Transbronchial lung cryobiopsy (TBLC) in the diagnosis of interstitial lung disease: experience of first 100 cases performed under conscious sedation with flexible bronchoscope

Abstract

Background

Diagnosing the aetiology of interstitial lung disease (ILD) may require histology via a surgical lung biopsy (SLB). SLB is associated with significant complications. Transbronchial lung cryobiopsy (TBLC) can provide large, adequate biopsies with fewer complications offering a potential alternative to SLB.

Aims

This study evaluated the safety, diagnostic yield and impact of TBLC on diagnostic certainty in the multidisciplinary diagnosis (MDD) of ILD within routine clinical practice.

Methods

A retrospective study of all TBLC performed in a tertiary institute from March 2014 to December 2016 was performed. Procedures were performed using a flexible bronchoscope and cryoprobe without fluoroscopic guidance.

Results

One hundred procedures were performed on 85 patients. A total of 272 cryobiopsies were obtained with a mean biopsy diameter of 5.9 ± 3.2 mm. Ninety-seven percent contained alveolated lung tissue. Diagnosis based against MDD gold standard was confirmed using TBLC in 67.1% of patients and in 72/100 procedures. Three patients proceeded to SLB. The addition of histological information changed the clinic-radiological diagnosis in twelve patients. The most common diagnosis based on clinical-radiologic-pathologic correlation at MDD was idiopathic pulmonary fibrosis (IPF) (51.2%) and hypersensitivity pneumonitis (15.9%). Moderate bleeding occurred in 18% of cases and five patients (5%) developed pneumothorax requiring intervention. Eleven patients required admission, with a mean length of stay of 1.3 ± 0.9 days.

Conclusion

TBLC aids the diagnosis of ILD in the appropriate patient and may be an acceptable alternative to SLB with fewer complications. Further work on standardizing the procedure is required.

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Fig. 1

Data availability

On request.

References

  1. 1.

    Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D (2013) 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 188(6):733–748. https://doi.org/10.1164/rccm.201308-1483ST

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, Flaherty KR, Wells A, Martinez FJ, Azuma A, Bice TJ, Bouros D, Brown KK, Collard HR, Duggal A, Galvin L, Inoue Y, Jenkins RG, Johkoh T, Kazerooni EA, Kitaichi M, Knight SL, Mansour G, Nicholson AG, Pipavath SNJ, Buendía-Roldán I, Selman M, Travis WD, Walsh S, Wilson KC (2018) Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 198(5):e44–e68. https://doi.org/10.1164/rccm.201807-1255ST

    Article  Google Scholar 

  3. 3.

    Fisher JH, Shapera S, To T, Marras TK, Gershon A, Dell S (2019) Procedure volume and mortality after surgical lung biopsy in interstitial lung disease. Eur Respir J 53(2). https://doi.org/10.1183/13993003.01164-2018

  4. 4.

    Han Q, Luo Q, Xie JX, Wu LL, Liao LY, Zhang XX, Chen RC (2015) Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: a systematic review and meta-analysis. J Thorac Cardiovasc Surg 149(5):1394–1401. e1391. https://doi.org/10.1016/j.jtcvs.2014.12.057

    Article  PubMed  Google Scholar 

  5. 5.

    Hutchinson JP, Fogarty AW, McKeever TM, Hubbard RB (2016) In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med 193(10):1161–1167. https://doi.org/10.1164/rccm.201508-1632OC

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Kondoh Y, Taniguchi H, Kitaichi M, Yokoi T, Johkoh T, Oishi T, Kimura T, Nishiyama O, Kato K, du Bois RM (2006) Acute exacerbation of interstitial pneumonia following surgical lung biopsy. Respir Med 100(10):1753–1759. https://doi.org/10.1016/j.rmed.2006.02.002

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ensminger SA, Prakash UB (2006) Is bronchoscopic lung biopsy helpful in the management of patients with diffuse lung disease? Eur Respir J 28(6):1081–1084. https://doi.org/10.1183/09031936.06.00013106

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Babiak A, Hetzel J, Krishna G, Fritz P, Moeller P, Balli T, Hetzel M (2009) Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration 78(2):203–208. https://doi.org/10.1159/000203987

    Article  PubMed  Google Scholar 

  9. 9.

    Griff S, Schönfeld N, Ammenwerth W, Blum TG, Grah C, Bauer TT, Grüning W, Mairinger T, Wurps H (2014) Diagnostic yield of transbronchial cryobiopsy in non-neoplastic lung disease: a retrospective case series. BMC Pulm Med 14:171. https://doi.org/10.1186/1471-2466-14-171

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Gershman E, Fruchter O, Benjamin F, Nader AR, Rosengarten D, Rusanov V, Fridel L, Kramer MR (2015) Safety of cryo-transbronchial biopsy in diffuse lung diseases: analysis of three hundred cases. Respiration 90(1):40–46. https://doi.org/10.1159/000381921

    Article  PubMed  Google Scholar 

  11. 11.

    Kropski JA, Pritchett JM, Mason WR, Sivarajan L, Gleaves LA, Johnson JE, Lancaster LH, Lawson WE, Blackwell TS, Steele MP, Loyd JE, Rickman OB (2013) Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease. PLoS One 8(11):e78674. https://doi.org/10.1371/journal.pone.0078674

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Casoni GL, Tomassetti S, Cavazza A, Colby TV, Dubini A, Ryu JH, Carretta E, Tantalocco P, Piciucchi S, Ravaglia C, Gurioli C, Romagnoli M, Gurioli C, Chilosi M, Poletti V (2014) Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One 9(2):e86716. https://doi.org/10.1371/journal.pone.0086716

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Fruchter O, Fridel L, El Raouf BA, Abdel-Rahman N, Rosengarten D, Kramer MR (2014) Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Respirology 19(5):683–688. https://doi.org/10.1111/resp.12296

    Article  PubMed  Google Scholar 

  14. 14.

    Sethi J, Ali MS, Mohananey D, Nanchal R, Maldonado F, Musani A (2019) Are Transbronchial cryobiopsies ready for prime time? A systematic review and meta-analysis. J Bronchology Interv Pulmonol 26(1):22–32. https://doi.org/10.1097/lbr.0000000000000519

    Article  PubMed  Google Scholar 

  15. 15.

    Tomassetti S, Wells AU, Costabel U, Cavazza A, Colby TV, Rossi G, Sverzellati N, Carloni A, Carretta E, Buccioli M, Tantalocco P, Ravaglia C, Gurioli C, Dubini A, Piciucchi S, Ryu JH, Poletti V (2016) Bronchoscopic lung cryobiopsy increases diagnostic confidence in the multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 193(7):745–752. https://doi.org/10.1164/rccm.201504-0711OC

    Article  PubMed  Google Scholar 

  16. 16.

    Du Rand IA, Blaikley J, Booton R, Chaudhuri N, Gupta V, Khalid S, Mandal S, Martin J, Mills J, Navani N, Rahman NM, Wrightson JM, Munavvar M (2013) British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax 68(Suppl 1):i1–i44. https://doi.org/10.1136/thoraxjnl-2013-203618

    Article  PubMed  Google Scholar 

  17. 17.

    Ronan N, Bennett DM, Khan KA, McCarthy Y, Dahly D, Bourke L, Chelliah A, Cavazza A, O’Regan K, Moloney F, Plant BJ, Henry MT (2018) Tissue andbronchoalveolar lavage biomarkers in idiopathic pulmonary fibrosis patients on pirfenidone. Lung 196(5):543–552. https://doi.org/10.1007/s00408-018-0140-8

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Ravaglia C, Bonifazi M, Wells AU, Tomassetti S, Gurioli C, Piciucchi S, Dubini A, Tantalocco P, Sanna S, Negri E, Tramacere I, Ventura VA, Cavazza A, Rossi A, Chilosi M, La Vecchia C, Gasparini S, Poletti V (2016) Safety and diagnostic yield of transbronchial lung cryobiopsy in diffuse parenchymal lung diseases: a comparative study versus video-assisted thoracoscopic lung biopsy and a systematic review of the literature. Respiration 91(3):215–227. https://doi.org/10.1159/000444089

    Article  PubMed  Google Scholar 

  19. 19.

    Lentz RJ, Taylor TM, Kropski JA, Sandler KL, Johnson JE, Blackwell TS, Maldonado F, Rickman OB (2018) Utility of flexible bronchoscopic cryobiopsy for diagnosis of diffuse parenchymal lung diseases. J Bronchology Interv Pulmonol 25(2):88–96. https://doi.org/10.1097/lbr.0000000000000401

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Ravaglia C, Wells AU, Tomassetti S, Gurioli C, Gurioli C, Dubini A, Cavazza A, Colby TV, Piciucchi S, Puglisi S, Bosi M, Poletti V (2019) Diagnostic yield and risk/benefit analysis of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases: a large cohort of 699 patients. BMC Pulm Med 19(1):16. https://doi.org/10.1186/s12890-019-0780-3

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Echevarria-Uraga JJ, Pérez-Izquierdo J, García-Garai N, Gómez-Jiménez E, Aramburu-Ojembarrena A, Tena-Tudanca L, Miguélez-Vidales JL, Capelastegui-Saiz A (2016) Usefulness of an angioplasty balloon as selective bronchial blockade device after transbronchial cryobiopsy. Respirology 21(6):1094–1099. https://doi.org/10.1111/resp.12827

    Article  PubMed  Google Scholar 

  22. 22.

    Dalvi PKG, Clum S, Markow M, DiNuoscio D, Rumbak M, Mangar D, Camporesi E (2016) Transbronchial lung cryobiopsy (TBLC) at a tertiary referral hospital: a two-year experience. Pulm Crit Care Med 1(4):2–4. https://doi.org/10.15761/PCCM.1000122

    Article  Google Scholar 

  23. 23.

    Bango-Álvarez A, Ariza-Prota M, Torres-Rivas H, Fernández-Fernández L, Prieto A, Sánchez I, Gil M, Pando-Sandoval A (2017) Transbronchial cryobiopsy in interstitial lung disease: experience in 106 cases - how to do it. ERJ Open Res 3(1). https://doi.org/10.1183/23120541.00148-2016

  24. 24.

    Ussavarungsi K, Kern RM, Roden AC, Ryu JH, Edell ES (2017) Transbronchial cryobiopsy in diffuse parenchymal lung disease: retrospective analysis of 74 cases. Chest 151(2):400–408. https://doi.org/10.1016/j.chest.2016.09.002

    Article  PubMed  Google Scholar 

  25. 25.

    Sriprasart T, Aragaki A, Baughman R, Wikenheiser-Brokamp K, Khanna G, Tanase D, Kirschner M, Benzaquen S (2017) A single US center experience of transbronchial lung cryobiopsy for diagnosing interstitial lung disease with a 2-scope technique. J Bronchology Interv Pulmonol 24(2):131–135. https://doi.org/10.1097/lbr.0000000000000366

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Wälscher J, Groß B, Eberhardt R, Heussel CP, Eichinger M, Warth A, Lasitschka F, Herth FJF, Kreuter M (2019) Transbronchial cryobiopsies for diagnosing interstitial lung disease: real-life experience from a tertiary referral center for interstitial lung disease. Respiration 97(4):348–354. https://doi.org/10.1159/000493428

    Article  PubMed  Google Scholar 

  27. 27.

    Dhooria S, Mehta RM, Srinivasan A, Madan K, Sehgal IS, Pattabhiraman V, Yadav P, Sivaramakrishnan M, Mohan A, Bal A, Garg M, Agarwal R (2018) The safety and efficacy of different methods for obtaining transbronchial lung cryobiopsy in diffuse lung diseases. Clin Respir J 12(4):1711–1720. https://doi.org/10.1111/crj.12734

    Article  PubMed  Google Scholar 

  28. 28.

    Poletti V, Benzaquen S (2014) Transbronchial cryobiopsy in diffuse parenchymal lung disease. A new star in the horizon. Sarcoidosis Vasc Diffuse Lung Dis 31(3):178–181

    PubMed  Google Scholar 

  29. 29.

    Hetzel J, Maldonado F, Ravaglia C, Wells AU, Colby TV, Tomassetti S, Ryu JH, Fruchter O, Piciucchi S, Dubini A, Cavazza A, Chilosi M, Sverzellati N, Valeyre D, Leduc D, Walsh SLF, Gasparini S, Hetzel M, Hagmeyer L, Haentschel M, Eberhardt R, Darwiche K, Yarmus LB, Torrego A, Krishna G, Shah PL, Annema JT, Herth FJF, Poletti V (2018) 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 95(3):188–200. https://doi.org/10.1159/000484055

    Article  Google Scholar 

  30. 30.

    Hetzel J, Eberhardt R, Petermann C, Gesierich W, Darwiche K, Hagmeyer L, Muche R, Kreuter M, Lewis R, Ehab A, Boeckeler M, Haentschel M (2019) Bleeding risk of transbronchial cryobiopsy compared to transbronchial forceps biopsy in interstitial lung disease - a prospective, randomized, multicentre cross-over trial. Respir Res 20(1):140. https://doi.org/10.1186/s12931-019-1091-1

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Deasy KF, Walsh LJ, Henry MT (2019) Endobronchial balloon blockers. A retrospective review of their implementation at Cork University Hospital for use in transbronchial lung cryobiopsy under conscious sedation. European Respiratory Journal 54(suppl 63):PA3103. https://doi.org/10.1183/13993003.congress-2019.PA3103

    Article  Google Scholar 

  32. 32.

    Maldonado F, Danoff SK, Wells AU, Colby TV, Ryu JH, Liberman M, Wahidi MM, Frazer L, Hetzel J, Rickman OB, Herth FJF, Poletti V, Yarmus LB (2020) Transbronchial cryobiopsy for the diagnosis of interstitial lung diseases: CHEST guideline and expert panel report. Chest 157(4):1030–1042. https://doi.org/10.1016/j.chest.2019.10.048

    Article  PubMed  Google Scholar 

  33. 33.

    Sharp C, McCabe M, Adamali H, Medford AR (2017) Use of transbronchial cryobiopsy in the diagnosis of interstitial lung disease-a systematic review and cost analysis. Qjm 110(4):207–214. https://doi.org/10.1093/qjmed/hcw142

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Poletti V, Hetzel J (2015) Transbronchial cryobiopsy in diffuse parenchymal lung disease: need for procedural standardization. Respiration 90(4):275–278. https://doi.org/10.1159/000439313

    Article  PubMed  Google Scholar 

  35. 35.

    Colby TV, Tomassetti S, Cavazza A, Dubini A, Poletti V (2017) Transbronchial cryobiopsy in diffuse lung disease: update for the pathologist. Arch Pathol Lab Med 141(7):891–900. https://doi.org/10.5858/arpa.2016-0233-RA

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Flaherty KR, Travis WD, Colby TV, Toews GB, Kazerooni EA, Gross BH, Jain A, Strawderman RL, Flint A, Lynch JP, Martinez FJ (2001) Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 164(9):1722–1727. https://doi.org/10.1164/ajrccm.164.9.2103074

    CAS  Article  Google Scholar 

  37. 37.

    Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, Sawahata M, Ogura T (2012) Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology 61(6):1026–1035. https://doi.org/10.1111/j.1365-2559.2012.04322.x

    Article  PubMed  Google Scholar 

  38. 38.

    Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, Coeck C, Clerisme-Beaty E, Rosenstock B, Quaresma M, Haeufel T, Goeldner RG, Schlenker-Herceg R, Brown KK (2019) Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 381(18):1718–1727. https://doi.org/10.1056/NEJMoa1908681

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Romagnoli M, Colby TV, Berthet JP, Gamez AS, Mallet JP, Serre I, Cancellieri A, Cavazza A, Solovei L, Dell’Amore A, Dolci G, Guerrieri A, Reynaud P, Bommart S, Zompatori M, Dalpiaz G, Nava S, Trisolini R, Suehs CM, Vachier I, Molinari N, Bourdin A (2019) Poor concordance between sequential transbronchial lung cryobiopsy and surgical lung biopsy in the diagnosis of diffuse interstitial lung diseases. Am J Respir Crit Care Med 199(10):1249–1256. https://doi.org/10.1164/rccm.201810-1947OC

    Article  Google Scholar 

  40. 40.

    Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, Mahar A, Myers JL, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Jo HE, Webster SE, Lin QT, Rhodes JE, Salamonsen M, Wrobel JP, Harris B, Don G, Wu PJC, Ng BJ, Oldmeadow C, Raghu G, Lau EMT (2020) Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med 8(2):171–181. https://doi.org/10.1016/s2213-2600(19)30342-x

    CAS  Article  Google Scholar 

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Authors

Contributions

All authors contributed to the study conception and design. Material preparation and analysis were performed by Anne O Mahony, Louise Burke, Alberto Cavazza, Marcus Kennedy, Michael Maher and Michael Henry. Data collection was performed by Anne O Mahony. The first draft of the manuscript was written by Anne O′ Mahony and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anne M. O’Mahony.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the local hospital research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent to undergo TBLC was obtained from all individual participants included in the study.

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O’Mahony, A.M., Burke, L., Cavazza, A. et al. Transbronchial lung cryobiopsy (TBLC) in the diagnosis of interstitial lung disease: experience of first 100 cases performed under conscious sedation with flexible bronchoscope. Ir J Med Sci (2021). https://doi.org/10.1007/s11845-020-02453-7

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Keywords

  • Diffuse lung disease
  • Idiopathic pulmonary fibrosis
  • Interstitial lung disease
  • Multidisciplinary diagnosis
  • Non-specific interstitial pneumonia
  • Transbronchial lung cryobiopsy
  • Usual interstitial pneumonia