Download PDF
Semin Respir Crit Care Med 2010; 31(2): 208-221
DOI: 10.1055/s-0030-1249117
© Thieme Medical Publishers

Bronchoscopic Monitoring after Lung Transplantation

Allan R. Glanville1
  • 1The Lung Transplant Unit, St. Vincent's Hospital, Darlinghurst, NSW, Australia
Further Information

Publication History

Publication Date:
30 March 2010 (online)

    Permissions and Reprints

ABSTRACT

Despite advances in gene and immunological monitoring techniques that hold great promise for the future, fiberoptic bronchoscopy remains the gold standard to establish the presence or absence of acute pulmonary allograft rejection or infection after lung transplantation (LT). There is general agreement that clinically mandated transbronchial lung biopsies enhance diagnostic precision and have a satisfactory risk:benefit ratio in experienced hands. Surveillance transbronchial biopsies have a lower yield but may provide longitudinal insight into immunological events in the allograft, which can assist long-term management. Indeed, much of our knowledge about the significance of allograft histopathological events over time has been garnered from centers that perform routine surveillance procedures, and it is exactly the balance between individual and community benefit which underscores discussion about the value of invasive monitoring. Obliterative bronchiolitis (OB) is the most common cause of late chronic allograft dysfunction leading to death after LT. Significant OB is invariably associated with reduced graft function, denoted physiologically by the bronchiolitis obliterans syndrome (BOS). Importantly, not all BOS is due to OB; hence the move to develop an all embracing phraseology for late graft dysfunction, specifically “chronic lung allograft dysfunction” (CLAD). The major risk factor for BOS was once thought to be acute cellular rejection (ACR), but new data support an important role for lymphocytic bronchiolitis (LB) independent of so-called vascular acute rejection, albeit when diagnosed and treated. This review examines the role of fiberoptic bronchoscopy after LT as a surveillance tool versus a clinically mandated diagnostic procedure.

KEYWORDS

Lung transplantation - bronchoscopy - monitoring

REFERENCES

  • 1 Higenbottam T, Stewart S, Penketh A, Wallwork J. Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients.  Transplantation. 1988;  46(4) 532-539
    CrossrefPubMedGoogle Scholar
  • 2 Hutter J A, Despins P, Higenbottam T, Stewart S, Wallwork J. Heart-lung transplantation: better use of resources.  Am J Med. 1988;  85(1) 4-11
    PubMedGoogle Scholar
  • 3 Magro C M, Klinger D M, Adams P W et al.. Evidence that humoral allograft rejection in lung transplant patients is not histocompatibility antigen-related.  Am J Transplant. 2003;  3(10) 1264-1272
    CrossrefPubMedGoogle Scholar
  • 4 Magro C M, Ross Jr P, Kelsey M, Waldman W J, Pope-Harman A. Association of humoral immunity and bronchiolitis obliterans syndrome.  Am J Transplant. 2003;  3(9) 1155-1166
    CrossrefPubMedGoogle Scholar
  • 5 Magro C M, Abbas A E, Seilstad K, Pope-Harman A L, Nadasdy T, Ross Jr P. C3d and the septal microvasculature as a predictor of chronic lung allograft dysfunction.  Hum Immunol. 2006;  67(4-5) 274-283
    CrossrefPubMedGoogle Scholar
  • 6 Westall G P, Snell G I, McLean C, Kotsimbos T, Williams T, Magro C. C3d and C4d deposition early after lung transplantation.  J Heart Lung Transplant. 2008;  27(7) 722-728
    CrossrefPubMedGoogle Scholar
  • 7 Morrell M R, Patterson G A, Trulock E P, Hachem R R. Acute antibody-mediated rejection after lung transplantation.  J Heart Lung Transplant. 2009;  28(1) 96-100
    CrossrefPubMedGoogle Scholar
  • 8 Astor T L, Galantowicz M, Phillips A, Palafox J, Baker P. Pulmonary capillaritis as a manifestation of acute humoral allograft rejection following infant lung transplantation.  Am J Transplant. 2009;  9(2) 409-412
    CrossrefPubMedGoogle Scholar
  • 9 Aboyoun C L, Tamm M, Chhajed P N et al.. Diagnostic value of follow-up transbronchial lung biopsy after lung rejection.  Am J Respir Crit Care Med. 2001;  164(3) 460-463
    CrossrefPubMedGoogle Scholar
  • 10 Hopkins P M, Aboyoun C L, Chhajed P N et al.. Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients.  J Heart Lung Transplant. 2002;  21(10) 1062-1067
    CrossrefPubMedGoogle Scholar
  • 11 Statement of the American Thoracic Society . Standardization of spirometry—1987 update.  Am Rev Respir Dis. 1987;  136(5) 1285-1298
    PubMedGoogle Scholar
  • 12 Estenne M, Maurer J R, Boehler A et al.. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria.  J Heart Lung Transplant. 2002;  21(3) 297-310
    CrossrefPubMedGoogle Scholar
  • 13 Chhajed P N, Aboyoun C, Chhajed T P et al.. Sedative drug requirements during bronchoscopy are higher in cystic fibrosis after lung transplantation.  Transplantation. 2005;  80(8) 1081-1085
    CrossrefPubMedGoogle Scholar
  • 14 Chhajed P N, Aboyoun C, Malouf M A et al.. Management of acute hypoxemia during flexible bronchoscopy with insertion of a nasopharyngeal tube in lung transplant recipients.  Chest. 2002;  121(4) 1350-1354
    CrossrefPubMedGoogle Scholar
  • 15 Chhajed P N, Aboyoun C, Malouf M A et al.. Prophylactic nasopharyngeal tube insertion prevents acute hypoxaemia due to upper-airway obstruction during flexible bronchoscopy.  Intern Med J. 2003;  33(7) 317-318
    CrossrefPubMedGoogle Scholar
  • 16 Chan C C, Abi-Saleh W J, Arroliga A C et al.. Diagnostic yield and therapeutic impact of flexible bronchoscopy in lung transplant recipients.  J Heart Lung Transplant. 1996;  15(2) 196-205
    PubMedGoogle Scholar
  • 17 Chhajed P N, Malouf M A, Glanville A R. Risk of bleeding associated with transbronchial lung biopsy.  Chest. 2003;  123(6) 2162
    CrossrefPubMedGoogle Scholar
  • 18 Bjørtuft O, Brosstad F, Boe J. Bronchoscopy with transbronchial biopsies: measurement of bleeding volume and evaluation of the predictive value of coagulation tests.  Eur Respir J. 1998;  12(5) 1025-1027
    CrossrefPubMedGoogle Scholar
  • 19 Kukafka D S, O'Brien G M, Furukawa S, Criner G J. Surveillance bronchoscopy in lung transplant recipients.  Chest. 1997;  111(2) 377-381
    CrossrefPubMedGoogle Scholar
  • 20 Diette G B, Wiener C M, White Jr P. The higher risk of bleeding in lung transplant recipients from bronchoscopy is independent of traditional bleeding risks: results of a prospective cohort study.  Chest. 1999;  115(2) 397-402
    CrossrefPubMedGoogle Scholar
  • 21 Scott J P, Fradet G, Smyth R L et al.. Prospective study of transbronchial biopsies in the management of heart-lung and single lung transplant patients.  J Heart Lung Transplant. 1991;  10(5 Pt 1) 626-636, discussion 636–637
    PubMedGoogle Scholar
  • 22 Vitulo P, Cremaschi P, Arbustini E et al.. Surveillance transbronchial biopsy in the diagnosis of acute lung rejection in heart and lung and lung transplant recipients.  Monaldi Arch Chest Dis. 1996;  51(1) 12-15
    PubMedGoogle Scholar
  • 23 Girgis R E, Reichenspurner H, Robbins R C, Reitz B A, Theodore J. The utility of annual surveillance bronchoscopy in heart-lung transplant recipients.  Transplantation. 1995;  60(12) 1458-1461
    CrossrefPubMedGoogle Scholar
  • 24 Guilinger R A, Paradis I L, Dauber J H et al.. The importance of bronchoscopy with transbronchial biopsy and bronchoalveolar lavage in the management of lung transplant recipients.  Am J Respir Crit Care Med. 1995;  152(6 Pt 1) 2037-2043
    PubMedGoogle Scholar
  • 25 Tiroke A H, Bewig B, Haverich A. Bronchoalveolar lavage in lung transplantation. State of the art.  Clin Transplant. 1999;  13(2) 131-157
    CrossrefPubMedGoogle Scholar
  • 26 Baz M A, Layish D T, Govert J A et al.. Diagnostic yield of bronchoscopies after isolated lung transplantation.  Chest. 1996;  110(1) 84-88
    CrossrefPubMedGoogle Scholar
  • 27 Chemaly R F, Yen-Lieberman B, Castilla E A et al.. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry.  J Clin Microbiol. 2004;  42(5) 2168-2172
    CrossrefPubMedGoogle Scholar
  • 28 Baz M A, Ghio A J, Roggli V L, Tapson V F, Piantadosi C A. Iron accumulation in lung allografts after transplantation.  Chest. 1997;  112(2) 435-439
    CrossrefPubMedGoogle Scholar
  • 29 Cahill B C, Hibbs J R, Savik K et al.. Aspergillus airway colonization and invasive disease after lung transplantation.  Chest. 1997;  112(5) 1160-1164
    CrossrefPubMedGoogle Scholar
  • 30 Dosanjh A K, Elashoff D, Kawalek A, Moss R B, Esrig S. Activation of eosinophils in the airways of lung transplantation patients.  Chest. 1997;  112(5) 1180-1183
    CrossrefPubMedGoogle Scholar
  • 31 Henke J A, Golden J A, Yelin E H, Keith F A, Blanc P D. Persistent increases of BAL neutrophils as a predictor of mortality following lung transplant.  Chest. 1999;  115(2) 403-409
    CrossrefPubMedGoogle Scholar
  • 32 Riise G C, Williams A, Kjellström C, Schersten H, Andersson B A, Kelly F J. Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung.  Eur Respir J. 1998;  12(1) 82-88
    CrossrefPubMedGoogle Scholar
  • 33 Zheng L, Walters E H, Ward C et al.. Airway neutrophilia in stable and bronchiolitis obliterans syndrome patients following lung transplantation.  Thorax. 2000;  55(1) 53-59
    CrossrefPubMedGoogle Scholar
  • 34 Vanaudenaerde B M, Wuyts W A, Geudens N et al.. Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients.  Respir Med. 2008;  102(3) 339-347
    CrossrefPubMedGoogle Scholar
  • 35 Vos R, Vanaudenaerde B M, De Vleeschauwer S I, Van Raemdonck D E, Dupont L J, Verleden G M. Plasma C-reactive protein levels correlate with markers of airway inflammation after lung transplantation: a role for systemic inflammation in bronchiolitis obliterans syndrome?.  Transplant Proc. 2009;  41(2) 595-598
    CrossrefPubMedGoogle Scholar
  • 36 Berry G J, Brunt E M, Chamberlain D The International Society for Heart Transplantation et al. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Lung Rejection Study Group.  J Heart Transplant. 1990;  9(6) 593-601
    PubMedGoogle Scholar
  • 37 Trulock E P, Ettinger N A, Brunt E M, Pasque M K, Kaiser L R, Cooper J D. The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures.  Chest. 1992;  102(4) 1049-1054
    CrossrefPubMedGoogle Scholar
  • 38 Stewart S, Fishbein M C, Snell G I et al.. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.  J Heart Lung Transplant. 2007;  26(12) 1229-1242
    CrossrefPubMedGoogle Scholar
  • 39 Yousem S A, Berry G J, Cagle P T et al.. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group.  J Heart Lung Transplant. 1996;  15(1 Pt 1) 1-15
    PubMedGoogle Scholar
  • 40 Yousem S A, Paradis I L, Dauber J H, Griffith B P. Efficacy of transbronchial lung biopsy in the diagnosis of bronchiolitis obliterans in heart-lung transplant recipients.  Transplantation. 1989;  47(5) 893-895
    CrossrefPubMedGoogle Scholar
  • 41 Kramer M R, Stoehr C, Whang J L et al.. The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy.  J Heart Lung Transplant. 1993;  12(4) 675-681
    PubMedGoogle Scholar
  • 42 Chamberlain D, Maurer J, Chaparro C, Idolor L. Evaluation of transbronchial lung biopsy specimens in the diagnosis of bronchiolitis obliterans after lung transplantation.  J Heart Lung Transplant. 1994;  13(6) 963-971
    PubMedGoogle Scholar
  • 43 Cagle P T, Brown R W, Frost A, Kellar C, Yousem S A. Diagnosis of chronic lung transplant rejection by transbronchial biopsy.  Mod Pathol. 1995;  8(2) 137-142
    PubMedGoogle Scholar
  • 44 Pomerance A, Madden B, Burke M M, Yacoub M H. Transbronchial biopsy in heart and lung transplantation: clinicopathologic correlations.  J Heart Lung Transplant. 1995;  14(4) 761-773
    PubMedGoogle Scholar
  • 45 Tazelaar H D, Nilsson F N, Rinaldi M, Murtaugh P, McDougall J C, McGregor C G. The sensitivity of transbronchial biopsy for the diagnosis of acute lung rejection.  J Thorac Cardiovasc Surg. 1993;  105(4) 674-678
    PubMedGoogle Scholar
  • 46 Flint A, Frank T S. Cytomegalovirus detection in lung transplant biopsy samples by polymerase chain reaction.  J Heart Lung Transplant. 1994;  13(1 Pt 1) 38-42
    PubMedGoogle Scholar
  • 47 Glanville A R, Gencay M, Tamm M et al.. Chlamydia pneumoniae infection after lung transplantation.  J Heart Lung Transplant. 2005;  24(2) 131-136
    CrossrefPubMedGoogle Scholar
  • 48 Rizzo M, Alevy Y G, Sundaresan S et al.. Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs.  J Heart Lung Transplant. 1998;  17(3) 241-249
    PubMedGoogle Scholar
  • 49 Stephenson A, Flint J, English J et al.. Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement.  Can Respir J. 2005;  12(2) 75-77
    PubMedGoogle Scholar
  • 50 Colombat M, Groussard O, Lautrette A et al.. Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation.  Hum Pathol. 2005;  36(4) 387-394
    CrossrefPubMedGoogle Scholar
  • 51 Girgis R E, Tu I, Berry G J et al.. Risk factors for the development of obliterative bronchiolitis after lung transplantation.  J Heart Lung Transplant. 1996;  15(12) 1200-1208
    PubMedGoogle Scholar
  • 52 Husain A N, Siddiqui M T, Montoya A, Chandrasekhar A J, Garrity E R. Post-lung transplant biopsies: an 8-year Loyola experience.  Mod Pathol. 1996;  9(2) 126-132
    PubMedGoogle Scholar
  • 53 Burton C M, Iversen M, Carlsen J, Andersen C B. Interstitial inflammatory lesions of the pulmonary allograft: a retrospective analysis of 2697 transbronchial biopsies.  Transplantation. 2008;  86(6) 811-819
    CrossrefPubMedGoogle Scholar
  • 54 Tazelaar H D, Prop J, Nieuwenhuis P, Billingham M E, Wildevuur C R. Airway pathology in the transplanted rat lung.  Transplantation. 1988;  45(5) 864-869
    CrossrefPubMedGoogle Scholar
  • 55 Yousem S A. Lymphocytic bronchitis/bronchiolitis in lung allograft recipients.  Am J Surg Pathol. 1993;  17(5) 491-496
    CrossrefPubMedGoogle Scholar
  • 56 Yousem S A, Dauber J A, Keenan R, Paradis I L, Zeevi A, Griffith B P. Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?.  Transplantation. 1991;  52(2) 306-309
    CrossrefPubMedGoogle Scholar
  • 57 Husain A N, Siddiqui M T, Holmes E W et al.. Analysis of risk factors for the development of bronchiolitis obliterans syndrome.  Am J Respir Crit Care Med. 1999;  159(3) 829-833
    CrossrefPubMedGoogle Scholar
  • 58 Glanville A R, Aboyoun C L, Havryk A, Plit M, Rainer S, Malouf M A. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation.  Am J Respir Crit Care Med. 2008;  177(9) 1033-1040
    CrossrefPubMedGoogle Scholar
  • 59 Ross D J, Marchevsky A, Kramer M, Kass R M. “Refractoriness” of airflow obstruction associated with isolated lymphocytic bronchiolitis/bronchitis in pulmonary allografts.  J Heart Lung Transplant. 1997;  16(8) 832-838
    PubMedGoogle Scholar
  • 60 Burton C M, Iversen M, Scheike T, Carlsen J, Andersen C B. Is lymphocytic bronchiolitis a marker of acute rejection? An analysis of 2,697 transbronchial biopsies after lung transplantation.  J Heart Lung Transplant. 2008;  27(10) 1128-1134
    CrossrefPubMedGoogle Scholar
  • 61 Tavora F, Drachenberg C, Iacono A, Burke A P. Quantitation of T lymphocytes in posttransplant transbronchial biopsies.  Hum Pathol. 2009;  40(4) 505-515
    CrossrefPubMedGoogle Scholar
  • 62 Tamm M, Sharples L D, Higenbottam T W, Stewart S, Wallwork J. Bronchiolitis obliterans syndrome in heart-lung transplantation: surveillance biopsies.  Am J Respir Crit Care Med. 1997;  155(5) 1705-1710
    CrossrefPubMedGoogle Scholar
  • 63 Chhajed P N, Aboyoun C, Malouf M A, Hopkins P M, Plit M L, Glanville A R. Risk factors and management of bleeding associated with transbronchial lung biopsy in lung transplant recipients.  J Heart Lung Transplant. 2003;  22(2) 195-197
    CrossrefPubMedGoogle Scholar
  • 64 Chakinala M M, Ritter J, Gage B F et al.. Yield of surveillance bronchoscopy for acute rejection and lymphocytic bronchitis/bronchiolitis after lung transplantation.  J Heart Lung Transplant. 2004;  23(12) 1396-1404
    CrossrefPubMedGoogle Scholar
  • 65 McWilliams T J, Williams T J, Whitford H M, Snell G I. Surveillance bronchoscopy in lung transplant recipients: risk versus benefit.  J Heart Lung Transplant. 2008;  27(11) 1203-1209
    CrossrefPubMedGoogle Scholar
  • 66 Valentine V G, Taylor D E, Dhillon G S et al.. Success of lung transplantation without surveillance bronchoscopy.  J Heart Lung Transplant. 2002;  21(3) 319-326
    CrossrefPubMedGoogle Scholar
  • 67 Valentine V G, Gupta M R, Weill D et al.. Single-institution study evaluating the utility of surveillance bronchoscopy after lung transplantation.  J Heart Lung Transplant. 2009;  28(1) 14-20
    CrossrefPubMedGoogle Scholar
  • 68 Hopkins P M, Aboyoun C L, Chhajed P N et al.. Association of minimal rejection in lung transplant recipients with obliterative bronchiolitis.  Am J Respir Crit Care Med. 2004;  170(9) 1022-1026
    CrossrefPubMedGoogle Scholar
  • 69 Yousem S A. Significance of clinically silent untreated mild acute cellular rejection in lung allograft recipients.  Hum Pathol. 1996;  27(3) 269-273
    CrossrefPubMedGoogle Scholar
  • 70 Schulman L L, Weinberg A D, McGregor C C, Suciu-Foca N M, Itescu S. Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation.  Am J Respir Crit Care Med. 2001;  163(2) 437-442
    PubMedGoogle Scholar
  • 71 Clelland C, Higenbottam T, Otulana B et al.. Histologic prognostic indicators for the lung allografts of heart-lung transplants.  J Heart Transplant. 1990;  9(3 Pt 1) 177-185, discussion 185–186
    PubMedGoogle Scholar
  • 72 Khalifah A P, Hachem R R, Chakinala M M et al.. Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome.  Am J Transplant. 2005;  5(8) 2022-2030
    CrossrefPubMedGoogle Scholar
  • 73 Hachem R R, Khalifah A P, Chakinala M M et al.. The significance of a single episode of minimal acute rejection after lung transplantation.  Transplantation. 2005;  80(10) 1406-1413
    CrossrefPubMedGoogle Scholar
  • 74 Burton C M, Iversen M, Scheike T, Carlsen J, Andersen C B. Minimal acute cellular rejection remains prevalent up to 2 years after lung transplantation: a retrospective analysis of 2697 transbronchial biopsies.  Transplantation. 2008;  85(4) 547-553
    CrossrefPubMedGoogle Scholar
  • 75 Sibley R K, Berry G J, Tazelaar H D et al.. The role of transbronchial biopsies in the management of lung transplant recipients.  J Heart Lung Transplant. 1993;  12(2) 308-324
    PubMedGoogle Scholar
  • 76 Boehler A, Vogt P, Zollinger A, Weder W, Speich R. Prospective study of the value of transbronchial lung biopsy after lung transplantation.  Eur Respir J. 1996;  9(4) 658-662
    CrossrefPubMedGoogle Scholar

Allan R GlanvilleM.B.B.S. 

The Lung Transplant Unit, Xavier 4

St. Vincent's Hospital, Victoria St., Darlinghurst, NSW, 2010 Australia

Email: aglanville@stvincents.com.au