Dataset Information

Systematic review and meta-analysis of clinical significance of autoantibodies for idiopathic pulmonary fibrosis.

ABSTRACT:

Objective

To clarify clinical significance of the sole presence of autoantibodies for idiopathic pulmonary fibrosis (IPF) without any other symptoms or signs suggestive of autoimmune disease.

Design

Systematic review and meta-analysis DATA SOURCES: Medline, EMBASE, Science Citation Index Expanded and Google Scholar were searched from 1 January 2002 through 12 February 2019.

Eligibility criteria for selecting studies

Primary studies addressing all-cause mortality and the development of a defined autoimmune disease for IPF with autoantibodies were included for the review.

Data extraction and synthesis

Two reviewers extracted relevant data and assessed risk of bias independently. Meta-analysis was conducted using a random-effects model if three or more studies reported the same outcome for a certain autoantibody. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation system.

Results

Out of 4603 records retrieved nine studies were included in this review. All studies contained some risk of bias. Based on pooled data myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was significantly associated with microscopic polyangiitis incidence with risk ratio (RR) of 20.2 (95% CI: 7.22 to 56.4) and antinuclear antibody (ANA) was also significantly associated with the development of connective tissue diseases with RR of 7.11 (p=0.001) (10 cases in 157 patients with ANA) in one study. However, there was no significant association of autoantibodies with all-cause mortality aside from MPO-ANCA and proteinase 3-ANCA in one study each. MPO-ANCA was not demonstrated to be associated with all-cause mortality by meta-analysis. The quality of evidence was deemed as either low or very low.

Conclusions

The presence of autoantibodies such as MPO-ANCA and ANA was demonstrated to be associated with the development of some autoimmune diseases for patients with IPF although there was no difference of all-cause mortality. However, the results should be interpreted with caution due to low evidence level.

Prospero registration number

CRD42017077336.

SUBMITTER: Kamiya H

PROVIDER: S-EPMC6550002 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:Idiopathic pulmonary fibrosis(IPF) is chronic fibrosing interstitial pneumonia of unknown aetiology. IPF is diagnosed based on the exclusion of known causes such as connective tissue diseases(CTDs). However, some patients fail to meet defined CTD criteria regardless of an implication of immunological involvement and these cases were described in a variety of terms. The classification criteria of this clinical entity consist of a combination of clinical, serological and morphological findings and it is reported to be distinct from IPF. However, the significance of the sole presence of autoantibodies complicated with IPF is still unknown. Therefore, this systematic review aims to clarify the significance of autoantibodies complicated with IPF. METHODS AND ANALYSIS:IPF with any autoantibody associated with CTDs is eligible for the review. Primary outcomes are all-cause mortality and pulmonary-cause mortality, while secondary outcomes include a progression of the disease, a deterioration of health-related quality of life and the development of a defined CTD. Primary studies of any type except a case report are included. Two reviewers search four electronic databases such as Medline, EMBASE, Science Citation Index Expanded and Google Scholar from each inception through 1 February 2018 and extract data independently. A risk of bias in individual studies is assessed by the Quality in Prognostic Studies tool. Meta-analysis is sought to be conducted if three or more studies report an outcome for a specific autoantibody with the same statistics. If it is inappropriate to combine data due to substantial heterogeneity, the result is reported qualitatively. Subgroup and sensitivity analyses are considered to identify the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to evaluate the evidence level of the result. ETHICS AND DISSEMINATION:There is no concerning ethical issue. The result will be sought for publication. PROSPERO REGISTRATION NUMBER:CRD42017077336.

Project description:BackgroundThe antifibrotics pirfenidone and nintedanib are both approved for the treatment of idiopathic pulmonary fibrosis (IPF) by regulatory agencies and are recommended by health technology assessment bodies. Other treatments such as N-acetylcysteine are used in clinical practice but have not received regulatory approval. No head-to-head trials have been conducted to directly compare the efficacy of these therapies in IPF.ObjectiveTo compare the efficacy of treatments for IPF.MethodsA systematic review was conducted up to April 2015. Phase II/III randomized controlled trials in adults with IPF were eligible. A Bayesian network meta-analysis (NMA) was used to compare pirfenidone, nintedanib, and N-acetylcysteine with respect to forced vital capacity (FVC) and mortality.ResultsNine studies were included in the NMA. For change from baseline in FVC, the NMA indicated that pirfenidone and nintedanib were more effective than placebo after 1 year (pirfenidone vs. placebo: difference = 0.12 liter (L), 95% credible interval [CrI] = 0.03-0.21 L; nintedanib vs. placebo: difference = 0.11 L, 95% CrI = 0.00-0.22 L). There was no evidence that N-acetylcysteine had an effect on FVC compared with placebo (N-acetylcysteine vs. placebo: difference = 0.01 L, 95% CrI = -0.15-0.17 L). Patients treated with pirfenidone also had a lower risk of experiencing a decline in percent predicted FVC of ≥ 10% over 1 year (odds ratio [OR]: 0.58, 95% CrI = 0.40-0.88), whereas there was no conclusive evidence of a difference between nintedanib and placebo (OR: 0.65, 95% CrI = 0.42-1.02). The NMA indicated that pirfenidone reduced all-cause mortality relative to placebo over 1 year (hazard ratio [HR]: 0.52, 95% CrI = 0.28-0.92). There was no evidence of a difference in all-cause mortality between nintedanib and placebo (HR: 0.70, 95% CrI = 0.32-1.55), or N-acetylcysteine and placebo (HR: 2.00, 95% CrI=0.46-8.62).ConclusionsOur primary analysis of the available evidence indicates that over 1 year, pirfenidone and nintedanib are effective at reducing lung-function decline, and pirfenidone may reduce the odds of experiencing a decline in percent predicted FVC of ≥10% compared with placebo in the first year of treatment. The results of our analysis also suggest that pirfenidone improves survival.DisclosuresFleetwood is an employee of Quantics Consulting. McCool and Glanville are employees of York Health Economics Consortium (YHEC). Quantics and YHEC received funding from F. Hoffmann-La Roche for conducting the systematic review and network meta-analysis reported in this paper. Edwards, Gsteiger, and Daigl are employees of F. Hoffmann-La Roche. Fisher was employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. The systematic review and network meta-analysis reported in this paper were conducted by Fleetwood (Quantics Consulting) and McCool and Glanville (YHEC), funded by F. Hoffmann-La Roche. The original network analysis was funded by InterMune. Study concept and design were contributed by Edwards, Gsteiger, and Daigl, along with Fleetwood, McCool, and Glanville. Fleetwood, McCool, and Glanville collected the data, with assistance from Edwards, Gsteiger, and Daigl. Data interpretation was performed by Fleetwood and Fisher, with assistance from the other authors. The manuscript was written by Fleetwood, McCool, and Glanville, with assistance from Edwards, Daigl, and Fisher, and revised by all the authors.

Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic oxido-inflammatory disorder of the lung. Oxidative stress is widely recognized as a central feature of IPF. Antioxidant therapy has been proposed as an effective treatment for IPF. An array of clinical trials describing the therapeutic impact of these drugs have been reporting albeit with conflicting evidence points. We performed a meta-analysis of trials in which efficacy of antioxidant therapy was compared with control in IPF. Systematic literature search was conducted in PubMed, EMBASE, the Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar till June 2016 by two independent researchers. Various outcomes such as changes in pulmonary function tests (change in vital capacity [ΔVC], change in forced vital capacity [ΔFVC], change in percentage of predicted vital capacity [Δ%VC], and change in percentage of predicted carbon monoxide diffusing capacity [Δ%DLco]), changes in 6 minutes walking test distance (Δ6MWT), rates of adverse events, and rates of death, were included. All statistical analyses were performed using RevMan V.5.3. Twelve studies (n = 1062) were identified that used antioxidants (N-acetylcysteine and lecithinized superoxide dismutase) as a treatment for IPF. Overall, there was no association of antioxidant therapy with ΔFVC (SMD = 0.27, 95% CI:-0.07 to 0.61; P = 0.12), ΔFVC (%) (SMD = -0.10, 95% CI:-0.56 to 0.36; P = 0.66) and 6MWT (SMD = -0.04, 95% CI:-0.11 to 0.20; P = 0.59) in IPF patients. However, combined antioxidant therapy was found to be associated with %VC (SMD = 0.37, 95% CI: 0.09 to 0.64; P = 0.008) and Δ%DLco (SMD = 0.15, 95% CI: 0.00 to 0.29; P = 0.05) in IPF patients. Strong evidence was obtained that the antioxidants increased adverse effects adverse events (OR = 1.56, 95% CI: 0.75 to 3.24; P = 0.23) but it did not associate mortality (OR = 0.96, 95% CI: 0.44 to 2.11; P = 0.92). The use of significant clinical heterogeneity, low statistical power, high dropout rates, duration of follow-ups, and dosing regimens of antioxidant agents. Combined antioxidant therapy seems to be a safe and effective therapy for IPF patients which provides a more beneficial effect in terms of VC, and DLco rather than monotherapy. Further randomized controlled trials with homogeneous outcome measures are needed.

Project description:OBJECTIVE:Lung transplantation remains the only curative treatment for end-stage lung disease, conferring a better survival for some IPF patients, but whether they should receive double lung transplantation (DLT) or single lung transplantation (SLT) is still controversial. The aim of this study was to determine which type of lung transplantation was more effective and relatively safe in IPF patients by meta-analysis. METHODS:Publications comparing overall survival (OS) or other perioperative characteristics between IPF patients undergoing SLT and DLT were selected from electronic databases. The hazard ratios (HRs) were abstracted or calculated to evaluate the survival outcome. Odds ratios (ORs) or mean differences (MDs) were used to compare the causes of death or perioperative parameters. A random-effect model was used to combine data. Heterogeneity was quantified by means of an I2 with 95% confidence interval (95% CI). The publication bias was estimated using the Eggers test with Begg's funnel plots. RESULTS:16 studies with 17,872 IPF cases who met the inclusion criteria were included in this meta-analysis. SLT was associated with declined post-transplant FEV1% (MD = -15.37, 95% CI:-22.28,-8.47; P<0.001), FVC % (MD = -12.52, 95% CI:-19.45,-5.59; P<0.001) and DLCO% (MD = -13.85, 95% CI:-20.42,-7.29; P<0.001), but no significant advantage of DLT over SLT was seen in the overall survival outcome (HR = 1.08, 95% CI: 0.91-1.29; P = 0.391). Subgroup analyses for studies of follow-up period ? 60 months also showed similar results (all P-values>0.05). Moreover, there was fewer deaths attributable to primary graft dysfunction in SLT recipients (OR = 0.31, 95% CI: 0.2-0.48; P<0.001), while more patients with SLT died of malignancy (OR = 3.44, 95% CI: 2.06-5.77; P<0.001). CONCLUSION:Our findings suggest that DLT was associated with better postoperative pulmonary function, but there was no difference in long-term overall survival between patients undergoing DLT and SLT. However, further high-quality and large-scale studies are needed to confirm these findings.

Project description:ObjectiveTo clarify prognostic factors of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF).DesignA systematic review and meta-analysis.Data sourcesMedline, Embase and Science Citation Index Expanded were searched from 2002 through 1 March 2019.Eligibility criteria for selecting studiesThe 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 synthesisTwo 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.ResultsOut 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).ConclusionsAPACHE 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 numberCRD42018106172.