Can ACE2 expression explain SARS-CoV-2 infection of the respiratory epithelia in COVID-19?

Infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) leads to coronavirus disease 2019 (COVID‐19), which poses an unprecedented worldwide health crisis, and has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The angiotensin converting enzyme 2 (ACE2) has been suggested to be the key protein used by SARS‐CoV‐2 for host cell entry. In their recent work, Lindskog and colleagues (Hikmet et al, 2020) report that ACE2 is expressed at very low protein levels—if at all—in respiratory epithelial cells. Severe COVID‐19, however, is characterized by acute respiratory distress syndrome and extensive damage to the alveoli in the lung parenchyma. Then, what is the role of the airway epithelium in the early stages of COVID‐19, and which cells need to be studied to characterize the biological mechanisms responsible for the progression to severe disease after initial infection by the novel coronavirus

Airways inflammation and treatment during acute exacerbations of COPD

INTRODUCTION: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation. OBJECTIVES: To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations. To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations. To speculate on future therapeutic options to modify inflammation during COPD exacerbations. RESULTS: During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes. Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive. CONCLUSION: Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations. This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects

A case report of an unusual non-mucinous papillary variant of CPAM type 1 with KRAS mutations

BACKGROUND: congenital pulmonary airway malformation (CPAM) is the most frequent congenital lung disorder. CPAM type 1 is the most common subtype, typically having a cystic radiological and histological appearance. Mucinous clusters in CPAM type 1 have been identified as premalignant precursors for mucinous adenocarcinoma. These mucinous adenocarcinomas and the mucinous clusters in CPAM commonly harbor a specific KRAS mutation. CASE PRESENTATION: we present a case of a 6-weeks-old girl with CPAM type 1 where evaluation after lobectomy revealed a highly unusual complex non-mucinous papillary architecture in all cystic parts, in which both mucinous clusters and non-mucinous papillary areas harbored the known KRAS mutation. CONCLUSIONS: we found that a KRAS mutation thought to be premalignant in mucinous clusters only, was also present in the other cyst lining epithelial cells of this unusual non-mucinous papillary variant of CPAM type 1, warranting clinical follow-up because of uncertain malignant potential

Recent advances in chronic obstructive pulmonary disease pathogenesis : from disease mechanisms to precision medicine

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease with a high personal and societal burden. Exposure to toxic particles and gases, including cigarette smoke, is the main risk factor for COPD. Together with smoking cessation, current treatment strategies of COPD aim to improve symptoms and prevent exacerbations, but there is no disease-modifying treatment. The biggest drawback of today's COPD treatment regimen is the 'one size fits all' pharmacological intervention, mainly based on disease severity and symptoms and not the individual's disease pathology. To halt the worrying increase in the burden of COPD, disease management needs to be advanced with a focus on personalized treatment. The main pathological feature of COPD includes a chronic and abnormal inflammatory response within the lungs, which results in airway and alveolar changes in the lung as reflected by (small) airways disease and emphysema. Here we discuss recent developments related to the abnormal inflammatory response, ECM and age-related changes, structural changes in the small airways and the role of sex-related differences, which are all relevant to explain the individual differences in the disease pathology of COPD and improve disease endotyping. Furthermore, we will discuss the most recent developments of new treatment strategies using biologicals to target specific pathological features or disease endotypes of COPD. (c) 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Removal of a giant intrathoracic cyst from the anterior mediastinum

A 45-year-old caucasian man with progressive dyspnea appeared to have a giant intrathoracic cyst in the anterior mediastinum encasing the heart and compressing both lungs. He underwent succesful removal of the cyst through a median sternotomy. Recovery was uneventful. Gross examination revealed a thin-walled cyst filled with clear fluid. Microscopic histopathologic examination revealed a cyst wall lined by cubic cells and underlying loose connective tissue with remnants of thymic tissue. The definitive diagnosis was an intrathoracic (simple) mesothelial cyst. An intrathoracic mesothelial cyst is a benign, generally asymptomatic tumor that can be located in the anterior cardiophrenic angle, the paravertebral or paratracheal regions, or in the anterior mediastinum. It can become rather large before it becomes symptomatic, at which point surgical removal is generally warranted

Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD

Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide. In the context of disease pathogenesis, both asthma and COPD involve chronic inflammation of the lung and are characterised by the abnormal release of inflammatory cytokines, dysregulated immune cell activity and remodelling of the airways. To date, current treatments still only manage symptoms and do not reverse the primary disease processes. In recent work, interleukin (IL)-1α and IL-1β have been suggested to play important roles in both asthma and COPD. In this review, we summarise overwhelming pre-clinical evidence for dysregulated signalling of IL-1α and IL-1β contributing to disease pathogenesis and discuss the paradox of IL-1 therapeutic studies in asthma and COPD. This is particularly important given recent completed and ongoing clinical trials with IL-1 biologics that have had varying degrees of failure and success as therapeutics for disease modification in asthma and COPD

Sarcoidosis presenting with glazy mucoid sputum and dyspnea:a case report

BACKGROUND: Patients with pulmonary sarcoidosis commonly present with a dry cough; a productive cough suggests a complicating airway infection or an alternative diagnosis such as tuberculosis or bronchiectasis. CASE PRESENTATION: A 36-year-old European (Frisian) woman recently diagnosed with pulmonary sarcoidosis presented with debilitating exertional dyspnea and cough productive of glazy mucoid sputum. Several different attempts including video-assisted thoracoscopic biopsies failed to reach a second or alternative diagnosis including an infectious, autoimmune or collagen-vascular condition. She responded to steroids but with poor tolerance to this treatment, which could not be tapered. After she was started on anti-tumor necrosis factor alpha (TNF-α) therapy with infliximab, 200 mg at three-monthly intervals, she has been fine for well over a decade. CONCLUSIONS: In this patient with sarcoidosis who had a productive cough accompanied by fever, an extensive workup and prolonged follow-up, an alternative or second diagnosis could be ruled out; we therefore conclude that this highly unusual presentation is part of the clinical spectrum of sarcoidosis