Serial Measurements of Circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and Periostin in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Therapy: An Exploratory Study

Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (TL,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and TL,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.

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High Levels of Plasma Protein C in Nephrotic Syndrome

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661225 ◽

1985 ◽

Vol 53 (01) ◽

pp. 005-007 ◽

Cited By ~ 16

Author(s):

I Pabinger-Fasching ◽

K Lechner ◽

H Niessner ◽

P Schmidt ◽

E Balzar ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Plasma Protein ◽

Protein C ◽

Inverse Correlation ◽

Elevated Plasma ◽

Significant Inverse Correlation ◽

At Iii ◽

Thrombotic Tendency ◽

Protein C Activity

SummaryIn patients with severe nephrotic syndrome determinations of plasma protein C : Ag levels (8 patients: 5 adults, 3 children) and protein C activity (3 out of 8 patients) revealed significantly elevated plasma protein C concentrations. Furthermore we observed a significant inverse correlation of protein C : Ag to AT III : Ag levels. No protein C : Ag could be detected in the urine of two patients studied. We conclude from our data, that changes of plasma protein C do not contribute to the high thrombotic tendency in nephrotic syndrome.

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4.2.1 Analysis of serial measurements in clinical practice. Comments

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365519209104647 ◽

1992 ◽

Vol 52 ◽

pp. 123-125

Keyword(s):

Clinical Practice ◽

Serial Measurements

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4.2 Analysis of serial measurements in clinical practice

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365519209104646 ◽

1992 ◽

Vol 52 ◽

pp. 105-121 ◽

Cited By ~ 1

Keyword(s):

Clinical Practice ◽

Serial Measurements

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Faculty Opinions recommendation of Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725419771.793539227 ◽

2017 ◽

Author(s):

Sergio Harari ◽

Antonella Caminati

Keyword(s):

Clinical Practice ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis

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Diagnostic and prognostic implications of 2018 guideline for the diagnosis of idiopathic pulmonary fibrosis in clinical practice

Scientific Reports ◽

10.1038/s41598-021-95728-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jooae Choe ◽

Byoung Soo Kwon ◽

Kyung-Hyun Do ◽

Hee Sang Hwang ◽

Jin Woo Song ◽

...

Keyword(s):

Clinical Practice ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Interobserver Agreement ◽

Usual Interstitial Pneumonia ◽

High Specificity ◽

Fluid Analysis ◽

Diagnostic Certainty ◽

Prognostic Stratification ◽

Prognostic Implications

AbstractThe purpose of this study was to evaluate the implications of the 2018 updated guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) in clinical practice compared to 2011 guideline. This study involved 535 patients including 339 IPF and 196 non-IPF, and we retrospectively evaluated CT classifications of usual interstitial pneumonia (UIP) by two guidelines. Interobserver agreement of 2018 criteria showed moderate reliability (κ = 0.53) comparable to 2011 (κ = 0.56) but interobserver agreement for probable UIP was fair (κ = 0.40). CT pattern of indeterminate for UIP was associated with better prognosis compared with the other groups (adjusted hazard ratio [HR] = 0.36, p < 0.001). Compared to possible UIP, probable UIP demonstrated a lower positive predictive value (PPV, 62.9% vs 65.8%). In analysis of patients with CT patterns of non-definite UIP, diagnosing IPF when CT pattern showed probable UIP with lymphocyte count ≤ 15% in BAL fluid, and either male sex or age ≥ 60 years showed a high specificity of 90.6% and a PPV of 80.8% in the validation cohort. The 2018 criteria provide better prognostic stratification than the 2011 in patients with possible UIP. BAL fluid analysis can improve the diagnostic certainty for IPF diagnosis in patients with probable UIP CT pattern.

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Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis

Respiratory Research ◽

10.1186/s12931-021-01801-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

H. Jessen ◽

N. Hoyer ◽

T. S. Prior ◽

P. Frederiksen ◽

M. A. Karsdal ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Progression ◽

Real World ◽

Progressive Disease ◽

Type Iii Collagen ◽

Type I ◽

Collagen Turnover ◽

Baseline Levels ◽

Longitudinal Biomarker

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. Methods Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. Results Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. Conclusion Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

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Adherence, Persistence, and Effectiveness in Real Life. Multicenter Long-Term Study on the Use of Pirfenidone and Nintedanib in the Treatment of Idiopathic Pulmonary Fibrosis

Journal of Pharmacy Practice ◽

10.1177/08971900211008625 ◽

2021 ◽

pp. 089719002110086

Author(s):

Fiorenzo Santoleri ◽

Luigia Auriemma ◽

Antonella Spacone ◽

Stefano Marinari ◽

Fabio Esposito ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pharmacological Study ◽

Functional Decline ◽

Real Life ◽

Point Of View ◽

Response To Treatment ◽

First Year ◽

Long Term Study ◽

Second Year

Background: In the treatment of idiopathic pulmonary fibrosis (IPF), nintedanib and pirfenidone, with their different mechanisms of action, lead to a reduction in the rate of progression of the fibrosis process measured by the reduction of functional decline, and, in particular, the decrease in forced vital capacity (FVC) and of the diffusion capacity of the lungs for carbon monoxide (DLCO). The objective of this study was to analyze real-life adherence, persistence and efficacy in the use of pirfenidone and nintedanib in the treatment of IPF. Methods: A non-interventional multicenter retrospective observational pharmacological study in real-life treat-ment at 1 and 2 years was conducted. Furthermore, we analyzed the levels of FVC and DLCO at 6 and 12 months, respectively, from the start of treatment. Results: We identified 144 patients in the period between January 2013 and April 2019. From the point of view of adherence, there is no difference between the two drugs, even though patients who used pirfenidone had increasingly higher values: 0.90 vs 0.89, in the first year, and 0.91 vs 0.84, in the second year. In the first year of treatment, the percentage of persistent patients was 67% and 76%, while in the second year, it dropped to 47% and 53% for pirfenidone and nintedanib, respectively. Conclusion: The stratification of the adherence values as a function of the response to treatment in terms of FVC at 12 months for both study drugs showed that patients with optimal response scored adherence of more than 90%.

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The Dependence of Renal 68Ga[Ga]-DOTATOC Uptake on Kidney Function and Its Relevance for Peptide Receptor Radionuclide Therapy with 177Lu[Lu]-DOTATOC

Diagnostics ◽

10.3390/diagnostics11071216 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1216

Author(s):

Falk Gühne ◽

Alexander Heinzig ◽

Philipp Seifert ◽

Robert Drescher ◽

Martin Freesmeyer

Keyword(s):

Kidney Function ◽

Specific Binding ◽

Correlation Coefficients ◽

Inverse Correlation ◽

Peptide Receptor Radionuclide Therapy ◽

Tracer Uptake ◽

Significant Inverse Correlation ◽

Peptide Receptor ◽

Pet Ct ◽

Induced Changes

Background: In addition to its SSTR-specific binding in tumors and healthy tissues, DOTATOC analogues accumulate in kidney parenchyma. Renal tracer uptake might be a surrogate of kidney function or dysfunction. This study aimed to evaluate if kidney function can be estimated from 68Ga[Ga]-DOTATOC uptake in PET/CT and its impact on the nephrotoxicity of 177Lu[Lu]-DOTATOC PRRT. Methods: Two cohorts of patients (A: 128 diagnostic patients; B: 32 PRRT patients) were evaluated retrospectively. SUV values of the kidneys, physiologically SSTR-expressing organs and in background compartments were assessed. Kidney function was calculated as eGFR by CKD-EPI creatinine equation. Pearson’s correlation coefficients and treatment-induced changes of uptake and kidney function were assessed and compared. Results: Kidney function and renal DOTATOC uptake showed a significant inverse correlation (R2 = 0.037; p = 0.029). Evaluated models of PET/CT measurements were not able to predict kidney function sufficiently. The uptake of other organs did not depend on eGFR. While the renal uptake increased after PRRT (p < 0.001), the kidney function did not change significantly (p = 0.382). Neither low pre-therapeutic eGFR nor high pre-therapeutic kidney uptake were risk factors of PRRT-induced deterioration in kidney function. Conclusion: The relevance of kidney function for renal 68Ga[Ga]-DOTATOC uptake is limited. The nephrotoxicity of 177Lu[Lu]-DOTATOC PRRT might be low and cannot be reliably predicted by pre-therapeutic measurements.

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Construct Validity for Self-Acceptance and Fear of Negative Evaluation

Psychological Reports ◽

10.2466/pr0.2001.89.2.386 ◽

2001 ◽

Vol 89 (2) ◽

pp. 386-386 ◽

Cited By ~ 5

Author(s):

Mark W. Durm ◽

Patricia E. Glaze

Keyword(s):

Construct Validity ◽

Inverse Correlation ◽

The Self ◽

Negative Evaluation ◽

Fear Of Negative Evaluation ◽

Significant Inverse Correlation ◽

Acceptance Scale ◽

Self Acceptance

For 55 students (13 men, 42 women) there was a significant inverse correlation for scores on the Self-acceptance Scale and scores on the Fear of Negative Evaluation Scale, thereby giving credence to the construct validity of both scales, that is, the more one accepts oneself, the less negative evaluation there is of oneself.

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