Exacerbation Of Idiopathic Interstitial Pneumonia Research Articles

＜Editors' Choice＞ Comparison of clinical features between patients with acute exacerbation of idiopathic interstitial pneumonia and collagen vascular disease-associated interstitial pneumonia.

Acute exacerbation (AE) of interstitial pneumonia (IP) shows poor prognosis, due to the typical histological pattern of diffuse alveolar damage superimposed upon lung fibrosis. The previous reports comparing clinical features between AE of idiopathic interstitial pneumonias (IIPs) and those of IPs with known etiology are limited. We retrospectively compared clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers at diagnosis of AE, treatment, and 3-month mortality between patients with AE of IIPs and collagen vascular disease-associated interstitial pneumonia (CVD-IP). We assessed 85 patients, comprising 66 patients with AE of IIPs (78%) and 19 patients with AE of CVD-IP (22%). The least absolute shrinkage and selection operator regression selected CCIS (hazard ratio, 1.281; 95% confidence interval, 1.055-1.556; P = 0.012) and log serum lactate dehydrogenase (LDH) (hazard ratio, 6.267; 95% confidence interval, 2.172-18.085; P < 0.001) as significant predictors of 3-month mortality among these patients. Also, the adjusted survival curves using sex, CCIS, and serum LDH showed no significant differences between these two groups. In conclusion, among AE patients, CCIS and serum LDH level may be more important prognostic factors for 3-month mortality rather than two classification of IP subtypes: IIPs and CVD-IP.

Impact of partial pressure of arterial oxygen and radiologic findings on postoperative acute exacerbation of idiopathic interstitial pneumonia in patients with lung cancer.

To establish accurate diagnostic criteria and predictors of treatment response for postoperative acute exacerbation (AE) in patients with lung cancer and idiopathic interstitial pneumonia (IIP). Among 93 patients with IIP who underwent surgery for lung cancer, suspected postoperative AE developed in 20 (21.5%). Patients were divided into a progressive AE group, comprising patients with bilateral alveolar opacities and decreasing PaO2 ≥ 10mmHg (n = 5); an incipient AE group, comprising patients with unilateral alveolar opacities and decreasing PaO2 ≥ 10mmHg (n = 10); and an indeterminate AE group, comprising patients with alveolar opacities but decreasing PaO2 < 10mmHg (n = 5). The progressive AE group had significantly higher 90-day mortality (80%) than the incipient AE group (10%, P = 0.017) or the indeterminate AE group (0%, P = 0.048). Bilateral opacities may indicate advanced AE and poor prognosis, whereas unilateral opacities may indicate an early stage of AE and a good prognosis. PaO2 < 10mmHg may indicate conditions other than AE. In patients with lung cancer and IIP, decreasing PaO2 and HRCT findings may allow for the initiation of rapid and accurate treatment strategies for postoperative AE.

A predictive model for acute exacerbation of idiopathic interstitial pneumonias.

Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) induces permanent pulmonary dysfunction and is potentially lethal. The unpredictable occurrence of AE-IIPs remains an important clinical issue in the management of IIPs. In this multicentre, retrospective, observational study, a predictive score for AE-IIPs was designed using clinical factors based on multivariate Fine-Gray analysis in patients with IIPs. Based on multivariate Fine-Gray analysis in an exploratory cohort of 487 patients with IIPs, the predictive score for AE-IIPs was determined as follows: 1 point each was added for honeycombing on high-resolution computed tomography (H), age >75 years (A) and lactate dehydrogenase level >222 U·L-1 (L); the total score ranged from 0 to 3 (HAL score). The HAL score discriminated the risk of AE-IIPs with a C-index of 0.62 (95% CI 0.56-0.67); this discrimination was verified in a validation cohort of 402 patients with IIPs with a C-index of 0.67 (95% CI 0.60-0.73). In a combined cohort, the estimated cumulative risks for AE-IIPs at 1, 2, 3, 5 and 10 years were 1.9%, 3.5%, 5.1%, 7.7% and 12.9%, respectively, in the total score 0 group; 4.7%, 8.3%, 12.0%, 17.7% and 28.4%, respectively, in the total score 1 group; and 8.0%, 14.2%, 19.7%, 28.7% and 43.0%, respectively, in the total score ≥2 group. Subgroup analysis revealed that the HAL score was applicable to patients with and without idiopathic pulmonary fibrosis. The HAL score discriminated the risk of AE-IIPs and could aid in the management of IIPs.

Efficacy of initial high- versus low-dose intravenous corticosteroid therapy in patients with acute exacerbation of idiopathic interstitial pneumonia: A nationwide observational study.

Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) has a high mortality. However, there is no established treatment for AE-IIPs. Therefore, we aimed to compare the efficacy of high- and low-dose corticosteroid therapies in AE-IIPs patients. Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from July 2010 to March 2018. Adult patients with AE-IIPs who received high-dose (methylprednisolone at a dose of 500-1000 mg/day for 3 days starting within 4 days after admission) or low-dose (methylprednisolone at a dose of 100-200 mg/day for at least 5 days starting within 4 days after admission) corticosteroid therapy were identified. Eligible patients (n = 17,317) were divided into the high-dose (n = 16,998) and low-dose (n = 319) groups. A stabilized inverse probability of treatment weighting using propensity scores was performed to compare outcomes between the groups. The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, infections during hospitalization, length of hospitalization, duration of steroid use, and discharge to home. The in-hospital mortality rates of the high- and low-dose corticosteroid groups were 50.6% and 47.0%, respectively. In-hospital mortality did not significantly differ between the two groups after stabilized inverse probability of treatment weighting, and the odds ratio in the low-dose corticosteroid group was 0.86 (95% confidence interval: 0.64-1.16; p = 0.33). The secondary outcomes also did not significantly differ between the groups. There was no significant difference in outcomes between patients with AE-IIPs who received high- and low-dose corticosteroid therapies.

Chemotherapy versus best supportive care in advanced lung cancer and idiopathic interstitial pneumonias: A retrospective multi-centre cohort study

BackgroundThe clinical questions of whether chemotherapy as initial treatment, compared with best supportive care (BSC), improves overall survival (OS) and whether it increases the occurrence risk of acute exacerbation of idiopathic interstitial pneumonia (IIP) in patients with advanced-stage lung cancer and IIP remain inconclusive. This study addresses these issues, given that chemotherapy-related acute exacerbation of IIP may be a direct cause of mortality in these patients. MethodsWe enrolled 1003 patients from 110 Japanese institutions and collected clinical profiles from 707 and 296 patients in the chemotherapy (men: women, 645:62; mean age, 70.4 ± 6.9 years) and BSC (men: women, 261:35; mean age, 75.2 ± 7.8) groups, respectively. We used propensity score matching to create 222 matched pairs from both groups using patient demographic data (age, sex, smoking status, performance status, history of acute exacerbation of IIP, desaturation on exertion, clinical diagnosis of IIP, high-resolution computed tomography findings, serum fibrotic markers, pulmonary function status, and lung cancer histopathology). Logistic or Cox regression analyses were performed using matched data to assess the effects of chemotherapy on the risk of acute exacerbation of IIP or OS, respectively. ResultsIn the well-matched cohort, chemotherapy improved OS (hazard ratio: 0.629, 95% confidence interval [CI]: 0.506–0.783, p < 0.0001); however, it involved significant acute exacerbation of IIP (odds ratio: 1.787, 95% CI: 1.026–3.113) compared to BSC. ConclusionsCompared with BSC, chemotherapy can improve OS in patients with advanced-stage lung cancer and IIP; however, it increases the risk of acute exacerbation of IIP.

P16‐90: Clinical comparison of patients with acute exacerbation of idiopathic interstitial pneumonias and secondary interstitial pneumonias

P16‐90: Clinical comparison of patients with acute exacerbation of idiopathic interstitial pneumonias and secondary interstitial pneumonias

P16‐63: Efficacy of high‐ versus low‐dose corticosteroid therapy in patients with acute exacerbation of idiopathic interstitial pneumonia: A nationwide observational study

P16‐63: Efficacy of high‐ versus low‐dose corticosteroid therapy in patients with acute exacerbation of idiopathic interstitial pneumonia: A nationwide observational study

P16‐59: Clinical significance of serum heart‐type fatty acid‐binding protein (H‐FABP) in acute exacerbation of idiopathic interstitial pneumonias

P16‐59: Clinical significance of serum heart‐type fatty acid‐binding protein (H‐FABP) in acute exacerbation of idiopathic interstitial pneumonias

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

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...

A Case Report of Acute Type B Dissection with ARDS Due to Acute Exacerbation of Idiopathic Interstitial Pneumonia

急性B型大動脈解離は，発症から治療途中にさまざまな合併症を伴う疾患である。われわれは，急性B型大動脈解離を発症し，間質性肺炎の急性増悪からARDSを発症した症例を経験したので報告する。80歳男性。主訴は背部痛。急性B型大動脈解離を認め，安静降圧管理を開始した。入院後3日目に呼吸苦を認め，酸素化不良でCTを施行したところ，特発性間質性肺炎の急性増悪および，それに伴うARDSの診断で，BiPAPとメチルプレドニゾロンを開始し軽快した。

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

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.

Risk factors for acute exacerbation of idiopathic interstitial pneumonia in patients undergoing lung cancer treatment.

Identifying risk factors for cancer treatment-related acute exacerbations (AEs) of idiopathic interstitial pneumonia (IIP) in patients with lung cancer. We retrospectively reviewed clinical records of 98 patients with concurrent lung cancer and IIPs diagnosed and treated at the Sapporo Medical University Hospital from January 2010 to December 2014. Of the 98 patients with concurrent lung cancer and IIPs, 14 patients (14.3%) had AEs. A total of 10 patients died. The univariate analysis revealed that the patients with idiopathic pulmonary fibrosis (IPF) or usual interstitial pneumonia (UIP) patterns on chest computed tomography (CT) had significantly higher rates of AE than those with non-IPF or non-UIP patterns, respectively. Further, those with a reduced percentage of forced vital capacity (%FVC) predictive values or elevated Krebs von den Lungen-6 (KL-6) presented significantly higher rates of AE. Our multivariate analysis identified that UIP pattern on chest CT and each 10% decrease in %FVC were significant independent risk factors for AEs. Of the 14 patients who experienced AEs, 10 cases were associated with cancer treatment. The treatment-specific incidences were 3/40 (7.5%) for surgery, 5/50 (10.0%) for chemotherapy, and 2/26 (7.7%) for radiation therapy. After comparing the AE incidences in 55 cases receiving one treatment (monotherapy group) and in 29 cases receiving two types of treatment or more (multitherapy group), we found no significant differences. Chest CT UIP patterns and reduced %FVC are independent risk factors for AE. Moreover, AE incidence did not increase in the multitherapy group compared with the monotherapy group.

Preoperative Evaluation of Patients With Interstitial Lung Disease

Preoperative Evaluation of Patients With Interstitial Lung Disease

Serum decorin is a potential prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis.

Decorin is a small leucine-rich repeat proteoglycan that plays a critical role in collagen fibrillogenesis, and regulates inflammation, wound healing and angiogenesis. In idiopathic pulmonary fibrosis (IPF), decorin is expressed in fibrotic lesions; furthermore, intratracheal gene transfer of decorin has been demonstrated to inhibit bleomycin-induced pulmonary fibrosis. Although these results suggest the critical role of decorin in pulmonary fibrosis, the role of decorin in the acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) has not been clarified in detail. Thus, the goal of this study was to determine the role of decorin in AE-IIP. We retrospectively analyzed AE-IIP patients who had been admitted to our hospital. First, serum decorin levels were compared among patients with AE-IIP, patients with stable idiopathic interstitial pneumonia (SD-IIP), and healthy subjects. Next, the relationship between serum decorin levels and clinical parameters was analyzed in AE-IIP patients. Finally, the association between serum decorin levels and prognosis was evaluated in AE-IIP patients. IIP was divided into IPF and non-IPF, according to the published guidelines. The serum decorin levels of AE-IIP patients were significantly lower than those of both healthy subjects and SD-IIP patients. Serum decorin levels were not related with the clinical parameters and prognosis, when all IIP patients were analyzed. In IPF patients, serum decorin levels had a significant correlation with oxygenation, and IPF patients with low serum decorin levels had a significantly higher survival rate than those with high serum decorin levels. Serum decorin levels are a potential prognostic biomarker in AE-IPF.

A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia

BackgroundIdiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers.MethodsPatients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies.ResultsSixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43–0.94], p = 0.022).ConclusionsThe ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.

Baseline serum syndecan-4 predicts prognosis after the onset of acute exacerbation of idiopathic interstitial pneumonia.

BackgroundPatients with idiopathic interstitial pneumonia can experience acute respiratory worsening, also known as acute exacerbation, with a large deterioration on prognosis. The precise mechanism remains unclear; however, syndecan-4 may be involved. Syndecan-4, a transmembrane heparan sulfate proteoglycan expressed in a variety of cells (e.g., epithelial cells, macrophages, fibroblasts, etc.), performs various biological roles by binding to several proteins through its heparan sulfate glycosaminoglycan side chains. The goal of this study was to clarify the role of syndecan-4 in acute exacerbation of idiopathic interstitial pneumonia.MethodsPatients with idiopathic interstitial pneumonia who had been sequentially admitted to our hospital due to acute exacerbation were retrospectively analyzed. First, serum syndecan-4 levels in the acute exacerbation and clinically stable phases were compared. Second, the relationship between serum syndecan-4 levels and clinical parameters was analyzed. Third, the relationship between serum syndecan-4 levels and prognosis was evaluated.ResultsSerum syndecan-4 levels were significantly lower in patients with acute exacerbation of idiopathic interstitial pneumonia than in patients in the clinically stable phase. Serum syndecan-4 levels also showed a significant positive correlation with white blood cell count and a weak positive tendency with KL-6 and baseline %VC. Prognosis was significantly worse in patients with idiopathic interstitial pneumonia with high baseline serum syndecan-4 levels than with low baseline levels. Multiple logistic analysis indicated baseline serum syndecan-4 level as the only prognostic predictor following acute exacerbation.ConclusionsBaseline serum syndecan-4 is a possible prognostic biomarker after the onset of acute exacerbation of idiopathic interstitial pneumonia.

Acute exacerbation of idiopathic interstitial pneumonia after nonpulmonary surgery under general anesthesia: a retrospective study.

Background: Idiopathic interstitial pneumonia (IIP) is associated with increased risk of acute exacerbation after lung surgery, which has a poor prognosis and can be fatal. Although some studies have investigated acute exacerbation of IIP after lung surgery, the incidence and risks of acute exacerbation of IIP after nonpulmonary surgery have not been reported. The aim of present study to evaluate the characteristics and risk factors for acute exacerbation of IIP after nonpulmonary surgery. Methods: We retrospectively reviewed the clinical characteristics of 2908 consecutive patients (1620 men, 1288 women; mean age, 61.7) who underwent nonpulmonary surgery under general anesthesia between April 2008 to April 2013. Using preoperative chest computed tomography images, we identified IIP cases and compared preoperative characteristics, laboratory findings, and anesthesia conditions among patients who did and did not develop AE. Results: We extracted 103 IIP patients who underwent nonpulmonary surgery; postoperative acute exacerbation of IIP developed in 8 (7.8%). Univariate analysis identified several risk factors, namely, emergency surgery, preoperative prednisolone use, high serum C-reactive protein, lactate dehydrogenase, white blood cell count, low serum albumin and propofol use during anesthesia. Conclusion: The results suggest that the incidences of postoperative acute exacerbation of IIP are similar after nonpulmonary and pulmonary surgery. In addition, propofol use during anesthesia is a possible risk factor for acute exacerbation of IIP after nonpulmonary surgery. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 156-164).

Study on Perioperative Administration of a Neutrophil Elastase Inhibitor for Interstitial Pneumonias

Although acute exacerbation of idiopathic interstitial pneumonias (IIPs) is a lethal complication after pulmonary resection for lung cancer with IIPs, there are no established methods to prevent its occurrence. This prospective randomized study was conducted to evaluate whether perioperative administration of the neutrophil elastase inhibitor sivelestat prevents acute exacerbation after surgery. The IIP patients with suspected lung cancers were randomly assigned to two groups before surgery: in group A (n= 65), sivelestat was perioperatively administered for 5 days; in group B (n= 65), no medications were administered. The primary endpoint was the frequency of acute exacerbation of IIPs. The secondary endpoints were perioperative changes in the lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, surfactant protein D and surfactant protein A values, and the safety of preoperative administration of sivelestat. Multivariate analyses were performed using a logistic regression model to identify the factors that predicted acute exacerbation. Acute exacerbation developed in 2 patients in group A and 1 patient in group B (p= 0.559). Administration of sivelestat did not contribute to decreasing the acute exacerbation as well as short- and long-term mortality. The differences were not statistically significant in perioperative lactate dehydrogenase, C-reactive protein, sialylated carbohydrate antigen, and surfactant protein D and A levels. No subjective adverse events were observed. A preoperative partial pressure oxygen level of less than 70 mm Hg was the only predictive factor identified in the logistic analysis (p= 0.019, hazard ratio 19.2). Perioperative administration of neutrophil elastase inhibitor appeared to be safe; however, it could not prevent the development of acute exacerbation after surgery in lung cancer patients with IIPs.

Postoperative pyothorax a risk factor for acute exacerbation of idiopathic interstitial pneumonia following lung cancer resection.

Acute exacerbation (AE) of idiopathic interstitial pneumonia (IP) is a potentially fatal postoperative complication following lung cancer resection. Postoperative pyothorax (PP) following development of a bronchopleural fistula (BPF) after lung surgery induces continuous inflammation and may affect the occurrence of AE. We investigated the relationship between AE and PP in patients who underwent pulmonary resection for lung cancer. A total of 941 patients who underwent lung resection due to primary lung cancer from 2006 to 2015 at our hospital were investigated. Of the 941 enrolled patients, 137 (14.6%) had idiopathic IP and were predominantly male (p<0.01). Pathological stage Ia and adenocarcinoma were observed at significantly high rates in the non-IP group (p<0.01). Patients with IP showed a tendency for a higher percentage of PP (p=0.054). Of the 137 patients with IP, 17 (12.4%) showed postoperative AE. Furthermore, PP was observed in three cases in the AE(+) group and two in the AE(-) group. PP had a correlation with a significantly higher incidence of AE (p=0.007). PP was found to be a significant risk factor for postoperative AE in lung cancer patients undergoing a pulmonary resection. Since IP itself is likely a risk factor for PP, prevention of BPF is important for patients with IP, as it can lead to PP.

Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic interstitial pneumonias

Background and objectiveWe hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of an acute exacerbation of the idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. The purpose of this study was to examine whether Ang-2 expression was associated with the pathogenesis of AE-IIPs. MethodsTwenty-three patients with AE-IIP patients, 18 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37 idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs) were enrolled. The serum level of Ang-2 was measured by an enzyme-linked immunosorbent assay. ResultsThe serum levels of Ang-2 were higher in AE-IIPs and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were also higher than in IPF patients. There was a positive correlation between the serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a significant positive correlation was found between the serum Ang-2 level and the CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level was not related to survival, the Ang-2 levels significantly declined in survivors during treatment, while they did not change in non-survivors. ConclusionsIncreased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIPs.