BACKGROUND: Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3+CD4+ and CD3+CD8+ lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). METHODS: We compared lymphocytes immune phenotypes, subsets, with CD3+, CD3+CD4+ and CD3+CD8+ cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. RESULTS: After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4/CD3+CD8 ratio showed the most significant differences between the non-smokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the non-smokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3+CD4+/CD3+CD8+ ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. CONCLUSIONS: Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.

Department of Immunology Faculty of Medicine and Dentistry and University Hospital Olomouc Olomouc Czech Republic

Department of Pathological Physiology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Respiratory Medicine Faculty of Medicine and Dentistry and University Hospital Olomouc Palacky University Olomouc Olomouc Czech Republic

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Zobrazit více v PubMed

Facco M, Cabrelle A, Teramo A, et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax 2011;66:144-50. 10.1136/thx.2010.140319 PubMed DOI

Meyer KC, Raghu G, Baughman RP, et al. An official American Thoracic Society clinical practice guidelines: The clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 2012;185:1004-14. 10.1164/rccm.201202-0320ST PubMed DOI

Danila E, Norkuniene J, Jurgauskiene L, et al. Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis. Clin Respir J 2009;3:214-21. 10.1111/j.1752-699X.2008.00126.x PubMed DOI

Celada LJ, Drake WP. Targeting CD4+ T cells for the treatment of sarcoidosis: a promising strategy? Immunotherapy 2015;7:57-66. 10.2217/imt.14.103 PubMed DOI PMC

Patterson KC, Chen ES. The pathogenesis of pulmonary sarcoidosis and implications for treatment. Chest 2018;153:1432-42. 10.1016/j.chest.2017.11.030 PubMed DOI

Crystal RG, Roberts WC, Hunninghake GW, et al. Pulmonary sarcoidosis: A disease characterized and perpetuated by activated lung T-lymphocytes. Ann Int Med 1981;94:73-94. 10.7326/0003-4819-94-1-73 PubMed DOI

Hunninghake GW, Crystal RG. Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity. N Engl J Med 1981;305:429-34. PubMed

Robinson BW, Rose AH, Thompson PJ, et al. Comparison of bronchoalveolar lavage helper/suppressor T-cell ratios in sarcoidosis versus other interstitial lung diseases. Aust N Z J Med 1987;17:9-15. 10.1111/j.1445-5994.1987.tb05041.x PubMed DOI

Petrek M, Kolek V. Determination of T-lymphocyte subsets in bronchoalveolar lavage of patients with pulmonary sarcoidosis. Acta Univ Palacki Olomuc Fac Med 1991;130:169-77. PubMed

Ward K, O'Connor C, Odlum C, et al. Prognostic value of bronchoalveolar lavage in sarcoidosis: the critical influence of disease presentation. Thorax 1989;44:6-12. 10.1136/thx.44.1.6 PubMed DOI PMC

Valeyre D, Prasse A, Nunes H, et al. Sarcoidosis. Lancet 2014;383:1155-67. 10.1016/S0140-6736(13)60680-7 PubMed DOI

Spagnolo P, Rossi G, Trisolini R, et al. Pulmonary sarcoidosis. Lancet Respir Med 2018;6:389-402. 10.1016/S2213-2600(18)30064-X PubMed DOI

Bonham CA, Strek ME, Patterson KC. From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis. Curr Opin Pulm Med 2016;22:484-91. 10.1097/MCP.0000000000000301 PubMed DOI PMC

Jara-Palomares L, Martin-Juan J, Gomez-Izquierdo L, et al. Bronchoalveolar lavage findings in patients with diffuse interstitial lung disease: prospective study of a cohort of 562 patients. Arch Bronconeumol 2009;45:111-7. 10.1016/j.arbres.2008.04.005 PubMed DOI

Lee W, Chung WS, Hong KS, et al. Clinical usefulness of bronchoalveolar lavage cellular analysis and lymphocyte subsets in diffuse interstitial lung diseases. Ann Lab Med 2015;35:220-5. 10.3343/alm.2015.35.2.220 PubMed DOI PMC

Tanriverdi H, Erboy F, Altinsoy B, et al. Bronchoalveolar lavage fluid characteristics of patients with sarcoidosis and non-sarcoidosis interstitial lung diseases: Ten-year experience of a single center in Turkey. Iran Red Crescent Med J 2015;17:e31103. 10.5812/ircmj.31103 PubMed DOI PMC

Roth C, Huchon GJ, Arnoux A, et al. Bronchoalveolar cells in advanced pulmonary sarcoidosis. Am Rev Respir Dis 1981;124:9-12. PubMed

Kucejko W, Chyczewska E, Naumnik W, et al. Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensitivity pneumonitis and idiopathic pulmonary fibrosis. Folia Histochem Cytobiol 2009;47:225-30. 10.2478/v10042-009-0028-9 PubMed DOI

Watters LC, King TE, Cherniack RM, et al. Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis. Am Rev Respir Dis 1986;133:104-9. 10.1164/arrd.1986.133.1.104 PubMed DOI

Valeyre D, Soler P, Clerici C, et al. Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease. Thorax 1988;43:516-24. 10.1136/thx.43.7.516 PubMed DOI PMC

Drent M, van Velzen-Blad H, Diamant M, et al. Relationship between presentation of sarcoidosis and T lymphocyte profile. A study in bronchoalveolar lavage fluid. Chest 1993;104:795-800. 10.1378/chest.104.3.795 PubMed DOI

Karimi R, Tornling G, Grunewald J, et al. Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on cumulative smoking history. PLoS One 2012;7:e34232. 10.1371/journal.pone.0034232 PubMed DOI PMC

Hunninghake GW, Costabel U, Ando M, et al. Statement on Sarcoidosis. Am J Respir Crit Care Med 1999;160:736-55. 10.1164/ajrccm.160.2.ats4-99 PubMed DOI

Petrek M, Kolek V. T-lymphocyte subpopulations in bronchoalveolar lavage in pulmonary sarcoidosis and in other diseases of the pulmonary interstitium. Cas Lek Cesk 1993;132:365-8. PubMed

Petrek M, Gibejova A, Drabek J, et al. CC chemokine receptor 5 (CCR5) mRNA expression in pulmonary sarcoidosis. Immunol Lett 2002;80:189-93. 10.1016/S0165-2478(01)00324-8 PubMed DOI

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1995;57:289-300.

Danila E, Jurgauskiene L, Malickaite R. BAL fluid cells and pulmonary function in different radiographic stages of newly diagnosed sarcoidosis. Adv Med Sci 2008;53:228-33. 10.2478/v10039-008-0014-z PubMed DOI

Danila E, Jurgauskiene L, Norkuniene J, et al. BAL fluid cells in newly diagnosed pulmonary sarcoidosis with different clinical activity. Ups J Med Sci 2009;114:26-31. 10.1080/03009730802579729 PubMed DOI PMC

Shigemitsu H, Azuma A. Sarcoidosis and interstitial pulmonary fibrosis; two distinct disorders or two ends of the same spectrum. Curr Opin Pulm Med 2011;17:303-7. 10.1097/MCP.0b013e3283486d52 PubMed DOI

Vasakova M, Sterclova M, Kolesar L, et al. Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases. Scand J Immunol 2009;69:268-74. 10.1111/j.1365-3083.2008.02222.x PubMed DOI

Antoniou KM, Soufla G, Proklou A, et al. Different activity of the biological axis VEGF-Flt-1 (fms-like tyrosine kinase 1) and CXC chemokines between pulmonary sarcoidosis and idiopathic pulmonary fibrosis: a bronchoalveolar lavage study. Clin Dev Immunol 2009;2009:537929. 10.1155/2009/537929 PubMed DOI PMC

Capelozzi VL, Faludi EP, Balthazar AB, et al. Bronchoalveolar lavage improves diagnostic accuracy in patients with diffuse lung disease. Diagn Cytopathol 2013;41:1-8. 10.1002/dc.21743 PubMed DOI

Ziegenhagen MW, Rothe ME, Schlaak M, et al. Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis. Eur Respir J 2003;21:407-13. 10.1183/09031936.03.00010403 PubMed DOI

Erkkilä S, Fröseth B, Hellström PE, et al. Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis. Sarcoidosis 1988;5:106-10. PubMed