Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study.
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ABSTRACT:
SUBMITTER: Suzuki T
PROVIDER: S-EPMC8079397 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acute exacerbation is a major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis. Although the real nature of it is still not clear and there is no proven effective therapy, progress has been made since the consensus definition and diagnostic criteria were proposed. The trial results of several new innovative therapies in idiopathic pulmonary fibrosis have suggested a potential for benefit in acute exacerbation of idiopathic pulmonary fibrosis, leading to double blind randomized clinical trials in this area. This article reviews the present knowledge on acute exacerbation of idiopathic pulmonary fibrosis, focusing on the triggering factors and treatment.
| S-EPMC7157478 | biostudies-literature
Project description:Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) results in poor survival. The objective of the present study was to elucidate the impact of asymmetrical ground-glass opacity (GGO) and/or consolidation on outcomes in patients with AE-IPF. The cases of 59 consecutive patients with AE-IPF were retrospectively reviewed. High-resolution computed tomography (HRCT) at diagnosis of an AE was assessed to determine the disease extent and asymmetry. Asymmetrical AE was defined as a right-to-left ratio of GGO and consolidation ≥2.0 or ≤0.5. The impacts of HRCT indices and other clinical parameters on 180-day mortality were analysed. The overall 180-day mortality rate was 59.2%, and asymmetrical AE was observed in 13 patients (22.0%). A multivariate analysis revealed that asymmetrical AE was a significant predictor of 180-day mortality (hazard ratio=0.36, p=0.047), long-term oxygen therapy before AE and serum lactate dehydrogenase levels. The 180-day mortality of patients with asymmetrical AE was significantly lower than that of patients with symmetrical AE (asymmetrical AE 30.8% versus symmetrical AE 68.2%, p=0.03). An asymmetrical distribution of GGO and/or consolidation is a predictor of survival in patients with AE-IPF.
| S-EPMC5555764 | biostudies-other
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic disease limited to the lung, with high variability in the course of disease from one patient to another. Patients with IPF may experience acute respiratory deteriorations; many of these acute declines are idiopathic and are termed acute exacerbations (AE) of IPF. In these cases, the exclusion of alternative causes of rapid deterioration, including heart failure, bilateral pneumonia or pulmonary embolism, is a challenging goal. AE may occur at any time during the course of IPF, although they are more common in patients with more progressive disease and gastroesophageal reflux. Surgical lung biopsy or even surgical procedures in organs other than the lungs may also trigger AE, mainly in rapidly progressive or advanced IPF. Current diagnostic criteria include the presence of new-onset ground glass opacities or airspace consolidation superimposed on an underlying usual interstitial pneumonia pattern seen on high-resolution computed tomography. The outcome is poor with a short-term mortality in excess of 50% despite therapy. Currently, there is no treatment with demonstrated efficacy for AE-IPF: empirical high-dose corticosteroid therapy is generally used, with or without immunosuppressive agents, with limited evidence. On the other hand, there is hope that new treatments to slow down progression of IPF will translate into a reduction of AE-IPF's occurrence. In conclusion, although significant progress in assessing disease severity in IPF has been made, AEs remain unpredictable and are associated with a high risk of death. Improvements in our understanding of the etiology, risk factors, clinical predictors and epidemiology are needed. It is the goal of clinical researchers in the field to provide respiratory physicians with evidence-based guidance to identify patients who may benefit from therapy for preventing or treating AE-IPF.
| S-EPMC7089322 | biostudies-literature
Project description:RationaleIdiopathic pulmonary fibrosis is a progressive, uniformly fatal interstitial lung disease. An acute exacerbation of idiopathic pulmonary fibrosis is an episode of acute respiratory worsening without an identifiable etiology. Occult viral infection has been proposed as a possible cause of acute exacerbation.ObjectivesTo use unbiased genomics-based discovery methods to define the role of viruses in acute exacerbation of idiopathic pulmonary fibrosis.MethodsBronchoalveolar lavage and serum from patients with acute exacerbation of idiopathic pulmonary fibrosis, stable disease, and acute lung injury were tested for viral nucleic acid using multiplex polymerase chain reaction, pan-viral microarray, and high-throughput cDNA sequencing.Measurements and main resultsFour of forty-three patients with acute exacerbation of idiopathic pulmonary fibrosis had evidence of common respiratory viral infection (parainfluenza [n = 1], rhinovirus [n = 2], coronavirus [n = 1]); no viruses were detected in the bronchoalveolar lavage from stable patients. Pan-viral microarrays revealed additional evidence of viral infection (herpes simplex virus [n = 1], Epstein-Barr virus [n = 2], and torque teno virus [TTV] [n = 12]) in patients with acute exacerbation. TTV infection was significantly more common in patients with acute exacerbation than stable controls (P = 0.0003), but present in a similar percentage of acute lung injury controls. Deep sequencing of a subset of acute exacerbation cases confirmed the presence of TTV but did not identify additional viruses.ConclusionsViral infection was not detected in most cases of acute exacerbation of idiopathic pulmonary fibrosis. TTV was present in a significant minority of cases, and cases of acute lung injury; the clinical significance of this finding remains to be determined.
| S-EPMC3136996 | biostudies-literature
Project description:OBJECTIVE:To clarify prognostic factors of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). DESIGN:A systematic review and meta-analysis. DATA SOURCES:Medline, Embase and Science Citation Index Expanded were searched from 2002 through 1 March 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:The review included primary studies addressing the association between the outcomes such as all-cause mortality of AE of IPF and its potential prognostic factors, which were designated as any clinical information related to the outcomes. DATA EXTRACTION AND SYNTHESIS:Two reviewers extracted relevant data independently and assessed risk of bias. Univariate results were pooled using a random-effect model if at least three studies were available. Prognostic factors were determined based on significant and consistent results on both univariate and multivariate analyses in the majority of studies. RESULTS:Out of a total of 6763 articles retrieved, 37 were eligible and 31 potential prognostic factors for all-cause mortality were selected. Each study was subject to certain methodological shortcomings. The following five factors were statistically significant by a meta-analysis of univariate results, which was confirmed by multivariate analysis, that is, Acute Physiology and Chronic Health Evaluation (APACHE) II score (HR 1.10, 1.01 to 1.19), partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio (ORs 0.99 in two studies and HRs 0.31 and 0.99 in two studies, respectively), lactate dehydrogenase (LDH) (HRs 1.002, 1.003, 1.01 and 1.02), white blood cell (WBC) count (OR 1.38, 1.04 to 1.83) and oxygen therapy before AE (HRs 3.68, 1.05 to 12.9 and 2.34, 1.04 to 5.28) (multivariate analysis, 95% CI). CONCLUSIONS:APACHE II score, PaO2/FiO2 ratio, LDH, WBC count and oxygen therapy before AE were deemed as prognostic factors of AE of IPF. Although there are some methodological limitations in this study, these findings are reliable due to consistent results by both univariate and multivariate analyses. PROSPERO REGISTRATION NUMBER:CRD42018106172.
| S-EPMC7299085 | biostudies-literature
Project description:Acute exacerbations of idiopathic pulmonary fibrosis are associated with high mortality and are of unknown cause. The effect of air pollution on exacerbations of interstitial lung disease is unknown. This study aims to define the association of air pollution exposure with acute exacerbation of idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis and corresponding air pollution data were identified from a longitudinal cohort. Air pollution exposures were assigned to each patient for ozone, nitrogen dioxide, particulate matter, sulfur dioxide and carbon monoxide based on geo-coded residential addresses. Cox proportional hazards models were used to estimate the association of air pollution exposures and acute exacerbations. Acute exacerbation was significantly associated with antecedent 6-week increases in mean level, maximum level and number of exceedances above accepted standards of ozone (hazard ratio (HR) 1.57, 95% CI 1.09-2.24; HR 1.42, 95% CI 1.11-1.82; and HR 1.51, 95% CI 1.17-1.94, respectively) and nitrogen dioxide (HR 1.41, 95% CI 1.04-1.91; HR 1.27, 95% CI 1.01-1.59; and HR 1.20, 95% CI 1.10-1.31, respectively). Increased ozone and nitrogen dioxide exposure over the preceding 6 weeks was associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis, suggesting that air pollution may contribute to the development of this clinically meaningful event.
| S-EPMC5555605 | biostudies-literature
Project description:Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients.
| S-EPMC5014970 | biostudies-literature
Project description:IntroductionIdiopathic pulmonary fibrosis (IPF) is a form of chronic fibrosing interstitial pneumonia with unknown disease aetiology. Acute exacerbation (AE) of IPF is an accelerated disease progression beyond its expected course. A 30-day mortality of AE of IPF is 40%. While death may occur, there is much variation in the clinical progression of this condition. Previous attempts have been made to investigate various possible prognostic factors for AE of IPF; however, they have yet to be confirmed. The aim of this systematic review is to clarify these prognostic factors.Methods and analysisIn this review, AE of IPF is the condition of interest, which has been defined according to previously established diagnostic criteria. The primary outcomes of interest include short-term all-cause mortality and pulmonary-cause mortality. The secondary outcomes of interest include long-term mortality and hospital separation for the disease. Primary studies investigating prognostic factors for AE of IPF are eligible for inclusion in this review. All study types are permitted except case reports. Two reviewers will search electronic databases, such as Medline and EMBASE, from 2002 to the 1 April 2019 and extract data independently. Risk of bias in individual studies will be assessed using the Quality in Prognostic Studies tool. Meta-analysis will be conducted for univariate data if at least three studies report the effect of a specific prognostic factor using similar statistical methods. Multivariate results will be reported qualitatively. Subgroup analysis and sensitivity analysis will be considered with the aim of generalising findings to the clinical settings and drawing more robust conclusions. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) method will be applied to evaluate the quality of evidence for each prognostic factor.Ethics and disseminationEthical approval will not be required. Results will be reported in a peer-reviewed scientific journal.Prospero registration numberCRD42018106172.
| S-EPMC6537967 | biostudies-literature
Project description:Purpose of reviewAcute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are the most frequent cause of death among patients with IPF. Here, we review the revised definition and diagnostic criteria for AE-IPF and discuss management strategies including mechanistically targeted investigational therapies for this complex syndrome.Recent findingsNovel therapies targeting various pathways including inflammation, autoimmunity and coagulation cascade involved in AE-IPF have recently been reported. Although most of these reports are small and uncontrolled, they have provided evidence to design larger randomized, controlled, multicenter studies to improve outcomes among patients with AE-IPF.SummaryAE-IPF has a dismal prognosis and current treatment consists mainly of supportive care and symptom palliation. There is a lack of consensus on current therapies for AE-IPF, including corticosteroids, but current randomized control studies for newer therapeutic strategies may hold promise.
| S-EPMC7732144 | biostudies-literature
Project description:The stimulator of interferon genes (STING) is a key adaptor protein mediating innate immune defense against DNA viruses. To investigate the role of STING in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), we isolated primary peripheral blood mononuclear cells (PBMCs) from patients and healthy controls (HCs). Raw264.7 and A549 cells were infected with herpes simplex virus type 1 (HSV-1). Mice with bleomycin-induced lung fibrosis were infected with HSV-1 to stimulate acute exacerbation of the lung fibrosis. Global gene expression profiling revealed a substantial downregulation of interferon-regulated genes (downstream of STING) in the AE-IPF group compared with the HC and stable IPF groups. The PBMCs of the AE-IPF group showed significantly reduced STING protein levels, increased levels of endoplasmic reticulum (ER) stress markers, and elevated apoptosis. HSV-1 infection decreased STING expression and stimulated the ER stress pathways in Raw264.7 and A549 cells in a time- and dose-dependent manner. HSV-1 infection exacerbated the bleomycin-induced lung injury in mice. In the primary bone marrow-derived macrophages of mice treated with bleomycin and HSV-1, STING protein expression was substantially reduced; ER stress was stimulated. Tauroursodeoxycholic acid, a known inhibitor of ER stress, partially reversed those HSV-1-mediated adverse effects in mice with bleomycin-induced lung injury. STING levels in PBMCs increased after treatment in patients showing improvement but remained at low levels in patients with deterioration. Viral infection may trigger ER stress, resulting in STING deficiency and AE-IPF onset.
| S-EPMC5732537 | biostudies-literature