P16‐67: Kinetic changes of serum KL‐6 levels predict disease progression in systemic sclerosis‐associated interstitial lung disease

Abstract Background: The clinical course of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable. The Krebs von den Lungen-6 (KL-6) glycoprotein is a promising biomarker for reflectingepithelial injury. However, serum KL-6 and its association with the progression of SSc-ILD have been understudied. Methods: We reviewed 77 consecutive patients with SSc-ILD seen from 2004 to 2016. A longitudinal study of forced vital capacity (FVC), serum KL-6 levels, and the changes in KL-6 levels from baseline (ΔKL-6) was conducted. The progression of ILD was defined as ≥10% relative decline in FVC predicted or 5%–10% decline in FVC predicted along with radiological progression on chest computed tomography. The risk factors for ILD progression were assessed by univariate and multivariate regression.Results: The 77 study patients included 58 women (75%). The median age of the study patients was 56 years, and 59 (79%) patients had diffuse cutaneous SSc. During a 5-year follow-up period, 10 (13%) showed rapid progression of ILD within 2 years, 39 (51%) had overall progressionduring the 5 years, and 28 (36%) had stable disease. Most patients with progressive ILD showed elevationsin serum KL-6 levels over the initial 1-year follow-up period. The best cut-off value for ΔKL-6 that predicted progression of ILD was 193 U/mL (sensitivity 81.6%, specificity 92.9%). Multivariate analysis with adjustment revealed that diffuse cutaneous SSc(hazard ratio [HR] 3.1; 95% confidence interval [CI] 1.05-9.36]) and ΔKL-6 > 193 U/mL from baseline(HR, 4.7; 95% CI, 2.14-10.4)were independent predictors for progression of SSc-ILD.Conclusion: Changes in the KL-6 level can be useful for predicting disease progression in patients withSSc-ILD.

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One-step closer to solve the mystery of predicting disease progression in systemic sclerosis associated interstitial lung disease?

Thorax ◽

10.1136/thoraxjnl-2021-217811 ◽

2021 ◽

pp. thoraxjnl-2021-217811

Author(s):

Anna-Maria Hoffmann-Vold ◽

Michael Kreuter

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Progression ◽

One Step

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Assessment of disease progression in systemic sclerosis-associated interstitial lung disease (SSc-ILD) patients using Functional Respiratory Imaging (FRI)

10.1183/13993003.congress-2019.pa4805 ◽

2019 ◽

Author(s):

Johan Clukers ◽

Kate Homer ◽

Maarten Lanclus ◽

Dennis Belmans ◽

Cedric Van Holsbeke ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Progression

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AB1279 Evaluation of different composite radiological indexes for assessment of interstitial lung disease progression in systemic sclerosis:

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-eular.1275 ◽

2013 ◽

Vol 71 (Suppl 3) ◽

pp. 710.17-710

Author(s):

L.P. Ananyeva ◽

V. Lesnyak ◽

O. Ovsyannikova ◽

O. Koneva ◽

D. Goryachev

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Progression

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Predictors of progression in systemic sclerosis patients with interstitial lung disease

European Respiratory Journal ◽

10.1183/13993003.02026-2019 ◽

2020 ◽

Vol 55 (5) ◽

pp. 1902026 ◽

Cited By ~ 11

Author(s):

Oliver Distler ◽

Shervin Assassi ◽

Vincent Cottin ◽

Maurizio Cutolo ◽

Sonye K. Danoff ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Progression ◽

Topoisomerase I ◽

Diagnostic Tools ◽

Systemic Autoimmune Disease ◽

High Resolution Computed Tomography ◽

Time Period ◽

Organ Systems

Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organ systems, including the lungs. Interstitial lung disease (ILD) is the leading cause of death in SSc.There are no valid biomarkers to predict the occurrence of SSc-ILD, although auto-antibodies against anti-topoisomerase I and several inflammatory markers are candidate biomarkers that need further evaluation. Chest auscultation, presence of shortness of breath and pulmonary function testing are important diagnostic tools, but lack sensitivity to detect early ILD. Baseline screening with high-resolution computed tomography (HRCT) is therefore necessary to confirm an SSc-ILD diagnosis. Once diagnosed with SSc-ILD, patients' clinical courses are variable and difficult to predict, although certain patient characteristics and biomarkers are associated with disease progression. It is important to monitor patients with SSc-ILD for signs of disease progression, although there is no consensus about which diagnostic tools to use or how often monitoring should occur. In this article, we review methods used to define and predict disease progression in SSc-ILD.There is no valid definition of SSc-ILD disease progression, but we suggest that either a decline in forced vital capacity (FVC) from baseline of ≥10%, or a decline in FVC of 5–9% in association with a decline in diffusing capacity of the lung for carbon monoxide of ≥15% represents progression. An increase in the radiographic extent of ILD on HRCT imaging would also signify progression. A time period of 1–2 years is generally used for this definition, but a decline over a longer time period may also reflect clinically relevant disease progression.

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Serum markers of pulmonary epithelial damage in systemic sclerosis‐associated interstitial lung disease and disease progression

Respirology ◽

10.1111/resp.13988 ◽

2020 ◽

Author(s):

Carmel J.W. Stock ◽

Rachel K. Hoyles ◽

Cecile Daccord ◽

Maria Kokosi ◽

Dina Visca ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Disease Progression ◽

Serum Markers ◽

Epithelial Damage

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Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis–associated interstitial lung disease are not predictive of disease progression

Arthritis & Rheumatism ◽

10.1002/art.22696 ◽

2007 ◽

Vol 56 (6) ◽

pp. 2005-2012 ◽

Cited By ~ 105

Author(s):

Nicole S. L. Goh ◽

Srihari Veeraraghavan ◽

Sujal R. Desai ◽

Derek Cramer ◽

David M. Hansell ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

Disease Progression

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Natural history of systemic sclerosis–related interstitial lung disease: How to identify a progressive fibrosing phenotype

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198319889549 ◽

2019 ◽

Vol 5 (2_suppl) ◽

pp. 31-40 ◽

Cited By ~ 5

Author(s):

Elizabeth R Volkmann

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Lung Function ◽

Natural History ◽

Lung Disease ◽

Disease Progression ◽

Rapid Progression ◽

History Of ◽

Rate Of Decline ◽

Patients Experience

The natural history of interstitial lung disease in patients with systemic sclerosis is highly variable. Historical observational studies have demonstrated that the greatest decline in lung function in systemic sclerosis occurs early in the course of the disease; however, not all patients experience a decline in lung function even in the absence of treatment. Furthermore, among patients who do experience a decline in lung function, the rate of decline can be either rapid or slow. The most common clinical phenotypes of systemic sclerosis–related interstitial lung disease are, therefore, as follows: (1) rapid progressors, (2) gradual progressors, (3) stabilizers, and (4) improvers. This review summarizes the features of systemic sclerosis–related interstitial lung disease patients who are more likely to experience rapid progression of interstitial lung disease, as well as those who are more likely not to experience interstitial lung disease progression. Understanding the clinical, biological, and radiographic factors that consistently predict interstitial lung disease–related outcomes in systemic sclerosis is central to our ability to recognize those patients who are at heightened risk for interstitial lung disease progression. With new options available for treating patients with systemic sclerosis–related interstitial lung disease, it is more important than ever to accurately identify patients who may derive the most benefit from aggressive systemic sclerosis–related interstitial lung disease therapy. Early therapeutic intervention in patients with this progressive fibrosing phenotype may ultimately improve morbidity and mortality outcomes in patients with systemic sclerosis–related interstitial lung disease.

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