Angiopoietin-1 and -2 Expression in Patients With Acute Exacerbation of Idiopathic Interstitial Pneumonias

Abstract Background Acute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs. Methods We retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs. Results Among the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death. Conclusions Our findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.

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Retrospective Analysis of Prognostic Factors for Acute Exacerbation of Idiopathic Interstitial Pneumonias

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3379 ◽

2019 ◽

Author(s):

K. Enokida ◽

T. Takihara ◽

Y. Horio ◽

M. Takahashi ◽

F. Takahashi ◽

...

Keyword(s):

Prognostic Factors ◽

Retrospective Analysis ◽

Acute Exacerbation ◽

Idiopathic Interstitial Pneumonias

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Prognostic significance of serum cytokines during acute exacerbation of idiopathic interstitial pneumonias treated with thrombomodulin

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000889 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000889

Author(s):

Toru Arai ◽

Hiroto Matsuoka ◽

Masaki Hirose ◽

Hiroshi Kida ◽

Suguru Yamamoto ◽

...

Keyword(s):

Multivariate Analysis ◽

Growth Factor ◽

Acute Exacerbation ◽

Prognostic Significance ◽

Serum Levels ◽

Survival Outcome ◽

Serum Samples ◽

Stepwise Selection ◽

Idiopathic Interstitial Pneumonias ◽

Serum Cytokines

BackgroundAcute exacerbation (AE) has been reported to herald a poor prognosis in idiopathic pulmonary fibrosis and is now thought to do so in idiopathic interstitial pneumonias (IIPs). However, the pathophysiology of AE-IIPs is not sufficiently understood. In our previously reported SETUP trial, we found better survival in patients with AE-IIPs treated with corticosteroids and thrombomodulin than in those treated with corticosteroids alone. In that study, we collected serum samples to evaluate changes in cytokine levels and retrospectively examined the prognostic significance and pathophysiological role of serum cytokines in patients with AE-IIPs.MethodsThis study included 28 patients from the SETUP trial for whom serial serum samples had been prospectively obtained. AE-IIPs were diagnosed using the Japanese Respiratory Society criteria. All patients were treated with intravenous thrombomodulin and corticosteroids from 2014 to 2016. Serum levels of 27 cytokines were measured using Bio-Plex. The high-resolution CT pattern at the time of diagnosis of AE was classified as diffuse or non-diffuse.ResultsUnivariate analysis revealed that higher serum levels of interleukin (IL)-2, IL-7, IL-9, IL-12, IL13, basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, interferon-γ inducible protein-10, platelet-derived growth factor and regulated on activation, normal T cell expressed and secreted (RANTES) at AE were significant predictors of 90-day survival. The HRCT pattern was also a significant clinical predictor of 90-day survival. Multivariate analysis with stepwise selection identified a higher serum RANTES level at AE to be a significant predictor of 90-day survival, including after adjustment for HRCT pattern. Multivariate analysis with stepwise selection suggested that a marked increase in the serum IL-10 level on day 8 could predict 90-day mortality.ConclusionsA higher serum RANTES level at AE the time of diagnosis predicted a good survival outcome, and an elevated serum IL-10 level on day 8 predicted a poor survival outcome.Trial registration numberUMIN000014969.

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Leukocytapheresis for the treatment of acute exacerbation of idiopathic interstitial pneumonias: a pilot study

The Journal of Medical Investigation ◽

10.2152/jmi.64.110 ◽

2017 ◽

Vol 64 (1.2) ◽

pp. 110-116

Author(s):

Akihiro Yamamoto ◽

Kiyoshi Hashimoto ◽

Akira Yamasaki ◽

Miki Takata ◽

Masato Morita ◽

...

Keyword(s):

Pilot Study ◽

Acute Exacerbation ◽

Idiopathic Interstitial Pneumonias

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Acute exacerbation of idiopathic interstitial pneumonias related to chemotherapy for lung cancer: nationwide surveillance in Japan

ERJ Open Research ◽

10.1183/23120541.00184-2019 ◽

2020 ◽

Vol 6 (2) ◽

pp. 00184-2019 ◽

Cited By ~ 1

Author(s):

Yuji Minegishi ◽

Akihiko Gemma ◽

Sakae Homma ◽

Kazuma Kishi ◽

Arata Azuma ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Study ◽

Acute Exacerbation ◽

Cell Lung Cancer ◽

Second Line ◽

First Line ◽

Idiopathic Interstitial Pneumonias ◽

Second Line Chemotherapy ◽

Nationwide Surveillance ◽

Line Chemotherapy

BackgroundChemotherapy-induced acute exacerbation (AEx) of idiopathic interstitial pneumonias (IIPs) seriously compromises the success of treatment of Japanese lung cancer patients. Here, we conducted a nationwide surveillance to clarify the risk of AEx and compare it with the survival benefit of chemotherapy for this population.MethodsAdvanced nonsmall cell lung cancer (NSCLC) or small cell lung cancer (SCLC) patients with IIPs were retrospectively analysed. For the surveillance of first-line chemotherapy in 2009, we gathered clinical data from 396 patients who received chemotherapy at 19 institutions between January 1990 and July 2009. In a consecutive retrospective study in 2012, we analysed data from 278 patients from 17 institutions who received second-line chemotherapy between April 2002 and March 2012.ResultsOf the 396 patients analysed, 13.1% developed chemotherapy-related AEx. Combination chemotherapies of carboplatin plus paclitaxel (CP) or carboplatin plus etoposide (CE) were frequently used as first-line treatments. The lowest incidence of AEx was 3.7% in CE, followed by 8.6% in CP. In the retrospective study, 16.2% of the 278 patients developed a second-line chemotherapy-related AEx. The overall response rate by second-line chemotherapy was 7.4% in NSCLC and 25.7% in SCLC. The median overall survival from second-line and first-line chemotherapy was 8.0 and 14.3 months in NSCLC, and 8.7 and 16.0 months in SCLC, respectively.ConclusionCombination chemotherapies consisting of CP or CE are candidates for standard first-line treatments for patients with advanced lung cancer accompanied by IIP. Second-line chemotherapy should be considered for patients remaining fit enough to receive it.

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