Clinical phenotyping in sarcoidosis management

Main Article Content

Giuseppe Domenico Rana
Miriana D'alessandro
Luigi Rizzi
Laura Bergantini
Paolo Cameli
Alfredo Vozza
Piersante Sestini
Patrizia Suppressa
Elena Bargagli

Keywords

sarcoidosis; biomarkers; phenotyping;

Abstract

Background: Sarcoidosis is an heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre study aim to analyse the clinical and immunological features of sarcoidosis and to identify a routine non-invasive biomarker useful in clinical practice.


Materials and methods: 129 Caucasian patients (median age IQR, 56 (47-62)) were enrolled retrospectively in the study. Medical history, routine laboratory findings, lung function results and radiological features from the last examination of October 2019 – February 2020 were gathered from the patients' clinical records.


Results: Irrespective of the symptoms at disease onset, at the last clinical examination the treatment group contained the same percentages of symptomatic and asymptomatic patients. Stratifying sarcoidosis population according to therapeutic management, the N/L ratio was higher in the treated group than in the non-treated group (p=0.0034). Receiver operating curve (ROC) analysis distinguished these two groups according to N/L ratio with an area under the curve (AUC) of 65.3% and a best cut-off value of 2.21. Peripheral N/L ratio was significantly higher in radiological stages 2-4 than in stages 0-1 (p=0.0090) distinguishing these two groups with an AUC of 64% and a best cut-off value of 2.13.


Discussion: In our multicentric cohort study similar periodic follow-up can be suggested for symptomatic and asymptomatic sarcoidosis patients at onset. In the heterogeneous context of this disease, N/L ratio proved to be a useful and simple routine laboratory biomarker related to disease activity and need for treatment.

Downloads

Download data is not yet available.
Abstract 219 | PDF Downloads 145

References

1. Baughman RP, Lower EE, Gibson K. Pulmonary manifestations of sarcoidosis. Presse Medicale Paris Fr 1983. giugno 2012;41(6 Pt 2):e289-302.
2. Moller DR. Potential etiologic agents in sarcoidosis. Proc Am Thorac Soc. 15 agosto 2007;4(5):465–8.
3. Drake WP, Oswald-Richter K, Richmond BW, Isom J, Burke VE, Algood H, et al. Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study. JAMA Dermatol. settembre 2013;149(9):1040–9.
4. Asakawa N, Uchida K, Sakakibara M, Omote K, Noguchi K, Tokuda Y, et al. Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients. PloS One. 2017;12(7):e0179980.
5. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 22 novembre 2007;357(21):2153–65.
6. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. agosto 1999;160(2):736–55.
7. Müller-Quernheim J, Schürmann M, Hofmann S, Gaede KI, Fischer A, Prasse A, et al. Genetics of sarcoidosis. Clin Chest Med. settembre 2008;29(3):391–414, viii.
8. Kreider ME, Christie JD, Thompson B, Newman L, Rose C, Barnard J, et al. Relationship of environmental exposures to the clinical phenotype of sarcoidosis. Chest. luglio 2005;128(1):207–15.
9. van Moorsel CHM. To progress understanding of disease triggers and modifiers in sarcoidosis, stratification is the key. Eur Respir J. 2017;50(6).
10. Consensus conference: activity of sarcoidosis. Third WASOG meeting, Los Angeles, USA, September 8-11, 1993. Eur Respir J. marzo 1994;7(3):624–7.
11. Bonham CA, Strek ME, Patterson KC. From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis. Curr Opin Pulm Med. 2016;22(5):484–91.
12. Nunes H, Uzunhan Y, Gille T, Lamberto C, Valeyre D, Brillet P-Y. Imaging of sarcoidosis of the airways and lung parenchyma and correlation with lung function. Eur Respir J. settembre 2012;40(3):750–65.
13. Keijsers RGM, Grutters JC. In Which Patients with Sarcoidosis Is FDG PET/CT Indicated? J Clin Med. 24 marzo 2020;9(3).
14. What Is the Neutrophil/Lymphocyte Ratio in Sarcoidosis? - PubMed [Internet]. [citato 22 maggio 2020]. Available at: https://pubmed.ncbi.nlm.nih.gov/26925745/?from_term=neutrophil%2Flymphocyte+sarcoidosis%2C+2016&from_sort=date&from_pos=2
15. Dirican N, Anar C, Kaya S, Bircan HA, Colar HH, Cakir M. The clinical significance of hematologic parameters in patients with sarcoidosis. Clin Respir J. 2016;10(1):32–9.
16. Sweiss NJ, Salloum R, Gandhi S, Ghandi S, Alegre M-L, Sawaqed R, et al. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations. PloS One. 5 febbraio 2010;5(2):e9088.
17. Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Statement Committee. American Thoracic Society. European Respiratory Society. World Association for Sarcoidosis and Other Granulomatous Disorders. Eur Respir J. ottobre 1999;14(4):735–7.
18. Keijsers RG, Veltkamp M, Grutters JC. Chest Imaging. Clin Chest Med. dicembre 2015;36(4):603–19.
19. Schupp JC, Freitag-Wolf S, Bargagli E, Mihailović-Vučinić V, Rottoli P, Grubanovic A, et al. Phenotypes of organ involvement in sarcoidosis. Eur Respir J. 2018;51(1).
20. Culver BH, Graham BL, Coates AL, Wanger J, Berry CE, Clarke PK, et al. Recommendations for a Standardized Pulmonary Function Report. An Official American Thoracic Society Technical Statement. Am J Respir Crit Care Med. 01 2017;196(11):1463–72.
21. Bargagli E, Olivieri C, Rottoli P. Cytokine modulators in the treatment of sarcoidosis. Rheumatol Int. dicembre 2011;31(12):1539–44.
22. Bargagli E, Magi B, Olivieri C, Bianchi N, Landi C, Rottoli P. Analysis of serum amyloid A in sarcoidosis patients. Respir Med. maggio 2011;105(5):775–80.
23. Bargagli E, Mazzi A, Mezzasalma F, Perrone A, Olivieri C, Prasse A, et al. The analysis of tryptase in serum of sarcoidosis patients. Inflammation. ottobre 2009;32(5):310–4.
24. Bargagli E, Bianchi N, Margollicci M, Olivieri C, Luddi A, Coviello G, et al. Chitotriosidase and soluble IL-2 receptor: comparison of two markers of sarcoidosis severity. Scand J Clin Lab Invest. 2008;68(6):479–83.
25. Bergantini L, Cameli P, d’Alessandro M, Vagaggini C, Refini RM, Landi C, et al. NK and NKT-like cells in granulomatous and fibrotic lung diseases. Clin Exp Med. novembre 2019;19(4):487–94.
26. Bergantini L, Bianchi F, Cameli P, Mazzei MA, Fui A, Sestini P, et al. Prognostic Biomarkers of Sarcoidosis: A Comparative Study of Serum Chitotriosidase, ACE, Lysozyme, and KL-6. Dis Markers. 2019;2019:8565423.
27. Cameli P, Gonnelli S, Bargagli E, d’Alessandro M, Bergantini L, Favetta V, et al. The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients. Respir Int Rev Thorac Dis. 2020;99(3):207–12.
28. d’Alessandro M, Carleo A, Cameli P, Bergantini L, Perrone A, Vietri L, et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med. maggio 2020;20(2):207–16.
29. d’Alessandro M, Bergantini L, Perrone A, Cameli P, Cameli M, Prasse A, et al. Serial investigation of Angiotensin-Converting Enzyme in sarcoidosis patients treated with Angiotensin-Converting Enzyme Inhibitor. Eur J Intern Med. 16 aprile 2020;
30. Kouranos V, Jacob J, Wells AU. Severe Sarcoidosis. Clin Chest Med. dicembre 2015;36(4):715–26.
31. Valeyre D, Bernaudin J-F, Uzunhan Y, Kambouchner M, Brillet P-Y, Soussan M, et al. Clinical presentation of sarcoidosis and diagnostic work-up. Semin Respir Crit Care Med. giugno 2014;35(3):336–51.
32. Zurkova M, Kolek V, Tomankova T, Kriegova E. Extrapulmonary involvement in patients with sarcoidosis and comparison of routine laboratory and clinical data to pulmonary involvement. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslov. dicembre 2014;158(4):613–20.
33. Li C-W, Tao R-J, Zou D-F, Li M-H, Xu X, Cao W-J. Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China. BMJ Open. 16 2018;8(2):e018865.
34. Nowinski A, Puscinska E, Goljan-Geremek A, Bednarek M, Kaminski D, Gorecka D. Comorbidities associated with sarcoidosis – Results from long-term observational study. Eur Respir J [Internet]. 1 settembre 2014 [citato 22 maggio 2020];44(Suppl 58). Available at: https://erj.ersjournals.com/content/44/Suppl_58/P461
35. Cohen PR, Kurzrock R. Sarcoidosis and malignancy. Clin Dermatol. giugno 2007;25(3):326–33.

Most read articles by the same author(s)