Eculizumab in patients with severe coronavirus disease 2019 (COVID-19) requiring continuous positive airway pressure ventilator support: Retrospective cohort study

Background Complement activation contributes to lung dysfunction in coronavirus disease 2019 (COVID-19). We assessed whether C5 blockade with eculizumab could improve disease outcome. Methods In this single-centre, academic, unblinded study two 900 mg eculizumab doses were added-on standard therapy in ten COVID-19 patients admitted from February 2020 to April 2020 and receiving Continuous-Positive-Airway-Pressure (CPAP) ventilator support from ≤24 hours. We compared their outcomes with those of 65 contemporary similar controls. Primary outcome was respiratory rate at one week of ventilator support. Secondary outcomes included the combined endpoint of mortality and discharge with chronic complications. Results Baseline characteristics of eculizumab-treated patients and controls were similar. At baseline, sC5b-9 levels, ex vivo C5b-9 and thrombi deposition were increased. Ex vivo tests normalised in eculizumab-treated patients, but not in controls. In eculizumab-treated patients respiratory rate decreased from 26.8±7.3 breaths/min at baseline to 20.3±3.8 and 18.0±4.8 breaths/min at one and two weeks, respectively (p<0.05 for both), but did not change in controls. Between-group changes differed significantly at both time-points (p<0.01). Changes in respiratory rate correlated with concomitant changes in ex vivo C5b-9 deposits at one (rs = 0.706, p = 0.010) and two (rs = 0.751, p = 0.032) weeks. Over a median (IQR) period of 47.0 (14.0–121.0) days, four eculizumab-treated patients died or had chronic complications versus 52 controls [HRCrude (95% CI): 0.26 (0.09–0.72), p = 0.010]. Between-group difference was significant even after adjustment for age, sex and baseline serum creatinine [HRAdjusted (95% CI): 0.30 (0.10–0.84), p = 0.023]. Six patients and 13 controls were discharged without complications [HRCrude (95% CI): 2.88 (1.08–7.70), p = 0.035]. Eculizumab was tolerated well. The main study limitations were the relatively small sample size and the non-randomised design. Conclusions In patients with severe COVID-19, eculizumab safely improved respiratory dysfunction and decreased the combined endpoint of mortality and discharge with chronic complications. Findings need confirmation in randomised controlled trials.

Pesticides Use and Impaired Lung Function Among Male Agricultural Farmers in Rural Sindh, Pakistan

Use of pesticides implicated in decrement in lung function, manifested as restrictive or obstructive dysfunction or both. Using comparative cross-sectional study design, authors conducted the study to determine an association of pesticide use with impairment in lung function (restrictive/obstructive pattern of lung function) among agricultural farmers. The data were collected using modified American Thoracic Society Division of Lung Disease (ATS-DLD-78A) questionnaire and spirometer measurements. Using multinomial logistic regression, the risk of both restrictive and obstructive lung dysfunction was found to be almost twice among pesticides users with each increasing year of exposure to pesticides (1.92 and 1.95, respectively) after adjusting for other covariates. There is a need for reliable monitoring and reporting procedures along with appropriate environmental policies and regulations for handling of pesticides. Interventional studies are needed where farmers could be trained on the proper use of personal protective equipment (PPE) to limit the exposure to pesticides.

Diagnostic Overview of COVID-19 Patients with Comorbid Type 2 Diabetes Mellitus at Royal Prima General Hospital Medan in 2020

COVID-19 is a disease caused by infection with a coronavirus known as SARS-CoV-2. COVID-19 patients with diabetes have a poor prognosis and thus have a shorter life expectancy than those without diabetes. This is because COVID-19 causes severe lung dysfunction and inflammation. The purpose of the study is to find out the description of diagnostic of COVID-19 patients with comorbid diabetes mellitus type 2 at Royal Prima general hospital Medan in 2020. The case study design method is descriptive with a retrospective approach, the sample size of 63 patient medical records is taken by purposive sampling, a complete medical record and analyzed with descriptive statistics. Most patients were aged more than 50 years old (66.7%) and female (50.8%). With symptoms of fever (84.1%), cough (87.3%), shortness of breath (87.3%), headache (28.6%), diarrhea (9.5%), nausea (42.9%), abdominal pain (31.7%), loss of smell (20.6%). The longest hospitalization time (11-20 days) (46%). It can be concluded that the most age is > 50 years, the most gender is female and the most clinical symptoms are cough and shortness of breath.

Reduced Lung Function and Progression to Prediabetes: A Prospective Study

Objective: Prediabetes is a state that people have blood glucose levels higher than normal but still not in diabetes range. There is a close relationship between impaired lung function and diabetes mellitus (DM). Reduced lung function can be present before the clinical evidence of diabetes or insulin resistance. Materials and Methods: The total number of subjects in this longitudinal study was 503 and compared with apparently healthy Kashmiri adults. All the subjects, at the time of their first visit, underwent Fasting Plasma Glucose (FPG) estimation, 2- hour oral glucose tolerance test (OGTT) and spirometry (FVC, FEV1 & FEV1/FVC). Those subjects who had normal glucose tolerance (NGT) were retested for glycemic status and spirometric values after a follow-up period of 2-18 (mean=10) months. Results: Out of total 503 subjects on follow up 483 (96%) had NGT and 20 (4%) had prediabetes. Percent predicted forced vital capacity (FVC) and % predicted forced expiratory volume in 1st second (FEV1) were significantly lower (P-value< 0.001) while as % predicted FEV1/FVC was significantly higher (P-value< 0.001) in prediabetes as compared to NGT group. Conclusion: Results of our study point out a predominantly restrictive pattern of lung dysfunction in the prediabetes group as compared to the NGT group.

Isolation of Mitochondria From Fresh Mice Lung Tissue

Direct analysis of isolated mitochondria enables a better understanding of lung dysfunction. Despite well-defined mitochondrial isolation protocols applicable to other tissues, such as the brain, kidney, heart, and liver, a robust and reproductive protocol has not yet been advanced for the lung. We describe a protocol for the isolation of mitochondria from lung tissue aiming for functional analyses of mitochondrial O2 consumption, transmembrane potential, reactive oxygen species (ROS) formation, ATP production, and swelling. We compared our protocol to that used for heart mitochondrial function that is well-established in the literature, and achieved similar results.

Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice

Human ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host’s organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction. In this study, we investigated the relationship between SIgA levels and eosinophils. We found that TLR2 and TLR4 signaling induces eosinophils and promotes SIgA production during Ascaris suum infection. Therefore, control of parasite burden during the pulmonary phase of ascariasis involves eosinophil influx and subsequent promotion of SIgA levels. In addition, we also demonstrate that eosinophils also participate in the process of tissue remodeling after lung injury caused by larval migration, contributing to pulmonary fibrosis and dysfunction in re-infected mice. In conclusion, we postulate that eosinophils play a central role in mediating host innate and humoral immune responses by controlling parasite burden, tissue inflammation, and remodeling during Ascaris suum infection. Furthermore, we suggest that the use of probiotics can induce eosinophilia and SIgA production and contribute to controlling parasite burden and morbidity of helminthic diseases with pulmonary cycles.

Breath exosomes: Proteomics and functional enrichment analysis in the development of methodology for future diagnostic devices.

<p><b>Exosomes are a type of extracellular vesicle that carry cargo, including proteins and nucleic acids, that reports on the conditions of their cell of origin. Exosomes can be isolated from a range of biological fluids, including blood and urine, and their use in clinical diagnostic applications has been extensively researched. Breath is an excellent source of biomarkers. Exosomes collected from exhaled breath concentrate offer untapped potential in the field. For example, exosomes secreted from the cells of the lung carry biomarkers of lung health and so report selectively on lung health. However, whilst several publications report the presence of breath exosomes, and some discuss potential applications, there is no published work on developing standardized procedures for isolating high purity exosomes for biomarker identification, nor have breath exosomes been extensively characterized. Studying exosomes can potentially increase the specificity of diagnosis with an ultimate goal to translate early diagnosis into early treatment.</b></p> <p>In this study we report results of optimized methodology for isolation of exosomes from human breath and undertaken phenotyping of breath exosomes by comparing them to cell-derived exosomes. Determining the benchmark proteome of breath exosomes became the major achievement of this study. The proteome profile of breath-derived exosomes was identified for the first time from exosomes obtained from the breath of 55 healthy volunteers indicating that the protein cargo of cell- and breath-derived exosomes are somewhat similar. The results of this study suggest that the exosomal breath proteome may be used in future studies identifying new biomarkers of lung dysfunction, including lung cancer. The possibility of identifying putative lung cancer biomarkers was shown using exosomes isolated from the lung cancer cell model (A549), from which four candidates were selected and examined. Promising results from time-resolved studies concluded that a FRET-based assay can be considered as a new way to prove the presence of exosomes and with an ability to differentiate between cancer and normal cells. We foresee the use of exosomes in non-invasive breath-based clinical applications for medical diagnostics for lung cancer as an important future application.</p>

Idiopathic Interstitial Pneumonias: A Review of the Past and Emerging Therapies

Purpose This article is an in-depth review of the complex classification, diagnosis, and treatment of idiopathic interstitial pneumonias (IIP), as well as emergence of new treatment options. Summary Idiopathic interstitial pneumonias consist of various subgroup classifications that require expert analysis of imaging and histology to accurately diagnose this broad group of patients. Timely and accurate assessment of these patients is key in developing an appropriate pharmacological plan. The pathophysiology of IIP is not well understood but has been linked to an immune response resulting in inflammation, fibrosis, or proliferation of lung tissue which reduces lung function. Lung transplantation is currently the only curative option for treatment, but many new antiproliferative and immunosuppressive agents are being used to effectively slow the progression of lung dysfunction. Conclusion An often mixed radiological and histological pattern along with the invasive nature of biopsy for gold standard diagnosis create a challenge for the accurate identification of IIP. Further understanding of these idiopathic interstitial pneumonias will pave the way forward to the emergence of new treatment options and updates to standards of care.

Breath exosomes: Proteomics and functional enrichment analysis in the development of methodology for future diagnostic devices.

<p><b>Exosomes are a type of extracellular vesicle that carry cargo, including proteins and nucleic acids, that reports on the conditions of their cell of origin. Exosomes can be isolated from a range of biological fluids, including blood and urine, and their use in clinical diagnostic applications has been extensively researched. Breath is an excellent source of biomarkers. Exosomes collected from exhaled breath concentrate offer untapped potential in the field. For example, exosomes secreted from the cells of the lung carry biomarkers of lung health and so report selectively on lung health. However, whilst several publications report the presence of breath exosomes, and some discuss potential applications, there is no published work on developing standardized procedures for isolating high purity exosomes for biomarker identification, nor have breath exosomes been extensively characterized. Studying exosomes can potentially increase the specificity of diagnosis with an ultimate goal to translate early diagnosis into early treatment.</b></p> <p>In this study we report results of optimized methodology for isolation of exosomes from human breath and undertaken phenotyping of breath exosomes by comparing them to cell-derived exosomes. Determining the benchmark proteome of breath exosomes became the major achievement of this study. The proteome profile of breath-derived exosomes was identified for the first time from exosomes obtained from the breath of 55 healthy volunteers indicating that the protein cargo of cell- and breath-derived exosomes are somewhat similar. The results of this study suggest that the exosomal breath proteome may be used in future studies identifying new biomarkers of lung dysfunction, including lung cancer. The possibility of identifying putative lung cancer biomarkers was shown using exosomes isolated from the lung cancer cell model (A549), from which four candidates were selected and examined. Promising results from time-resolved studies concluded that a FRET-based assay can be considered as a new way to prove the presence of exosomes and with an ability to differentiate between cancer and normal cells. We foresee the use of exosomes in non-invasive breath-based clinical applications for medical diagnostics for lung cancer as an important future application.</p>