Poor prognostic factors for relapse of interstitial lung disease in microscopic polyangiitis: the Japanese multicentre REVEAL cohort study.
This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy.
We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission.
Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality.
The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.
Matsuda S
，Kotani T
，Okazaki A
，Nishioka D
，Masuda Y
，Shiomi M
，Watanabe R
，Taniguchi T
，Manabe A
，Kadoba K
，Yoshida T
，Hiwa R
，Yamamoto W
，Hashimoto M
，Takeuchi T
... -
《-》
Biomarkers of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.
Interstitial Lung Disease (ILD) represents the most common extra-articular manifestation of Rheumatoid Arthritis (RA) and is a major cause of mortality. This study aims to identify and evaluate biomarkers associated with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).
We searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for studies related to biomarkers of RA-ILD up until October 7, 2023. The Newcastle-Ottawa Scale (NOS) and standards recommended by the Agency for Healthcare Research and Quality (AHRQ) were used for quality assessment, and meta-analysis was conducted using Stata18.0 software.
A total of 98 articles were assessed for quality, 48 of which were included in the meta-analysis. 83 studies were of high quality, and 15 were of moderate quality. The meta-analysis showed significant differences in biomarkers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, Rheumatoid Factor (RF), Krebs von den Lungen-6 (KL-6), Surfactant Protein D (SP-D), Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9), Matrix Metalloproteinase-7 (MMP-7), C-X-C Motif Chemokine Ligand 10 (CXCL-10), and Neutrophil-to-Lymphocyte Ratio (NLR) between RA-ILD patients and RA patients. However, Platelet-to-Lymphocyte Ratio [Platelet-to-Lymphocyte Ratio (PLR)], Cancer Antigen 125 [Cancer Antigen 125 (CA-125)], and Cancer Antigen 153 [Cancer Antigen 153 (CA-153)] did not show significant differences between the two groups. KL-6, MMP-7, and Human Epididymis Protein 4 (HE4) are negatively correlated with lung function, and KL-6 is associated with the prognosis of RA-ILD.
Biomarkers hold promising clinical value for prediction, diagnosis, severity assessment, and prognosis evaluation in RA-ILD. However, these findings need to be validated through multicenter, large-sample, prospective cohort studies.
https://www.crd.york.ac.uk/prospero/, identifier CRD42023448372.
Guo L
，Wang J
，Li J
，Yao J
，Zhao H
... -
《Frontiers in Immunology》
Evaluating the diagnostic and prognostic utility of serial KL-6 measurements in connective tissue disease patients at risk for interstitial lung disease: correlations with pulmonary function tests and high-resolution computed tomography.
Interstitial lung diseases associated with connective tissue diseases (CTD-ILD) necessitate reliable biomarkers for effective management. This study assesses the utility of serial Krebs von den Lungen-6 (KL-6) measurements in predicting disease activity and progression in CTD-ILD patients.
In a prospective cohort study at a tertiary care center, 50 patients with CTD at risk of or diagnosed with ILD were enrolled. KL-6 levels and pulmonary function tests (PFTs) were measured at baseline, 6, and 12 months, alongside high-resolution computed tomography (HRCT).
Initial KL-6 levels were inversely correlated with PFTs, with mean values starting at 504.96 U/mL (SD ± 508.46), escalating to 739.42 U/mL (SD ± 612.75) at 6 months, and peaking at 1150.27 U/mL (SD ± 1106.70) by 12 months, reflecting disease progression. Higher KL-6 levels were consistently linked with declines in Forced Vital Capacity (FVC) (p = 0.019) and Diffusing Capacity for Carbon Monoxide (DLCO) (p < 0.001). Radiologically, increased KL-6 correlated with subpleural thickening (p = 0.003), septal thickening (p = 0.036), ground-glass opacities (p = 0.018), and other signs of advanced ILD. Sensitivity and specificity of KL-6 for detecting ILD were 86.7% and 71.4%, respectively, at a ≥ 400 U/mL threshold, improving at higher thresholds. Over the study period, patients with elevated KL-6 levels demonstrated more pronounced radiological and functional deterioration.
Serial KL-6 measurements effectively reflect disease activity and progression in CTD-ILD, with strong correlations to functional and radiological outcomes. These findings support the use of KL-6 as a valuable biomarker in the routine clinical management of these complex disorders. Our study demonstrates the significant predictive value of KL-6 for both the diagnosis and monitoring of CTD-ILD, suggesting its integration into clinical practice can enhance patient care and treatment strategies.
Álvarez Troncoso J
，Porto Fuentes Ó
，Fernández Velilla M
，Gómez Carrera L
，Soto Abánades C
，Martínez Robles E
，Sorriguieta Torre R
，Ríos Blanco JJ
... -
《BMC Pulmonary Medicine》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
