Prognostic role of Krebs von den Lungen-6 (KL-6) measurement in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Abstract Objectives Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease with limited therapeutic options. The measurement of Krebs von den Lungen-6 (KL-6) glycoprotein has been proposed for evaluating the risk of IPF progression and predicting patient prognosis, but the robustness of available evidence is unclear. Methods We searched Medline and Embase databases for peer-reviewed literature from inception to April 2020. Original articles investigating KL-6 as prognostic marker for IPF were retrieved. Considered outcomes were the risk of developing acute exacerbation (AE) and patient survival. Meta-analysis of selected studies was conducted, and quantitative data were uniformed as odds ratio (OR) or hazard ratio (HR) estimates, with corresponding 95% confidence intervals (CI). Results Twenty-six studies were included in the systematic review and 14 were finally meta-analysed. For AE development, the pooled OR (seven studies) for KL-6 was 2.72 (CI 1.22–6.06; p=0.015). However, a high degree of heterogeneity (I2=85.6%) was found among selected studies. Using data from three studies reporting binary data, a pooled sensitivity of 72% (CI 60–82%) and a specificity of 60% (CI 52–68%) were found for KL-6 measurement in detecting insurgence of AE in IPF patients. Pooled HR (seven studies) for mortality prediction was 1.009 (CI 0.983–1.036; p=0.505). Conclusions Although our meta-analysis suggested that IPF patients with increased KL-6 concentrations had a significant increased risk of developing AE, the detection power of the evaluated biomarker is limited. Furthermore, no relationship between biomarker concentrations and mortality was found. Caution is also needed when extending obtained results to non-Asian populations.

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An increased risk of lung cancer in combined pulmonary fibrosis and emphysema patients with usual interstitial pneumonia compared with patients with idiopathic pulmonary fibrosis alone: a systematic review and meta-analysis

Therapeutic Advances in Respiratory Disease ◽

10.1177/17534666211017050 ◽

2021 ◽

Vol 15 ◽

pp. 175346662110170

Author(s):

Qianqian Chen ◽

Ping Liu ◽

Hong Zhou ◽

Hui Kong ◽

Weiping Xie

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Interstitial Pneumonia ◽

Fixed Effects ◽

Meta Analysis ◽

Usual Interstitial Pneumonia ◽

Fixed Effects Model ◽

Increased Risk

Background: Lung cancer is an important complication of combined pulmonary fibrosis and emphysema (CPFE). Whether the risk of lung cancer is higher in CPFE patients with usual interstitial pneumonia (UIP) than those with idiopathic pulmonary fibrosis (IPF) alone, remains controversial. We conducted this systematic review and meta-analysis to evaluate the prevalence of lung cancer in CPFE patients with UIP compared with IPF patients. Methods: We searched the PubMed, Embase, and Cochrane databases for studies that focused on the incidence of lung cancer in CPFE/UIP and IPF groups. We used a fixed-effects model to analyze the odds ratios (ORs) with 95% confidence intervals (CIs) according to data heterogeneity. The cumulative effects based on the publication year and sample size were assessed by cumulative meta-analysis. Results: A total of nine studies with 933 patients, including 374 CPFE patients with UIP, fulfilled the inclusion criteria. Overall, CPFE patients with UIP have a higher risk of lung cancer than those with IPF alone (OR = 2.69; 95% CI: 1.78–4.05). There were increased risks of lung cancer in CPFE/UIP patients with the presence of emphysema (OR = 2.93; 95% CI: 1.79–4.79) or emphysema in ⩾10% of the lung volume (OR = 2.22; 95% CI: 1.06–4.68). Conclusions: Our systematic review and meta-analysis indicated a significantly higher prevalence of lung cancer in CPFE patients with UIP than in patients with IPF alone. The reviews of this paper are available via the supplemental material section.

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Efficacy and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis patients: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽

10.1136/bmjopen-2021-050004 ◽

2021 ◽

Vol 11 (12) ◽

pp. e050004

Author(s):

Wenjuan Wu ◽

Lingxiao Qiu ◽

Jizhen Wu ◽

Xueya Liu ◽

Guojun Zhang

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Adverse Events ◽

Acute Exacerbation ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomised Controlled

ObjectivesIdiopathic pulmonary fibrosis (IPF) has been defined as a distinctive type of chronic fibrotic disease, characterised by a progressive decline in lung function and a common histological pattern of interstitial pneumonia. To analyse the efficacy and safety of pirfenidone in the treatment of IPF, a systematic review and meta-analysis was performed.DesignThis is a meta-analysis study.ParticipantsPatients were diagnosed as IPF.InterventionsUse of pirfenidone.Primary and secondary outcomeProgression-free survival (PFS), acute exacerbation and worsening of IPF and Impact on adverse events.MeasuresThe inverse variance method for the random-effects model was used to summarise the dichotomous outcomes, risk ratios and 95% CIs.ResultsA total of 9 randomised controlled trials with 1011 participants receiving pirfenidone and 912 controls receiving placebo were summarised. The pooled result suggested a statistically significant difference inall-cause mortality after pirfenidone use, with a summarised relative ratio of 0.51 (p<0.01). Longer PFS was observed in patients receiving pirfenidone compared with those who were given placebo (p<0.01). The IPF groups presented a high incidence of adverse events with a pooled relative ratio of 3.89 (p<0.01).ConclusionsPirfenidone can provide survival benefit for patients with IPF. Pirfenidone treatment was also associated with a longer PFS, a lower incidence of acute exacerbation and worsening of IPF.

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The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Respiratory Research ◽

10.1186/s12931-021-01839-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ching-Yi Chen ◽

Chao-Hsien Chen ◽

Cheng-Yi Wang ◽

Chih-Cheng Lai ◽

Chien-Ming Chao ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Usual Care ◽

Antimicrobial Therapy ◽

Antimicrobial Agents ◽

Meta Analysis ◽

Lung Function Decline ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Abstract Background The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. Methods We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). Results Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI − 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI − 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). Conclusions In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

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Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis

Annals of Pharmacotherapy ◽

10.1177/1060028020964451 ◽

2020 ◽

pp. 106002802096445

Author(s):

Enrica Di Martino ◽

Alessio Provenzani ◽

Patrizio Vitulo ◽

Piera Polidori

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

World Health ◽

Effect Model ◽

All Cause Mortality ◽

Positive Effect

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

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Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis

Journal of Drug Assessment ◽

10.1080/21556660.2019.1597726 ◽

2019 ◽

Vol 8 (1) ◽

pp. 55-61 ◽

Cited By ~ 5

Author(s):

Aristeidis Skandamis ◽

Chara Kani ◽

Sophia L. Markantonis ◽

Kyriakos Souliotis

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Meta Analysis

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Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Pulmonary Pharmacology & Therapeutics ◽

10.1016/j.pupt.2016.07.009 ◽

2016 ◽

Vol 40 ◽

pp. 95-103 ◽

Cited By ~ 51

Author(s):

Paola Rogliani ◽

Luigino Calzetta ◽

Francesco Cavalli ◽

Maria Gabriella Matera ◽

Mario Cazzola

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Meta Analysis

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Prognosis of Adults with Idiopathic Pulmonary Fibrosis Without Effective Therapies: A Systematic Review and Meta-Analysis

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3392 ◽

2019 ◽

Author(s):

Y.H. Khor ◽

H. Barnes ◽

Y. Ng ◽

N. Goh ◽

C.F. McDonald ◽

...

Keyword(s):

Systematic Review ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Meta Analysis

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Prognostic factors for acute exacerbation of idiopathic pulmonary fibrosis: protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-028226 ◽

2019 ◽

Vol 9 (5) ◽

pp. e028226

Author(s):

Hiroyuki Kamiya ◽

Ogee Mer Panlaqui

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Prognostic Factor ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Acute Exacerbation ◽

Case Reports ◽

Meta Analysis ◽

Scientific Journal ◽

Grade Method

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

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