Biomarker signatures for progressive idiopathic pulmonary fibrosis

2021 ◽  
pp. 2101181
Author(s):  
Britt Clynick ◽  
Tamera J. Corte ◽  
Helen E. Jo ◽  
Iain Stewart ◽  
Ian N. Glaspole ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Progression Free Survival ◽  
Intercellular Adhesion Molecule ◽  
Lasso Regression ◽  
Intercellular Adhesion Molecule 1 ◽  
Clinical Endpoints ◽  
Proteomic Data ◽  
Proteomic Approach ◽  
One Year

RationaleIdiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers has the potential for guiding management in clinical practice.ObjectivesWe assessed the prognostic role of serum biomarkers in three independent IPF cohorts, the Australian IPF Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).MethodsIn the AIPFR, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. Least absolute shrinkage and selection operator (LASSO) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at one-year in AIPFR, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in PROFILE. Four significantly replicating biomarkers were aggregated into a progression index (PI) model based on tertiles of circulating concentrations.Main ResultsOne-hundred and eighty-nine participants were included in the AIPFR cohort, 205 participants from the TLF, and 122 participants from the PROFILE cohorts. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at one-year. Proteomic data did not replicate. The PI in the AIPFR, TLF and PROFILE predicted risk of progression, mortality and progression-free survival. A statistical model incorporating PI demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP model alone in all cohorts, and significantly so within incidence based TLF and PROFILE cohorts.ConclusionA panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

Serum levels of small HDL particles are negatively correlated with death or lung transplantation in an observational study of idiopathic pulmonary fibrosis

2021 ◽  
pp. 2004053
Author(s):  
Amisha V. Barochia ◽  
Maryann Kaler ◽  
Nargues Weir ◽  
Elizabeth M. Gordon ◽  
Debbie M. Figueroa ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Transplantation ◽  
Serum Lipids ◽  
Serum Levels ◽  
High Density Lipoproteins ◽  
Discovery Cohort ◽  
Clinical Endpoints ◽  
Multivariable Analyses ◽  
Lipids And Lipoproteins

BackgroundSerum lipoproteins, such as high density lipoproteins (HDL), may influence disease severity in idiopathic pulmonary fibrosis (IPF). Here, we investigated associations between serum lipids and lipoproteins and clinical endpoints in IPF.MethodsClinical data and serum lipids were analyzed from a discovery cohort (59 IPF subjects, 56 healthy volunteers) and validated using an independent, multicenter cohort (207 IPF subjects) from the Pulmonary Fibrosis Foundation registry. Associations between lipids and clinical endpoints (FVC, forced vital capacity; 6MWD, 6 min walk distance; GAP (Gender Age Physiology) index; death or lung transplantation) were examined using Pearson's correlation and multivariable analyses.ResultsSerum concentrations of small HDL particles (S-HDLPNMR), measured by nuclear magnetic resonance (NMR) spectroscopy, correlated negatively with the GAP index in the discovery cohort of IPF subjects. The negative correlation of S-HDLPNMR with GAP index was confirmed in the validation cohort of IPF subjects. Higher levels of S-HDLPNMR were associated with lower odds of death or its competing outcome, lung transplantation (OR of 0.9 for each 1 μmol·L−1 increase in S-HDLPNMR, p<0.05), at 1, 2, and 3 years from study entry in a combined cohort of all IPF subjects.ConclusionsHigher serum levels of S-HDLPNMR are negatively correlated with the GAP index, as well as with lower observed mortality or lung transplantation in IPF subjects. These findings support the hypothesis that S-HDLPNMR may modify mortality risk in patients with IPF.

scholarly journals WARFARIN USE IS ASSOCIATED WITH INCREASED MORTALITY AT ONE YEAR IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS

CHEST Journal ◽  
2020 ◽  
Vol 158 (4) ◽  
pp. A1061
Author(s):  
Syeda Fatima Naqvi ◽  
Sana Ali ◽  
Yousaf Hadi ◽  
Sarah Sofka
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
One Year

scholarly journals Differences in the Biomarker Profile of De Novo Acute Heart Failure versus Decompensation of Chronic Heart Failure

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1701
Author(s):  
Sylwia Nawrocka-Millward ◽  
Jan Biegus ◽  
Magdalena Hurkacz ◽  
Mateusz Guzik ◽  
Marta Rosiek-Biegus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
De Novo ◽  
Composite Endpoint ◽  
Serum Lactate ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Patient Profile ◽  
One Year

The perception of acute heart failure (AHF) as a single entity is increasingly outdated, as distinct patient profiles can be discerned. Key heart failure (HF) studies have previously highlighted the difference in both the course and prognosis of de novo AHF and acute decompensated chronic HF (ADHF). Accordingly, distinct AHF profiles with differing underlying pathophysiologies of disease progression can be shown. We compared a range of selected biomarkers in order to better describe the profile of de novo AHF and ADHF, including the inter alia—serum lactate, bilirubin, matrix metallopeptidase 9 (MMP-9), follistatin, intercellular adhesion molecule 1 (ICAM-1), lipocalin and galectin-3. The study comprised 248 AHF patients (de novo = 104), who were followed up for one year. The biomarker data of the de novo AHF and ADHF profiles was then compared in order to link biomarkers to their prognosis. Our study demonstrated that, although there are similarities between each patient profile, key biomarker differences do exist—predominantly in terms of NTproBNP, serum lactate, bilirubin, ICAM-1, follistatin, ferritin and sTfR (soluble transferrin receptor). ADHF tended to have compromised organ function and higher risks of both one-year mortality and composite endpoint (one-year mortality or rehospitalization for heart failure) hazard ratios (HR) (95% CI): 3.4 (1.8–6.3) and 2.8 (1.6–4.6), respectively, both p < 0.0001. Among the biomarkers of interest: sTfR HR (95% CI): 1.4 (1.04–1.8), NGAL(log) (neutrophil gelatinase-associated lipocalin) HR (95% CI): 2.0 (1.3–3.1) and GDF-15(log) (growth/differentiation factor-15) HR (95% CI): 4.0 (1.2–13.0) significantly impacted the one-year survival, all p < 0.05.

scholarly journals FDA-approved Antitussive Dextromethorphan Enhances Antifibrotic Effectiveness of Pirfenidone in Bleomycin-induced Mice and Patients with Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Nana Liu ◽  
Yubao Wang ◽  
Jie Huang ◽  
Yunze Du ◽  
Luqing Wei ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Reactions ◽  
Controlled Trial ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Randomized Controlled ◽  
Model Study ◽  
One Year

Abstract Background: We aimed to investigate whether dextromethorphan (DM), an antitussive agent, could improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure.Methods: A bleomycin-induced mouse pulmonary fibrosis model study and an open-label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.Results: In the animal study, pirfenidone combined with DM protected the mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone or DM alone, as indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary function (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF compared with pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between the pirfenidone-DM group and the pirfenidone group.Conclusions: Pirfenidone plus DM may be a better strategy to modify IPF than pirfenidone alone. The efficacy and safety of the combination of pirfenidone and DM for patients with IPF warrants further verification by a double-blind randomized controlled trial (RCT).

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