Pneumonia is the leading infectious cause of mortality worldwide and one of the most common lower respiratory tract infections that is contributing significantly to the burden of antibiotic consumption. Due to the complexity of its pathophysiology, it is widely accepted that clinical diagnosis and prognosis are inadequate for the accurate assessment of the severity of the disease. The most challenging task for a physician is the risk stratification of patients with community-acquired pneumonia. Herein, early diagnosis is essential in order to reduce hospitalization and mortality. Procalcitonin and C-reactive protein remain the most widely used biomarkers, while interleukin 6 has been of particular interest in the literature. However, none of them appear to be ideal, and the search for novel biomarkers that will most sufficiently predict the severity and treatment response in pneumonia has lately intensified. Although our insight has significantly increased over the last years, a translational approach with the application of genomics, metabolomics, microbiomics, and proteomics is required to better understand the disease. In this review, we discuss this rapidly evolving area and summarize the application of novel biomarkers that appear to be promising for the accurate diagnosis and risk stratification of pneumonia.

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The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar–capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation. At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function. A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity. Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD. Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.

Background Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes. Methods Endobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining. Results In all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034). In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes. Conclusions Bronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

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Common to several allergic diseases is the generation of immunoglobulin E (IgE) by plasma cells, when exposed to an innocuous antigen. Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway inflammatory diseases. Asthma is mediated in some patients through eosinophilic inflammatory mechanisms that include allergic sensitization and Th2-mediated immune airway response. COPD, on the other hand is mainly considered a Th1-mediated inflammatory process with neutrophilic predominance or a non-Th2 inflammation, occasionally associated with the presence of airway bacteria or viruses. IgE production appears to play an important role in the development of both COPD and asthma, as it has been associated to respiratory symptoms, lung function, bacterial and viral infections, airway remodeling and bronchial hyperreactivity in both diseases. The aim of this review is to summarize all current data concerning the role of specific and total IgE in COPD and asthma and to highlight similarities and differences in view of possible therapeutic interventions.

Fiber-optic bronchoscopy with endobronchial biopsy (EBB) has become an important tool for accurate diagnosis and treatment selection in airway diseases. In a recent study, histopathological EBB findings revealed an overlapping COPD-asthma phenotype; however, the challenge of selecting the proper lung region for biopsy was raised because dissimilarities in the histology of different lobes could affect the homogeneity of samples. 1 In the present study, we compared histopathological features among different lung lobes of severe asthmatics. MethodsWe included 30 patients with severe asthma undergoing evaluation for bronchial thermoplasty. The study was approved by the local institutional review board (EKNZ 2016-01057). The patient characteristics are shown in Table 1. Diagnosis of asthma was based on European Respiratory Society/American Thoracic Society guidelines and according to Global Initiative for Asthma 2019 criteria. Bronchoscopy procedures were performed by two senior pneumologists, transnasally or transorally, with the patients in the semirecumbent position. Nasal anesthesia was achieved by 2% lidocaine gel and the patients received propofol in repeated IV boluses, as previously described. [2][3][4] During the procedure, diagnostic EBB specimens were obtained from firstand second-generation bronchi using 2.2-mm-wide single use biopsy forceps with Endo-Glide Sheath (Radial Jaw, Boston Scientific). We chose to assemble samples from proximal airways because airway smooth muscle cell (ASMC) mass does not increase significantly in peripheral small airways of asthmatic patients. 5,6 From each patient, we obtained 10 EBBs from five locations: right upper lobe (one biopsy), middle lobe (two biopsies), right lower lobe (three biopsies), lingula (one biopsy), and left lower lobe (three biopsies). Specimens were washed in phosphate-buffered saline, fixed in formalin, and transferred to pathology. For each specimen, five sequential sections were stained with hematoxylin and eosin and Elastica van Gieson, adding to 5 to 15 analytic units per lobe and up to 50 analytic units per patient that were evaluated blindly by two senior pathologists for: (1) inflammation in the stroma, tissue lymphocyte/eosinophil/ granulocyte infiltration and thickening of reticular basement membrane (BM), using a 0 to 3 scale: 0 ¼ absence/ normal, 1 ¼ mild-moderate, 2-3 ¼ severe; (2) ASMC mass (total percentage of

Community-acquired pneumonia (CAP) is the third most common cause of death globally. Due to the complexity of CAP, it is widely accepted that, currently, clinical prognosis and diagnosis is inadequate for the assessment of the severity of the disease. With the aim to determining the initial treatment and the appropriate level of intervention, several clinical scores of severity and biomarkers have been developed. Both biomarkers and clinical scoring systems are expected to determine the different aspects of the host factor and the response to therapy, in order for physicians to be able to make an accurate benefit/risk assessment that will lead to proper diagnosis and correct prescription of antibiotics. This review aims to highlight the prognostic and diagnostic accuracy of various laboratory and clinical parameters in CAP and discuss the perspectives for the reduction of CAP mortality.