scholarly journals Prognostic Value of Serum Osteopontin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xianhua Gui ◽  
Xiaohua Qiu ◽  
Miaomiao Xie ◽  
Yaqiong Tian ◽  
Cao Min ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acute Exacerbation ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Alveolar Epithelial Cells ◽  
Healthy Controls ◽  
Alveolar Epithelial

Background. Acute exacerbation (AE) is a common cause of rapid deterioration and high mortality in idiopathic pulmonary fibrosis (IPF) patients. Osteopontin (OPN) plays an important role in IPF, but the studies about serum OPN in AE-IPF are unclear. We aimed to investigate whether OPN had a potential prognostic value in acute exacerbation and mortality in IPF. Methods. Thirty-two patients with AE-IPF, 39 with S-IPF, and 20 healthy controls were included. Serum OPN and KL-6 levels were compared between AE-IPF and S-IPF. Logistic regression analysis was applied to identify the predicted value of OPN for AE. Kaplan–Meier curves were used to display survival, and Cox proportional hazards regression was used to identify risk for mortality. Results. In AE-IPF patients, serum OPN levels were significantly higher than in S-IPF subjects (p<0.001) or healthy controls (p<0.001). Immunohistochemical staining in lung transplant specimens of IPF showed strong expression of OPN in the alveolar epithelial cells lining honeycomb space and alveolar macrophages accumulating in interalveolar spaces adjacent to the fibrotic lesion. Serum OPN was correlated with higher C-reactive protein (CRP) and lactate dehydrogenase (LDH). Serum OPN, KL-6, CRP, LDH, percent forced vital capacity (FVC%), and percent diffusing capacity (DLCO%) in IPF were correlated with AE status, with respective odds ratios of 1.305 (p=0.004), 1.001 (p=0.010), 1.039 (p=0.002), 1.035 (p<0.001), 0.950 (p=0.024), and 0.929 (p=0.010). Serum OPN (above 3.24 ng/ml) was associated with an increasing risk of mortality (p=0.019). Multivariate Cox regression demonstrated an association of OPN levels with mortality risk (p=0.036). Conclusion. Elevated OPN could be a potential serum predictor for AE status and survival in IPF patients.

scholarly journals Plasma Leptin Is Elevated in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Mengshu Cao ◽  
Jeffery J. Swigris ◽  
Xin Wang ◽  
Min Cao ◽  
Yuying Qiu ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acute Exacerbation ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Plasma Concentrations ◽  
Cox Proportional Hazards ◽  
Healthy Controls ◽  
Cox Regression Analysis ◽  
Plasma Leptin

Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes.Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival.Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p=0.0003) or healthy controls (p<0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2(p=0.007;p=0.005;p=0.003;p=0.033;andp=0.032,resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p=0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p=0.004).Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients.

Improved Prognostic Prediction by Combination of Early Initiation of Polymyxin B Hemoperfusion with Modified Gender-Age-Physiology Index in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

2021 ◽  
pp. 1-7
Author(s):  
Keiji Oishi ◽  
Arata Azuma ◽  
Shinji Abe ◽  
Yoriyuki Murata ◽  
Kenji Sakamoto ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Acute Exacerbation ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Chronic Phase ◽  
Polymyxin B ◽  
Pulse Therapy ◽  
Cox Proportional Hazards ◽  
Steroid Pulse

<b><i>Introduction:</i></b> Respiratory failure from acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) has been reported to have beneficial effects on patients with AE-IPF. Whether patient characteristics influence the extent of this benefit remains unclear. <b><i>Methods:</i></b> We retrospectively examined the records of 30 patients with AE-IPF who underwent PMX-DHP. The favorable factors of survival were determined using Cox proportional hazards analyses. <b><i>Results:</i></b> The 1- and 12-month survival rates after PMX-DHP were 70.0% and 50.0%, respectively. The multivariate analysis revealed that low modified Gender-Age-Physiology (GAP) index (≤8 points) (hazard ratio [HR] 0.317, <i>p</i> = 0.015) and PMX-DHP received within 48 h of steroid pulse (HR 0.289, <i>p</i> = 0.012) were favorable factors. Notably, even in the patients with high modified GAP index (&#x3e;8 points), that is, more advanced IPF, those who received PMX-DHP within 48 h of steroid pulse had a better prognosis than those who did after 48 h of the steroid pulse (<i>p</i> = 0.032). <b><i>Conclusions:</i></b> Early PMX-DHP initiation in patients with AE-IPF, specifically within 48 h after the steroid pulse therapy, may improve prognosis regardless of the severity of chronic phase of IPF before AE-IPF.

FRI0485 RISK OF PROGRESSION OF IDIOPATHIC PULMONARY FIBROSIS TO CONNECTIVE TISSUE DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 840-841
Author(s):  
B. Ghang ◽  
S. H. Nam ◽  
Y. G. Kim ◽  
B. Yoo ◽  
C. K. Lee
Keyword(s):  
Risk Factors ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Rheumatoid Factor ◽  
Connective Tissue Disease ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Survival Duration ◽  
Citrullinated Protein

Background:Connective tissue disease (CTD) may be observed during the course of idiopathic pulmonary fibrosis (IPF). However, clinical factors associated with the development of CTD in patients with IPF have not yet been identified. These factors might be valuable clues for determining the pathogenesis of pulmonary fibrosis in patients with CTD. We hypothesize that some IPF patients have a clinically significant association with autoimmunity, and that autoantibodies are important biomarkers for identifying these patients.Objectives:Based on this hypothesis, we investigated whether the serology criteria (anti-neutrophil cytoplasmic antibody (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonitis with autoimmune features (IPAF)) were associated with the development of CTD during the clinical course of IPF in the patients from our previous study(1), with a particular focus on which antibodies have a significant association with the development of CTD.Methods:We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014, and investigated the length of time from first visit to the clinic for IPF diagnosis (baseline) to CTD diagnosis by an expert rheumatologist in patients with IPF. Multivariable Cox proportional-hazards models with backward elimination were used to investigate the risk factors for the development of CTD.Results:CTD developed in 15 patients at a median of 2.1 years (range 1.2 to 4.8) after IPF diagnosis. All these patients had ANCA or autoantibodies that met the serology criteria for IPAF. A significant number of IPF patients with high titers of RF, ACPA or MPO-ANCA tested at first visit to the clinic progressed to CTD(Figure 1). Survival duration for IPF patients with progression to CTD was 5.3 [3.8; 6.7] years, which was significantly longer than for the IPF patients without progression to CTD (2.9 [1.7; 4.8], p = 0.001). Independent risk factors for development of CTD in IPF patients included female gender (adjusted hazard ratio (HR) 5.319, p = 0.0082), titer of rheumatoid factor (RF) (adjusted HR 1.006, p = 0.022), titer of anti-citrullinated protein antibody (ACPA) (adjusted HR 1.009, p = 0.0011), and titer of myeloperoxidase (MPO) ANCA (adjusted HR 1.02, p < 0.0001).Figure 1.Connective tissue disease development in each autoantibody positive IPF patient. ACPA = anti–citrullinated protein antibody; ANA = antinuclear antibody; CTD = connective tissue disease; MPA = microscopic polyangiitis; PAN = polyarteritis nodosa; RA = rheumatoid arthritis; RF = rheumatoid factor; UCTD = Undifferentiated connective tissue disease; SjS = Sjögren’s syndrome.Conclusion:We observed development of CTD in IPF patients with ANCA or autoantibodies that met the IPAF serology criteria. Among these autoantibodies, RF, ACPA, and MPO-ANCA were significantly associated with the development of CTD in IPF patients. Progression to CTD is uncommon in IPF patients, but a significant number of IPF patients with high titers of RF, ACPA or MPO-ANCA progressed to connective tissue disease. IPF with high titers of RF, ACPA or MPO-ANCA might be the initial clinical manifestation of connective tissue disease. Further studies are needed to investigate the role of RF, ACPA, and MPO-ANCA in development of pulmonary fibrosis.References:[1]Ghang B, Lee J, Chan Kwon O, Ahn SM, Oh JS, Hong S, et al. Clinical significance of autoantibody positivity in idiopathic pulmonary fibrosis. Respir Med. 2019;155:43-8.Disclosure of Interests:None declared

scholarly journals Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 83 ◽  
Author(s):  
Francesco Salton ◽  
Maria Volpe ◽  
Marco Confalonieri
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Options ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Serious Disease

Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

Patient gender bias on the diagnosis of idiopathic pulmonary fibrosis

Thorax ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 407-412 ◽  
Author(s):  
Deborah Assayag ◽  
Julie Morisset ◽  
Kerri A Johannson ◽  
Athol U Wells ◽  
Simon L F Walsh
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Proportional Hazards ◽  
Usual Interstitial Pneumonia ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Diagnostic Confidence ◽  
Patient Gender ◽  
And Gender ◽  
Gender Influences

BackgroundPatient sex has clinical and prognostic implications in idiopathic pulmonary fibrosis (IPF). It is not known if sex-related and gender-related discrepancies exist when establishing a diagnosis of IPF. The aim was to determine how patient gender influences the diagnosis of IPF and the physician’s diagnostic confidence.MethodsThis study was performed using clinical cases compiled from a single centre, then scored by respiratory physicians for a prior study. Using clinical information, physicians were asked to provide up to five diagnoses, together with their diagnostic confidence. Logistic regression was used to assess the odds of receiving a diagnosis of IPF based on patient gender. Prognostic discrimination between IPF and non-IPF was used to assess diagnostic accuracy with Cox proportional hazards modelling.ResultsSixty cases were scored by 404 physicians. IPF was diagnosed more frequently in men compared with women (37.8% vs 10.6%; p<0.0001), and with greater mean diagnostic confidence (p<0.001). The odds of a male patient receiving an IPF diagnosis was greater than that of female patients, after adjusting for confounders (OR=3.05, 95% CI: 2.81 to 3.31), especially if the scan was not definite for the usual interstitial pneumonia pattern. Mortality was higher in women (HR=2.21, 95% CI: 2.02 to 2.41) than in men with an IPF diagnosis (HR=1.26, 95% CI: 1.20 to 1.33), suggesting that men were more often misclassified as having IPF.ConclusionPatient gender influences diagnosis of IPF: women may be underdiagnosed and men overdiagnosed with IPF.

scholarly journals miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0158367 ◽  
Author(s):  
Supparerk Disayabutr ◽  
Eun Kyung Kim ◽  
Seung-Ick Cha ◽  
Gary Green ◽  
Ram P. Naikawadi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Alveolar Epithelial

scholarly journals The NLRP3-Inflammasome-Caspase-1 Pathway Is Upregulated in Idiopathic Pulmonary Fibrosis and Acute Exacerbations and Is Inducible by Apoptotic A549 Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Benedikt Jäger ◽  
Benjamin Seeliger ◽  
Oliver Terwolbeck ◽  
Gregor Warnecke ◽  
Tobias Welte ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Nlrp3 Inflammasome ◽  
Cathepsin B ◽  
A549 Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Caspase 1 ◽  
Acute Exacerbations

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease harboring significant morbidity and mortality despite recent advances in therapy. Regardless of disease severity acute exacerbations (IPF-AEs) may occur leading to considerable loss of function and are the leading cause of death in IPF. Histologic features of IPF-AE are very similar to acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the role of the NLRP3 inflammasome in IPF and IPF-AE. Bronchoalveolar lavage (BAL) cells were sampled from patients with IPF (n = 32), IPF-AE (n = 10), ARDS (n = 7) and healthy volunteers (HV, n = 37) and the NLRP3-inflammasome was stimulated in-vitro. We found the NLRP3 inflammasome to be hyper-inducible in IPF compared to HV with increased IL-1ß and pro-IL-1ß levels on ELISA upon stimulation as well as increased caspase-1 activity measured by caspase-1p20 immunoblotting. In IPF-AE, IL-1ß was massively elevated to an extent similar to ARDS. To evaluate potential mechanisms, we co-cultured BAL cells with radiated A549 cells (a model to simulate apoptotic alveolar epithelial cells), which led to increased NLRP3 mRNA expression and increased caspase-1 dependent IL-1ß production. In the presence of a reactive oxygen species (ROS) inhibitor (diphenyleneiodonium) and a cathepsin B inhibitor (E64D), NLRP3 expression was suppressed indicating that induction of NLRP3 activation following efferocytosis of apoptotic A549 cells is mediated via ROS and cathepsin-B. In summary, we present evidence of involvement of the NLRP3 inflammasome-caspase pathway in the pathogenesis of IPF-AE, similarly to ARDS, which may be mediated by efferocytosis of apoptotic alveolar epithelial cells in IPF.

scholarly journals Clinical Outcomes of Patients with Combined Idiopathic Pulmonary Fibrosis and Emphysema in the IPF-PRO Registry

Lung ◽  
2022 ◽  
Author(s):  
Hyun J. Kim ◽  
Laurie D. Snyder ◽  
Megan L. Neely ◽  
Anne S. Hellkamp ◽  
David L. Hotchkin ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Baseline Variable ◽  
Former Smokers ◽  
The Impact ◽  
Baseline Covariates

Abstract Purpose To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators’ review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration ClinicalTrials.gov, NCT01915511; registered August 5, 2013.

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