Streptococcus pneumoniae is a major cause of community-acquired pneumonia and death from infectious diseases in industrialized countries. Lung airway and alveolar epithelial cells comprise an important barrier against airborne pathogens. Cyclooxygenase (COX)-derived prostaglandins, such as PGE(2), are considered to be important regulators of lung function. Herein, we tested the hypothesis that pneumococci induced COX-2-dependent PGE(2) production in pulmonary epithelial cells. Pneumococci-infected human pulmonary epithelial BEAS-2B cells released PGE(2). Expression of COX-2 but not COX-1 was dose and time dependently increased in S. pneumoniae-infected BEAS-2B cells as well as in lungs of mice with pneumococcal pneumonia. S. pneumoniae induced degradation of IkappaBalpha and DNA binding of NF-kappaB. A specific peptide inhibitor of the IkappaBalpha kinase complex blocked pneumococci-induced PGE(2) release and COX-2 expression. In addition, we noted activation of p38 MAPK and JNK in pneumococci-infected BEAS-2B cells. PGE(2) release and COX-2 expression were reduced by p38 MAPK inhibitor SB-202190 but not by JNK inhibitor SP-600125. We analyzed interaction of kinase pathways and NF-kappaB activation: dominant-negative mutants of p38 MAPK isoforms alpha, beta(2), gamma, and delta blocked S. pneumoniae-induced NF-kappaB activation. In addition, recruitment of NF-kappaB subunit p65/RelA and RNA polymerase II to the cox2 promoter depended on p38 MAPK but not on JNK activity. In summary, p38 MAPK- and NF-kappaB-controlled COX-2 expression and subsequent PGE(2) release by lung epithelial cells may contribute significantly to the host response in pneumococcal pneumonia.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently discovered coronavirus which has caused a global outbreak of severe pneumonia with complications leading to hypoxic respiratory failure, acute respiratory distress syndrome (ARDS), cytokine storm, disseminated intravascular coagulation (DIC), and even gastrointestinal symptoms. While ground-glass opacity (GGO) is a typical radiographic finding associated most frequently with COVID-19 pneumonia, other less commonly noted atypical radiographic lung features include isolated lobar or segmental consolidation without GGO, discrete small nodules (centrilobular, “tree-in-bud”), lung cavitation, and smooth interlobular septal thickening with pleural effusion. Pneumomediastinum in COVID-19 patients has rarely been reported. A finding of pneumopericardium is unusual too. This report discusses the case of a young male with COVID-19 pneumonia who was found to have both these features on computed tomographic (CT) scans of his chest on presentation.
Vaping’s popularity has grown exponentially since its introduction to the US market in 2003. Its use has sky-rocketed since the unveiling of the vaping pods in 2017 which may account for the advent of the vaping related illnesses we are now seeing. Substances such as nicotine solution, tetrahydrocannabinol (THC) oil, cannabidiol (CBD) oil, and butane hash oil (BHC) packaged in cartridges available in various flavors and concentrations are aerosolized by the heating of metal coils in the e-cigarette/vaping devices. Cases from all over the country have recently been coming to light in which vaping has led to severe acute pulmonary disease or vaping-associated-pulmonary-injury (VAPI). A vast majority of the presenting patients in the reported cases have required hospitalization and intensive care, needing supplemental oxygen and even endotracheal intubation and mechanical ventilation. 98% of patients present with respiratory symptoms (dyspnea, hypoxia, chest pain, cough, hemoptysis), 81% of patients have gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), and 100% of patients have constitutional symptoms such as fever, chills, and fatigue/malaise on presentation. Although based on history and clinical presentation it is reasonable to have a high suspicion for VAPI, diagnostic workup to rule out alternative underlying causes such as infection, malignancy, or autoimmune process should be performed before establishing the diagnosis. Computed Tomography (CT) scans of the chest have predominantly shown ground-glass opacity in the lungs, often with areas of lobular or subpleural sparing. Although lung biopsies have been performed on a relatively low number of cases, lung injury patterns so far have shown acute fibrinous pneumonitis, diffuse alveolar hemorrhage, or organizing pneumonia, usually bronchiolocentric, and accompanied by bronchiolitis. Treatment plans that have led to clinical improvement in the reported cases center around high-dose systemic steroids, although there are a lack of data regarding the best regimen and the absolute need for corticosteroids. The role of antibiotics appears to be limited once infection has definitively been ruled out. We present the case of a young male who vaped THC oil and developed severe acute pulmonary injury requiring mechanical ventilation and showed a remarkable response to high dose steroid therapy with improvement in clinical symptoms and resolution of diffuse ground glass opacity on repeat HRCT scan.
BACKGROUND: A procalcitonin (PCT) level is commonly ordered to distinguish between bacterial and viral etiologies of lower respiratory tract infections as it is typically negative in the absence of inflammatory conditions and bacterial infections. With COVID-19 causing an influx of patients presenting with respiratory symptoms, clinicians are in need of useful tools to guide management of these patients. Given the inflammation that is caused by COVID-19, it is currently unknown whether PCT continues to be a reliable or useful test in suspected and confirmed cases of COVID-19 pneumonia. OBJECTIVE: To determine whether PCT remains a clinically useful test in patients who present with lower respiratory tract symptoms in the era of COVID-19. DESIGN: Single-center retrospective cohort studyPARTICIPANTS: 243 adults with lower respiratory tract symptoms who presented to the hospital through the emergency department between April 11, 2020 and May 18, 2020 who received both a COVID-19 test as well as a PCT level. MAIN MEASURES: COVID-19 positivity/negative, PCT level KEY RESULTS: It was found that patients with COVID-19 consistently had negative procalcitonin levels (<0.25ng/mL). Based on the odds ratio, a patient with a positive PCT level was 3.4 times more likely to test negative for COVID than a patient with a PCT level <0.25ng/mL. (1)=13.895, p<0.001. CONCLUSIONS: There is a highly significant association between a negative procalcitonin and positive COVID-19 infection, thus supporting the continued use of PCT in the COVID-19 era.
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