Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to ...alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.
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Acute respiratory distress syndrome Confalonieri, Marco; Salton, Francesco; Fabiano, Francesco
European respiratory review,
2017-Jun-30, Volume:
26, Issue:
144
Journal Article
Peer reviewed
Open access
Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 ...indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.
Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF ...pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial⁻mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.
Despite the fact that epithelial-mesenchymal transition (EMT) is a common downstream mechanism of all fibrosing diseases, whether it represents a leading process in the development of idiopathic ...pulmonary fibrosis has been widely discussed and is still a matter of debate. According to the most recent advances, EMT is thought to be mainly driven by the overexpression of several developmental pathways upstream of dysfunctional epithelial regeneration, which indeed normally occurs after damage and during tissue turnover. Future research should likely be directed at investigating the molecular mechanisms underlying epithelial dysfunction, in order to allow for both the removal of the wording "idiopathic" from idiopathic pulmonary fibrosis ("IPF") and for the identification of earlier and more effective therapeutic targets than the late process of fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) with unknown etiology in which gradual fibrotic scarring of the lungs leads to usual interstitial ...pneumonia (UIP) and, ultimately, to death. IPF affects three million people worldwide, and the only currently available treatments include the antifibrotic drugs nintedanib and pirfenidone, which effectively reduce fibrosis progression are, unfortunately, not effective in curing the disease. In recent years, the paradigm of IPF pathogenesis has shifted from a fibroblast-driven disease to an epithelium-driven disease, wherein, upon recurrent microinjuries, dysfunctional alveolar type II epithelial cells (ATII) are not only unable to sustain physiological lung regeneration but also promote aberrant epithelial–mesenchymal crosstalk. This creates a drift towards fibrosis rather than regeneration. In the context of this review article, we discuss the most relevant mechanisms involved in IPF pathogenesis with a specific focus on the role of dysfunctional ATII cells in promoting disease progression. In particular, we summarize the main causes of ATII cell dysfunction, such as aging, environmental factors, and genetic determinants. Next, we describe the known mechanisms of physiological lung regeneration by drawing a parallel between embryonic lung development and the known pathways involved in ATII-driven alveolar re-epithelization after injury. Finally, we review the most relevant interventional clinical trials performed in the last 20 years with the aim of underlining the urgency of developing new therapies against IPF that are not only aimed at reducing disease progression by hampering ECM deposition but also boost the physiological processes of ATII-driven alveolar regeneration.
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Non-invasive ventilation (NIV) has been increasingly used in COVID-19 patients. The limited physiological monitoring and the unavailability of respiratory mechanic measures, usually obtainable during ...invasive ventilation, is a limitation of NIV for ARDS and COVID-19 patients management.
This pilot study was aimed to evaluate the feasibility of non-invasively monitoring respiratory mechanics by oscillometry in COVID-19 patients with moderate-severe acute respiratory distress syndrome (ARDS) receiving NIV.
15 COVID-19 patients affected by moderate-severe ARDS at the RICU (Respiratory Intensive Care Unit) of the University hospital of Cattinara, Trieste, Italy were recruited. Patients underwent oscillometry tests during short periods of spontaneous breathing between NIV sessions.
Oscillometry proved to be feasible, reproducible and well-tolerated by patients. At admission, 8 of the 15 patients showed oscillometry parameters within the normal range which further slightly improved before discharge. At discharge, four patients had still abnormal respiratory mechanics, not exclusively linked to pre-existing respiratory comorbidities. Lung mechanics parameters were not correlated with oxygenation.
Our results suggest that lung mechanics provide complementary information for improving patients phenotyping and personalisation of treatments during NIV in COVID 19 patients, especially in the presence of respiratory comorbidities where deterioration of lung mechanics may be less coupled with changes in oxygenation and more difficult to identify. Oscillometry may provide a valuable tool for monitoring lung mechanics in COVID 19 patients receiving NIV.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Objective
The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 ...pneumonia.
Methods
This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study.
Results
Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity).
Conclusion
CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.
The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive ...respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical-radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (P
) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical-physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
Background: Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ∼3 years. Several risk factors have been identified, such as age, genetic predisposition, ...tobacco exposure, and gastro-oesophageal reflux disease (GERD). Prevalence of GERD in IPF is high and may affect 87% of patients, of whom only half (47%) report symptoms. Objective: The aim of this study is to review current evidence regarding the correlation between GERD and IPF and to evaluate the current studies regarding treatments for GERD-IPF. Methods: A review to identify research papers documenting an association between GERD and IPF was performed. Results: We identified several studies that have confirmed the association between GERD and IPF, with an increased acid exposure, risk of gastric aspiration and bile acids levels in these patients. Few studies focused their attention on GERD treatment, showing how antiacid therapy was not able to change IPF evolution. Conclusions: This review investigating the correlation between GERD and IPF has confirmed the hypothesized association. However, further large prospective studies are needed to corroborate and elucidate these findings with a focus on preventative and treatment strategies.
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