The diagnosis of diffuse parenchymal lung disease (DPLD) may require invasive procedures after all noninvasive tools have failed. The clinical context in which these diseases develop and the radiological patterns are crucial for defining the timing and the methods to be used. After the introduction in clinical practice of HRCT scan, the evaluation of imaging patterns, along with the immunological status of the patient and the clinical course of the disease (acute vs. chronic) seem to be crucial to choose the best diagnostic procedure

Cancellieri, A

Casoni, GL

Chilosi, M

Gurioli, C

Poletti, V

Robalo-Cordeiro, C

Romagnoli, M

Tomassetti, S

Name not available

The transbonchial lung biopsy for diagnosis of diffuse parenchymal lung disease; Pro

CHUC Institutional Repository

Repositório Institucional dos Hospitais da Universidade de Coimbra

ARTICLE IN PRESS+ModelRPPNEU-24; No. of Pages 4Rev Port Pneumol. 2011;xxx(xx):xxx—xxxwww.revportpneumol.orgSPECIAL ARTICLEThe  transbonchial  lung  biopsy  for diagnosis  of diffuse  parenchymallung disease;  ProG.L. Casonia, C.R. Cordeiro Jr.b, S. Tomassetti a, M. Romagnoli a, M. Chilosi c,A.  Cancellierid, C. Gurioli a, V. Poletti a,∗a Thoracic  Department,  GB  Morgagni  Hospital,  Forlì,  Italyb Department  of  Pulmonology  and  Allergology,  Coimbra  University  Hospital,  Coimbra,  Portugalc Department  Pathology,  Verona  University,  Verona,  Italyd Department  of  Pathology,  Ospedale  Maggiore,  Bologna,  ItalyReceived  21  February  2011;  accepted  5  March  2011KEYWORDSTransbonchial  lungbiopsy;Diffuse  parenchymallung  disease;High  Resolution  CTscanAbstract  The  diagnosis  of  diffuse  parenchymal  lung  disease  (DPLD)  may  require  invasive  pro-cedures after  all  noninvasive  tools  have  failed.  The  clinical  context  in  which  these  diseasesdevelop  and  the  radiological  patterns  are  crucial  for  deﬁning  the  timing  and  the  methods  to  beused. After  the  introduction  in  clinical  practice  of  HRCT  scan,  the  evaluation  of  imaging  pat-terns, along  with  the  immunological  status  of  the  patient  and  the  clinical  course  of  the  disease(acute vs.  chronic)  seem  to  be  crucial  to  choose  the  best  diagnostic  procedure.© 2011  Sociedade  Portuguesa  de  Pneumologia.  Published  by  Elsevier  España,  S.L.  All  rightsreserved.PALAVRAS-CHAVEBiópsia  pulmonartransbrônquica;Doenc¸a  difusa  doparênquimapulmonar;A  biópsia  pulmonar  transbrônquica  para  o  diagnóstico  de  doenc¸a difusa  doparênquima  pulmonar;  ProResumo  O  diagnóstico  de  doenc¸a  difusa  do  parênquima  pulmonar  (DDPP)  pode  necessitarde procedimentos  invasivos  caso  todas  as  técnicas  não  invasivas  tenham  falhado.  O  contextoclínico no  qual  estas  doenc¸as  se  desenvolvem  e  os  padrões  radiológicos  são  importantes  paraa deﬁnic¸ão  de  tempo  e  métodos  a  serem  utilizados.  Após  a  introduc¸ão  na  prática  clínica  daPlease  cite  this  article  in  press  as:  Casoni  GL,  et  al.  The  translung  disease;  Pro. Rev  Port  Pneumol.  2011.  doi:10.1016/j.rppnImagem  de  AltaResoluc¸ão TAC de  alta  resoluc¸ão  (HRCT),  a  avaliac¸ão  dos  padrões  de  imagem,  juntamente  com  o  estadoimunológico  do  doente  e  o  curso  clínico  da  doenc¸a  (aguda  vs.  crónica),  revelam-se  importantespara seleccionar  o  melhor  procedimento  de  diagnóstico.© 2011  Sociedade  Portuguesa  de  Pneumologia.  Publicado  por  Elsevier  España,  S.L.  Todos  osdireitos reservados.∗ Corresponding author.E-mail address: venerino.poletti@gmail.com (V. Poletti).Tmhd0873-2159/$  –  see  front  matter  ©  2011  Sociedade  Portuguesa  de  Pneumolodoi:10.1016/j.rppneu.2011.05.003bonchial  lung  biopsy  for  diagnosis  of  diffuse  parenchymaleu.2011.05.003he  diagnosis  of  diffuse  parenchymal  lung  disease  (DPLD)ay  require  invasive  procedures  after  all  noninvasive  toolsave  failed.  The  clinical  context  in  which  these  diseasesevelop  and  the  radiological  patterns  are  crucial  for  deﬁninggia.  Published  by  Elsevier  España,  S.L.  All  rights  reserved. IN+ModelR2tttldtmecibicclprncbetoTn(bnrfctsiTtamrbiihBdottsobeicrtittnbl(ac(aoaiom(pign(peaotDgpttstmmla(sotreviewed  22  patients  with  known  UIP  (21  cases  diagnosed  bysurgical  biopsy,  1  case  diagnosed  by  clinical  and  radiologicfeatures)  and  then  retrospectively  examined  transbronchialbiopsies  (TBLB)  from  these  patients.  They  concluded  thatARTICLEPPNEU-24; No. of Pages 4 he  timing  and  the  methods  to  be  used.  After  the  introduc-ion  in  clinical  practice  of  High  Resolution  CT  scan  (HRCT),he  evaluation  of  imaging  patterns,  along  with  the  immuno-ogical  status  of  the  patient  and  the  clinical  course  of  theisease  (acute  vs.  chronic)  seem  to  be  crucial  in  choosinghe  best  diagnostic  procedure.1,2 In  the  immunocompro-ised  patients  who  develop  DPLD,  a  prompt  diagnosis  isssential  for  a  better  survival.  In  this  circumstance,  bron-hoalveolar  lavage  (BAL),  especially  when  the  bronchoscopes  guided  by  HRCT  scan  ﬁndings  performed  a  few  hoursefore,  is  generally  of  value  in  diagnosing  opportunisticnfections,  alveolar  proteinosis,  alveolar  hemorrhage  andapillaritis,  lymphomatous  or  leukemic  lung  inﬁltration,arcinomatous  lymphangitis,  disseminated  hematogenousung  metastases,  hypersensitivity  pneumonitis,  eosinophilicneumonitis  or  diffuse  alveolar  damage  due  to  drugs  oradiation.  In  these  cases,  when  a  conclusive  diagnosis  isot  obtained  by  BAL  ﬂuid  analysis  or  in  most  immuno-ompetent  patients  who  develop  DPLD,  transbronchial  lungiopsy  (TBLB)  or  even  open  lung  biopsy  could  be  consid-red.  The  TBLB  forceps  makes  it  possible  to  obtain  lungissue  through  the  bronchial  routes  and  the  specimens  sobtained  usually  represent  from  the  centrilobular  regions.3,4herefore,  the  disorders  that  are  centered  around  termi-al  and  respiratory  bronchioles  [respiratory  bronchiolitisRB),  tuberculosis,  lobular  infectious  pneumonia,  cellularronchiolitis]  or  signiﬁcantly  involve  these  structures  (orga-izing  pneumonia)  or  are  distributed  along  the  lymphaticoutes  (sarcoidosis,  carcinomatous  lymphangitis)  may  berequently  sampled  by  the  forceps.4,5 In  1965,  Andersen  andolleagues  at  the  Mayo  Clinic  described  for  the  ﬁrst  timehe  rigid  bronchoscopic  technique  of  TBLB6 and  in  the  sub-equent  trials  they  reported  that  lung  tissue  was  obtainedn  84%  of  patients  with  DPLD  by  using  the  technique  ofBLB.7 The  introduction  of  the  ﬂexible  bronchoscope  inhe  late  1960s  increased  the  popularity  of  the  techniquend  demonstrated  that  TBLB  with  the  ﬂexible  instrumentay  be  obtained  with  minimal  mortality  and  morbidity.  Cur-ently  TBLB  is  a  well-established  diagnostic  technique  usedy  almost  all  bronchoscopists,  and  the  ﬂexible  bronchoscopes  used  almost  exclusively.  The  main  complication  of  TBLBs  bleeding;  less  frequent  complications  are  pneumothorax,ypoxemia,  or  cardiac  arrhythmias  during  the  procedure.leeding  occurs  to  some  degree  in  virtually  all  TBLB  proce-ures  and  it  is  the  main  limiting  factor  in  obtaining  morer  larger  biopsy  samples.  Bleeding  is  a  major  concern  tohe  bronchoscopist  because  of  the  limited  options  availableo  manage  excessive  bleeding  through  the  ﬂexible  broncho-cope.  The  suction  channel  of  the  typical  bronchoscope  isnly  2  mm  in  diameter,  and  the  volume  of  blood  that  cane  suctioned  through  the  channel  is  therefore  limited.  How-ver,  to  minimize  the  consequence  of  hemorrhage  by  TBLB,t  is  possible  to  perform  the  procedure  using  the  rigid  bron-hoscopy  and  placing  a  non  inﬂated  Fogarty  balloon  and  aigid  aspirator  (4  mm  in  diameter)  in  lobar  bronchus  nearhe  biopsy  segment.  The  Fogarty  balloon  can  be  promptlynﬂated  in  case  of  bleeding.  In  this  way  it  is  much  easiero  control  the  bleeding  complications.8,3 The  main  utility  ofPlease  cite  this  article  in  press  as:  Casoni  GL,  et  al.  The  translung  disease;  Pro. Rev  Port  Pneumol.  2011.  doi:10.1016/j.rppnhe  TBLB  rests  in  the  possibility  of  making  a  speciﬁc  diag-osis  in  a  patient  with  DPLD  and  avoiding  a  surgical  lungiopsy.  Some  studies  have  demonstrated  that  the  morpho-ogic  ﬁndings  of  interstitial  inﬂammation  and  ﬁbrosis  in  TBLBFsaa PRESSG.L.  Casoni  et  al.such  as  in  the  diagnosis  of  idiopathic  interstitial  pneumonia)ppeared  to  have  little  relevance  to  subsequent  clini-al  course.9 While  the  monomorphous  histological  patternsorganizing  pneumonia,  eosinophilic  pneumonia,  diffuselveolar  damage  with  or  without  eosinophils,  alveolar  hem-rrhage  with  or  without  capillaritis,  alveolar  proteinosis)re  easily  identiﬁable  in  small  lung  fragments  (but  onlyn  agreement  with  clinical,  radiological  and  other  lab-ratory  data),4,10 the  tiny  specimens  obtained  by  TBLBay  not  be  sufﬁcient  to  deﬁne  the  histological  patternusual  interstitial  pneumonitis,  desquamative  interstitialneumonitis,  nonspeciﬁc  interstitial  pneumonitis,  ﬁbros-ng  type).  However,  from  the  morphological  point  of  view,enerous  TBLB  may  also  provide  good  specimens  for  a  diag-osis  of  a  pattern  called  nonspeciﬁc  interstitial  pneumoniaNSIP),  cellular  variant  in  speciﬁc  clinical  settings  such  asolymyositis-dermatomyositis-related  interstitial  lung  dis-ase,  drug  toxicity  ore  in  cases  of  unknown  etiology11lthough  surgical  lung  biopsy  is  considered  the  best  way  tobtain  enough  tissue  to  demonstrate  this  pattern.  The  ques-ion  of  which  kind  of  biopsy  should  be  performed  to  diagnosePLD  has  a  long  and  controversial  history.  Certainly,  the  sur-ical  lung  biopsy  provides  substantially  more  material  forathological  study,  but  the  procedure  requires  general  anes-hesia,  and  one  or  more  days  in  the  hospital  with  a  chestube  in  place.  Moreover,  some  reports  have  shown  that  thisurgical  procedure  may  be  associated  with  increased  mor-ality  in  certain  states  of  the  disease.  In  the  experience  ofany  interstitial  lung  disease  centers  across  the  world  theedian  mortality  is  4-6%  within  30  days  following  surgicalung  biopsy  for  UIP12,13 but  biopsy  performed  at  the  time  ofcute  exacerbation  (AE)  resulted  in  higher  30-day  mortality28.6%)  compared  to  non-AE.14 Therefore,  in  recent  yearsome  studies  have  sought  to  increase  the  diagnostic  yieldf  transbronchial  lung  biopsy  in  diagnosis  of  DPLD  to  avoidhe  surgical  lung  biopsy.  In  this  respect,  Berbescu  et  al15bonchial  lung  biopsy  for  diagnosis  of  diffuse  parenchymaleu.2011.05.003igure  1  Transbronchial  lung  biopsy.  Diagnosis:  Carcinomato-us lymphangitis  due  to  gastric  adenocarcinoma.  The  lymphaticsre dilated  and  surrounded  by  neoplastic  acini.  Pulmonaryrtery neoplastic  microangiopathy  is  also  present.ARTICLE IN PRESS+ModelRPPNEU-24; No. of Pages 4The  transbonchial  lung  biopsy  for  diagnosis  of  diffuse  parenchymal  lung  disease;  Pro  3FocehttpiisFigure  2  Transbronchial  lung  biopsy.  Intraalveolar  ﬁbrotic  budtypically  observed  in  cryptogenetic  organizing  pneumonia.a  diagnosis  of  UIP  was  possible  on  the  TBLB  in  seven  sub-jects,  and  in  two  others  that  the  ﬁndings  were  consistentwith  UIP.  As  a  rationale  for  the  use  of  TBLB,  the  authorsreported  the  high  mortality  within  30  days  following  surgi-cal  lung  biopsy  for  UIP.  However  in  a  critical  editorial  Churgand  Schwarz  dampened  this  enthusiasm  and  suggested  that‘‘the  collective  wisdom  be  followed  and  that  TBLB  shouldnot  be  used  to  diagnose  IPF/UIP’’  because  the  morpho-logic  ﬁndings  of  interstitial  inﬂammation  and  ﬁbrosis  in  TBLBappeared  to  have  little  relevance  to  the  subsequent  clini-cal  course.16 However  that  has  not  stopped  the  tenacity  ofother  researchers  in  assessing  the  improved  diagnostic  yieldusing  non-surgical  methods  for  the  histological  diagnosis  ofﬁbrosing  diffuse  lung  disease.  In  a  study,8 we  reported  a  sig-niﬁcant  diagnostic  yield  and/or  better  preserved  specimens(Fig.  1,  2)  when  TBLB  were  performed  under  general  anes-Please  cite  this  article  in  press  as:  Casoni  GL,  et  al.  The  translung  disease;  Pro. Rev  Port  Pneumol.  2011.  doi:10.1016/j.rppnthesia  with  rigid  bronchoscope  using  larger  forceps  (calledJumbo  forceps)  (Fig.  3)  and  without  pulling  them  through  thebiopsy  channel.  Then  a  new  way  of  obtaining  TBLB  using  ﬂex-ible  cryoprobes  was  recently  proposed  (Fig.  4a,  b,  c).  ThepmtlFigure  4  (a)  A  ﬂexible  cryoprobe  is  shown.  The  metal  tip,  can  bebiopsy obtained  by  ﬂexible  cryoprobes  with  lung  sample  attachedspecimens showing  a  bronchiole  and  lung  parenchyma  (interstitial  inigure  3  Jumbo  forcep  with  a  lung  sample  that  is  poured  outf the  tip  of  the  forceps.ryosurgical  equipment  operates  by  the  Joule-Thompsonffect,  which  dictates  that  a  compressed  gas  released  atigh  ﬂow  rapidly  expands  and  creates  a  very  low  tempera-ure.  The  advantage  of  the  cryoprobe  is  that  large  pieces  ofissue  can  be  extracted  with  the  freeze-thaw  cycle.  The  ﬁrstublished  data17,18 indicate  that,  especially  in  idiopathicnterstitial  pneumonia,  transbronchial  cryobiopsy  could  addmportant  information.  The  size  of  the  samples  obtainedeems  to  increase  the  diagnostic  yield  signiﬁcantly  com-bonchial  lung  biopsy  for  diagnosis  of  diffuse  parenchymaleu.2011.05.003ared  to  forceps  biopsies.  Transbronchial  cryobiopsies  areuch  larger  than  conventional  forceps  biopsies  but  smallerhan  surgical  lung  biopsies.  Despite  having  a  potentiallyarge  defect  in  the  lung  parenchyma,  the  occurrence  of visualized  under  ﬂuoroscopic  control.  (b)  Transbronchial  lung to  the  metal  tip.  (c)  Hematoxylin  Eosin  (low  power).  Largeﬂammation;  preserved  lung  architecture). IN+ModelR4pfTapddIdwoiopwcbcoacitbgcetlCAeRARTICLEPPNEU-24; No. of Pages 4 neumothorax  and  bleeding  was  low  compared  to  data  fromorceps  biopsies.  These  data,  therefore,  indicate  that  theBLB  may  have  even  greater  potential  role  in  the  diagnosticlgorithm  of  DLDL  (even  in  its  ﬁbrosing  variants).Furthermore,  when  TBLB  was  introduced  into  clinicalractice,  a  positive  biopsy  by  the  TBLB  technique  waseﬁned  as  diagnostic  histology,  histology  that  supported  aiagnosis,  or  histology  consistent  with  the  ﬁnal  diagnosis.ndeed,  most  of  the  published  reports  have  focused  on  theiagnostic  accuracy  of  histologic  analysis  of  TBLB  in  patientsith  diffuse  lung  disorders.  In  contrast  there  were  no  datan  how  TBLB  results  are  used  by  clinicians.  In  a  very  interest-ng  study,  Ensminger  and  Prakash19 evaluated  if  the  resultsf  the  TBLB  were  clinically  useful  in  the  management  ofatients  with  diffuse  pulmonary  disorders.  In  the  study  TBLBas  considered  useful  if:  (a)  it  resulted  in  a  speciﬁc  clini-al  diagnosis,  (b)  a  speciﬁc  management  decision  was  madeased  on  the  biopsy  result,  or  (c)  certain  pathologic  pro-esses  were  excluded  on  the  basis  of  the  biopsy  result  andther  clinical  information.  The  results  indicated  that  TBLB  is clinically  useful  test  in  approximately  75%  of  procedures,ertainly  not  a  negligible  percentage.In  view  of  the  above  data,  we  believe  that  the  use  of  TBLBn  the  diagnosis  of  DLDL  is  useful  and  safe,  but  certainly  stilloo  underestimated  and  undervalued  by  most  clinicians.  Weelieve  that  a  future  topic  in  the  study  of  DPLD  should  be  areater  implementation  of  the  techniques  of  immunohisto-hemistry,  molecular  biology  and  microarray  to  be  appliedven  on  tiny  samples  obtained  from  the  TBLB  to  increasehe  diagnostic  yield  and  reduce  the  need  to  refer  to  surgicalung  biopsy  for  diagnosis.onﬂict of interestsuthors  declare  that  they  don’t  have  any  conﬂict  of  inter-sts.eferences1. Du Bois RM, Costabel U. Diffuse lung diseases: Classiﬁcation anddiagnostic approach. In: Gibson GJ, Geddes DM, Costabel U,Sterk PJ, Corrin B, editors. Respiratory Medicine. Amsterdam:Elsevier Sciences; 2003. p. 1545—56.2. Leslie KO, Gruden JF, Parish JM, Scholand MB. TransbronchialBiopsy Interpretation in the Patient With Diffuse ParenchymalLung Disease. Arch Pathol Lab Med. 2007;131:407—23.Please  cite  this  article  in  press  as:  Casoni  GL,  et  al.  The  translung  disease;  Pro. Rev  Port  Pneumol.  2011.  doi:10.1016/j.rppn3. Becker HD, Shirakawa T, Tanaka F, Muller KM, Herth F.Transbronchial (transbronchoscopic) lung biopsy in immuno-compromised patient. Pulmonary Endoscopy and BiopsyTechniques. Eur Respir Monogr. 1998;3:193—208. PRESSG.L.  Casoni  et  al.4.  Poletti V, Patelli M, Ferracini R, Simonetti M, Spiga L.Transbronchial lung biopsy in inﬁltrative lung disease. Theimportance of the pathologic approach. Sarcoidosis Vasc Dif-fuse Lung Dis. 1988;5:43—50.5. Ryu JH, Olson EJ, Midthun DE, Swensen SJ. Diagnostic approachto the patient with diffuse lung disease. Mayo Clin Proc.2002;77:1221—7.6. Andersen HA, Fontana RS, Harrison Jr EG. Transbroncho-scopic lung biopsy in diffuse pulmonary disease. Dis Chest.1965;48:187—92.7. Andersen HA. Transbronchoscopic Lung Biopsy for Dif-fuse Pulmonary Diseases. Results in 939 Patients. Chest.1978;73:734—6.8. Casoni GL, Gurioli C, Chhajed PN, Chilosi M, Zompatori M,Olivieri D, et al. The value of transbronchial lung biopsy usingjumbo forceps via rigid bronchoscope in diffuse lung disease.Monaldi Arch Chest Dis. 2008;69:59—64.9. Wilson RK, Fechner RE, Greenberg SD, Estrada R, Stevens PM.Clinical implications of a ‘‘nonspeciﬁc’’ transbronchial biopsy.Am J Med. 1978;65:252—6.10. Poletti V, Cazzato S, Minicuci N, Zompatori M, Burzi M,Schiattone ML. The diagnostic value of bronchoalveolar lavageand transbronchial lung biopsy in cryptogenic organizing pneu-monia. Eur Respir J. 1996;9:2513—6.11. Watanabe K, Higuchi K, Ninomiya K, Ohshima T, Aritomi T,Kawabata Y, et al. Steroid treatment based on the ﬁndings oftransbronchial biopsy in idiopathic interstitial pneumonia. EurRespir J. 2002;20:1213—9.12. Lettieri CJ, Veerappan GR, Helman DL, Mulligan CR, Shorr AF.Outcomes and Safety of Surgical Lung Biopsy for InterstitialLung Disease. Chest. 2005;127:1600—5.13. Kreider ME, Hansen-Flaschen J, Ahmad NN, Rossman MD,Kaiser LR, Kucharczuk JC, et al. Complications of Video-Assisted Thoracoscopic Lung Biopsy in Patients with InterstitialLung Disease. Ann Thorac Surg. 2007;83:1140—5.14. Park JH, Kim DK, Kim DS, Koh Y, Lee SD, Kim WS,  et al.Mortality and risk factors for surgical lung biopsy in patientswith idiopathic interstitial pneumonia. Eur J Cardiothorac Surg.2007;31:1115—9.15. Berbesku EA, Katzenstein AL, Snow JL, Zisman DA. Trans-bronchial biopsy in usual interstitial pneumonia. Chest.2006;129:1126—31.16. Andrew Churg A, Schwarz M. Transbronchial Biopsy andUsual Interstitial Pneumonia A New Paradigm? Chest.2006;129:1117—8.17. Babiak A, Hetzel J, Krishna G, Fritz P, Moeller P, Balli T, et al.Transbronchial Cryobiopsy: A New Tool for Lung Biopsies. Res-piration. 2009;78:203—12.18. Pajares V, Torrego A, Puzo C, Lerma E, Gil De Bernabé MA,Franquet T. Transbronchial Lung Biopsy Using Cryoprobes. Archbonchial  lung  biopsy  for  diagnosis  of  diffuse  parenchymaleu.2011.05.003Bronconeumol. 2010;46:111—5.19. Ensminger SA, Prakash UB. Is bronchoscopic lung biopsy helpfulin the management of patients with diffuse lung disease? EurRespir J. 2006;28:1081—4.

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The transbonchial lung biopsy for diagnosis of diffuse parenchymal lung disease; Pro

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