EBioMedicine

RationaleExtracellular vesicles (EVs) have emerged as important mediators in cell-cell communication and disease pathogenesis; however, their relevance in pulmonary hypertension (PH) secondary to HIV infection is yet to be explored. ObjectiveTo examine the role of circulating small EVs and monocyte-derived macrophage (MDM) EVs in the development of HIV-associated PH MethodsEVs isolated from plasma of HIV-infected drug users and non-users with/without PH and from supernatants of HIV-infected MD...

RationalePulmonary hypertension associated with bronchopulmonary dysplasia is a severe complication of preterm birth resulting in high mortality of up to 50% within the first 2 years of life. There is a direct relationship between bronchopulmonary dysplasia severity and incidence of associated pulmonary hypertension. However, it is challenging to clinically characterize severe bronchopulmonary dysplasia with and without pulmonary hypertension and there is need for better understanding of the two...

Pneumonia is the leading infectious disease killer worldwide and commonly requires admission to critical care. Despite its prevalence, the underpinning biology of severe pneumonia remains incompletely understood. We performed multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically dissect a cohort of patients with suspected severe pneumonia. Our data revealed three lung-restricted transcriptionally defined severe pneumonia endotyp...

COVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombo...

SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or pa...

Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection in patients with Coronavirus Disease 2019 (COVID-19) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage (DAD), excess inflammation, pneumocyte hyperplasia and proliferation, and formation of platelet aggregates or thromboemboli. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cel...

BackgroundPathogenesis of Coronavirus disease 2019 (Covid-19) is poorly understood. Most histologic studies come from post-mortem analysis, with existing data indicating that histologic features of acute respiratory distress syndrome are typically present in fatal cases. However, this observation may be misleading, due to confounding factors in pre-terminal disease, including injury resulting from prolonged mechanical ventilation. Ante-mortem lung biopsy may provide major pathogenetic insights, ...

Mucus plugging leading to airway obstruction is a hallmark of chronic respiratory diseases, yet the biology of plugs and their contribution to airway inflammation remain poorly defined. Through guided retrieval and analysis of plugs from patients with allergic bronchopulmonary aspergillosis, we identify Charcot-Leyden crystals that are formed from eosinophil-derived Galectin-10 as ubiquitous and mechanistic components that generate highly localized type 2 inflammatory niches. These niches exhibi...

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fibrotic lung disorder of unknown cause, affecting about three million people worldwide. Being a multifactorial disease, complex genetic and environmental factors contribute to its susceptibility. Therefore, we conducted a two-staged systematic literature search and meta-analyses of published genetic association studies on IPF. MethodsThe first search was performed using PubMed and Web of Science, retrieving a total of 5642 articles, of which 5...

Cardiovascular disease (CVD) is a serious worldwide health concern that necessitates the development of novel diagnostic techniques for early identification and personalized healthcare management. Even before the insights provided by gut microbiota, current research has demonstrated the importance of circulating microbiome (CMB) in the evolution of cardiometabolic illness risk and progression. We developed a nanobiosensor that uses specific labeled capture probes with perovskite quantum dots (PQ...

Uncontrolled airway mucus is associated with diverse diseases. We hypothesized that the physical characteristics of infiltrating granulocytes themselves affect the clinical properties of mucus. Surgically obtained nasal mucus from patients with eosinophilic chronic rhinosinusitis (ECRS) and neutrophil-dominant non-eosinophilic chronic rhinosinusitis (non-ECRS) was assessed in terms of computed tomography (CT) density, viscosity, water content, wettability, and granulocyte-specific proteins. In a...

BackgroundPrevious studies indicate a protective role for SARS-CoV-2 vaccination against development of pulmonary post-acute sequelae of COVID (PASC). We compared clinical, imaging, histopathology and ultrastructural features of pulmonary PASC with and without prior vaccination in a consecutive cohort of 54 unvaccinated, 17 partially vaccinated and 28 fully vaccinated patients who presented with dyspnea on exertion after mild COVID-19 (without hospitalization). MethodsPatients underwent full cl...

We detected active alveolar regrowth in the lung of a 58-year-old COVID-19 patient who underwent lung transplantation due to severe lung hemorrhage. Specifically, immunohistological and scanning electronic microscopy analyses revealed that alveolar type II epithelial cells (AT2 cells) accumulate in response to viral pneumonia and that these AT2 cells actively proliferate and differentiate into squamous AT1-like alveolar epithelial cells. Thus, our work establishes that alveolar regrowth does occ...

RationaleNon-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells and mediators causing acute symptoms when driving the hypersensitivity reaction to acetylsalicylic acid (ASA) ingestion, remain poorly defined. ObjectivesTo investigate the dynamics of nasal mediators during ASA provocation in N-ERD patients before and twenty-four weeks after therapy with the IL-4 recep...

The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not would be highly desirable. Coagulaopathies are a common accompaniment to COVID-19, especially micro-clots within the lungs. We show here that microclots can be detected in the native plasma of COVID-19 patient, and in particular that such clots are a...

Prior studies testing biomarkers of residual lung abnormalities after COVID-19 are limited by sampling within the first year after acute COVID-19 illness and lack of external validation of findings. In three independent, international, racially and ethnically diverse prospective cohorts of survivors of moderate to critical COVID-19, we systematically tested 18 circulating biomarkers of inflammation, aging, endothelial activation, pulmonary epithelial function, fibrosis, and fibrinolysis. We foun...

SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in ac...

PurposePneumoconiosis is characterized by pulmonary fibrosis. The activation of fibroblasts play an important role in the pathological development of pulmonary fibrosis. Chest CT, as a conventional examination to diagnose pulmonary fibrosis of pneumoconiosis, cannot evaluate the fibrosis activity. The application value of 18F-FAPI in pneumoconiosis is unclear. This study aimed to clarify the feasibility of 18F-FAPI PET/CT in non-invasively monitoring the activity evolution of pulmonary fibrosis ...

BackgroundWomen with SLE have an elevated risk of cardiovascular disease. Many women with SLE frequently report chest pain in the absence of obstructive coronary artery disease (CAD) due to coronary microvascular dysfunction (CMD), a form of ischemia with no obstructive CAD. Echocardiographic studies have shown that SLE patients have reduced left ventricular (LV) function, which may also correlate with higher SLE disease activity scores. As such, we used cardiac magnetic resonance imaging (cMRI)...

The current trend in cardio-oncology places major emphasis on circulatory toxicity induced by cancer therapy. Whether malignancy itself is a direct contributing factor to cardiovascular dysfunctions and baroreflex dysregulation in patients with cancer, however, has rarely appeared in literature. The present study addressed this largely overlooked aspect of cardio-oncology by evaluating blood pressure, heart rate and baroreflex functionality before and after curative surgery in patients with oral...