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Pulmonary acute and chronic diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and pulmonary hypertension, are considered to be major health issues worldwide. Cellular therapies with Mesenchymal Stem Cells (MSCs) offer a new therapeutic approach for chronic and acute lung diseases related to their anti-inflammatory, immunomodulatory, regenerative, pro-angiogenic and anti-fibrotic properties. Such therapeutic effects can be attributed to MSC-secretome, made of free soluble proteins and extracellular vesicles (EVs). This review summarizes the recent findings related to the efficacy and safety of MSC-derived products in pre-clinical models of lung diseases, pointing out the biologically active substances contained into MSC-secretome and their mechanisms involved in tissue regeneration. A perspective view is then provided about the missing steps required for the secretome "pharmaceuticalization" into a high quality, safe and effective medicinal product, as well as the formulation strategies required for EV non-invasive route of administration, such as inhalation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort., Methods: FEV 1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV 1 and FVC., Results: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV 1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV 1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline., Conclusion: Leisure-time vigorous physical activity was associated with higher FEV 1 and FVC over a 10-year period among current smokers, but not with FEV 1 and FVC decline., Competing Interests: Competing interests: PD reports consulting fees from ALK, Stallergènes Greer, Circassia, Chiesi, Thermofisher Scientific and Ménarini, and AGC reports grants from Chiesi Farmaceutici and from GlaxoSmithKline Italy, during the conduct of the study. Other authors declare no competing interests related to this work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Simple Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic coronavirus disease-2019 (COVID-19), which can lead to severe pneumonia and acute respiratory distress syndrome (ARDS). The immune system plays a key role in the defense against COVID-19. Nonetheless, if dysregulated and hyperactivated, the immune response can trigger the deleterious "cytokine storm". Multiple studies are aimed at finding potential immunomodulators to rebalance the immune response against the virus, thus limiting its dangerous effects. Moreover, the development of vaccines against SARS-CoV-2 has represented a global challenge. The aim of this narrative review is to describe the state-of-the-art knowledge on the immune system response in COVID-19 and to underline the main therapeutic strategies and the key role of vaccines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a "cytokine storm", a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the "cytokine storm" has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included. [ABSTRACT FROM AUTHOR]

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, Mwurzburg and Mwhitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the Mwurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the Mwurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with Mwurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The Mwhitstable allele was detected by intron 4 sequencing of SERPINA1 gene. Mwurzburg and Mwhitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to describe the radiological features of chronic thromboembolic pulmonary disease (CTEPD), not yet systematically described in the literature. Furthermore, we compared vascular scores between CTEPD and chronic thromboembolic pulmonary hypertension (CTEPH) patients, trying to explain why pulmonary hypertension does not develop at rest in CTEPD patients. Methods: Eighty-five patients (40 CTEPD, 45 CTEPH) referred to our centre for pulmonary endarterectomy underwent dual-energy computed tomography pulmonary angiography (DE-CTPA) with iodine perfusion maps; other 6 CTEPD patients underwent single-source CTPA. CT scans were reviewed independently by an experienced cardiothoracic radiologist and a radiology resident to evaluate scores of vascular obstruction, hypoperfusion and mosaic attenuation, signs of pulmonary hypertension and other CT features typical of CTEPH. Results: Vascular obstruction burden was similar in the two groups (p = 0.073), but CTEPD patients have a smaller extension of perfusion defects in the iodine map (p = 0.009) and a smaller number of these patients had mosaic attenuation (p < 0.001) than CTEPH patients, suggesting the absence of microvascular disease. Furthermore, as expected, the two groups were significantly different considering the indirect signs of pulmonary hypertension (p < 0.001). Conclusions: CTEPD and CTEPH patients have significantly different radiological characteristics, in terms of signs of pulmonary hypertension, mosaic attenuation and iodine map perfusion extension. Importantly, our results suggest that the absence of peripheral microvascular disease, even in presence of an important thrombotic burden, might be the reason for the absence of pulmonary hypertension in CTEPD. Key Points: • CTEPD and CTEPH patients have significantly different radiological characteristics. • The absence of peripheral microvascular disease might be the reason for the absence of pulmonary hypertension in CTEPD. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that Mesenchymal Stem/Stromal Cells (MSCs) exert their therapeutic effects by the release of secretome, made of both soluble proteins and nano/microstructured extracellular vesicles (EVs). In this work, for the first time, we proved by a proteomic investigation that adipose-derived (AD)-MSC-secretome contains alpha-1-antitrypsin (AAT), the main elastase inhibitor in the lung, 72 other proteins involved in protease/antiprotease balance, and 46 proteins involved in the response to bacteria. By secretome fractionation, we proved that AAT is present both in the soluble fraction of secretome and aggregated and/or adsorbed on the surface of EVs, that can act as natural carriers promoting AAT in vivo stability and activity. To modulate secretome composition, AD-MSCs were cultured in different stimulating conditions, such as serum starvation or chemicals (IL-1β and/or dexamethasone) and the expression of the gene encoding for AAT was increased. By testing in vitro the anti-elastase activity of MSC-secretome, a dose-dependent effect was observed; chemical stimulation of AD-MSCs did not increase their secretome anti-elastase activity. Finally, MSC-secretome showed anti-bacterial activity on Gram-negative bacteria, especially for Klebsiella pneumoniae. These preliminary results, in addition to the already demonstrated immunomodulation, pave the way for the use of MSC-secretome in the treatment of AAT-deficiency lung diseases. [ABSTRACT FROM AUTHOR]