Asthma Associated Cytokines Regulate the Expression of SARS-CoV-2 Receptor ACE2 in the Lung Tissue of Asthmatic Patients

It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.

C-Arm Cone-Beam CT Virtual Navigation Versus Conventional CT Guidance in the Transthoracic Lung Biopsy: A Case-Control Study

C-arm cone-beam computed tomography (CBCT) virtual navigation-guided lung biopsy has been developed in the last decade as an alternative to conventional CT-guided lung biopsy. This study aims to compare the biopsy accuracy and safety between these two techniques and explores the risk factors of biopsy-related complications. A total of 217 consecutive patients undergoing conventional CT- or C-arm CBCT virtual navigation-guided lung biopsy from 1 June 2018 to 31 December 2019 in this single-center were retrospectively reviewed. Multiple factors (e.g., prior emphysema, lesion size, etc.) were compared between two biopsy techniques. The risk factors of complications were explored by using logistic regression. The patients’ median age and male-to-female ratio were 63 years and 2.1:1, respectively. Eighty-two (82) patients (37.8%) underwent conventional CT-guided biopsies, and the other 135 patients (62.2%) C-arm CBCT virtual navigation-guided biopsies. Compared with patients undergoing C-arm CBCT virtual navigation-guided lung biopsies, patients undergoing conventional CT-guided lung biopsies showed higher needle repositioning rate, longer operation time, and higher effective dose of X-ray (52.4% vs. 6.7%, 25 min vs. 15 min, and 13.4 mSv vs. 7.6 mSv, respectively; p < 0.001, each). In total, the accurate biopsy was achieved in 215 of 217 patients (99.1%), without a significant difference between the two biopsy techniques (p = 1.000). The overall complication rates, including pneumothorax and pulmonary hemorrhage/hemoptysis, are 26.3% (57/217), with most minor complications (56/57, 98.2%). The needle repositioning was the only independent risk factor of complications with an odds ratio of 6.169 (p < 0.001). In conclusion, the C-arm CBCT virtual navigation is better in percutaneous lung biopsy than conventional CT guidance, facilitating needle positioning and reducing radiation exposure. Needle repositioning should be avoided because it brings about more biopsy-related complications.

Preventive tract embolization with gelatin sponge slurry is safe and considerably reduces pneumothorax after CT-guided lung biopsy with use of large 16–18 coaxial needles

Objective: To evaluate the clinical impact of the tract embolization technique using gelatin sponge slurry after percutaneous CT-guided lung biopsy. Methods: We retrospectively compared coaxial needle CT-guided lung biopsies performed without embolization (100 patients) and with the tract embolization technique using a mixture of iodine and gelatin sponge slurry (105 patients) between June 2012 and July 2020. Uni- and multivariate analyses were performed between groups to determine risk factors of pneumothorax. Results: Patients with gelatin sponge slurry tract embolization had statistically lower rates of pneumothorax ((17.1% vs 39%, p < 0.001). In univariate analysis, tract embolization (OR = 0.32, CI = 0.17–0.61 p<0.001) and nodule size >2 cm (OR = 0.33 CI = 0.14–0.8 p = 0.013) had a protective effect on pneumothorax. The puncture path lengths > 2–20 mm and >20 mm were risk factors for pneumothorax (OR = 3.35 IC = 1.44–8.21 p = 0.006 and OR = 4.36 CI = 1.98–10.29 p<0.001, respectively). In multivariate regression analysis, tract embolization had a protective effect of pneumothorax (OR = 0.25, CI = 0.12–0.51, p < 0.001). The puncture path lengths > 2–20 mm and >20 mm were risk factors for pneumothorax (p = 0.030 and p = 0.002, respectively). Conclusions: The tract embolization technique using iodinated gelatin sponge slurry is safe and considerably reduces pneumothorax after percutaneous CT-guided lung biopsy. Our results suggest that it could be use in clinical routine. Advances in knowledge: The systemic use of gelatin sponge slurry is safe and reduces considerably the rate of pneumothorax upon needle removal when CT-guided core biopsies are performed using large 16–18G coaxial needles.

The Impact of Microplastic on Human Health

Background: Microplastics are considered an emerging contaminant due to their wide distribution and production in the environment, representing constant exposure to humans. However, little is known about the effects it can trigger in the body. Objective: To establish a concrete relationship between microplastics and the human body, their means of production, exposure, systemic responses, and diseases caused by their presence Methods: In this context, a review article of foreign and national literature was developed, through the PubMed and Scielo Indexers, where studies were found that address the production of plastic, the paths that lead to the production of microplastics and the exposure and damage that it represents to human health, being possible to exclude the literary sums with a publication date before 2017 Results: hey showed that translocation of the residues occurs to the circulatory and lymphatic system via the respiratory and gastrointestinal tracts. Once in the body, microplastic can stimulate a chronic inflammatory response that functions as a precursor to neoplasia and fibrosis, or carry toxic compounds such as heavy metals, endogenous disruptors, biofilms, and persistent organic pollutants. In addition, lung biopsies have shown plastic fibers in patients with respiratory diseases, highlighting a potentially dangerous accumulation. Conclusion: The present moment demonstrates that experimental research to prove the effect of microplastics is extremely necessary, since the controversy among authors and the repetition of information already described affirm that the research done so far is not sufficient.

Optimization of the Lung Biopsy Procedure: A Primer

Image-guided lung biopsy plays a very important role in the diagnosis and management of lung lesions. As a diagnostic tool, it demands a high diagnostic yield and a low complication rate. It is imperative to balance the diagnostic yield and patient safety during lung biopsies. The aim of this article is to review the standard practice guidelines of lung biopsy, to describe the techniques used to minimize the complications associated with lung biopsy, and to describe the management of complications.

The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model

Streptococcus pneumoniae (Spn) colonises respiratory epithelia but can also invade lung cells causing pneumonia. We developed an ex vivo model with human airway epithelial (HAE) cells harvested from lung biopsies to study Spn colonisation and translocation. Flow-cytometry, confocal imaging and electron microscopy studies identified the epithelial lineage with signs of differentiation (beating cilia, mucus, and tight junctions). HAE cells were challenged with Spn wild-type TIGR4 (wtSpn) or its isogenic ΔcomC quorum sensing-deficient mutant. ΔcomC mutant colonised significantly less than wtSpn at 6 h post-inoculation but at significantly higher levels at 19 h and 30 h. Translocation correlated inversely with colonisation density. Transepithelial electric resistance (TEER) decreased after pneumococcal infection and correlated with increased translocation for both strains. Confocal imaging illustrated colocalisation of intracellular Spn with both cilia and zonulin-1 and prominent microcolony formation with wtSpn but disintegration of microcolony structures over time with ΔcomC mutant. ΔcomC caused a more pronounced release of both zonulin-1 and lactate dehydrogenase into the supernatant at later time points than wtSpn, suggesting that cytotoxicity is likely not the mechanism leading to translocation. There was a density- and time-dependent increase of inflammatory cytokines from human HAE cells infected with ΔcomC compared with wtSpn, including increased levels of the NLRP3 inflammasome-related IL-18. In conclusion, our experiments indicate that ComC system allows a higher organisational level of population structure resulting in microcolony formation, increased early colonisation and subsequent translocation. We propose that ComC inactivation unleashes a very different and possibly more virulent phenotype that merits further investigation.

Transthoracic lung biopsy for pulmonary nodules ≤20mm in the routine clinical care

BACKGROUNDComputed tomography (CT) screening has improved lung cancer survival, yet increasingly detected small lung lesions. The number of transthoracic lung biopsies (TTLB) for small nodules is thus expected to rise significantly.RESEARCH QUESTIONTo evaluate the diagnostic accuracy and safety of CT-guided TTLB for nodules ≤20 mm versus nodules >20mm.STUDY DESIGN AND METHODSData for CT-guided TTLBs from 474 consecutive patients were prospectively collected over a 3-year period (198 lesions ≤20 mm and 276 lesions >20 mm) in a teaching hospital and analysed in terms of diagnostic performance and complications.RESULTSThere were more conclusive biopsies in the >20 mm lesion group (n=236; 85.5%) than in ≤20 mm lesion group (n=140; 70.7%; p<0.001). The overall accuracy, sensitivity, specificity, and negative predictive value for diagnosing malignant lesions after first TTLB were 88.4%, 84%, 100%, and 70.1% for ≤20 mm lesions and 94.2%, 93%, 100%, and 74.6% for >20 mm lesions, respectively. Pneumothorax requiring drainage was significantly more common for ≤20 mm lesions, compared to TTLB of larger lesions (9.6% versus 4.3%; p=0.02). Prolonged hospital stay due to pneumothorax occurred in 27 (17.4%) TTLBs of ≤20 mm lesions and 15 (7%) TTLBs of >20mm lesions (p=0.002). There were no deaths. The only variable significantly associated with diagnostic failure in the ≤20mm lesion group was the radiologist's experience.INTERPRETATIONTTLBs for lesions ≤20 mm were associated with slightly lower diagnostic performance, whereas the higher rate of major complications was still inferior to that extrapolated from United States insurance databases.

Diagnostic yield of CT-guided lung biopsies: how can we limit negative sampling?

Objectives: To investigate whether lesion imaging features may condition the outcome of CT-guided Lung Biopsy (CTLB) and to develop a scoring system of biopsy outcome prediction. Methods: This is a single center retrospective study on 319 CTLBs that were performed in 319 patients (167 males/ 152 females, mean age 68 ± 12.2). Uni- and multivariate analysis were performed aiming to assess the imaging features that are likely to be corelated to a negative biopsy outcome and patients were stratified in groups accordingly. Results: Technical success was 100%. 78% of the biopsies (250/319) led to a concrete histology report (218 malignant/ 32 benign). The remaining lesions led to concrete histology at a second attempt that occurred on a later time. Multivariate analysis revealed increased risk of inconclusive result for nodules with low FDG uptake (OR = 2.64, 95% CI 1.4–4.97; p = 0.003), for nodules with diameter smaller than 18 mm (OR = 2.03, 95% CI 1.14–3.62; p = 0.017) and for nodules that are located in one of the lung bases (OR = 1.96, 95% CI 1.06–3.62; p = 0.033). Three different groups of patients were identified accordingly with low (<30%), medium (30–50%) and high (>50%) probability of obtaining an inconclusive biopsy sample. Conclusions: This study confirms that percutaneous CT guided biopsy in nodules that are either small in diameter or present low PET-FDG uptake or are in one of the lung bases may lead to inconclusive histology. This information should be factored when planning percutaneous biopsies of such nodules in terms of patient informed consent and biopsy strategy. Advances in knowledge: Inconclusive histology after lung biopsy may be subject to factors irrelevant to technical success. Lung biopsy histology outcomes may be predicted and avoided after adequate planning

Morphological Alterations and Stress Protein Variations in Lung Biopsies Obtained from Autopsies of COVID-19 Subjects

Molecular chaperones, many of which are heat shock proteins, play a role in cell stress response and regulate the immune system in various ways, such as in inflammatory/autoimmune reactions. It would be interesting to study the involvement of these molecules in the damage done to COVID-19-infected lungs. In our study, we performed a histological analysis and an immunomorphological evaluation on lung samples from subjects who succumbed to COVID-19 and subjects who died from other causes. We also assessed Hsp60 and Hsp90 distribution in lung samples to determine their location and post-translational modifications. We found histological alterations that could be considered pathognomonic for COVID-19-related lung disease. Hsp60 and Hsp90 immunopositivity was significantly higher in the COVID-19 group compared to the controls, and immunolocalization was in the plasma membrane of the endothelial cells in COVID-19 subjects. The colocalization ratios for Hsp60/3-nitrotyrosine and Hsp60/acetylate-lisine were significantly increased in the COVID-19 group compared to the control group, similar to the colocalization ratio for Hsp90/acetylate-lisine. The histological and immunohistochemical findings led us to hypothesize that Hsp60 and Hsp90 might have a role in the onset of the thromboembolic phenomena that lead to death in a limited number of subjects affected by COVID-19. Further studies on a larger number of samples obtained from autopsies would allow to confirm these data as well as discover new biomarkers useful in the battle against this disease.

The role of thoracoscopic lung biopsy in the management of children with solid organ malignancies and suspected lung metastases in a developing country

Background Accurate diagnosis of lung lesions appearing on computed tomographic (CT) imaging in children with solid organ malignancies can be difficult. Therefore, this study aimed to determine, in a developing country setting, (1) the utility of thoracoscopic lung biopsy for assessment of suspected lung metastases in solid organ malignancies, and (2) the pathology of biopsied lesions suspected to be malignancies. The electronic records of all patients with solid organ malignancies who underwent thoracoscopic lung biopsies for suspected metastases at a tertiary hospital in South Africa between January 2012 and December 2017 were analysed retrospectively. Results A total of 29 thoracoscopic biopsies were taken from 25 patients. In eight biopsies (27.6%), viable metastatic tumour was identified; in one, a completely necrotic tumour was found. Seven patients (28.0%) were found to have infective aetiologies which required alternative therapies: of these, three patients had tuberculosis; three had bronchopneumonia and one had a fungal lung infection. Other findings included haemorrhagic infarction (n = 1); non-specific fibrosis (n = 1) and reactive lymph node (n = 1). In ten biopsies (34.5%), no lesion was found on thoracoscopy. Conclusions Thoracoscopy was found to improve the management of children with solid organ malignancies and suspected metastases. Thoracoscopy enabled many patients to avoid additional chemotherapy and radiotherapy and its negative consequences and enabled therapy for specific benign pathologies including infections.