1. BI 1. Practical Approach neutropenia and infiltrates 1 Febrile neutropenia and bilateral infiltrates ► Learning Objectives  Describe expected results from BAL, TBLB, and TBNA in this case.  Describe risks of TBLB.  Describe 3 ways to manage TBLB-related bleeding.

2. BI 1. Practical Approach neutropenia and infiltrates 2 Case description (practical approach 1) ► AA is a 64 year old physician with history of lymphoma, febrile neutropenia and bilateral infiltrates. Bronchoalveolar lavage is offered, but the referring physician insists on tissue biopsy to exclude neoplasm.

3. BI 1. Practical Approach neutropenia and infiltrates 3 The Practical Approach Initial EvaluationProcedural Strategies Techniques and ResultsLong term Management Examination and, functional status Examination and, functional status Significant comorbidities Significant comorbidities Support system Support system Patient preferences and expectations Patient preferences and expectations Indications, contraindications, and results Indications, contraindications, and results Team experience Team experience Risk-benefits analysis and therapeutic alternatives Risk-benefits analysis and therapeutic alternatives Informed Consent Informed Consent Anesthesia and peri-operative care Anesthesia and peri-operative care Techniques and instrumentation Techniques and instrumentation Anatomic dangers and other risks Anatomic dangers and other risks Results and procedure-related complications Results and procedure-related complications Outcome assessment Outcome assessment Follow-up tests and procedures Follow-up tests and procedures Referrals Referrals Quality improvement Quality improvement

4. BI 1. Practical Approach neutropenia and infiltrates 4 Initial Evaluations ► Lymphoma history  Type of lymphoma, Hodgkin’s, NHL, chronic low grade LL  Lung involvement: mediastinal LAN, lung nodules  Treatment received, response to treatment, and staging ► Treatment  Chemotherapy regimen, duration of neutropenia ► Drug toxicity: cardiac and lung ► Type of infection influence by neutropenia duration  Radiation given, length, duration, XRT field  Complications of previous treatment ► Comorbidities  Smoker, ? Previous Pulmonary function tests  Prednisone: dosage/duration  Bleeding risks: plavix/aspirin, stopped for 3 days

5. BI 1. Practical Approach neutropenia and infiltrates 5 Initial Evaluation ► Presentation  Fever, AMS, hypoxia, possible toxic/septic appearance  Unknown: tachypnea, duration of symptoms, previous antibiotics/antifungal, prophylactic medications given ► Physical Exam  Decreased breath sounds bilateral expiratory wheezes  LE edema and erythematous rash in back ► Pulmonary edema, infection, drug rxn  Unknown: perineal/skin, IV access exam, exclude other sources of infection. ► Laboratory  Chemistry, check uremia, renal function, coag,  Consider BNP (cardiac), galactomannan Ag (aspergillus), CMV PCR

6. BI 1. Practical Approach neutropenia and infiltrates 6 Initial Evaluation ► Radiographic  CXR diffuse bilateral infiltrates  CT scan: diffused, ground glass opacities RUL, LLL, subcarinal adenopathy  Unknown: previous films, duration of findings ► Patient’s Preference  Unknown, needs to discuss with family as altered mental status ► Family  Wife and children with good medical background  Level of support/involvement unknown  Who has durable power for health care  Needs to discuss diagnostic concerns, procedures, risk/benefits with family

7. BI 1. Practical Approach neutropenia and infiltrates 7 Procedural Strategies ► Likely differential for diffuse infiltrates in immunocompromised host  infection: bacterial, PCP, CMV, fungal, mycobacterial  Pulmonary edema cardiac and non-cardiac  Leukoagglutinin rxn, diffused alveolar hemorrhage, alveolar proteinosis  Radiation  Drugs  recurrence of lymphoma in subcarinal lymph node ► Approach to treatment: empiric broad spectrum antibiotics and antifungal and follow versus invasive workup ► Indications/expected benefits of an invasive work up  Narrow differential  avoid prolonged duration of toxic medications, drug resistance  Avoid missed diagnosis that would affect treatment and outcome  Confirm treatment plans  Provide prognosis to family

8. BI 1. Practical Approach neutropenia and infiltrates 8 Procedural Strategies ► Bronchoscopy  Bronchoscopy with BAL ► Good for infection: bacterial, viral, fungal, AFB culture ► BAL established dx in 65% bacterial (CI: 43-84%), 75% of viral (CI 43- 95%), and 40% of fungal infection (17-69%)*  Consider protected specimen brush ► Provided exclusive diagnosis in 13% of bacterial infection in which BAL was negative  Consider transbronchial biopsies ► Improve diagnostic yield for non- infectious etiology ► In one case series, TBB provided exclusive diagnosis in 2/47 (4%) infectious etiology (CMV and candida PNA) ► May help differentiate invasive fungal/CMV; however, most doctor assume invasive in BAL positive ► Non infectious etiology: Bronchiolitis obliterans, drug induced pneumonitis, ARDS, alveolar hemorrhage ► TBB provided exclusive diagnosis in 15/81 (19%) of non-infectious etiology ► Added risks of bleeding and pneumothorax ► Avoid repeat procedure if BAL is non-diagnostic *Jain et al. Role of flexible bronchoscopy in immunocompromised patients with Lung Infiltrates. Chest Vol 125 (2). 2004.

9. BI 1. Practical Approach neutropenia and infiltrates 9 Procedural Strategies Sampling Procedure Diagnostic Yield (infectious & non-infectious) [95% CI] BAL, n = 99 38% [30-47%] 38% [30-47%] TBB, n =45 44% [27-51%] PSB, n =42 13% [6-24%] BAL + PSB, n = 40 45% [32-58%] BAL + TBB, n =40 70% [57-80%] BAL + TBB +PBS, n=25 86% [71-94%] *Jain et al. Role of flexible bronchoscopy in immunocompromised patients with Lung Infiltrates. Chest Vol 125 (2). 2004.

10. BI 1. Practical Approach neutropenia and infiltrates 10 Procedural Strategies  Consider transcarinal needle aspirate ► Yield for needle aspirate for lymphoma is lower, 30- 40%. Flow cytometry and immunochemistry can improve yield to 86%. ► Mediastinal Tru-cut biopsy is best for architecture, especially important for low grade lymphoma  Not possible in most patients  Core transcarinal histology needle may be adequate  Consider local expertise for biopsies, transcarinal needle for both the operator and the lab/path department.

11. BI 1. Practical Approach neutropenia and infiltrates 11 Procedural Techniques and Results ► Patient Factors:  Consider intubation if unstable patient: tachypnea, sepsis, hypotension  If unstable: bedside BAL/brush and no biopsies  Cautions with propofol if hypotensive *Grebski et al. Chest. 1994. Vol 106, 414-420

12. BI 1. Practical Approach neutropenia and infiltrates 12 Procedural Techniques and Results ► Techniques and instrumentation  Stable patient: conscious sedation w versed/fentanyl through the nares  Unstable patient: Intubate, bedside procedure through ET tube with bite block  If brushing: used protected specimen brush for microbiology  BAL segment with infiltrates ► Single sided versus bilateral ► Bilateral LUL & RLL lavage can increase yield in PCP in non-HIV patient* ► For pneumonia, lavage on single involve radiologic segment adequate  Transbronchial biopsies: ► Should be done unilateral lung, avoid B pneumothorax ► LL prefer as easier to manage bleeding in dependent region of lung  Transcarinal needle: use large bore cutting needle for more tissue for flow cytometry and immunochemistry. ► Anatomic danger/risks  Bleeding, pneumothorax, prolonged hypoxemia, respiratory failure *Grebski et al. Chest. 1994. Vol 106, 414-420

13. BI 1. Practical Approach neutropenia and infiltrates 13 Long-term Management Plan ► Outcome assessments  Does procedure change management?  Additional diagnostic yield with brush, transbronchial biopsy, TCNA ► Follow up  Serial CXR and CT with treatment  Consider open lung biopsy if findings and clinical deterioration persist despite treatment

14. BI 1. Practical Approach neutropenia and infiltrates 14 Q 1: Should TBLB be performed ? ► Added diagnostic yield for infection is low. ► May help improve diagnostic yield for non- infectious etiology. ► Limited treatment options for non-infectious etiologies. ► Consider time course of presentation, if acute, likely infectious and TBLB not helpful. ► Consider bleeding risks and patient safety.

15. BI 1. Practical Approach neutropenia and infiltrates 15 Q 2: Should transcarinal needle aspiration be performed? ► Lower diagnostic yield for lymphoma. ► Consider pathologist expertise for diagnosis of lymphoma from TBNA. JabbingPiggyback Cough Hub against wall Modified, from UpToDate To view video, please see Video Archive PA 1

16. BI 1. Practical Approach neutropenia and infiltrates 16 Q 3: Medications and Bleeding Risk ► Plavix increases risk of bleeding with transbronchial biopsy. ► Risk increased when Plavix is taken with aspirin. ► Aspirin alone does not increase bleeding risk and does not need to be stopped prior to procedure. ► Recommendation: stop Plavix 5-7 days prior to plan transbronchial biopsy. Ernst et al. Chest 2006; 129: 734-737.

17. BI 1. Practical Approach neutropenia and infiltrates 17 Q 4: What if referring physician insists on a biopsy right away? ► Do what you consider to be safest for the patient, even if it means refusing to do the biopsy. ► In case of acute onset of pulmonary infiltrates and fever with in the setting of neutropenia, most likely etiology is infectious. TBLB adds very little to the diagnostic yield for infection and increases risk, especially in patient with respiratory compromise, altered mental statues, and on plavix.

18. BI 1. Practical Approach neutropenia and infiltrates 18 Q 5: What procedure do you recommend? ► Bronchoscopy with BAL in LUL and RLL ► If non-diagnostic and patient does not improve with empiric therapy, repeat imaging and consider repeat bronchoscopy with TBLB of gravity dependent areas of right lower lobe.

19. BI 1. Practical Approach neutropenia and infiltrates 19 All efforts are made by Bronchoscopy International to maintain currency of online information. All published multimedia slide shows, streaming videos, and essays can be cited for reference as: Bronchoscopy International: Practical Approach ©, an Electronic On- Line Multimedia Slide Presentation. http://www.Bronchoscopy.org/PracticalApproach/htm. Published 2009 (Please add “Date Accessed”). Thank you

20. BI 1. Practical Approach neutropenia and infiltrates 20 Prepared with the assistance of Dana Tran M.D. www.bronchoscopy.org