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Open Access 01-04-2021 | Hypersensitivity Pneumonitis | INTERSTITIAL LUNG DISEASE

Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Registry-Based Descriptive Study

Authors: David Lang, Kaveh Akbari, Andreas Horner, Magdalena Hepp, Bernhard Kaiser, Herwig Pieringer, Bernd Lamprecht

Published in: Lung | Issue 2/2021

Abstract

Purpose

To evaluate the association of peripheral blood (PBL) and broncho-alveolar lavage (BAL) biomarkers with inflammatory versus fibrotic high-resolution computed tomography (HRCT) findings in interstitial lung disease (ILD) patients.

Methods

HRCT findings of 127 consecutive ILD-board patients were semi-quantitatively evaluated: reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), parenchymal nodules (NDL) and mosaic attenuation (MOS) as active inflammatory. Each HRCT finding was assessed in six distinct lung regions, resulting scores were graded as minimal (0–1 regions involved), medium (2–4) or extensive (5–6). Associations of routinely assessed PBL/BAL biomarkers with these HRCT scores were evaluated using Spearman correlation coefficients and graphical presentation; significance was tested by applying Kruskal–Wallis tests.

Results

Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil to lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations with inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (p = 0.032) and CON (p = 0.027) extent, eosinophil fraction by TBR (p = 0.006) and NLR by CON (p = 0.009). C-reactive protein was significantly related to GGO (p = 0.023) and CON (p = 0.004), BAL lymphocyte fraction to GGO (p = 0.017) extent.

Conclusion

Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns.

Trial registration

This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the Federal State of Upper-Austria (EK Number. I-26-17).

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Richeldi L, Cottin V, du Bois RM et al (2016) Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the TOMORROW and INPULSIS® trials. Respir Med 113:74–79. https://doi.org/10.1016/j.rmed.2016.02.001CrossRefPubMed

Noble PW, Albera C, Bradford WZ et al (2016) Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J 47:243–253. https://doi.org/10.1183/13993003.00026-2015CrossRefPubMedPubMedCentral

Maher TM, Corte TJ, Fischer A et al (2019) Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. https://doi.org/10.1016/S2213-2600(19)30341-8CrossRefPubMed

Flaherty KR, Wells AU, Cottin V et al (2019) Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 381:1718–1727. https://doi.org/10.1056/NEJMoa1908681CrossRefPubMed

Ito Y, Arita M, Kumagai S et al (2017) Serological and morphological prognostic factors in patients with interstitial pneumonia with autoimmune features. BMC Pulm Med 17:111. https://doi.org/10.1186/s12890-017-0453-zCrossRefPubMedPubMedCentral

Tashkin DP, Roth MD, Clements PJ et al (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4:708–719. https://doi.org/10.1016/S2213-2600(16)30152-7CrossRefPubMedPubMedCentral

Park IN, Jegal Y, Kim DS et al (2009) Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J 33:68–76. https://doi.org/10.1183/09031936.00158507CrossRefPubMed

Kolb M, Vašáková M (2019) The natural history of progressive fibrosing interstitial lung diseases. Respir Res 20:57. https://doi.org/10.1186/s12931-019-1022-1CrossRefPubMedPubMedCentral

Wijsenbeek M, Cottin V (2020) Spectrum of fibrotic lung diseases. N Engl J Med 383:958–968. https://doi.org/10.1056/NEJMra2005230CrossRefPubMed

10.

Heukels P, Moor CC, von der Thüsen JH et al (2019) Inflammation and immunity in IPF pathogenesis and treatment. Respir Med 147:79–91. https://doi.org/10.1016/j.rmed.2018.12.015CrossRefPubMed

11.

Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ et al (2012) Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 366:1968–77. https://doi.org/10.1056/NEJMoa1113354CrossRef

12.

Khanna D, Denton CP, Lin CJF et al (2018) Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis 77:212–220. https://doi.org/10.1136/annrheumdis-2017-211682CrossRefPubMed

13.

Distler O, Highland KB, Gahlemann M et al (2019) Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med 380:2518–2528. https://doi.org/10.1056/NEJMoa1903076CrossRefPubMed

14.

Walsh SLF, Devaraj A, Enghelmayer JI et al (2018) Role of imaging in progressive-fibrosing interstitial lung diseases. Eur Respir Rev 27:180073. https://doi.org/10.1183/16000617.0073-2018CrossRefPubMed

15.

Jeny F, Brillet P-Y, Kim Y-W et al (2019) The place of high-resolution computed tomography imaging in the investigation of interstitial lung disease. Expert Rev Respir Med 13:79–94. https://doi.org/10.1080/17476348.2019.1556639CrossRefPubMed

16.

Salisbury ML, Tolle LB, Xia M et al (2017) Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients. Respir Med 131:229–235. https://doi.org/10.1016/j.rmed.2017.08.025CrossRefPubMedPubMedCentral

17.

Flaherty KR (2003) Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 58:143–148. https://doi.org/10.1136/thorax.58.2.143CrossRefPubMedPubMedCentral

18.

Yunt ZX, Chung JH, Hobbs S et al (2017) High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: relationship to survival. Respir Med 126:100–104. https://doi.org/10.1016/j.rmed.2017.03.027CrossRefPubMed

19.

Lynch DA, Sverzellati N, Travis WD et al (2018) Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med 6:138–153. https://doi.org/10.1016/S2213-2600(17)30433-2CrossRefPubMed

20.

Raghu G, Remy-Jardin M, Myers JL et al (2018) Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 198:e44–e68. https://doi.org/10.1164/rccm.201807-1255STCrossRefPubMed

21.

von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457. https://doi.org/10.1016/S0140-6736(07)61602-XCrossRef

22.

Fischer A, Antoniou KM, Brown KK et al (2015) An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 46:976–987. https://doi.org/10.1183/13993003.00150-2015CrossRefPubMed

23.

Gruden JF, Naidich DP, Machnicki SC et al (2019) An algorithmic approach to the interpretation of diffuse lung disease on chest CT imaging. Chest. https://doi.org/10.1016/j.chest.2019.10.017CrossRefPubMed

24.

Kim M, Lee SM, Song J-W et al (2017) Added value of prone CT in the assessment of honeycombing and classification of usual interstitial pneumonia pattern. Eur J Radiol 91:66–70. https://doi.org/10.1016/j.ejrad.2017.03.018CrossRefPubMed

25.

Meyer KC (2014) The clinical utility of bronchoalveolar lavage in interstitial lung disease—is it really useful? Expert Rev Respir Med 8:133–135. https://doi.org/10.1586/17476348.2014.879827CrossRefPubMed

26.

Meyer KC, Raghu G, Baughman RP et al (2012) An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 185:1004–1014. https://doi.org/10.1164/rccm.201202-0320STCrossRefPubMed

27.

Lang D, Akbari K, Lamprecht B, Fellner F (2018) Initial patient characteristics and standardized quantification of radiological findings in nonspecific interstitial pneumonia. Pneumologie 72:S48–S48. https://doi.org/10.1055/s-0037-1619245CrossRef

28.

Lang D, Akbari K, Horner A et al (2020) Standardized computed tomography findings as determinants of local and systemic inflammation in interstitial lung disease patients. In: B42 ILD Epidemiol I [Internet]. American Thoracic Society, pp A3392–A3392. https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A3392

29.

Gambichler T, Tigges C, Burkert B et al (2010) Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis. Eur J Med Res 15:44. https://doi.org/10.1186/2047-783X-15-1-44CrossRefPubMedPubMedCentral

30.

Bonhomme O, André B, Gester F et al (2019) Biomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature. Rheumatology 58:1534–1546. https://doi.org/10.1093/rheumatology/kez230CrossRefPubMed

31.

Huemer F, Lang D, Westphal T et al (2019) Baseline absolute lymphocyte count and ECOG performance score are associated with survival in advanced non-small cell lung cancer undergoing PD-1/PD-L1 blockade. J Clin Med 8:1014. https://doi.org/10.3390/jcm8071014CrossRefPubMedCentral

32.

Welker L (2004) Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases. Eur Respir J 24:1000–1006. https://doi.org/10.1183/09031936.04.00101303CrossRefPubMed

33.

Costabel U, Bonella F, Ohshimo S, Guzman J (2010) Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med 31:404–408. https://doi.org/10.1055/s-0030-1262207CrossRefPubMed

34.

Veeraraghavan S, Latsi PI, Wells AU et al (2003) BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia. Eur Respir J 22:239–244. https://doi.org/10.1183/09031936.03.00105202CrossRefPubMed

35.

Ando K, Nakashita T, Kaneko N et al (2016) Associations between peripheral blood eosinophil counts in patients with systemic sclerosis and disease severity. Springerplus 5:1401. https://doi.org/10.1186/s40064-016-3106-4CrossRefPubMedPubMedCentral

36.

Kakugawa T, Sakamoto N, Sato S et al (2016) Risk factors for an acute exacerbation of idiopathic pulmonary fibrosis. Respir Res 17:79. https://doi.org/10.1186/s12931-016-0400-1CrossRefPubMedPubMedCentral

37.

Boomars KA, Wagenaar SS, Mulder PG et al (1995) Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis. Thorax 50:1087–1092. https://doi.org/10.1136/thx.50.10.1087CrossRefPubMedPubMedCentral

38.

Vettori S, Cuomo G, Iudici M et al (2014) Early systemic sclerosis: serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels. J Clin Immunol 34:663–668. https://doi.org/10.1007/s10875-014-0037-0CrossRefPubMed

39.

Davoine F, Lacy P (2014) Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front Immunol. https://doi.org/10.3389/fimmu.2014.00570CrossRefPubMedPubMedCentral

40.

Zhang L, Wu G, Gao D et al (2016) Factors associated with interstitial lung disease in patients with polymyositis and dermatomyositis: a systematic review and meta-analysis. PLoS ONE 11:e0155381. https://doi.org/10.1371/journal.pone.0155381CrossRefPubMedPubMedCentral

41.

Gao H, Zhang X-W, He J et al (2018) Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients. Medicine (Baltimore) 97:e11003. https://doi.org/10.1097/MD.0000000000011003CrossRef

42.

Liu X, Mayes MD, Pedroza C et al (2013) Does C-reactive protein predict the long-term progression of interstitial lung disease and survival in patients with early systemic sclerosis? Arthr Care Res (Hoboken) 65:1375–1380. https://doi.org/10.1002/acr.21968CrossRef

43.

Åttingsberg E, Hoyer N, Wilcke T, Prior TS, Bendstrup E, Shaker S (2019) Lactate dehydrogenase as a biomarker of advanced disease in idiopathic pulmonary fibrosis. In: Idiopathic interstitial pneumonias [Internet]. European Respiratory Society, p PA4701. http://erj.ersjournals.com/lookup/doi/10.1183/13993003.congress-2019.PA4701

44.

Gharsalli H, Mlika M, Sahnoun I et al (2018) The utility of bronchoalveolar lavage in the evaluation of interstitial lung diseases: a clinicopathological perspective. Semin Diagn Pathol 35:280–287. https://doi.org/10.1053/j.semdp.2018.08.003CrossRefPubMed

Title: Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Registry-Based Descriptive Study
Authors: David Lang
Kaveh Akbari
Andreas Horner
Magdalena Hepp
Bernhard Kaiser
Herwig Pieringer
Bernd Lamprecht
Publication date: 01-04-2021
Publisher: Springer US
Keywords: Hypersensitivity Pneumonitis
Idiopathic Pulmonary Fibrosis
Computed Tomography
Bronchiectasis
Computed Tomography
Biomarkers
Published in: Lung / Issue 2/2021
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-021-00434-w

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Abstract

Purpose

Methods

Results

Conclusion

Trial registration

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