Proteomic characterization of idiopathic pulmonary fibrosis patients: stable versus acute exacerbation

Acute exacerbations (AEs) are among the main causes of death in idiopathic pulmonary fibrosis (IPF) patients. In this study proteomic comparative analysis of bronchoalveolar lavage (BAL) fluid samples was performed in stable IPF patients versus AEs IPF group to identify AE pathogenetic mechanisms and novel potential predictive biomarkers. A functional proteomic analysis of BAL fluid samples from stable and AE-IPF patients was conducted in a population of 27 IPF patients. Fifty-one differentially abundant spots were observed and identified by mass spectrometry. Enrichment analysis found proteins of interest involved in the regulation of macrophages and lipid metabolism receptors. In acute exacerbation IPF group, differentially abundant proteins were involved in propagation of the β-catenin WNT transduction signal, and proteins up-regulated in lung carcinogenesis (IGKC, S100A9, PEDF, IGHG1, ALDOA, A1AT, HPT, CO3 and PIGR) and acute phase proteins involved in protease-antiprotease imbalance (such as A1AT fragments). Dot-blot analysis of A1AT C-36 peptide allowed validating our findings, confirming up-regulation in AE IPF patients and suggesting its potential pathogenetic role. A crucial role of protease/antiprotease imbalance, clathrin-mediated endocytosis signalling and carcinogenesis emerged in IPF patients developing acute exacerbations.

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Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis

European Respiratory Journal ◽

10.1183/13993003.01339-2016 ◽

2017 ◽

Vol 49 (5) ◽

pp. 1601339 ◽

Cited By ~ 62

Author(s):

Harold R. Collard ◽

Luca Richeldi ◽

Dong Soon Kim ◽

Hiroyuki Taniguchi ◽

Inga Tschoepe ◽

...

Keyword(s):

Risk Factors ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Exacerbation ◽

Supplemental Oxygen ◽

Rank Test ◽

Risk Of Mortality ◽

Acute Exacerbations ◽

The Impact ◽

Similar Risk

Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations.

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Faculty Opinions recommendation of Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials.

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

10.3410/f.718033775.793483588 ◽

2013 ◽

Author(s):

Venerino Poletti ◽

Claudia Ravaglia

Keyword(s):

Clinical Trials ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Exacerbation ◽

Outcome Measure

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Faculty Opinions recommendation of Acute exacerbation of idiopathic pulmonary fibrosis. an international working group report.

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

10.3410/f.726421746.793524896 ◽

2016 ◽

Author(s):

Jay H Ryu

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Exacerbation ◽

Working Group ◽

International Working Group ◽

Group Report

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Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes

Surgery Today ◽

10.1007/s00595-021-02343-0 ◽

2021 ◽

Author(s):

Akira Iyoda ◽

Yoko Azuma ◽

Susumu Sakamoto ◽

Sakae Homma ◽

Atsushi Sano

Keyword(s):

Lung Cancer ◽

Surgical Treatment ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Exacerbation

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Changes in Neutrophil–Lymphocyte or Platelet–Lymphocyte Ratios and Their Associations with Clinical Outcomes in Idiopathic Pulmonary Fibrosis

Journal of Clinical Medicine ◽

10.3390/jcm10071427 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1427

Author(s):

Steven D. Nathan ◽

Jayesh Mehta ◽

John Stauffer ◽

Elizabeth Morgenthien ◽

Ming Yang ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Clinical Outcomes ◽

Predictive Biomarkers ◽

Phase Iii ◽

Response To Treatment ◽

Reference Ranges ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

The Relationship

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF.

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Initial therapeutic dose of corticosteroid for an acute exacerbation of IPF is associated with subsequent early recurrence of another exacerbation

Scientific Reports ◽

10.1038/s41598-021-85234-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryo Yamazaki ◽

Osamu Nishiyama ◽

Sho Saeki ◽

Hiroyuki Sano ◽

Takashi Iwanaga ◽

...

Keyword(s):

Risk Factors ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Therapeutic Dose ◽

Early Recurrence ◽

Time To Recurrence ◽

Acute Exacerbations ◽

Patient Groups ◽

The Mean ◽

Mean Time

AbstractSome patients with idiopathic pulmonary fibrosis (IPF) undergo recurrent acute exacerbations (AEs). This study aimed to elucidate the risk factors for recurrent AEs of IPF (AE-IPF). Consecutive patients with IPF admitted for their first AE-IPF between January 2008 and December 2018 were retrospectively recruited. Of 63 patients admitted for an AE-IPF and discharged alive, 9 (14.3%) developed a recurrence of AE within 1 year. The mean time to recurrence was 233 ± 103 days. Total doses (mg/month and mg/kg/month) of corticosteroids administered over day 1 to 30 after the AE were significantly higher in patients without recurrences of AE-IPF (5185 ± 2414 mg/month, 93.5 ± 44.0 mg/kg/month) than the doses in patients with recurrences (3133 ± 1990 mg/month, 57.2 ± 37.7 mg/kg/month) (p = 0.02 and p = 0.03, respectively). However, no differences were observed between the total doses of corticosteroids administered over days 31 to 60, 61 to 90, 91 to 120, and 151 to 180 after the AE. Furthermore, differences between the administration rates of immunosuppressive and antifibrotic treatments administered to the 2 patient groups were not significant. An increased total dose of corticosteroid administered over day 1 to 30 after an AE-IPF was associated with a decreased risk of subsequent recurrence of AE-IPF within 1 year after the first AE.

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