Top

Lung

Published in:

01-04-2020 | Hypersensitivity Pneumonitis | INTERSTITIAL LUNG DISEASE

Change in Serum Biomarker CA 15-3 as an Early Predictor of Response to Treatment and Survival in Hypersensitivity Pneumonitis

Authors: S. A. Moll, I. A. Wiertz, A. D. M. Vorselaars, H. J. T. Ruven, C. H. M. van Moorsel, J. C. Grutters

Published in: Lung | Issue 2/2020

Abstract

Background

Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a heterogeneous course of disease and treatment response. Cancer antigen 15-3 (CA 15-3), part of mucin 1, is believed to reflect epithelial cell injury and lung permeability and could be a potential biomarker for treatment response in HP.

Objective

To assess the value of CA 15-3 as a predictive biomarker in non-fibrotic and fibrotic HP during immunosuppressive therapy.

Design

Serum levels of CA 15-3 and pulmonary function tests (PFTs) were retrospectively retrieved from 48 HP patients treated with prednisone or cyclophosphamide at initiation of therapy (baseline), after 3 and 6 months. Pearson's correlation coefficient was computed to assess correlations between change in serum levels and PFT. Survival was evaluated using Kaplan–Meier curves.

Results

After 6 months of immunosuppressive therapy CA 15-3 levels decreased significantly compared to baseline (p = 0.001). Change in CA 15-3 after 6 months correlated with FVC change (r = − 0.469; p = 0.001). Correlations with FVC change were observed in prednisone-treated HP (r = − 0.514; p = 0.005) and fibrotic HP (r = − 0.417; p = 0.007). Three-month CA 15-3 change correlated with 6-month FVC change (r = − 0.599; p < 0.001). CA 15-3 declines of at least 7.9% after 6 months were associated with increased survival compared to minor CA 15-3 changes (HR 0.34; p = 0.020).

Conclusion

Serum CA 15-3 correlates with PFT during 6 months of immunosuppressive therapy in HP. Interestingly, early CA 15-3 changes could predict future PFT. Furthermore, a decrease in CA 15-3 is related to longer survival. Therefore, serum CA 15-3 is a promising biomarker for implementation in HP care.

Bourke SJ, Dalphin JC, Boyd G, McSharry C, Baldwin CI, Calvert JE (2001) Hypersensitivity pneumonitis: current concepts. Eur Respir J Suppl 32:81s–92sPubMed

Salisbury ML, Myers JL, Belloli EA, Kazerooni EA, Martinez FJ, Flaherty KR (2016) Diagnosis and treatment of fibrotic hypersensitivity pneumonia: Where we stand and where we need to go. Am J Respir Crit Care Med 196(6):690–699CrossRef

Planes C, Valeyre D, Loiseau A, Bernaudin JF, Soler P (1994) Ultrastructural alterations of the air-blood barrier in sarcoidosis and hypersensitivity pneumonitis and their relation to lung histopathology. Am J Respir Crit Care Med 150(4):1067–1074CrossRef

Spagnolo P, Rossi G, Cavazza A, Bonifazi M, Paladini I, Bonella F, et al (2015) Hypersensitivity pneumonitis: a comprehensive review. J Investig Allergol Clin Immunol 25(4):237–250; quiz follow 250

Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F et al (2003) Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 168(8):952–958CrossRef

Miller MR (2015) Does the use of per cent of predicted have any evidence base? Eur Respir J 45(2):322–323CrossRef

Hermans C, Bernard A (1999) Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 159(2):646–678CrossRef

Ley B, Brown KK, Collard HR (2014) Molecular biomarkers in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 307(9):L681–L691CrossRef

Ishikawa N, Hattori N, Yokoyama A, Kohno N (2012) Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 50(1):3–13CrossRef

10.

Janssen R, Grutters JC, Sato H, van Velzen-Blad H, Zanen P, Kohno N et al (2005) Analysis of KL-6 and SP-D as disease markers in bird fancier's lung Sarcoidosis. Vasc Diffuse Lung Dis 22(1):51–57

11.

Kobayashi J, Kitamura S (1995) KL-6: a serum marker for interstitial pneumonia. Chest 108(2):311–315CrossRef

12.

Kohno N (1999) Serum marker KL-6/MUC1 for the diagnosis and management of interstitial pneumonitis. J Med Invest 46(3–4):151–158PubMed

13.

Takahashi T, Munakata M, Ohtsuka Y, Kamachi A, Sato R, Homma Y et al (2000) Serum KL-6 concentrations in dairy farmers. Chest 118(2):445–450CrossRef

14.

Kruit A, Gerritsen WB, Pot N, Grutters JC, van den Bosch JM, Ruven HJ (2010) CA 15-3 as an alternative marker for KL-6 in fibrotic lung diseases Sarcoidosis. Vasc Diffuse Lung Dis 27(2):138–146

15.

Rusanov V, Kramer MR, Raviv Y, Medalion B, Guber A, Shitrit D (2012) The significance of elevated tumor markers among patients with idiopathic pulmonary fibrosis before and after lung transplantation. Chest 141(4):1047–1054CrossRef

16.

Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824CrossRef

17.

Ricci A, Mariotta S, Bronzetti E, Bruno P, Vismara L, De Dominicis C et al (2009) Serum CA 15-3 is increased in pulmonary fibrosis Sarcoidosis. Vasc Diffuse Lung Dis 26(1):54–63

18.

Kawase S, Hattori N, Ishikawa N, Horimasu Y, Fujitaka K, Furonaka O et al (2011) Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease. Respir Res. https://doi.org/10.1186/1465-9921-12-97 CrossRefPubMedPubMedCentral

19.

Kohno N, Awaya Y, Oyama T, Yamakido M, Akiyama M, Inoue Y et al (1993) KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis 148(3):637–642CrossRef

20.

Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M (1989) New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 96(1):68–73CrossRef

21.

Yokoyama A, Kohno N, Hamada H, Sakatani M, Ueda E, Kondo K et al (1998) Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 158(5 Pt 1):1680–1684CrossRef

22.

Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K et al (2002) Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 165(3):378–381CrossRef

23.

Hamai K, Iwamoto H, Ishikawa N, Horimasu Y, Masuda T, Miyamoto S et al (2016) Comparative study of circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as disease markers of idiopathic pulmonary fibrosis. Dis Markers. https://doi.org/10.1155/2016/4759040 CrossRefPubMedPubMedCentral

24.

Okada M, Suzuki K, Nakanishi T, Nakashima M (2006) Serum levels of KL-6 are positively correlated with those of CA15-3 in patients with interstitial pneumonia associated with collagen diseases. Respirology 11(4):509–510CrossRef

25.

Morisset J, Johannson KA, Vittinghoff E, Aravena C, Elicker BM, Jones KD et al (2017) Use of mycophenolate mofetil or azathioprine for the management of fibrotic hypersensitivity pneumonitis. Chest 151(3):619–625CrossRef

26.

Lota HK, Keir GJ, Hansell DM, Nicholson AG, Maher TM, Wells AU et al (2013) Novel use of rituximab in hypersensitivity pneumonitis refractory to conventional treatment. Thorax 68(8):780–781CrossRef

27.

Kokkarinen JI, Tukiainen HO, Terho EO (1992) Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung. Am Rev Respir Dis 145(1):3–5CrossRef

28.

Vorselaars AD, van Moorsel CH, Zanen P, Ruven HJ, Claessen AM, van Velzen-Blad H et al (2015) ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy. Respir Med 109(2):279–285CrossRef

29.

Guiot J, Moermans C, Henket M, Corhay JL, Louis R (2017) Blood Biomarkers in Idiopathic Pulmonary Fibrosis. Lung 195(3):273–280CrossRef

30.

Singh S, Collins BF, Sharma BB, Joshi JM, Talwar D, Katiyar S et al (2017) Interstitial lung disease in India. Results of a prospective registry. Am J Respir Crit Care Med 195(6):801–813CrossRef

31.

Sumida H, Asano Y, Tamaki Z, Aozasa N, Taniguchi T, Toyama T et al (2018) Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: a longitudinal observational study. J Dermatol 45(12):1425–1433CrossRef

32.

Fathi M, Helmers S, Lundberg IE (2012) KL-6: a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med 271(6):589–597CrossRef

33.

Wakamatsu K, Nagata N, Kumazoe H, Oda K, Ishimoto H, Yoshimi M et al (2017) Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis. Respir Investig 55(1):16–23CrossRef

34.

Satoh H, Kurishima K, Ishikawa H, Ohtsuka M (2006) Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 260(5):429–434CrossRef

35.

Molina R, Barak V, van Dalen A, Duffy MJ, Einarsson R, Gion M et al (2005) Tumor markers in breast cancer—European Group on Tumor Markers recommendations. Tumour Biol 26(6):281–293CrossRef

36.

Fu Y, Li H (2016) Assessing clinical significance of serum CA15-3 and carcinoembryonic antigen (CEA) levels in breast cancer patients: a meta-analysis. Med Sci Monit 22:3154–3162CrossRef

Title: Change in Serum Biomarker CA 15-3 as an Early Predictor of Response to Treatment and Survival in Hypersensitivity Pneumonitis
Authors: S. A. Moll
I. A. Wiertz
A. D. M. Vorselaars
H. J. T. Ruven
C. H. M. van Moorsel
J. C. Grutters
Publication date: 01-04-2020
Publisher: Springer US
Keywords: Hypersensitivity Pneumonitis
Pulmonary-Function Tests
Biomarkers
Published in: Lung / Issue 2/2020
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-020-00330-9

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Design

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2020

Needle Aspiration Versus Closed Thoracostomy in the Treatment of Spontaneous Pneumothorax: A Meta-analysis

Resveratrol Attenuates Intermittent Hypoxia-Induced Lung Injury by Activating the Nrf2/ARE Pathway

High Expression of CARM1 Inhibits Lung Cancer Progression by Targeting TP53 by Regulating CTNNB1

Real-Life Study of Mepolizumab in Idiopathic Chronic Eosinophilic Pneumonia

Chitotriosidase Activity in Plasma and COPD Exacerbations

Is Vimentin the Cause or Effect of Obstructive Sleep Apnea Development?

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials