scholarly journals Can biomarkers of extracellular matrix remodelling and wound healing be used to identify high risk patients infected with SARS-CoV-2?: lessons learned from pulmonary fibrosis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
D. J. Leeming ◽  
F. Genovese ◽  
J. M. B. Sand ◽  
D. G. K. Rasmussen ◽  
C. Christiansen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Interstitial Lung Diseases ◽  
Lessons Learned ◽  
Lung Function Decline ◽  
Tissue Remodelling

AbstractPulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor’s consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.

scholarly journals Gender differences at presentation of idiopathic pulmonary fibrosis in Sweden

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dimitrios Kalafatis ◽  
Jing Gao ◽  
Ida Pesonen ◽  
Lisa Carlson ◽  
C. Magnus Sköld ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Gender Differences ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Poor Quality ◽  
Smoking History ◽  
Cross Sectional

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis mainly affecting males. Differences in clinical presentation between genders may be important both for the diagnostic work-up and for follow-up. In the present study, we therefore explored potential gender differences at presentation in a Swedish cohort of IPF-patients. Methods We studied patients included in the Swedish IPF- registry over a three-year period from its launch in 2014. A cross-sectional analysis was performed for data concerning demographics, lung function, 6- min walking test (6MWT) and quality of life (QoL) (King’s Brief Interstitial Lung Disease (K-BILD) score). Results Three hundred forty- eight patients (250 (72%) males, 98 (28%) females, median age 72 years in both genders) were included in the registry during the study period. Smoking history (N = 169 (68%) vs. N = 53 (54%), p < 0.05), baseline lung function (Forced vital capacity, % of predicted (FVC%): 68.9% ± 14.4 vs. 73.0% ± 17.7, p < 0.05; Total lung capacity, % of predicted (TLC%): 62.2% ± 11.8 vs. 68.6% ± 11.3%, p < 0.001) were significantly different at presentation between males and females, respectively. Comorbidities such as coronary artery disease (OR: 3.5–95% CI: 1.6–7.6) and other cardiovascular diseases (including atrial fibrillation and heart failure) (OR: 3.8–95% CI: 1.9–7.8) also showed significant differences between the genders. The K- BILD showed poor quality of life, but no difference was found between genders in total score (54 ± 11 vs. 54 ± 10, p = 0.61 in males vs. females, respectively). Conclusions This study shows that female patients with IPF have a more preserved lung function than males at inclusion, while males have a significant burden of cardiovascular comorbidities. However, QoL and results on the 6MWT did not differ between the groups. These gender differences may be of importance both at diagnosis and follow- up of patients with IPF.

scholarly journals A Ferroptosis-Related Gene Signature for Lung Function and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Yupeng Li ◽  
Shangwei Ning ◽  
Yi Yang ◽  
Hong Chen ◽  
Chen Wang
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mirna Target ◽  
Integrin Subunit ◽  
Ppi Network ◽  
Lung Dysfunction ◽  
Key Genes

Abstract Background: Rapid advances in genetic and genomic technologies have begun to reshape our understanding of idiopathic pulmonary fibrosis (IPF). Ferroptosis, an iron-dependent form of regulated cell death, play an important role in the development of IPF. Therefore, our study aimed to explore the role of ferroptosis-related genes (FRGs) and their correlation with lung dysfunction and quality of life in patients with IPF. Methods: Datasets were acquired by researching the Gene Expression Omnibus. FRGs were acquired by researching GeneCard database and PubMed. Ferroptosis-related differentially expressed genes (FRDEGs) were identified according to integrating FRGs and the DEGs identified in the GSE110147 dataset. Candidate key genes were identified from the miRNA-target FRDEGs network and protein-protein interactions (PPI) network. The relationship between key genes and lung function or quality of life was calculated using the GSE32537 datasets.Results: 293 FRGs were obtained, and 71 FRDEGs were identified. According to enrichment analysis, cell growth and death and pathways associated cancer were the important pathways, and significant biological processes were mainly consisted of cellular responses to stimulus and various situations. In addition, this study constructed an PPI network and a miRNA-target network based on the 71 FRDEGs, determined 19 candidate key genes. Furthermore, acyl-CoA synthetase long chain family member 1 (ACSL1), integrin subunit beta 8 (ITGB8) and ceruloplasmin (CP) were identified as the key genes. The expression level of ACSL1 was the strongest predictor for lung function (negatively) including percent predicted forced vital capacity (FVC% predicted) and percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and quality of life (negatively). In addition, ITGB8 and CP were negatively associated with FVC% predicted. According to DrugBank and PubMed, 4 drugs and 16 drugs have been found to act on ACSL1 and CP, respectively. Conclusion: These results imply that FRGs may shed new understanding on disease mechanism and provide potential biomarkers and therapy target to predict IPF progression.

Late Breaking Abstract - The SF-36 quality of life scales are sensitive measures of lung function decline

2021 ◽  
Author(s):  
Jorunn Kirkeleit ◽  
Trond Riise ◽  
Debbie Jarvis ◽  
Francisco Gomez Real ◽  
Christer Janson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Lung Function Decline ◽  
Sf 36

scholarly journals Potential of nintedanib in treatment of progressive fibrosing interstitial lung diseases

2019 ◽  
Vol 54 (3) ◽  
pp. 1900161 ◽  
Author(s):  
Lutz Wollin ◽  
Jörg H.W. Distler ◽  
Elizabeth F. Redente ◽  
David W.H. Riches ◽  
Susanne Stowasser ◽  
...  
Keyword(s):  
Lung Function ◽  
Tyrosine Kinases ◽  
Lung Diseases ◽  
Evidence Base ◽  
Interstitial Lung Diseases ◽  
Lung Pathology ◽  
Lung Function Decline ◽  
Approved Drugs

A proportion of patients with fibrosing interstitial lung diseases (ILDs) develop a progressive phenotype characterised by decline in lung function, worsening quality of life and early mortality. Other than idiopathic pulmonary fibrosis (IPF), there are no approved drugs for fibrosing ILDs and a poor evidence base to support current treatments. Fibrosing ILDs with a progressive phenotype show commonalities in clinical behaviour and in the pathogenic mechanisms that drive disease worsening. Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD). In vitro data demonstrate that nintedanib inhibits several steps in the initiation and progression of lung fibrosis, including the release of pro-inflammatory and pro-fibrotic mediators, migration and differentiation of fibrocytes and fibroblasts, and deposition of extracellular matrix. Nintedanib also inhibits the proliferation of vascular cells. Studies in animal models with features of fibrosing ILDs such as IPF, SSc-ILD, rheumatoid arthritis-ILD, hypersensitivity pneumonitis and silicosis demonstrate that nintedanib has anti-fibrotic activity irrespective of the trigger for the lung pathology. This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis. A trial of nintedanib in patients with progressive fibrosing ILDs other than IPF (INBUILD) will report results in 2019.

scholarly journals Efficacy of the combination of modern medicine and traditional Chinese medicine in pulmonary fibrosis arising as a sequelae in convalescent COVID-19 patients: a randomized multicenter trial

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhen-Hui Lu ◽  
Chun-Li Yang ◽  
Gai-Ge Yang ◽  
Wen-Xu Pan ◽  
Li-Guang Tian ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Modern Medicine ◽  
Randomized Controlled ◽  
Parallel Group

Abstract Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. Methods Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. Discussion Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. Trial registration: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).

scholarly journals A ferroptosis-related gene signature for lung function and quality of life in patients with idiopathic pulmonary fibrosis

2021 ◽  
Author(s):  
Yupeng Li ◽  
Shangwei Ning ◽  
Yi Yang ◽  
Hong Chen ◽  
Chen Wang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mirna Target ◽  
Integrin Subunit ◽  
Ppi Network ◽  
Lung Dysfunction ◽  
Key Genes

Abstract Background: Rapid advances in genetic and genomic technologies have begun to reshape our understanding of idiopathic pulmonary fibrosis (IPF). Ferroptosis, an iron-dependent form of regulated cell death, play an important role in the development of IPF. Therefore, our study aimed to explore the role of ferroptosis-related genes (FRGs) and their correlation with lung dysfunction and quality of life in patients with IPF. Methods: Datasets were acquired by researching the Gene Expression Omnibus. FRGs were acquired by researching GeneCard database and PubMed. Ferroptosis-related differentially expressed genes (FRDEGs) were identified according to integrating FRGs and the DEGs identified in the GSE110147 dataset. Candidate key genes were identified from the miRNA-target FRDEGs network and protein-protein interactions (PPI) network. The relationship between key genes and lung function or quality of life was calculated using the GSE32537 datasets.Results: 293 FRGs were obtained, and 71 FRDEGs were identified. According to enrichment analysis, cell growth and death and pathways associated cancer were the important pathways, and significant biological processes were mainly consisted of cellular responses to stimulus and various situations. In addition, this study constructed an PPI network and a miRNA-target network based on the 71 FRDEGs, determined 19 candidate key genes. Furthermore, acyl-CoA synthetase long chain family member 1 (ACSL1), integrin subunit beta 8 (ITGB8) and ceruloplasmin (CP) were identified as the key genes. The expression level of ACSL1 was the strongest predictor for lung function (negatively) including percent predicted forced vital capacity (FVC% predicted) and percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and quality of life (negatively). In addition, ITGB8 and CP were negatively associated with FVC% predicted. According to DrugBank and PubMed, 4 drugs and 16 drugs have been found to act on ACSL1 and CP, respectively. Conclusion: These results imply that FRGs may shed new understanding on disease mechanism and provide potential biomarkers and therapy target to predict IPF progression.

scholarly journals The Efficacy of Treating Pulmonary Fibrosis and Pulmonary Function Injury in COVID-19 with the Fuzheng Huayu Tablets: study protocol for a multicenter randomized controlled trial

2020 ◽  
Author(s):  
Fei Jing ◽  
Haina Fan ◽  
Zhimin Zhao ◽  
Feng Xing ◽  
Yingchun He ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Recovery Period ◽  
Life Assessment ◽  
Control Group ◽  
Pulmonary Dysfunction ◽  
Experimental Group

Abstract Background: Some patients with COVID-19 have been found pulmonary dysfunction and/or fibrosis in the recovery period, especially severe cases, but there are no certain drugs or treatment to cope with this situation. Previous studies proved the efficacy of FZHY on lung fibrosis induced by Bleomycin in animals and improvement of pulmonary function in COPD patients. We design this trial to carry out the clinical study that the effects of FZHY Tablets on pulmonary fibrosis and/or pulmonary function injury in the recovery period of COVID-19 and expect to improve the prognosis.Methods/design: This is a double-blind, placebo-controlled, randomized, multicenter clinical trial. It enrolls 160 patients who had been diagnosed with COVID-19, but currently they are negative for viral testing and have developed pulmonary fibrosis or pulmonary dysfunction. They are randomly divided equally into control group and experimental group. All patients are given basic treatment such as respiratory function rehabilitation training and vitamin C. The control group is given placebo of FZHY, and the experimental group is given FZHY. Each patient will be observed for 24 weeks and followed up for 8 weeks. The primary outcome for the trial is a composite endpoint consisting of lung function and HRCT. Secondary outcomes include clinical symptoms, oxygen saturation and quality of life assessment. Discussion: The trial is designed to test the hypothesis that treating pulmonary fibrosis or pulmonary dysfunction after SARS-CoV-2 infection with FZHY will improve the patient’s lung function or the pathological manifestation of pulmonary fibrosis, and improve the quality of life. Trial registration: Clinical Trials.gov, ID: NCT04279197. Registered on 12 April 2020.

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