IL-33/ST2 Axis in Organ Fibrosis

Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis

Calprotectin in lung diseases

Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This review aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix. The findings of this review potentially introduce CLP in daily clinical practice within the spectrum of respiratory diseases

Repeated Antigen-Based Rapid Diagnostic Testing for Estimating the Coronavirus Disease 2019 Prevalence from the Perspective of the Workers’ Vulnerability before and during the Lockdown

Background: No previous study has investigated the SARS-CoV-2 prevalence and the changes in the proportion of positive results due to lockdown measures from the angle of workers’ vulnerability to coronavirus in Greece. Two community-based programs were implemented to evaluate the SARS-CoV-2 prevalence and investigate if the prevalence changes were significant across various occupations before and one month after lockdown. Methods: Following consent, sociodemographic, clinical, and job-related information were recorded. The VivaDiag™ SARS-CoV-2 Antigen Rapid Test was used. Positive results confirmed by a real-time Reverse Transcriptase Polymerase Chain Reaction for SARS-COV-2. Results: Positive participants were more likely to work in the catering/food sector than negative participants before the lockdown. Lockdown restrictions halved the new cases. No significant differences in the likelihood of being SARS-CoV-2 positive for different job categories were detected during lockdown. The presence of respiratory symptoms was an independent predictor for rapid antigen test positivity; however, one-third of newly diagnosed patients were asymptomatic at both time points. Conclusions: The catering/food sector was the most vulnerable to COVID-19 at the pre-lockdown evaluation. We highlight the crucial role of community-based screening with rapid antigen testing to evaluate the potential modes of community transmission and the impact of infection control strategies

Calprotectin in Lung Diseases

Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This review aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix. The findings of this review potentially introduce CLP in daily clinical practice within the spectrum of respiratory diseases

Cutting-Edge Approaches in Respiratory and Critical Care Medicine

The COVID-19 pandemic has affected health care across the world, with respiratory and critical care medicine being affected the most [...

The Role of Small Airway Disease in Pulmonary Fibrotic Diseases

Small airway disease (SAD) is a pathological condition that affects the bronchioles and non-cartilaginous airways 2 mm or less in diameter. These airways play a crucial role in respiratory function and are often implicated in various pulmonary disorders. Pulmonary fibrotic diseases are characterized by the thickening and scarring of lung tissue, leading to progressive respiratory failure. We aimed to present the link between SAD and fibrotic lung conditions. The evidence suggests that SAD may act as a precursor or exacerbating factor in the progression of fibrotic diseases. Patients with fibrotic conditions often exhibit signs of small airway dysfunction, which can contribute to worsening respiratory symptoms and decreased lung function. Moreover, individuals with advanced SAD are at a heightened risk of developing fibrotic changes in the lung. The interplay between inflammation, environmental factors, and genetic predisposition further complicates this association. The early detection and management of SAD can potentially mitigate the progression of fibrotic diseases, highlighting the need for comprehensive clinical evaluation and research. This review emphasizes the need to understand the evolving connection between SAD and pulmonary fibrosis, urging further detailed research to clarify the causes and potential treatment between the two entities

Estimates of COVID-19 Risk Factors among Social Strata and Predictors for a Vulnerability to the Infection

Coronavirus disease 2019 (COVID-19) has emerged as a potentially severe disease, especially for individuals presenting with certain underlying medical conditions. We analyzed the rates of comorbidities and symptoms to reveal the potential severity of the pandemic in Volos, one of the most air-polluted cities in Greece. Environmental and health-related predictors for SARS-CoV-2 infection were investigated. A web-based questionnaire was disseminated through social media in the first half of March 2021 during a five-month strict lockdown. Sociodemographic data, preexisting medical conditions, frequency of clinical symptoms, and COVID-19 information were recorded. The study population consisted of 2000 responders. Four-fifths of the participants reported comorbidities that could increase vulnerability to severe COVID-19. Respiratory symptoms were reported from the unemployed and from retirees, and cold-related symptoms were reported in the education sector and in undergraduates. Women and younger generations shaped social vulnerability to respiratory infections similar to the elderly. SARS-CoV-2 infection was reported in 3.7% of the study population. Common headache (OR 2; CI 1189–3013; p = 0.007) and prior pneumonia (OR 1.9; CI 1024–2898; p = 0.04) were significant predictors for susceptibility to SARS-CoV-2 infection. The importance of monitoring society through community-based questionnaires is highlighted, for predicting and preventing future widespread transmission of infectious diseases

Venous Thromboembolic Disease in Chronic Inflammatory Lung Diseases: Knowns and Unknowns

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients