Surveillance Bronchoscopy in Lung Transplant Recipients

doi:10.1378/chest.111.2.377

Chest

Volume 111, Issue 2, February 1997, Pages 377-381

https://doi.org/10.1378/chest.111.2.377 Get rights and content

Study objectives

To establish whether a consensus exists among active transplant centers regarding the use and interpretation of information obtained by surveillance bronchoscopic lung biopsy (SBLB).

Design

Prospective standardized questionnaire answered via mail and telephone communications.

Participants

A five page, 18-question survey was sent to all lung transplant programs listed by the United Network of Organ Sharing in North America, as well as eight selected international programs. Ninety-one surveys were sent to 83 North American and eight international programs. Seventy-four programs (81%) responded. Seventeen programs (19%) were excluded secondary to inactivity. The remaining 57 programs (63%) were included in final data analysis.

Interventions

None.

Results

Sixty-eight percent (39/57) of the responding programs perform SBLBs. Ninety-two percent of the programs performing SBLBs do so within the first month, and 69% continue to do so on a regular basis. Sixty-nine percent (27/39) of programs performing SBLBs continue to do so after 1 year. Eighty-six percent (32/37) of respondents believe that SBLB impacts on patient management at least 10% of the time. Technically, 90% (35/39) take biopsy specimens from more than one lobe per SBLB session. Fifty-nine percent (23/39) took 6 to 10 biopsy specimens per session, 33% (13/39) took three to five biopsy specimens, and 7% (4/39) took >10 biopsy specimens per session. Eighty-six percent (32/37) of the responding centers reported treating asymptomatic rejection at grade 2A, while 14% (5/37) waited until histologic grade 3A before beginning treatment. Complications from SBLB were minimal with <5% rates of pneumothorax, requirement for chest tube placements, or significant bleeding during SBLB reported by >95% of the programs performing SBLB.

Conclusion

Most active lung transplant centers perform SBLBs and do so on a regular basis. However, a wide range of opinion exists over the utility and technique of SBLB and the impact of its results influencing outcome in the lung transplant recipient. To answer these questions, a randomized multicentered trial or registry to determine the effect of SBLB on lung transplant recipient morbidity and mortality is required.

Section snippets

Materials and Methods

A five-page, 18-question survey was mailed to all LT programs listed in the United Network of Organ Sharing directory in the fall of 1994, as well as eight programs in Europe and Australia that had presented abstracts on LT at the 1994 American Thoracic Society annual meeting. The following topics were included in the questionnaire: (1) the type of LT procedures performed and the center's LT volume over the previous 12 months; (2) the frequency of performing SBLB and pattern of use; (3) the

Demographics of Responding Programs

Of the responding programs, 100% performed single LT, 90% performed DLT, and 74% performed HLT. The activity of each of the respondents (eg, based on the number of transplants performed over the previous 12 months) is shown in Figure 1. Most of the responding programs performed at least 10 transplantations per year.

Frequency and Timing of SBLB Among Respondents

Of the respondents, 68% (39/57) included SBLB as part of their routine postoperative treatment of the LT recipient, which was statistically significant when compared with programs

Discussion

Our results demonstrate that most transplant programs utilize some form of SBLB. Respondents who perform SBLB perceive that information obtained from the procedure changes management at least 10% of the time, and complications of SBLB are perceived as rare and clinically insignificant. Ninety percent of transplant centers generally agree that biopsy specimens should be taken from more than one lobe of the lung and 59% believe that 6 to 10 biopsy samples are necessary to adequately screen for

References (26)

K Bando et al.
Obliterative bronchiolitis after lung and heart-lung transplantation
J Thorac Cardiovasc Surg
(1995)
VA Starnes et al.
Evaluation of heart-lung transplant recipients with prospective, serial transbronchial biopsies and pulmonary function studies
J Thorac Cardiovasc Surg
(1989)
EP Trulock et al.
The role of transbronchial biopsy in the treatment of lung transplant recipients: an analysis of 200 consecutive patients
Chest
(1992)
JD Cooper et al.
Results of single and bilateral lung transplantation in 131 consecutive recipients
J Thorac Cardiovasc Surg
(1994)
BA Otulana et al.
The use of home spirometry in detecting acute lung rejection and infection following heart-lung transplantation
Chest
(1990)
Society for Heart and Lung Transplantation
Twelfth official report—1995
J Heart Lung Transplant
(1995)
S Lewis et al.
Outcome of lung transplant recipients without surveillance lung biopsies in a new program [abstract]
chest
(1994)
SR Patel et al.
Lung transplantation: the Cleveland Clinic experience
Clev Clin J Med
(1993)
SA Yousem et al.
Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?
Transplantation
(1991)
JP Scott et al.
Risk factors for obliterative bronchiolitis in heart-lung transplant recipients
Transplantation
(1991)

SA Yousem et al.

A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection

J Heart Transplant

(1990)

T Higenbottam et al.

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients

Transplantation

(1988)

RK Sibley et al.

The role of transbronchial biopsies in the management of lung transplant recipients

J Heart Lung Transplant

(1993)

Cited by (58)

Interventional pulmonology techniques in lung transplantation
2023, Respiratory Medicine
Lung transplantation is a key therapeutic option for several end-stage lung diseases.
Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications.
We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation.
We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications.
The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia).
First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation.
High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.
Donor-derived cell-free DNA as a composite marker of acute lung allograft dysfunction in clinical care
2022, Journal of Heart and Lung Transplantation
As a marker of underlying lung allograft injury, donor-derived cell-free DNA (dd-cfDNA) may be used to identify episodes of acute allograft injury in lung transplant recipients. We investigated the utility of dd-cfDNA to monitor subjects at risk of acute rejection or infection in routine clinical practice.
This multicenter, retrospective cohort study collected data from lung transplant recipients within 3 years of transplant at 4 centers between March 24, 2020 and September 1, 2020. During this period, as part of routine care during the COVID-19 pandemic, these centers implemented a home-based surveillance program using plasma dd-cfDNA in preference to surveillance bronchoscopy. Dd-cfDNA was used to detect acute lung allograft dysfunction (ALAD) – a composite endpoint of acute rejection and infection. dd-cfDNA levels in patients with ALAD were compared to stable patients. The performance characteristics of dd-cfDNA ≥ 1.0% to detect ALAD were estimated.
A total of 175 patients underwent 380 dd-cfDNA measurements, of which 290 were for routine surveillance purposes. dd-cfDNA was higher in patients with ALAD than stable patients (Median (IQR) 1.7% (0.63, 3.1) vs 0.35% (0.22, 0.79), p < 0.001). As an indication of underlying ALAD during surveillance testing, the estimated sensitivity of dd-cfDNA ≥1% was 73.9%, specificity of 87.7%, positive predictive value of 43.4% and negative predictive value of 96.5%.
dd-cfDNA identified acute lung allograft dysfunction in asymptomatic lung transplant patients that may not have been identified by using a clinically indicated biopsy strategy alone. dd-cfDNA <1.0% may be useful in ruling out acute rejection and infection, supporting its use as a potential noninvasive marker for surveillance monitoring.
The impact of C4d testing on tissue adequacy in lung transplant surveillance
2020, Annals of Diagnostic Pathology
Surveillance transbronchial biopsies are routinely used to assess lung allograft rejection. While the criteria for diagnosing acute cellular rejection have been well-established, the morphological findings associated with antibody mediated rejection are variable. To increase the sensitivity for antibody mediated rejection, a portion of a biopsy can be used for C4d immunofluorescence testing, along with histologic findings and donor specific antibodies. When the number of alveolar pieces in a biopsy is small, the relative utility of sending one piece for C4d testing is unclear.
Pathology reports of 1400 surveillance transbronchial lung biopsies from 2008 to 2017 were reviewed to obtain the number of pieces of alveolar parenchyma in each case. Based on a standard definition of adequacy as five pieces of well-expanded alveolar parenchyma, reports with five fragments were grouped as “adequate”, four pieces as a “marginal” sample, and three or less were considered an “inadequate” sample.
Of the 1400 biopsies, 653 specimens had 5 or more pieces of alveolar parenchyma.747 specimens were submitted with less than 5 pieces and 290 of those were considered marginal. In all marginal cases, a piece was withheld for C4d immunofluorescence testing.
About 21% of specimens would have the recommended 5 pieces of alveolar parenchyma if not for the withholding of pieces for C4d IF testing. Over the span of 10 years, 290 such cases were recorded at our institution. Given this nontrivial impact, it is unclear if C4d immunofluorescence testing should be performed on surveillance transbronchial biopsies when the number of pieces in the specimen is marginal.
Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation
2020, Cytokine
Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings.
We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups “ACR”, “infection”, “combined ACR and infection” and “no pathologic process”. No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation.
Acute Rejection and Antibody-Mediated Rejection in Lung Transplantation
2017, Clinics in Chest Medicine
Citation Excerpt :
Furthermore, a significant number of patients will have more than a single episode of ACR.22,24,26 Because episodes of ACR are often clinically silent, many transplant programs have adopted a surveillance bronchoscopy and transbronchial lung biopsy protocol to identify ACR early with the hope that treatment might mitigate the risk of higher-grade ACR or the development of CLAD and improve survival in a high-risk patient population.28,29 However, this approach remains controversial, and other programs advocate performing bronchoscopy only if patients develop signs or symptoms of allograft dysfunction to avoid the potential risks of surveillance procedures.30
Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection
2014, American Journal of Transplantation
Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25⁺ and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96–98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

View all citing articles on Scopus

View full text

Chest

Surveillance Bronchoscopy in Lung Transplant Recipients

Study objectives

Design

Participants

Interventions

Results

Conclusion

Section snippets

Materials and Methods

Demographics of Responding Programs

Frequency and Timing of SBLB Among Respondents

Discussion

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Chest

J Thorac Cardiovasc Surg

Chest

Twelfth official report—1995

J Heart Lung Transplant

Outcome of lung transplant recipients without surveillance lung biopsies in a new program [abstract]

chest

Lung transplantation: the Cleveland Clinic experience

Clev Clin J Med

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Transplantation

Risk factors for obliterative bronchiolitis in heart-lung transplant recipients

Transplantation

A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection

J Heart Transplant

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients

Transplantation

The role of transbronchial biopsies in the management of lung transplant recipients

J Heart Lung Transplant