This study further approaches immune-related interstitial lung disease adverse event in patients undergoing immune checkpoint inhibitor (ICI) monotherapy, ICI plus chemotherapy and ICI plus anti-VEGF therapy in the postmarketing period. Reports for ICI-related interstitial lung disease adverse event from the FDA Adverse Event Reporting System (FAERS) database between 2014 and 2022 were analysed in this study. The reporting odds ratio (ROR) and Bayesian confidence propagation neural networks of information components (IC) were computed to identify disproportionate reporting of ICI-related interstitial lung disease. 44,964,609 records were extracted from the FAERS database, with 9150 records for interstitial lung disease after ICI treatment. Men had a slightly higher reporting frequency than women (63.07% vs. 25.69%). The morbidity rate (2.05%) of acute respiratory distress syndrome was low, the fatality rate (67.55%) was the highest, the time to onset was relatively short. Within 3 months, the cumulative proportion of ICI-related interstitial lung disease records was 75.03%. The ICI plus anti-VEGF therapy group had the lowest frequency of interstitial lung disease adverse events compared to the ICI monotherapy group and the ICI plus chemotherapy group (IC025 = 1.72, IC025 = 3.21, IC025 = 3.22). Moreover, ICI plus anti-VEGF therapy group had the narrowest spectrum of interstitial lung disease among these three therapeutic regimens. This study showed substantial characteristics of a spectrum of interstitial lung disease adverse events after different ICI regimens. Notably, ICI plus anti-VEGF therapy might be a treatment method that can to some extent control ICI-related interstitial lung disease. These data provide some important information for clinicians to weigh the risks and benefits of different ICI regimens.

To compare the similarities and differences between the Montreux definition and the Berlin definition in terms of the prevalence, mortality, and complications of neonatal acute respiratory distress syndrome (ARDS). We retrospectively analyzed the data of neonates with respiratory failure treated in a neonatal intensive care unit (NICU) between 1 November 2019 and 31 December 2021. In total, 554 infants had neonatal ARDS (524 infants, Montreux definition; 549 infants, Berlin definition). The prevalence (3.1% vs. 3.3%, p = 0.438) and mortality (18.9% vs.18.0%, p = 0.716) of neonatal ARDS did not differ between the definitions. Among the 519 infants meeting both definitions, key clinical outcomes did not differ between the definitions such as ventilation duration, NICU stay, complication rates, and antibiotic use, except for nitric oxide inhalation. The Montreux and Berlin definitions identified an additional 5 and 30 patients, respectively, not captured by the other definition. The rate of inhaled nitric oxide treatment (20.0% vs. 0%, p = 0.013), air leaks (20.0% vs. 0%, p = 0.013), and invasive ventilation duration (110.00 vs.0.00 h, p = 0.002) significantly differed between the above two groups. Sixty-two patients had moderate and severe ARDS according to the Montreux and Berlin definitions, respectively. The rates of adverse outcomes (e.g., mortality, invasive ventilation time) among these patients were similar to the rates among patients with moderate ARDS according to both definitions than among patients with severe ARDS according to both definitions. Conclusion: The prevalence, mortality, and most complications of neonatal ARDS were similar between the Montreux and Berlin definitions, which mainly differed in terms of the severity of neonatal ARDS. What is Known: • The Montreux definition was first proposed for the diagnosis of neonatal acute respiratory distress syndrome and was established in 2017. To date, the Montreux definition has not been compared with other diagnostic definitions of ARDS. What is New: • The study suggests that perinatal lung disease need not be excluded in the diagnosis of neonatal ARDS, and that the Montreux definition is more applicable to neonates, taking into account their specific physiological characteristics.

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2 ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.

Fatal "cytokine storms (CS)" observed in critically ill COVID-19 patients are consequences of dysregulated host immune system and over-exuberant inflammatory response. Acute respiratory distress syndrome (ARDS), multi-system organ failure, and eventual death are distinctive symptoms, attributed to higher morbidity and mortality rates among these patients. Consequent efforts to save critical COVID-19 patients via the usage of several novel therapeutic options are put in force. Strategically, drugs being used in such patients are dexamethasone, remdesivir, hydroxychloroquine, etc. along with the approved vaccines. Moreover, it is certain that activation of the resolution process is important for the prevention of chronic diseases. Until recently Inflammation resolution was considered a passive process, rather it's an active biochemical process that can be achieved by the use of specialized pro-resolving mediators (SPMs). These endogenous mediators are an array of atypical lipid metabolites that include Resolvins, lipoxins, maresins, protectins, considered as immunoresolvents, but their role in COVID-19 is ambiguous. Recent evidence from studies such as the randomized clinical trial, in which omega 3 fatty acid was used as supplement to resolve inflammation in COVID-19, suggests that direct supplementation of SPMs or the use of synthetic SPM mimetics (which are still being explored) could enhance the process of resolution by regulating the aberrant inflammatory process and can be useful in pain relief and tissue remodeling. Here we discussed the biosynthesis of SPMs, & their mechanistic pathways contributing to inflammation resolution along with sequence of events leading to CS in COVID-19, with a focus on therapeutic potential of SPMs.

Electrical injuries to humans from a lightning strike are associated with significant rates of morbidity and fatality. High-voltage injuries including those caused by lightning strikes are pulmonary edema, pulmonary contusion, acute respiratory distress syndrome, and pulmonary hemorrhages. Patients who get injured experience secondary trauma in addition to direct and indirect injury. In this report, we present the case of a 62-year-old male patient with complaints of shortness of breath, vomiting, and hoarseness of voice. The patient's treatment included airway protection, antibiotics, corticosteroids, and supportive care; however, the patient did not survive due to a severe lung contusion.

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

Acute respiratory distress syndrome (ARDS) still represents a major challenge with high mortality rates and altered quality of life. Many well-designed studies have failed to improve ARDS outcomes. Heterogeneity of etiologies, mechanisms of lung damage, different lung mechanics, and different treatment approaches may explain these failures. At the era of personalized medicine, ARDS phenotyping is not only a field of research, but a bedside consideration when implementing therapy. ARDS has moved from being a simple syndrome to a more complex area of subgrouping. Intensivists must understand these phenotypes and therapies associated with a better outcome.

Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI.

Recently, the world has been dealing with a destructive global pandemic Coronavirus disease 2019 (COVID-19) infection, since 2020; there were millions of infections and hundreds of thousands of deaths worldwide. With sequencing generations of the virus, around 60% are expected to become infected during the pandemic. Unfortunately, no drug or vaccine has been approved because no real evidence from clinical trials in treatment was reached. According to current thinking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mortality is caused by a cytokine storm syndrome in patients with hyper-inflammatory conditions, resulting in acute respiratory distress and finally death. In this review, we discuss the various types of natural immune-modulatory agents and their role in the management of SARS-CoV-2, and cytokine storm syndrome. For example, Polyphenols as natural products can block the binding of SARS-CoV-2 spike protein to host cell receptor ACE2, stop viral entry into the host cell and block viral RNA replication. Also, saikosaponins (A, B2, C, and D), triterpene glycosides, which are isolated from medicinal plants exert antiviral action against HCoV-22E9, and Houttuynia cordata water extract has antiviral effects on SARS-CoV. Moreover, eucalyptus oil has promising potential for COVID-19 prevention and treatment. There is an urgent need for research to improve the function of the human immune system all over the world. As a result, actions for better understanding and improving the human immune system are critical steps toward mitigating risks and negative outcomes. These approaches will be strongly recommended for future emerging viruses and pathogens.

Similar to other causes of acute respiratory distress syndrome, coronavirus disease 2019 (COVID-19) is characterized by the aberrant expression of vascular injury biomarkers. We present the first report that circulating plasma bone morphogenetic proteins (BMPs), BMP9 and pBMP10, involved in vascular protection, are reduced in hospitalized patients with COVID-19.

The respiratory tract is one of the frontline barriers for biological defense. Lung epithelial intercellular adhesions provide protection from bacterial and viral infections, and prevent invasion into deep tissues by pathogens. Dysfunction of lung epithelial intercellular adhesion caused by pathogens is associated with development of several diseases, such as acute respiratory distress syndrome (ARDS), pneumonia, and asthma. To elucidate the pathological mechanism of respiratory infections, two-dimensional cell cultures and animal models are commonly used, though are not useful for evaluating host specificity or human biological response. With the rapid progression and worldwide spread of severe acute respiratory syndrome coronavirus-2, there is increasing interest in the development of a 3D in vitro lung model for analyzing interactions between pathogens and hosts. However, some models possess unclear epithelial polarity or insufficient barrier functions, and need the use of complex technologies, have high cost, and long cultivation terms. We previously reported about the fabrication of 3D cellular multilayers using a layer-by-layer (LbL) cell coating technique with extracellular matrix protein, fibronectin (FN), and gelatin (G). In the present study, such an LbL cell coating technique was utilized to construct a human 3D lung model in which a monolayer of the human lower airway epithelial adenocarcinoma cell line Calu-3 cells was placed on 3D-cellular multilayers composed of FN-G-coated human primary pulmonary fibroblast cells. The 3D lung model thus constructed demonstrated an epithelial-fibroblast layer that maintained uniform thickness until seven days of incubation. Moreover, expressions of E-cadherin, ZO-1, and mucin in the epithelial layer were observed by immunohistochemical staining. Epithelial barrier integrity was evaluated using transepithelial electrical resistance values. The results indicate that the present constructed human 3D lung model is similar to human lung tissues, and also features epithelial polarity and a barrier function, thus is considered useful for evaluating infection and pathological mechanisms related to pneumonia and several pathogens.