The bronchoscopic probe-based confocal laser endomicroscopy to diagnose diffuse parenchymal lung diseases

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Frank Reichenberger
Edith Silbernagel
Michael Lindner
Elvira Stacher-Priehse
Julien Dinkel
Herbert Stepp
Wolfgang Gesierich
Juergen Behr


interstitial lung disease, diffuse parenchymal lung disease, bronchoscopy, probe based confocal laser endomicroscopy, imaging


Background: Diagnosis of diffuse parenchymal lung disease (DPLD) is based on clinical evaluation, radiological imaging and histology. However, additional techniques are warranted to improve diagnosis. 

Aims and objective: Probe based confocal laser endomicroscopy (pCLE) allows real time in vivo visualisation of the alveolar compartment during bronchoscopy based on autofluorescence of elastic fibres. We used pCLE (Cellvizio®, Mauna Kea Technology. Inc, Paris, France) to characterise alveolar patterns in patients with different types of DPLD.

Methods: In this pilot study we included 42 therapy naive patients (13 female, age 72,6 +/- 2,3 years), who underwent bronchoscopy for workup of DPLD. pCLE images were obtained during rigid bronchoscopy in affected lung segments according to HR-CT scan, followed by cryobiopsies in the identical area. Diagnoses were made by a multidisciplinary panel.

The description of pCLE patterns based on the degree of distortion of the hexagonal alveolar pattern, the density of alveolar structures, the presence of consolidations or loaded alveolar macrophages (AM). The assessment was performed by 2 investigators blinded for the final diagnosis.

Results: The normal lung showed a typical alveolar loop pattern. In amiodarone lung disease loaded AM were predominant. COP showed characteristic focal consolidations. IPF was characterized by significant distortion and destruction, NSIP showed significant increase in density, and chronic HP presented with consolidations, mild distortion and density.

Conclusion: pCLE shows potential as an adjunctive bronchoscopic imaging technique in the differential diagnosis of DPLD. Structured and quantitative analysis of the images is required.


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1 Tomassetti S, Ravaglia, Poletti V. Diffuse parenchymal lung disease.
Eur Respir Rev. 2017 Apr 26;26(144).

2 Castillo D, Walsh S, Hansell DM, Vasakova M, Cottin V, Altinisik G, Palmucci S, Sterclova M, Harari S, Richeldi L, Vancheri C, Wells AU; ERICE ILD working group. Validation of multidisciplinary diagnosis in IPF. Lancet Respir Med. 2018 Feb;6(2):88-89.

3 Travis WD, Costabel U, Hansell DM, et al. ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013 Sep 15;188(6):733-48

4. Hodnett PA, Naidich DP. Fibrosing interstitial lung disease. A practical
high-resolution computed tomography-based approach to diagnosis and management and a review of the literature. Am J Respir Crit Care Med. 2013 Jul 15;188(2):141-9

5. Interstitial lung diseases in European Lung White Book, editors J Gibson, R Loddenkemper, Y Sibille, B Lundbäck. Part C, Chapter 22. Page 256- 269, 2013.
6. Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med. 2018 Feb;6(2):138-153.

7 Martinez FJ, Chisholm A, Collard HR, Flaherty KR, Myers J, Raghu G, et al. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir Med 2017;5:61–71
8. Sgalla G, Kulkarni T, Antin-Ozerkis D, Thannickal VJ, Richeldi L.Update in Pulmonary Fibrosis 2018. Am J Respir Crit Care Med. 2019 Aug 1;200(3):292-300
9. Hetzel J, Maldonado F, Ravaglia C, Wells AU, et al. Transbronchial Cryobiopsies for the Diagnosis of Diffuse Parenchymal Lung Diseases: Expert Statement from the Cryobiopsy Working Group on Safety and Utility and a Call for Standardization of the Procedure. Respiration. 2018;95(3):188-200.

10 Thiberville L, Salaun M, Bourg-Heckly G. In vivo confocal microendoscopy: from the proximal bronchus down to the pulmonary acinus. Eur Respir Monogr 2010;48:73–89.

11. Thiberville L, Salaün M. Bronchoscopic advances: on the way to the cells.
Respiration. 2010;79(6):441-9.

12 Newton RC, Kemp SV, Yang GZ, Elson DS, Darzi A, Shah PL. Imaging parenchymal lung diseases with confocal endomicroscopy. Respir Med. 2012 Jan;106(1):127-37.

13 Meng P, Tan GL, Low SY, Takano A, Ng YL, Anantham D. Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases. J Thorac Dis. 2016; 8(12): 3505-3514.

14. Newton RC, Kemp SV, Yang GZ, Darzi A, Sheppard MN, Shah PL. Tracheobronchial
amyloidosis and confocal endomicroscopy. Respiration. 2011;82(2):209-11.

15. Danilevskaya O, Averyanov A, Lesnyak V, Chernyaev A, Sorokina A. Confocal
laser endomicroscopy for diagnosis and monitoring of pulmonary alveolar
proteinosis. J Bronchology Interv Pulmonol. 2015 Jan;22(1):33-40.

16 Salaün M, Roussel F, Bourg-Heckly G, Vever-Bizet C, Dominique S, Genevois A, Jounieaux V, Zalcman G, Bergot E, Vergnon JM, Thiberville L. In vivo probe-based confocal laser endomicroscopy in amiodarone-related pneumonia. Eur Respir J. 2013 Dec;42(6):1646-58.

17 Salaün M, Roussel F, Hauss PA, Lachkar S, Thiberville L. In vivo imaging of pulmonary alveolar proteinosis using confocal endomicroscopy. Eur Respir J. 2010 Aug;36(2):451-3.

18 Morisse H, Heyman L, Salaün M, Favennec L, Picquenot JM, Bohn P, Thiberville L. In vivo molecular microimaging of pulmonary aspergillosis. Med Mycol. 2013 May;51(4):352-60.

19 Shafiek H, Fiorentino F, Cosio BG, et al. Usefulness of Bronchoscopic Probe-Based Confocal Laser Endomicroscopy in the Diagnosis of Pneumocystis jirovecii Pneumonia. Respiration. 2016;92(1):40-7.

20 Yserbyt J, Dooms C, Janssens W, Verleden GM. Endoscopic advanced imaging of the respiratory tract: exploring probe-based confocal laser endomicroscopy in emphysema. Thorax. 2018 Feb;73(2):188-190.

21 Shah PL, Kemp SV, Newton RC, Elson DS, Nicholson AG, Yang GZ. Clinical
Correlation between Real-Time Endocytoscopy, Confocal Endomicroscopy, and
Histopathology in the Central Airways. Respiration. 2017;93(1):51-57. Epub 2016
Nov 18. PubMed PMID: 27855380.

22 Newton RC, Kemp SV, Shah PL, Elson D, Darzi A, Shibuya K, Mulgrew S, Yang GZ.
Progress toward optical biopsy: bringing the microscope to the patient. Lung.
2011 Apr;189(2):111-9. doi: 10.1007/s00408-011-9282-7. Epub 2011 Feb 20. Review.
PubMed PMID: 21336942.

23 Salaün M, Guisier F, Dominique S, Genevois A, Jounieaux V, Bergot E, Thill C,
Piton N, Thiberville L. In vivo probe-based confocal laser endomicroscopy in
chronic interstitial lung diseases: Specific descriptors and correlation with
chest CT. Respirology. 2019 Feb 27: 783-791.

24 Singh SJ, Puhan MA, Andrianopoulos V, et. al. An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease. Eur Respir J. 2014 Dec;44(6):1447-78.

25 Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, King TE Jr, Collard HR. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012 May 15;156(10):684-91

26 Oldham JM, Adegunsoye A, Valenzi E, et al. Characterisation of patients with interstitial pneumonia with autoimmune features. Eur Respir J 2016; 47: 1767–1775

27 Silbernagel E, Bondesson D, Behr J, Dinkel J, Reichenberger F. Taking Another View on Lung Fibrosis. Am J Respir Crit Care Med. 2018; 197: 947-948.

28 Poletti V, Ravaglia C, Tomassetti S. Transbronchial cryobiopsy in diffuse parenchymal lung diseases. Curr Opin Pulm Med. 2016 May;22(3):289-96.

29. Wijmans L, Bonta PI, Rocha-Pinto R, de Bruin DM, Brinkman P, Jonkers RE, Roelofs JJTH, Poletti V, Hetzel J, Annema JT. Confocal Laser Endomicroscopy as a Guidance Tool for Transbronchial Lung Cryobiopsies in Interstitial Lung Disorder. Respiration. 2018 Nov 14:1-5.

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