Pub Date : 2023-12-04DOI: 10.1101/2023.12.03.23299330
Daniel Gagiannis, Carsten Hackenbroch, Fabian Zech, Frank Kirchhoff, Wilhelm Bloch, Katharina Junghans, Konrad Steinestel
Background: Previous 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). Methods: Patients underwent full clinical evaluation including autoantibody (ANA/ENA) serology, high-resolution computed tomography (HRCT), bronchioloalveolar lavage fluid (BAL) analysis and transbronchial biopsy followed by histopathological and ultrastructural analysis and SARS-CoV-2 immunohistochemistry. Results: While vaccinated patients were younger (p=0.0056), included more active smokers (p=0.0135) and a longer interval since infection (35 vs. 17 weeks, p=0.0002), dyspnea on exertion and impaired lung function were not different between vaccinated and unvaccinated patients. Ground glass opacities in HRCT and centrilobular fibrosis were more frequent in unvaccinated patients (p=0.0154 and p=0.0353), but presence of autoantibodies, BAL lymphocytosis and bronchiolitis were common findings in all groups. While vaccination against SARS-CoV-2 is associated with a longer time span between infection and consultation along with a reduced frequency of ground glass opacities and centrilobular fibrosis, impaired lung function, bronchiolitis and presence of autoantibodies are comparable between vaccinated and unvaccinated patients. Residual virus was not detected in lung tissue in all but 1 patient. Conclusion: While differences between the investigated groups with regard to age, smoking status and SARS-CoV-2 variants have to be taken into account, a proposed protective role of SARS-CoV-2 vaccination against pulmonary PASC is so far not fully explained by clinical and histopathology findings.
背景:以往的研究表明，SARS-CoV-2疫苗对COVID急性后肺部后遗症(PASC)的发展具有保护作用。我们比较了54例未接种疫苗、17例部分接种疫苗和28例完全接种疫苗的肺部PASC患者的临床、影像学、组织病理学和超微结构特征，这些患者在轻度COVID-19(未住院)后运动时出现呼吸困难。方法:对患者进行全面的临床评估，包括自身抗体(ANA/ENA)血清学、高分辨率计算机断层扫描(HRCT)、细支气管肺泡灌洗液(BAL)分析、经支气管活检、组织病理学和超微结构分析以及SARS-CoV-2免疫组织化学。结果:虽然接种疫苗的患者更年轻(p=0.0056)，包括更多的活跃吸烟者(p=0.0135)和较长的感染间隔(35 vs. 17周，p=0.0002)，但接种疫苗和未接种疫苗的患者在运动时呼吸困难和肺功能受损方面没有差异。未接种疫苗的患者HRCT磨玻璃影和小叶中心纤维化更常见(p=0.0154和p=0.0353)，但存在自身抗体、BAL淋巴细胞增多和细支气管炎在所有组中都是常见的发现。虽然接种SARS-CoV-2疫苗与感染和就诊之间的时间间隔较长以及磨玻璃混浊和小叶中心纤维化的频率降低有关，但在接种疫苗和未接种疫苗的患者之间，肺功能受损、细支气管炎和自身抗体的存在是相似的。除1例患者外，其余患者肺组织均未检出病毒残留。结论:虽然研究组之间在年龄、吸烟状况和SARS-CoV-2变异方面的差异必须考虑在内，但SARS-CoV-2疫苗对肺部PASC的保护作用迄今尚未得到临床和组织病理学结果的充分解释。
{"title":"Effect of mRNA vaccination on pulmonary sequelae after mild COVID-19","authors":"Daniel Gagiannis, Carsten Hackenbroch, Fabian Zech, Frank Kirchhoff, Wilhelm Bloch, Katharina Junghans, Konrad Steinestel","doi":"10.1101/2023.12.03.23299330","DOIUrl":"https://doi.org/10.1101/2023.12.03.23299330","url":null,"abstract":"Background: Previous 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). Methods: Patients underwent full clinical evaluation including autoantibody (ANA/ENA) serology, high-resolution computed tomography (HRCT), bronchioloalveolar lavage fluid (BAL) analysis and transbronchial biopsy followed by histopathological and ultrastructural analysis and SARS-CoV-2 immunohistochemistry. Results: While vaccinated patients were younger (p=0.0056), included more active smokers (p=0.0135) and a longer interval since infection (35 vs. 17 weeks, p=0.0002), dyspnea on exertion and impaired lung function were not different between vaccinated and unvaccinated patients. Ground glass opacities in HRCT and centrilobular fibrosis were more frequent in unvaccinated patients (p=0.0154 and p=0.0353), but presence of autoantibodies, BAL lymphocytosis and bronchiolitis were common findings in all groups. While vaccination against SARS-CoV-2 is associated with a longer time span between infection and consultation along with a reduced frequency of ground glass opacities and centrilobular fibrosis, impaired lung function, bronchiolitis and presence of autoantibodies are comparable between vaccinated and unvaccinated patients. Residual virus was not detected in lung tissue in all but 1 patient. Conclusion: While differences between the investigated groups with regard to age, smoking status and SARS-CoV-2 variants have to be taken into account, a proposed protective role of SARS-CoV-2 vaccination against pulmonary PASC is so far not fully explained by clinical and histopathology findings.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":" 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138494248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-02DOI: 10.1101/2023.12.01.23299310
Md. Safiullah Sarker, Rubiyat Jahan
Objective COVID-19 pandemic is a danger for the whole world. Also, our knowledge about acute kidney injury (AKI) in COVID-19 patients is incomplete. Few studies informed that the problem of AKI is a common complication, but other studies concluded that AKI is only an unusual event during COVID-19 infection. This study using meta-analysis tools aimed to find disease progression and mortality risk in affected population.
{"title":"Connecting the Dots: Systematic Exploration of COVID-19 and Acute Kidney Injury through Meta-Analysis","authors":"Md. Safiullah Sarker, Rubiyat Jahan","doi":"10.1101/2023.12.01.23299310","DOIUrl":"https://doi.org/10.1101/2023.12.01.23299310","url":null,"abstract":"<strong>Objective</strong> COVID-19 pandemic is a danger for the whole world. Also, our knowledge about acute kidney injury (AKI) in COVID-19 patients is incomplete. Few studies informed that the problem of AKI is a common complication, but other studies concluded that AKI is only an unusual event during COVID-19 infection. This study using meta-analysis tools aimed to find disease progression and mortality risk in affected population.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":" 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138494249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-30DOI: 10.1101/2023.11.30.23299186
Catalina Lizano-Barrantes, Olatz Garin, Karina Mayoral, Alexandra L. Dima, Angels Pont, M. Araceli Caballero-Rabasco, Manuel Praena-Crespo, Laura Valdesoiro-Navarrete, María Teresa Guerra, Alberto Bercedo-Sanz, Montse Ferrer, the ARCA Group
Introduction We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroids-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma.
{"title":"Impact of Treatment Adherence and Inhalation Technique on asthma outcomes of Pediatric Patients: A Longitudinal Study","authors":"Catalina Lizano-Barrantes, Olatz Garin, Karina Mayoral, Alexandra L. Dima, Angels Pont, M. Araceli Caballero-Rabasco, Manuel Praena-Crespo, Laura Valdesoiro-Navarrete, María Teresa Guerra, Alberto Bercedo-Sanz, Montse Ferrer, the ARCA Group","doi":"10.1101/2023.11.30.23299186","DOIUrl":"https://doi.org/10.1101/2023.11.30.23299186","url":null,"abstract":"<strong>Introduction</strong> We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroids-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"81 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138504278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-30DOI: 10.1101/2023.11.29.23299130
Matt S. Zinter, Christopher C. Dvorak, Madeline Y. Mayday, Gustavo Reyes, Miriam R. Simon, Emma M. Pearce, Hanna Kim, Peter J. Shaw, Courtney M. Rowan, Jeffrey J. Auletta, Paul L. Martin, Kamar Godder, Christine N. Duncan, Nahal R. Lalefar, Erin M. Kreml, Janet R. Hume, Hisham Abdel-Azim, Caitlin Hurley, Geoffrey D.E. Cuvelier, Amy K. Keating, Muna Qayed, James S. Killinger, Julie C. Fitzgerald, Rabi Hanna, Kris M. Mahadeo, Troy C. Quigg, Prakash Satwani, Paul Castillo, Shira J. Gertz, Theodore B. Moore, Benjamin Hanisch, Aly Abdel-Mageed, Rachel Phelan, Dereck B. Davis, Michelle P. Hudspeth, Greg A. Yanik, Michael A. Pulsipher, Imran Sulaiman, Leopoldo N. Segal, Birgitta A. Versluys, Caroline A. Lindemans, Jaap J. Boelens, Joseph L. DeRisi, the Pediatric Transplantation and Cell Therapy Consortium
Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children’s hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.
{"title":"Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients","authors":"Matt S. Zinter, Christopher C. Dvorak, Madeline Y. Mayday, Gustavo Reyes, Miriam R. Simon, Emma M. Pearce, Hanna Kim, Peter J. Shaw, Courtney M. Rowan, Jeffrey J. Auletta, Paul L. Martin, Kamar Godder, Christine N. Duncan, Nahal R. Lalefar, Erin M. Kreml, Janet R. Hume, Hisham Abdel-Azim, Caitlin Hurley, Geoffrey D.E. Cuvelier, Amy K. Keating, Muna Qayed, James S. Killinger, Julie C. Fitzgerald, Rabi Hanna, Kris M. Mahadeo, Troy C. Quigg, Prakash Satwani, Paul Castillo, Shira J. Gertz, Theodore B. Moore, Benjamin Hanisch, Aly Abdel-Mageed, Rachel Phelan, Dereck B. Davis, Michelle P. Hudspeth, Greg A. Yanik, Michael A. Pulsipher, Imran Sulaiman, Leopoldo N. Segal, Birgitta A. Versluys, Caroline A. Lindemans, Jaap J. Boelens, Joseph L. DeRisi, the Pediatric Transplantation and Cell Therapy Consortium","doi":"10.1101/2023.11.29.23299130","DOIUrl":"https://doi.org/10.1101/2023.11.29.23299130","url":null,"abstract":"Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children’s hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"82 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138504277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-29DOI: 10.1101/2023.11.28.23299134
Peter D Sottile, Bradford Smith, Marc Moss, David J Albers
Objective Invasive mechanical ventilation can worsen lung injury. Ventilator dyssynchrony (VD) may propagate ventilator-induced lung injury (VILI) and is challenging to detect and systematically monitor because each patient takes approximately 25,000 breaths a day yet some types of VD are rare, accounting for less than 1% of all breaths. Therefore, we sought to develop and validate accurate machine learning (ML) algorithms to detect multiple types of VD by leveraging esophageal pressure waveform data to quantify patient effort with airway pressure, flow, and volume data generated during mechanical ventilation, building a computational pipeline to facilitate the study of VD.
{"title":"The Development, Optimization, and Validation of Four Different Machine Learning Algorithms to Identify Ventilator Dyssynchrony","authors":"Peter D Sottile, Bradford Smith, Marc Moss, David J Albers","doi":"10.1101/2023.11.28.23299134","DOIUrl":"https://doi.org/10.1101/2023.11.28.23299134","url":null,"abstract":"<strong>Objective</strong> Invasive mechanical ventilation can worsen lung injury. Ventilator dyssynchrony (VD) may propagate ventilator-induced lung injury (VILI) and is challenging to detect and systematically monitor because each patient takes approximately 25,000 breaths a day yet some types of VD are rare, accounting for less than 1% of all breaths. Therefore, we sought to develop and validate accurate machine learning (ML) algorithms to detect multiple types of VD by leveraging esophageal pressure waveform data to quantify patient effort with airway pressure, flow, and volume data generated during mechanical ventilation, building a computational pipeline to facilitate the study of VD.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"83 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138504276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27DOI: 10.1101/2023.11.27.23299076
Wasim Talib Mahdi Al Masoodi, Sami Waheed Radhi, Habiba Khdair Abdalsada, Hussein Kadhem Al-Hakeim
Background: Long-COVID is a complicated condition with prolonged SARS-CoV-2 symptoms. Several variables have been studied in this illness. Among the less studied variables are galanin and its receptor (GalR1). The Galanin system is involved in the pathophysiology of several age-related chronic disorders, including alcoholism, chronic pain, and bowel and skin inflammation. The aim of the study is to correlate the galanin system parameters with clinical and biochemical variables in Long-COVID. Methods: Serum levels of albumin, electrolytes, GAL, GALR1, and C-reactive protein (CRP) are measured by ELISA technique in 90 Long-COVID patients and 60 recovered subjects who are free from any symptoms of Long-COVID. Results: The study showed a significantly increased Galanin, GALR1, and the Gal/GALR1 ratio. On the contrary, serum albumin, total calcium, ionized calcium, total magnesium, and the ionized calcium/magnesium ratio were significantly decreased. Galanin and Galanin/GALR1 showed significant age-related associations (ρ=0.353, p<0.01) and (ρ=0.218, p<0.05), respectively. The lowest SpO2 was associated with Galanin (ρ=-0.295, p<0.01) and GALR1 (ρ=-0.232, p<0.05), respectively. According to ROC analysis results, the highest sensitivities for differentiating between patients and non-patient subjects were Galanin (71.7%) and GALR1 (60.0%). Conclusions: Galanin, GALR1, and Long-COVID disease are directly correlated. However, more research is needed to find out exactly what roles plasma Galanin and its receptor play in Long-COVID disease.
背景:长冠状病毒是一种复杂的疾病，其症状持续时间较长。在这种疾病中已经研究了几个变量。其中研究较少的变量是丙氨酸及其受体(GalR1)。甘丙肽系统参与了一些与年龄相关的慢性疾病的病理生理，包括酒精中毒、慢性疼痛、肠道和皮肤炎症。该研究的目的是将丙氨酸系统参数与长期covid的临床和生化变量联系起来。方法:采用ELISA技术检测90例长冠肺炎患者和60例无长冠肺炎症状的康复者血清白蛋白、电解质、GAL、GALR1和c反应蛋白(CRP)水平。结果:研究显示Galanin, GALR1和Gal/GALR1比值显著升高。血清白蛋白、总钙、离子钙、总镁、离子钙/镁比均显著降低。Galanin和Galanin/GALR1分别表现出显著的年龄相关性(ρ=0.353, p < 0.01)和(ρ=0.218, p < 0.05)。最低SpO2与Galanin (ρ=-0.295, p<0.01)和GALR1 (ρ=-0.232, p<0.05)相关。根据ROC分析结果，区分患者和非患者受试者的敏感度最高的是Galanin(71.7%)和GALR1(60.0%)。结论:甘丙氨酸、GALR1与长冠病直接相关。然而，需要更多的研究来确定血浆丙氨酸及其受体在长冠状病毒病中的确切作用。
{"title":"Correlation between Galanin and its receptor with the serum electrolytes in Long-COVID patients","authors":"Wasim Talib Mahdi Al Masoodi, Sami Waheed Radhi, Habiba Khdair Abdalsada, Hussein Kadhem Al-Hakeim","doi":"10.1101/2023.11.27.23299076","DOIUrl":"https://doi.org/10.1101/2023.11.27.23299076","url":null,"abstract":"<strong>Background:</strong> Long-COVID is a complicated condition with prolonged SARS-CoV-2 symptoms. Several variables have been studied in this illness. Among the less studied variables are galanin and its receptor (GalR1). The Galanin system is involved in the pathophysiology of several age-related chronic disorders, including alcoholism, chronic pain, and bowel and skin inflammation. The aim of the study is to correlate the galanin system parameters with clinical and biochemical variables in Long-COVID. <strong>Methods:</strong> Serum levels of albumin, electrolytes, GAL, GALR1, and C-reactive protein (CRP) are measured by ELISA technique in 90 Long-COVID patients and 60 recovered subjects who are free from any symptoms of Long-COVID. <strong>Results:</strong> The study showed a significantly increased Galanin, GALR1, and the Gal/GALR1 ratio. On the contrary, serum albumin, total calcium, ionized calcium, total magnesium, and the ionized calcium/magnesium ratio were significantly decreased. Galanin and Galanin/GALR1 showed significant age-related associations (ρ=0.353, p<0.01) and (ρ=0.218, p<0.05), respectively. The lowest SpO2 was associated with Galanin (ρ=-0.295, p<0.01) and GALR1 (ρ=-0.232, p<0.05), respectively. According to ROC analysis results, the highest sensitivities for differentiating between patients and non-patient subjects were Galanin (71.7%) and GALR1 (60.0%). <strong>Conclusions:</strong> Galanin, GALR1, and Long-COVID disease are directly correlated. However, more research is needed to find out exactly what roles plasma Galanin and its receptor play in Long-COVID disease.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"85 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138504275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-17DOI: 10.1101/2023.11.15.23298577
Sonali Singh, Jessica Longmate, David Onion, Paul Williams, Miguel Camara, Alan R Smyth, Helen Barr, Luisa Martinez-Pomares
Chronic inflammation dominates disease pathogenesis in Cystic Fibrosis (CF) and there is a need to characterise CF immunity. Whole blood cultures offer a cost-effective and non-invasive approach to investigate immune responses within the host environment. Here we used whole blood cultures to investigate the differentiation potential of monocytes (CD45+CD14+ cells) in CF (N=10) and controls (N=8) in the presence and absence of exogenous macrophage-colony stimulatory factor (M-CSF) or granulocyte-macrophage (GM)-CSF with and without interleukin (IL)-4. In CF and control cultures, CD45+CD14+ cells upregulated HLA-DR expression in all instances, and increased CD206 in the presence of GM-CSF with and without IL-4, and CD209 in the presence of GM-CSF and IL-4. In CF, we consistently observed reduced upregulation of CD206 in response to GM-CSF and a positive correlation between CD206 expression and lung function (FEV1). This was unique to cultured monocytes, and not seen with any other marker. These results highlight the potential of whole blood cultures to reveal cellular characteristics in differentiating monocytes related to clinical parameters that could guide the identification of novel biomarkers in CF.
{"title":"CD206 upregulation in monocytes within whole blood cultures correlates with lung function in Cystic Fibrosis: a pilot study","authors":"Sonali Singh, Jessica Longmate, David Onion, Paul Williams, Miguel Camara, Alan R Smyth, Helen Barr, Luisa Martinez-Pomares","doi":"10.1101/2023.11.15.23298577","DOIUrl":"https://doi.org/10.1101/2023.11.15.23298577","url":null,"abstract":"Chronic inflammation dominates disease pathogenesis in Cystic Fibrosis (CF) and there is a need to characterise CF immunity. Whole blood cultures offer a cost-effective and non-invasive approach to investigate immune responses within the host environment. Here we used whole blood cultures to investigate the differentiation potential of monocytes (CD45+CD14+ cells) in CF (N=10) and controls (N=8) in the presence and absence of exogenous macrophage-colony stimulatory factor (M-CSF) or granulocyte-macrophage (GM)-CSF with and without interleukin (IL)-4. In CF and control cultures, CD45+CD14+ cells upregulated HLA-DR expression in all instances, and increased CD206 in the presence of GM-CSF with and without IL-4, and CD209 in the presence of GM-CSF and IL-4. In CF, we consistently observed reduced upregulation of CD206 in response to GM-CSF and a positive correlation between CD206 expression and lung function (FEV1). This was unique to cultured monocytes, and not seen with any other marker. These results highlight the potential of whole blood cultures to reveal cellular characteristics in differentiating monocytes related to clinical parameters that could guide the identification of novel biomarkers in CF.","PeriodicalId":501074,"journal":{"name":"medRxiv - Respiratory Medicine","volume":"88 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138504265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-16DOI: 10.1101/2023.11.14.23298442
Emanuele Marchi, Timothy Stopford Christopher Hinks, Matthew Richardson, Latifa Khalfaoui, Fiona Symon, Poojitha Rajasekar, Rachel Clifford, Beverley Hagardon, Cary D Austin, Julia MacIsaac, Michael S Kobor, Salman Siddiqui, Jordan S Mar, Joseph R Arron, David Choy, Peter H Bradding
Rationale: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS-responsiveness. Methods: Randomised open-label bronchoscopy study of high dose ICS therapy in 30 healthy adult volunteers randomised 2:1 to i) fluticasone propionate 500 mcg bd or ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. Measurements and main results: ICS induced small between-group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type-2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell-mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA-DQB2, CD96, PTPN7), B cell immunity (CD20, immunoglobulin heavy and light chains), and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL-17-dependent gene signature was not upregulated by ICS. Conclusions: In healthy airways, 4-week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type-2 inflammation. This implies that homeostasis in health involves tonic type-2 signalling in the airway mucosa, which is exquisitely sensitive to ICS.
理由:吸入皮质类固醇(ICS)对健康气道的影响尚不明确。目的:描述ICS对健康气道基因表达的影响，避免疾病相关基因改变和ICS反应性疾病相关改变引起的混淆。方法:在30名健康成年志愿者中进行随机开放标签支气管镜研究，以2:1随机分配到i)丙酸氟替卡松500 mcg / d或ii)不治疗，为期4周。实验室工作人员对分配不知情。采用免疫组织化学、大量RNA测序、DNA甲基化阵列和宏基因组学分析活检和刷牙。测量结果和主要结果:ICS诱导的血液和固有层嗜酸性粒细胞数量组间差异较小，但对其他免疫病理特征、血液中性粒细胞、FeNO、FEV1、微生物组或DNA甲基化没有影响。ICS治疗上调了72个刷牙基因和53个活组织检查基因，下调了82个刷牙基因和416个活组织检查基因。两种组织中下调最多的基因是典型的2型炎症标志物(FCER1A、CPA3、IL33、CLEC10A、SERPINB10和CCR5)、T细胞介导的适应性免疫(TARP、TRBC1、TRBC2、PTPN22、TRAC、CD2、CD8A、HLA-DQB2、CD96、PTPN7)、B细胞免疫(CD20、免疫球蛋白重链和轻链)和先天免疫，包括CD48、Hobit、RANTES、Langerin和GFI1。ICS没有上调il -17依赖性基因特征。结论:在健康气道中，4周的ICS暴露降低了与先天和适应性免疫相关的基因表达，并降低了2型炎症标志物。这表明健康的内稳态涉及气道粘膜的强直性2型信号，这对ICS非常敏感。
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