scholarly journals Baseline plasma KL-6 level predicts adverse outcomes in patients with idiopathic pulmonary fibrosis receiving nintedanib: a retrospective real-world cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tang-Hsiu Huang ◽  
Chin-Wei Kuo ◽  
Chian-Wei Chen ◽  
Yau-Lin Tseng ◽  
Chao-Liang Wu ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Real World ◽  
Hepatic Injury ◽  
Cox Proportional Hazards ◽  
Adverse Outcomes ◽  
Sensitivity Analyses ◽  
Close Monitoring ◽  
Increased Risk

Abstract Background Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. Methods We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. Results Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13–10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89–19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63–12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16–24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06–73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. Conclusions For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.

scholarly journals Longitudinal clinical outcomes in a real-world population of patients with idiopathic pulmonary fibrosis: the PROOF registry

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wim A. Wuyts ◽  
Caroline Dahlqvist ◽  
Hans Slabbynck ◽  
Marc Schlesser ◽  
Natacha Gusbin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Clinical Outcomes ◽  
Real World ◽  
Lung Transplant ◽  
World Population ◽  
Duration Of Treatment

Abstract Background The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry. Methods Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013–2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed. Results The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months. Conclusions The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower. Trial registration PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherche (CNER) N201309/03–12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.

scholarly journals Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): Results from a real-world study

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261684
Author(s):  
Eung Gu Lee ◽  
Tae-Hee Lee ◽  
Yujin Hong ◽  
Jiwon Ryoo ◽  
Jung Won Heo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Real World ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Laboratory Data ◽  
Unknown Etiology ◽  
The Real

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. Methods This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. Results Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48–0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37–0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. Conclusions Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.

scholarly journals Correction to: Baseline plasma KL-6 level predicts adverse outcomes in patients with idiopathic pulmonary fibrosis receiving nintedanib: a retrospective real-world cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tang-Hsiu Huang ◽  
Chin-Wei Kuo ◽  
Chian-Wei Chen ◽  
Yau-Lin Tseng ◽  
Chao-Liang Wu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Real World ◽  
Adverse Outcomes

An amendment to this paper has been published and can be accessed via the original article.

Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elena Aloisio ◽  
Federica Braga ◽  
Chiara Puricelli ◽  
Mauro Panteghini
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Binary Data ◽  
Meta Analysis ◽  
Mortality Prediction ◽  
Asian Populations ◽  
Increased Risk ◽  
Using Data ◽  
Patient Prognosis

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

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

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.

Pulmonary Function Tests and Idiopathic Pulmonary Fibrosis

CHEST Journal ◽  
1997 ◽  
Vol 111 (1) ◽  
pp. 7-8 ◽  
Author(s):  
Steven H. Kirtland ◽  
Richard H. Winterbauer
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Function Tests

scholarly journals Association Between Room Location and Adverse Outcomes in Hospitalized Patients

2018 ◽  
Vol 12 (2) ◽  
pp. 21-29 ◽  
Author(s):  
Anoop Mayampurath ◽  
Christopher Ward ◽  
John Fahrenbach ◽  
Cynthia LaFond ◽  
Michael Howell ◽  
...  
Keyword(s):  
Critical Illness ◽  
Severity Of Illness ◽  
Adverse Outcomes ◽  
Sensitivity Analyses ◽  
Additional Risk Factor ◽  
Inhospital Mortality ◽  
Additional Risk ◽  
Increased Risk ◽  
Euclidean Distances ◽  
Time Of Admission

Objective: To investigate whether a patient’s proximity to the nurse’s station or ward entrance at time of admission was associated with increased risk of adverse outcomes. Method: We conducted a retrospective cohort study of consecutive adult inpatients to 13 medical–surgical wards at an academic hospital from 2009 to 2013. Proximity of admission room to the nurse’s station and to the ward entrance was measured using Euclidean distances. Outcomes of interest include development of critical illness (defined as cardiac arrests or transfer to an intensive care unit), inhospital mortality, and increase in length of stay (LOS). Results: Of the 83,635 admissions, 4,129 developed critical illness and 1,316 died. The median LOS was 3 days. After adjusting for admission severity of illness, ward, shift, and year, we found no relationship between proximity at admission to nurse’s station our outcomes. However, patients admitted to end of the ward had higher risk of developing critical illness (odds ratio [ OR] = 1.15, 95% confidence interval [CI] = [1.08, 1.23]), mortality ( OR = 1.16, 95% CI [1.03, 1.33]), and a higher LOS (13-hr increase, 95% CI [10, 15] hours) compared to patients admitted closer to the ward entrance. Similar results were observed in sensitivity analyses adjusting for isolation room patients and considering patients without room transfers in the first 48 hr. Conclusions: Our study suggests that being away from the nurse’s station did not increase the risk of these adverse events in ward patients, but being farther from the ward entrance was associated with increase in risk of adverse outcomes. Patient safety can be improved by recognizing this additional risk factor.

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