Download Utility of fiberoptic bronchoscopy in bone marrow transplant

Bone Marrow Transplantation, (1997) 20, 681–687
 1997 Stockton Press All rights reserved 0268–3369/97 $12.00
Utility of fiberoptic bronchoscopy in bone marrow transplant patients
P White1,2,3, JT Bonacum1,2 and CB Miller2
Departments of 1Medicine and 2Oncology, 3Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions,
Baltimore, MD, USA
Summary:
Fiberoptic bronchoscopy (FOB) has been reported to
have a high diagnostic yield and to be safe in BMT
patients with pulmonary infiltrates. At our institution,
BMT patients with respiratory symptoms and/or pulmonary infiltrates had a thoracic CT and bronchoalveolar lavage (BAL). Transbronchial biopsy (TBBx) was
considered if the platelet count could be raised to
.30 × 109/l. From March 1993 to August 1995, 52
patients had 68 FOBs (42 BAL + TBBx, 26 BAL only)
for 60 episodes of clinical pneumonia. Patients’ characteristics were: 38 males, mean age 42 years, and 39 allogeneic BMTs. Of the 68 FOBs, 47 were performed to
evaluate diffuse infiltrates, 10 were done on mechanically ventilated patients, and 50 of the FOBs were preceded by a platelet transfusion. Thirty-one percent of
FOBs (21 FOBs, 19 patients) were diagnostic. Twentyfour percent of FOBs (11 diagnostic FOBs, six nondiagnostic FOBs) changed therapy. Ten complications
(15%) occurred in 10 FOBs (five acute respiratory failure, three pneumothoraces, one nose bleed, one death).
Hospital and 6-month survival based on episodes of
clinical pneumonia were 47 and 32%, respectively.
Patients who had a diagnostic FOB or a FOB that
changed treatment did not have better hospital or 6month survival compared to patients who had FOBs
that were nondiagnostic or did not change treatment.
FOB in our BMT patient population, had a low diagnostic yield (31%), infrequently changed treatment (24%),
a significant complication rate (15%) and was not associated with improved patient survival. The role of routine diagnostic FOB in BMT patients with pulmonary
infiltrates and/or respiratory symptoms should be reevaluated.
Keywords: BMT; bronchoscopy; FOB; pulmonary
infection
Bone marrow transplantation (BMT), is a well accepted
form of treatment for certain hematologic and nonhematologic malignancies, and various hematologic or immunologic disorders. Pulmonary complications following BMT
include: (1) infection (bacterial, viral, fungal, parasitic); (2)
Correspondence: Dr P White, The Johns Hopkins University, Division of
Pulmonary and Critical Medicine, 720 Rutland Avenue, Ross Research
Building, Room 858, Baltimore, MD 21205-2196, USA
Received 12 March 1997; accepted 19 June 1997
idiopathic noninfectious pneumonia; (3) pulmonary edema
(hydrostatic or noncardiogenic); (4) respiratory failure
(pulmonary and extrapulmonary etiologies); (5) inflammatory conditions (diffuse alveolar damage (DAD), bronchiolitis obliterans organizing pneumonia (BOOP), bronchiolitis
obliterans (BO), and pulmonary graft-versus-host disease);
(6) pulmonary hemorrhage; and (7) pulmonary venoocclusive disease (VOD). Clinical signs, symptoms, and
radiographic infiltrates consistent with pneumonia occur in
30–60% of patients following BMT and the mortality rate
is 60–80%. 1,2 Fiberoptic bronchoscopy (FOB), a safe well
tolerated procedure capable of obtaining samples from distal airways and alveoli, is commonly used to evaluate BMT
patients with undiagnosed pulmonary infiltrates.2–4 In BMT
patients with pulmonary infiltrates 50–80% of FOBs provide a definitive diagnosis.5–12 Prior reports of FOB in BMT
patients have emphasized diagnosis,5–10,12 and have not
indicated the impact of FOB on directing pharmacologic
therapy5,6,7,9,11,13 or stressed patient survival.5,8,11
The use of FOB to evaluate pulmonary infiltrates in BMT
patients was not previously standardized at our institution.
Although the medical literature indicates that FOB in BMT
patients with pulmonary infiltrates is a safe and valuable
diagnostic procedure, its impact on providing a diagnosis,
guiding treatment, and patient outcome at our institution
was unclear. A data base was established to collect existing
clinical information to assess the yield, impact on treatment, safety and survival in BMT patients who had FOB to
evaluate respiratory symptoms and/or pulmonary infiltrates.
Materials and methods
Patient population
The Johns Hopkins Oncology Center (JHOC) BMT unit has
18 inpatient beds and performs approximately 150 marrow
transplantations per year (|50 allogeneic, |100 autologous)
for hematologic malignancies and aplastic anemia. (Patients
who have autologous BMT following high-dose chemotherapy for breast cancer or ovarian cancer are not cared
for on this unit and are not included in this data base.)
Since March 1993, pulmonary physicians evaluating BMT
patients for respiratory symptoms (cough, dyspnea, and/or
chest pain), fevers and/or pulmonary infiltrates were
encouraged but not required to perform FOB for: (1)
patients with diffuse infiltrates provided pulmonary edema
is excluded on clinical grounds; (2) patients with focal
infiltrates or pulmonary nodules greater than 2 cm in diameter who did not respond promptly to empiric antibiotics
FOB in BMT patients
P White et al
682
and/or antifungal therapy. This approach was approved by
the JHOC BMT Clinical Studies Committee and the JHOC
Pulmonary and Critical Care Medicine Committee. Data
were collected on all BMT patients who had FOB between
17 March 1993 and 31 August 1995 for respiratory symptoms and/or undiagnosed pulmonary infiltrates.
Data collection
Existing clinical data were obtained from the Oncology
Center Information Systems computer, the Johns Hopkins
Medical Institutions computer, the patient’s hospital chart
and FOB reports. The following data were collected for
each patient within 48 h of FOB: age, gender, underlying
diagnosis, type and date of BMT, type of infiltrate on chest
CT (diffuse vs focal), FOB procedure(s) performed
(bronchoalveolar lavage (BAL), and transbronchial biopsy
(TBBx) vs BAL alone), FOB results (microbiology, cytopathology, histology), FOB complications (pneumothorax,
acute respiratory failure requiring mechanical ventilation
within 24 h of FOB, estimated blood loss .30 ml, death
within 24 h of FOB), platelet number and white blood cell
count, and whether the patient had a platelet transfusion
prior to FOB. We also recorded change in pharmacologic
treatment, date of discharge or death, vital status 6 months
after FOB, and results of autopsy or post mortem lung
biopsy performed within 10 days of FOB.
Diagnostic criteria
Identification of Pneumocystis carinii or Legionella species
from FOB specimens was assumed to be diagnostic of parenchymal lung infection. Bacterial pneumonia was diagnosed in patients on antibiotics when thoracic CT showed
an alveolar infiltrate and: (a) blood or pleural fluid cultures
grew pathogenic bacteria; or (b) histologic evidence of
acute bacteria pneumonia was demonstrated by surgical
lung biopsy or autopsy; or (c) quantitative bacterial cultures
from BAL fluid grew .105 colony-forming units. In
patients not on antibiotics, in addition to the above, a compatible Gram stain (organisms and neutrophils) and heavy
growth was adequate for diagnosing bacterial pneumonia.
Cytomegalovirus (CMV) pneumonia was diagnosed by a
positive CMV culture (standard viral culture, or early antigen culture) and/or characteristic ‘owl-eyed’ intranuclear
and/or intracytoplasmic inclusions on BAL cytopathology
or TBBx histology. Invasive pulmonary aspergillosis (IPA)
was diagnosed in neutropenic patients with compatible
infiltrates/nodules on CT by microscopic identification of
septate hyphal forms consistent with Aspergillus (BAL
cytopathology or potassium hydroxide (KOH), and/or lung
histology) or positive BAL cultures. In non-neutropenic
patients IPA was diagnosed by demonstration of tissue
invasion by fungal forms consistent with Aspergillus. Candida pneumonia was diagnosed by a positive BAL culture
and histologic evidence of tissue invasion. DAD, BOOP,
BO were diagnosed by standard surgical pathology criteria.
TBBx specimens which were ‘consistent with’ DAD,
BOOP, or BO were recorded as diagnostic.
Chest CT criteria
Diffuse pulmonary infiltrates were defined as bilateral
infiltrates that involved >1 lobe. Presumed basilar atelectasis with bilateral pleural effusion were coded as diffuse
infiltrates. Focal infiltrates were defined as unilateral infiltrates involving one lung (uninvolved ipsilateral lobes and
contralateral lung appear normal). Pulmonary nodule(s)
(,3 cm in diameter), pulmonary mass (.3 cm in diameter),
were coded as focal infiltrates.
Patient management
A change in patient management was defined as the withdrawal or addition of a pharmacologic treatment within 72
h of the procedure for nondiagnostic FOB and within 48 h
of the result for a diagnostic FOB.
Bronchoscopy technique
FOB was performed by a Pulmonary and Critical Care
Medicine fellow and attending physician. The patient or
surrogate signed informed consent prior to the procedure
which was performed in either a dedicated Endoscopy Unit
(spontaneously breathing patient) or in the patient’s room
(mechanically ventilated patient). Patients were monitored
with continuous electrocardiograms and pulse oximetry.
Blood pressure was monitored every 5–10 min. The standard practice for sedation was i.v. midazolam (typical dose
5 mg) and i.v. fentanyl (typical dose 100 mg). The nasal
passage, vocal cords and airways were anesthetized with
lidocaine. If the patient’s heart rate was ,100 b.p.m., i.v.
atropine (0.5–1 mg) was administered. FOB in mechanically ventilated patients was performed via a swivel-Y
adaptor while the patient was ventilated with 100% oxygen.
Mechanically ventilated patients were sedated as outlined
above and commonly received short-acting neuromuscular
blocking agents. The bronchoscopist determined which
lung segment(s) were lavaged and/or biopsied. In general,
the middle lobe or lingula was lavaged and/or biopsied for
diffuse infiltrates, and the subsegment most affected on CT
was lavaged and/or biopsied for focal infiltrates. BAL was
done using 20 ml or 50 ml aliquots of room temperature
normal saline. A total of 80 to 150 ml of saline (typical
amount 100 ml) was instilled. Contraindications to FOB
or BAL were: uncooperative patient, active bronchospasm,
hemodynamic instability, unstable arrhythmia, and refractory hypoxemia (PaO2 ,100 mmHg on high flow oxygen
via non-rebreather face mask). TBBx were performed with
fluoroscopy using 2 ml elipcoid cupped forceps. The number of TBBx attempted was determined by the operator
(generally 3–6). In addition to the general contraindications
to FOB, contraindications to TBBx were: (1) 1 h post-platelet transfusion platelet number ,30 × 109/l; (2) PT .15
s; (3) PTT .1.3 times control; (4) BUN .50 mg/dl; (5)
spontaneous mucocutaneous bleeding; and (6) mechanical
ventilation with positive end expiratory pressure. An anteroposterior chest X-ray was obtained 15–45 min after
TBBx to examine for pneumothorax. BAL fluid was submitted to cytopathology and microbiology (gram stain and
aerobic bacterial culture; Legionella culture and direct flu-
FOB in BMT patients
P White et al
Table 1
683
Patient demographics
Diagnosis
M/F
Mean age
(range)
Allogeneic
BMT
Autologous
BMT
Hospital
survivors
6-month
survivors
CML (n = 15)
AML (n = 10)
ALL (n = 5)
NHL (n = 14)
Hodgkin’s disease (n = 2)
Other (n = 6) a
11/4
6/4
5/0
11/3
1/1
4/2
35.6
46.9
42.4
49.8
24
41.5
(18–53)
(22–64)
(31–52)
(33–61)
(23–25)
(24–58)
15
10
4
6
1
3
0
0
1
8
1
3
10
4
0
8
1
5
5
2
0
7
1
4
Total (n = 52)
38/14
42
(18–68)
39
13
28
19
CML = chronic myelogenous leukemia; AML = acute myelogenous leukemia; ALL = acute lymphocytic leukemia; NHL = non-Hodgkin’s lymphoma;
M = male; F = female.
Survival data are based on episodes of clinical pneumonia (n = 60).
a
Others were: aplastic anemia (1), multiple myeloma (3), choriocarcinoma (1), germ cell (1).
orescent antibody, mycology culture and KOH preparation,
mycobacteriology fluorochrome stain and culture, and viral
cultures for CMV including early antigen culture, herpes
simplex virus, respiratory syncytial virus, influenza virus,
parainfluenza virus, and adenovirus). TBBx specimens
were placed in 10% formaldehyde and submitted for histology, acid fast stains and methenamine silver stains.
Statistical analysis
All statistics (mean, x2, Kaplan–Meier survival analysis)
were calculated using the SPSS statistical package (version
6.1). x2 test was used to compare variables. P < 0.05 was
considered statistically significant. When a patient had .1
FOB, Kaplan–Meier analysis was done using data from the
first FOB.
Results
Between 17 March 1993 and 31 August 1995, 391 patients
had BMT (123 allogeneic, 268 autologous). During this
period, 52 patients (39 allogeneic and 13 autologous; 32%
of allogeneic BMTs, 5% of autologous BMTs, P , 0.0001)
underwent 68 FOBs (42 BAL and TBBx, 26 BAL alone)
for 60 episodes of clinical pneumonia (fever, respiratory
symptoms and/or pulmonary infiltrates). Ten patients had
two FOBs, three patients had three FOBs, and eight patients
had FOB for two separate episodes of clinical pneumonia.
Patient demographics, pre-BMT diagnosis, type of transplant and survival are listed in Table 1.
Of the 68 FOBs, 47 (69%) were done to evaluate diffuse
infiltrates, 21 (31%) were done to evaluate focal infiltrates,
10 (15%) were done on mechanically ventilated patients,
50 (74%) were done after a platelet transfusion and 14
(21%) were done when the total white blood cell count
was ,5 × 109/l.
The number of days after BMT when a patient had FOB
(,30 days, 30–90 days, .90 days) was not significantly
associated with the diagnostic yield, change in treatment,
or patient survival (Table 2).
Table 3 reports the results (diagnosis, change in treatment, outcome) of FOB. Thirty-one percent of FOBs (21
FOBs in 19 patients) yielded a diagnosis (CMV 10, PCP
2, IPA 3, Candida 2, bacterial pneumonia 2, Legionella
pneumonia 1, DAD 2, BOOP 1, and BO 1). One of the
diagnostic FOBs yielded two diagnoses (CMV and bacterial pneumonia) and one yielded three diagnoses (CMV,
Legionella, IPA). One patient had FOB twice for the same
episode of CMV pneumonia. Nineteen pulmonary infections were identified in 17 FOBs in 13 patients. The diagnostic yield of FOB for focal vs diffuse infiltrates was 24
vs 34%, respectively (P = 0.40). Four noninfectious diagnoses were established with four FOBs in four patients.
Forty-seven FOBs in 33 patients were nondiagnostic. Seventeen (24%) FOBs (11 diagnostic FOBs and six nondiagnostic FOBs) in 14 patients (15 episodes of pneumonia)
changed therapy. Therapy was not changed in either of the
two FOBs that yielded .1 diagnosis.
Of the 68 FOBs, 65 (96%) were done when the patient
was receiving antibiotics, 40 (59%) when the patient was
on amphotericin, 19 (28%) when the patient was on ganciclovir or fosconnate, 32 (47%) when the patient was on
antibiotics and amphotericin (18 without acyclovir, 14 with
acyclovir), and six (9%) when the patient was on antibiotics, amphotericin and ganciclovir or fosconnate.
Four patients had surgical lung biopsies done following a
nondiagnostic FOB (two BAL and TBBx, two BAL alone).
Three of the surgical biopsies yielded a definitive diagnosis
(two BOOP, one pulmonary VOD) and two changed treatTable 2
Timing of FOB
Days post-BMT at FOB
Total
P value a
,30
30–90
.90
No. FOB
Dx FOB
Change in Rx
25
5
3
24
11
9
19
5
5
68
21
17
NS
NS
NS
Hosp survivors
6 mo survivors
12
7
4
4
12
8
28
19
NS
NS
Calculated by x2 analysis.
Dx = diagnostic; Rx = treatment; NS = not significant.
The number of days status post-BMT when FOB was done was not significantly associated with diagnostic yield or survival. Dx FOB and change
in Rx are based on number of FOB (n = 68). Survival data are based on
number of individual episodes of clinical pneumonia (n = 60).
a
FOB in BMT patients
P White et al
Table 3
Results of FOB in BMT patients
Diagnostic proceduresa
CT infiltrates
Change
Rx
Diffuse
Focal
BAL
TBBx
BAL/TBBx
8
2
1
2
2
1
2
0
2
0
0
0
7
1
3
0
2
1
0
0
0
1
0
0
3
1
0
1
0
0
Noninfectious
DAD (n = 2)
BOOP (n = 1)
BO (n = 1)
Total
2
1
1
19
0
0
0
5
0
0
0
13
2
1
1
5
Nondiagnostic
31
16
0
0
Infection
CMV (n = 10)
PCP (n = 2)
IPA (n = 3)
Candida (n = 2)
Bacterial (n = 2)
Legionella (n = 1)
Survivors
Hospital
6 month
7
2
1
1
0
0
3
1
1
0
1
0
1
1
0
0
0
0
0
0
0
5
0
0
0
11
0
1
0
7
0
0
0
2
0
6
21
17
BAL = bronchoalveolar lavage; TBBx = transbronchial biopsy; Change Rx = change in treatment.
a
BAL = diagnosis by BAL only; TBBx = diagnosis by TBBx only; BAL/TBBx diagnosis = present on both BAL and TBBx.
For diagnostic FOBs CT infiltrates and diagnostic procedures are based on the number of identified diagnoses (n = 24 in FOBs). Change in Rx data is
based on number of FOBs (n = 68). Survival data are based on number of episodes of clinical pneumonia (n = 60).
1.0
0.9
Change in therapy
0.8
Cumulative survival
ment (BOOP, and pulmonary VOD). Seven patients had
examination of post mortem lung tissue within 10 days of
FOB (five autopsies, two lung biopsies) of which one
yielded a diagnosis not found on the prior FOB (CMV
pneumonia).
Hospital and 6-month survival for the 60 episodes of
clinical pneumonia was 47 and 32%, respectively (Table
1). Survival by Kaplan–Meier analysis demonstrated that
patients who had a diagnostic FOB or a FOB that changed
therapy did not have an increased probability of survival
compared to patients who had a FOB that did not yield a
diagnosis or change therapy (Figures 1 and 2).
0.7
No change in therapy
0.6
0.5
0.4
0.3
0.2
Log-rank; P = 0.68
1.0
0.1
Diagnostic FOB
0.9
0.0
0.8
Cumulative survival
684
0
Non-diagnostic FOB
0.7
30
60
90
120
150
180
Days post-bronchoscopy
0.6
Figure 2 There was no difference in survival between patients who had
FOBs that did nor did not change therapy.
0.5
0.4
Complications
0.3
Ten complications (15%) occurred in 10 FOBs involving
nine patients. Five patients (7%) required mechanical ventilation for acute respiratory failure within 24 h of FOB.
Three pneumothoraces (4%) occurred (two after BAL in
mechanically ventilated patients, one after TBBx and BAL
in a spontaneously breathing patient) but none required a
chest tube and all resolved with conservative management.
There was one bleeding complication (1.5%): a nose bleed
requiring packing. There were no episodes of significant
parenchymal hemorrhage following TBBx or BAL. One
0.2
Log-rank; P = 0.34
0.1
0.0
0
30
60
90
120
150
180
Days post-bronchoscopy
Figure 1 There was no difference in survival between patients who had
diagnostic or nondiagnostic FOBs.
FOB in BMT patients
P White et al
patient (1.5%) died within 24 h of FOB. An autopsy indicated the cause of death was sepsis and there was no indication that the patient’s death was related to the procedure.
Overall, two of the nine patients (22%) who had FOBrelated complications (pneumothorax, mechanical ventilation) were discharged alive from the hospital. This was
not statistically different from hospital survival in patients
without FOB-related complications (51%; P = 0.30).
Discussion
In our BMT patient population, FOB had a low diagnostic
yield (31%), infrequently changed therapy (24%), and a
significant complication rate (15%). Hospital and 6-month
survival in patients who had a diagnostic FOB or a FOB
that changed treatment was not different compared to
patients who had a nondiagnostic FOB or a FOB which did
not change therapy.
This observation raises an important issue. What is the
role of FOB in evaluating BMT patients with pulmonary
infiltrates and respiratory symptoms? A diagnostic procedure may benefit a patient by: (1) providing a diagnosis;
(2) guiding treatment; (3) predicting prognosis. In this
report, FOB was found wanting on all three accounts. This
raises the question whether the risk of FOB justifies the
benefit and should FOB be done routinely to evaluate pulmonary infiltrates in BMT patients. A definitive statement
would require this observation be confirmed in a large controlled clinical trial comparing survival in BMT patients
with clinical pneumonia randomized to empiric antimicrobial therapy with or without FOB and antimicrobial therapy
dictated by FOB and/or other invasive diagnostic procedures. Enthusiasm for such a clinical trial is problematic.
Multiple uncontrolled reports have failed to show improved
survival in immunocompromised patients who had open
lung biopsies, 14 and FOB has a high diagnostic yield for
CMV pneumonia, a common cause of diffuse pulmonary
infiltrates in BMT patients.7,8
The medical literature for FOB in BMT patients is summarized in Table 4. FOB has been reported to yield a specific diagnosis in 42% (13) to 89% (8) of patients. The
yield in our series (31%) was less than expected based on
the medical literature. The explanation for this was not
obvious. Patient population, treatment protocols, and
patient selection criteria vary between institutions and may
influence the diagnostic yield of FOB and patient survival.
Our patient population was heterogenous, was identified
prospectively, and all FOBs were clinically indicated. The
spectrum and timing of diagnosis in our series were similar
to previous reports, 1–3 suggesting that the low diagnostic
yield was not an artifact of the patient population or selection criteria.
In allogeneic BMT patients, CMV pneumonia is the most
common pulmonary infection between 30–180 days after
marrow transplant.1–3 Historically, the incidence of CMV
pneumonia at our institution has been low (allogeneic, 12%;
autologous, 2%).15 Other BMT centers have reported an
incidence as high as 25% for allogeneic BMT patients.2,3
Idiopathic pneumonia syndrome (IPS) in BMT patients is
a clinical syndrome characterized by signs and symptoms
of pneumonia with non-lobar pulmonary infiltrates without
evidence of lower respiratory infection defined as a lack of
improvement on broad spectrum antibiotics and/or a nondiagnostic FOB.16 The historical incidence of idiopathic interstitial pneumonitis (defined as PO2 on room air ,70
mmHg, nonlobar pulmonary infiltrates in the absence of
heart failure and no evidence of infection based on culture
and histology of lung tissue) at our BMT center was 19%
and 7% for allogeneic and autologous BMT patients,
respectively.17 The incidence of IPS at other BMT centers
is similar (10–20%).16 The reduction in the number of cases
of CMV pneumonia relative to idiopathic interstitial pneumonitis responsible for diffuse infiltrates at our BMT center
could partly account for the low FOB diagnostic yield seen
in this series, given that IPS cannot be definitively diagnosed by FOB.
In our series, FOB diagnosed nine of 10 patients with
clinically recognized CMV pneumonia. This is similar to
other reports in BMT patients.7,8 The single case of CMV
pneumonia not identified by FOB in this report was diagnosed at autopsy 10 days after FOB in a patient with
chronic graft-versus-host disease, CMV colitis, CMV
viremia, acute respiratory distress syndrome and multiorgan system failure. Post-mortem lung pathology showed
‘extensive acute organizing diffuse alveolar damage’ and
‘rare CMV positive cells’. Our experience with CMV pneumonia strongly suggests that the low overall diagnostic
yield of FOB was not an artifact of a technical problem in
obtaining, transporting, processing or culturing specimens.
The yield of FOB in our series was not spuriously
depressed by overly stringent diagnostic criteria. The diagnostic criteria were similar to those used by others.6,7,12 The
diagnosis of BOOP, BO, and DAD by TBBx were included
which, given the size of the biopsies, may not be representative of the actual lung pathology.18 The diagnostic yield
for FOB would be 25% if these noninfectious TBBx diagnoses are excluded. If the diagnostic criteria were too rigorous, but the information obtained from FOB was used to
direct patient management, or improved patient outcome,
this would be reflected in the change in therapy (Tables 2
and 3) and survival data (Figures 1 and 2). This was not
the case.
The addition of TBBx was of limited benefit. TBBx with
aggressive platelet support was safe (no cases of pneumothorax requiring a chest tube or significant parenchymal
bleeding in 42 FOBs). But, TBBx provided only one
additional infectious diagnoses (Candida pneumonia) and
never by itself changed therapy. These results support the
contention that the routine use of TBBx in this setting cannot be recommended.2,8
In this series, all patients had CT scans within 48 h of
FOB. CT scans are more sensitive than plain chest X-rays
in detecting lung nodules and metastasis,19 and may be
more sensitive than chest X-rays in detecting early invasive
pulmonary aspergillosis and other opportunistic pulmonary
infections in BMT patients.19,20 Fewer pathogenic organisms may be present in the lung when CT demonstrates
pulmonary infiltrates not seen on chest X-ray. This may
translate into a lower recovery rate by FOB.
BMT patients with infiltrates are commonly on multiple
broad spectrum antibiotics with or without antifungal
685
FOB in BMT patients
P White et al
686
Table 4
Clinical characteristic and utility of FOB in BMT patients: previous studies
Ref.
Number
patients
Episodes of
pneumonias
Type of BMT
Springmeyer et al5
22
23
NR
Cordonnier et al6
36
46
Allogeneic
Cordonnier et al7
Springmeyer et al8
69
15
81
15
Allogeneic
NR
Milburn et al 9
30
40
Allogeneic
Abu-Farsakh et al 13
77
NR
Campbell et al 10
27
27
Autologous 56%
Allogeneic 44%
NR
Weiss et al 11
47
66
Dunagan et al12
71
NR
Current study
52
60
Pretransplant 11%
Autologous 9%
Allogeneic 80%
NR
Autologous 25%
Allogeneic 75%
%
Infiltrates
%
Diagnostic
bronchoscopy
Complications
Diffuse
58 (TBBx)
NR
Diffuse 48
Focal 52
NR
Diffuse
52 (BAL)
13%
(Bleeding)
0%
66 (BAL)
89
(BAL/TBBx)
80 (BAL)
NR
40%
(Bleeding)
0%
32
NR
42 (BAL)
NR
79
74
(BAL/TBBx)
47 (BAL)
11% (PNX)
74
12%
NR
46
(BAL/TBBx)
27%
(major 8%)
61
31
(BAL/TBBx)
15%
53
Diffuse 48
Focal 45
Normal 7
NR
NR
Diffuse 62
Focal 29
No infiltrate 9
Diffuse 54
Focal 40
No infiltrate 6
Diffuse 69
Focal 31
Hospital
mortality
(%)
24
50
NR = not reported.
and/or antiviral therapy. The early and aggressive use of
these empiric therapies may decrease the FOB yield for
infectious pneumonias. Prior antibiotic therapy in immunocompetent patients with ventilator-associated pneumonia
drastically reduces the sensitivity and specificity of bronchoscopically obtained quantitative bacterial cultures.21,22
In this series, 94% of FOBs were done when the patient was
receiving empiric antimicrobial therapy. One other study of
FOB in BMT patients has reported the prevalence of
empiric therapy (94%).12 Prophylactic or pre-emptive antimicrobial therapy is common in BMT patients because preventing infections or treating asymptomatic infections
rather than treating established infections is associated with
better patient survival.23
The complication rate for FOB in this series was 15%
emphasizing that FOB is not a benign undertaking in BMT
patients. Although six of the FOB complications (five
mechanical ventilation and one death) may not have been
a direct consequence of the procedure, the adverse event
rate directly attributable to FOB would be 6%. FOB complications in BMT patients has been reported to vary
between 0% and 40% (Refs 6, 8 and 9; Table 4). The explanation for the wide range of complication rates in the literature is not certain. The study methods of prior reports
(retrospective, based on FOB reports or bronchoscopist’s
recall, lack of defined outcomes, no comment regarding
data verification) suggest serious limitations and a likelihood of under reporting and/or a tendency to report only
serious or obvious complications. For example, two large
series of FOB complications in general medical patients
report no cases of arrhythmias in 69 000 FOBs,24,25 while
two studies specifically assessing the risk of arrhythmias
during FOB documented major arrhythmias in 11 and 18%
of FOBs.26,27
In our series, respiratory failure requiring mechanical
ventilation was the most common adverse event due to
FOB (7%) and is similar to a report in 71 BMT patients
(4%; P = 0.46).12 The five patients who required mechanical ventilation for respiratory failure after FOB had diffuse
infiltrates, and high oxygen requirements (50–100% O2 via
face mask) prior to FOB. Which patients would have
required mechanical ventilation had they not had FOB is
not known. The temporal relationship between FOB and
mechanical ventilation speaks for itself, and the grim prognosis (approximately 95% hospital mortality) of BMT
patients who require mechanical ventilation is well documented.2,3 Hospital survival for our BMT patients who
were mechanically ventilated at FOB or within 24 h of FOB
was 15%.
In BMT patients, two studies have reported the impact
of FOB on therapy.8 Campbell et al10 reported that 63% of
FOBs were used to modify therapy and Dunagan et al12
reported that 42% of FOBs altered antimicrobial treatment.
In this report only a quarter of FOBs changed therapy and,
as in the above referenced studies, this did not translate into
improved survival. Patient survival, in addition to being
easier to define than diagnostic FOB or change in treatment,
is the most important outcome.
Based on this series, the value of routine diagnostic FOB
in BMT patients with clinical pneumonia should be reevaluated. The diagnostic yield was low, the results
infrequently change treatment and the knowledge gained by
FOB did not improve patient survival. This observation
may not be unique to our institution. We suggest that a
FOB in BMT patients
P White et al
randomized trial assessing the efficacy of empiric treatment
without FOB, empiric treatment with FOB (current
practice), and protocol-directed treatment based on FOB
(including discontinuing antimicrobial therapy based on a
nondiagnostic FOB) should be considered to better define
the use of FOB in this patient population.
11
Acknowledgements
13
We would like to thank David Shade for his statistical analysis
of the data. We would also like to thank Heather Murphy for her
manuscript preparation.
14
12
15
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