTP and AUF-1 proteins, respectively.Methods: 39 patients diagnosed with COPD were studied in steady state. Of these, 16 patients were characterized by eosinophilic inflammation (in at least two of three consecutive measurements, blood eosinophils were >4 % and >300/μL in absolute count) and 23 patients were characterized with non-eosinophilic inflammation. The …

Introduction COPD is an independent risk factor for lung carcinoma and lung cancer more likely to occur in smokers with airflow obstruction than those with normal lung function.1 IL-22 is produced by innate lymphoid cells and mediates its cellular effects via a heterodimer receptor complex composed of two different subunits (IL-22 receptor subunit 1 (IL-22R1) and IL-10R2). IL-22 signaling regulates pro-survival, cell migration, mitogenic and anti-apoptotic effects, leading to enhancement of tumor growth and metastasis. IL-22 is overexpressed in lung cancer tissues, malignant pleural effusions, and serum of NSCLC patients.2Aim We attempted to determine lung tissue IL-22 levels in patients with early-stage NSCLC with and without COPD.Method The expression of IL-22 was studied with immunohistochemistry.Results 85 patients were recruited 12 of which with coexistent COPD confirmed by spirometry. Expression …