Bronchoalveolar Lavage for Diagnosis of Pneumonia in the Immunocompromised Child

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Bronchoalveolar

Lavage

for Diagnosis

of

Pneumonia

in the Immunocompromised

Child

Lorry R. Frankel, MD, David W. Smith, MBChB,

and Norman J. Lewiston, MD

From the Department of Pediatrics, Stanford University Medical Center, Stanford, California

ABSTRACT. Seven children with immunocompromised

states were referred to the pediatric bronchoscopy ser-vice for evaluation of pneumonia. Flexible fiberoptic

bronchoscopy accompanied with bronchoalveolar

la-vage was performed in all seven of these children. A

definitive diagnosis was made for six of these seven

patients. The diagnosis included Pneumocystis carinii in three, Candida albicans in two, and cytomegalovirus in one. There were no complications associated with the procedure. Flexible fiberoptic bronchoscopy with bron-choalveolar lavage should be considered early in the

evaluation of the immunocompromised child with

pneumonia. Pediatrics 1988;81:785-788; immunocom-promised patient, pneumonia, bronchoalveolar lavage.

Children who receive cancer chemotherapy or

immunosuppressive therapy for organ

transpian-tations or have other forms of immunodeficiency are at risk for pneumonia from such agents as

Pneumocystis carinii, cytomegalovirus,

Aspergil-us

fumigatus, Candida albicans, and others. Open lung biopsy has become established as an effective

diagnostic technique allowing for identification of

the infecting organism in this group of high-risk

patients.’ However, this procedure is invasive,

re-quires general anesthesia, and carries a risk for morbidity and mortality particularly in the

crit-ically ill patient.

Fiberoptic bronchoscopy is useful in the eva!-uation of adults with pulmonary infiltrates or an-atomic airway lesions.2 The Olympus mode! BF4B2 (Olympus Corp, New Hyde Park, NY) is the smallest bronchoscope used routinely in this population. It has a 4.8-mm diameter with a

2.0-Received for publication June 22, 1987; accepted July 31, 1987. Reprint requests to (L.R.F.) Department of Pediatrics, Stan-ford University Medical Center, Stanford, CA 94305.

mm suction channel which permits the use of

bi-opsy forceps and protected brushes for the

collec-tion of tissue and bacteriologic specimens. The

large size of this bronchoscope precludes its use

in pediatric patients other than adolescents. The

Olympus pediatric bronchoscope BF3C4

(Olym-pus Corp) has a 1.2-mm diameter suction channel

which is too small to permit the use of currently available forceps or protected brushes. This

chan-nel is useful, however, for bronchoalveolar lavage.

We report our recent experience with

bronchoal-veolar lavage performed through the flexible

fi-beroptic bronchoscope in immunocompromised

children with acute pulmonary disease for the

purpose of diagnosing the acute infecting agent.

MATERIALS AND METHODS

Seven children from 0.7 to 15 years of age were

referred to the pediatric bronchoscopy service for

evaluation of pneumonia. Five of the patients

were receiving chemotherapy for malignancy. The other two patients were receiving

immuno-suppressive therapy following cardiac transplan-tation. All seven patients were febrile with diffuse

pulmonary disease diagnosed from physical and

chest x-ray film findings. All patients required

supplemental oxygen and four patients required

mechanical ventilation for ventilatory failure.

Bronchoscopy was performed through an

in-dwelling endotracheal tube in the four patients

requiring mechanical ventilation and

transnas-ally in the other three. Sedation and analgesia

were induced with fentanyl citrate (2.0 to 10.0 g/

kg) and diazepam (0.05 to 0.1 mg/kg). In addition,

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786 BRONCHOALVEOLAR LAVAGE

the bronchoscope into the airway, 1% lidocaine (1

to 3 mL) was administered through the suction

channel to provide topical anaesthesia.

Following the inspection of the airway, the tip

ofthe bronchoscope was lodged in a subsegmental

bronchus of an involved lobe. Six or seven lavages

of 3 to 10 mL of saline (without bacteriostatic

agent) were introduced through the suction

chan-nel. The fluid was suctioned back through the

sue-tion channel and trapped in a sterile collection

chamber. Approximately 60% of the volume

in-troduced was retrieved.

The bronchoalveolar lavage fluid received

stan-dard processing for bacteria, viruses and fungi,

including Gram stain, KOH preps, and acid-fast

stains. A shell vial assay in which human foreskin

fibroblasts were used, was performed for

cyto-megalovirus identification. In addition, the

re-maining bronchoalveolar lavage fluid was

centri-fuged at 3,500 rpm in a cytocentrifuge (Damon

IEC HN-SII centrifuge, Needham Heights, MA)

for ten minutes. The supernatant was discarded

and smears were made from the sediment on clear

glass slides. The smears were either air dried and

then stained with Gomori methanamine silver

stain or immediately placed in 95% ethyl alcohol before drying for Papanicolaou stain for cytology.

RESULTS

A specific infectious agent was identified in six

of the seven patients (Table). Organisms

identi-fled were P carinii in three patients, C albicans

in two, and cytomegalovirus in one. Patient 3

TABLE. Immunocompromised Patient Profile

underwent flexible fiberopic bronchoscopy twice

for worsening pulmonary status. The first

bron-choalveolar lavage was positive for C albicans by

KOH stain and culture. The second was positive for both cytomegalovirus (shell viral assay

posi-tive) and enterococcus (by routine culture). A

blood culture positive for cytomegalovirus was

ob-tamed 48 hours following the second

bronchos-copy. This patient’s respiratory status transiently

improved following therapy directed against the

infecting organisms. In the seventh patient, no

organisms were obtained by bronchoalveolar

la-vage and a subsequent open lung biopsy similarly

failed to demonstrate an infectious agent. The

open lung biopsy was complicated’by the

devel-opment of a bronchopleural fistula. During

bron-choalveolar lavage, oxyhemoglobin saturations

remained greater than 90% in all patients.

DISCUSSION

There now is considerable experience with the

use of flexible fiberoptic bronchoscopy in the

awake but sedated pediatric patients. It has been

ofbenefit in the diagnosis ofanatomic lesions and

dynamic airway problems such as

laryngoma-lacia, tracheomalacia, or bronchomalacia.3’4 A

skilled operator can remove mucoid plugs even in

small patients with lobar atelectasis or make the

diagnosis of recurrent aspiration pneumonia by

using bronchoalveolar lavage to detect lipid-laden

macrophages.5’6 This procedure has proven to be

safe with minimal morbidity, even in patients in

respiratory distress.

Patient Sex Age Underlying Diagnosis and Pulmonary

No. Abnormalities

1 F 34 mo Acute lymphoblastic leukemia, respi-ratory failure, mechanical ventilation

2 F 15 yr Spinal cord tumor, respiratory failure,

mechanical ventilation

3 F 3 yr 11/86: postoperative heart

transplan-tation, mechanical ventilation; 12/86: worsening pulmonary status, me-chanical ventilation

4 M 8 mo Non-Hodgkin lymphoma, increasing respiratory distress and oxygen

re-quirement

5 M 9 mo Postoperative heart transplantation, in-creasing oxygen requirement

6 M 6 yr Burkitt lymphoma, increasing oxygen requirement

7 F 16 mo Acute lymphoblastic leukemia, me-chanical ventilation

Method of Diagnosis of Causative Agent

Bronchoalveolar lavage positive: Pneu-mocystis from Gomori methanamine silver stain

Bronchoalveolar lavage positive:

Can-dida albicans pneumonia from KOH

and culture

Bronchoalveolar lavage positive: C al-bicans

Bronchoalveolar lavage positive: cyto-megalovirus and enterococcus

Bronchoalveolar lavage positive: Pneu-mocystis from Gomori methanamine silver stain

Bronchoalveolar lavage positive: Pneu

-mocystis from Gomori methanamine silver stain

Bronchoalveolar lavage positive: Pneu

-mocystis from Gomori methanamine silver stain

Bronchoalveolar lavage negative: open lung biopsy: nonspecific inflamma-tory cells

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.

Figure. Slide of Gomori methanamine silver-stained specimen showing Pneumocystis carinii in bronchoalveolar lavage fluid

(

x 1,000).

Using flexible fiberoptic bronchoscopy to make

the microbiologic diagnosis of pulmonary

infil-trates with bronchoalveolar lavage is problematic because passage of the bronchoscope through the

naso- and oropharynx contaminates the suction

channel with the flora ofthese regions. Therefore, the culture of organisms such as Hemophilus

in-fi

uenzae, pneumococcus, or Staphylococcus aureus

from bronchoalveolar lavage fluid is difficult to interpret. The organism may have been recovered from the lung or from the nasopharynx. Recently, Kahn and Jones7 and Thorp et a18 described the

utility of quantitative colony counts in

distin-guishing nasopharyngeal contamination from pulmonary infection.

The benefit of making a specific diagnosis of pulmonary infection in immunocompromised pe-diatric patients has been established. Prober et a!’ reviewed the results of open lung biopsy in 44 immunocompromised children. In this series, 72% of the biopsy specimens were positive for an

in-fectious organism. The biopsy findings resulted in

the alteration of therapy in 65% of the patients. They concluded that open lung biopsy is a valu-able diagnostic procedure in the immunocom-promised pediatric patient with pulmonary

disease.

The routine use of open lung biopsy to evaluate respiratory tract infection in adults recently has been questioned because of lack of evidence that the risks of the surgery outweigh the benefit to patient survival.9 To date, no such analysis has been made in pediatric patients.

Williams et al’#{176}performed flexible fiberoptic bronchoscopy as the initial diagnostic procedure on 35 immunocompromised adults with diffuse pulmonary infiltrates. They were able to make a

definitive diagnosis in 20 of these patients using

a combination ofbrushings, biopsies, and lavages. Six of the remaining patients had an infectious agent found on subsequent open lung biopsy,

giv-ing a sensitivity of 77% for bronchoscopy for the

series. They found, however, that bronchoalveolar

lavage was less reliable than brushings. Bron-choalveolar lavage has been shown to have a 90%

sensitivity in adults with acquired

immunodefi-ciency and acute pulmonary disease.” Finally, Leigh et al’2 described the diagnosis of P carinii

using bronchoalveolar lavage in two

immunocom-promised pediatric patients.

In summary, we were able to make the

diag-nosis of pneumonia in six of seven patients. This

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bron-788 BRONCHOALVEOLAR LAVAGE

choscopy with bronchoalveolar lavage performed on the patients in this series added important di-agnostic information in six ofthe seven cases with no demonstrable morbidity or mortality. We rec-ommend this procedure for the diagnosis of pneu-monia in the immunocompromised child as early in the disease course as possible, preferably before the onset of respiratory failure.

ACKNOWLEDGMENTS

We thank Holly Edwards, for preparing this

manu-script, and John Summerville, MD, for technical

assistance.

REFERENCES

1. Prober CG, Whyte H, Smith CR: Open lung biopsy in im-munocompromised children with pulmonary infiltrates.

Am J Dis Child 1984;138:60-63

2. Zavala DC: Diagnostic fiberoptic bronchoscopy: Technique and results of biopsy in 600 patients. Chest

1975;68:12-19

3. Wood RE: Spelunking in the pediatric airways:

Explora-tions with the flexible fiberoptic bronchoscope. Pediatr Clin North Am 1984;31:785

4. Wood RE, Sherman JM: Pediatric flexible bronchoscopy.

Ann Otol 1980;89:414

5. Nussbaum E: Flexible fiberoptic bronchoscopy and its ap-plication in infantile atelectasis. Clin Pediatr 1985; 24:379-382

6. Nussbaum E, Maggi JC, Mathis R, et al: Association of

lipid-laden alveolar macrophages and gastroesophageal reflux in children. J Pedtatr 1987;110:190-194

7. Kahn FW, Jones JM: Diagnosing bacterial respiratory

in-fection by bronchoalveolar lavage. J Infect Dis 1987; 155:862-869

8. Thorpe JE, Baughman RP, Frame VF, et al:

Bronchoal-veolar lavage for diagnosing acute bacterial pneumonia.

J Infect Dis 1987;155:855-861

9. Robin ED, Conor MB: Lung biopsy in immunocomprom-ised patients. Chest 1986;89:276

10. Williams D, Yungbluth M, Adams G, et al: The role of fiberoptic bronchoscopy in the evaluation of immunocom-promised hosts with diffuse pulmonary infiltrates, Am Rev Respir Dis 1985;131:880-885

11. Stover DE, White DA, Romano PA, et al: Diagnosis of pul-monary disease in acquired immune deficiency syndrome (AIDS): Role ofbronchoscopy and bronchoalveolar lavage.

Am Rev Respir Dis 1984;130:659-662

12. Leigh MW, Henshaw NG, Wood RE: Diagnosis of

Pneu-mocystis carinii pneumonia in pediatric patients using

bronchoscopic bronchoalveolar lavage. Pediatr Infect Dis

1985;4:408-410

ERRATA

In the Letter to the Editor, “Diagnosis of Meningitis” (Pediatrics

1988;81:603), the table at the top of the second column was not related to the letter and should not have been printed.

In the Letter to the Editor, “Urine Latex Particle Agglutination” (Pedi-atrics 1988;81:470), the name Leslie L. Barton, MD, should have been listed

as the coauthor.

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1988;81;785

Pediatrics

Lorry R. Frankel, David W. Smith and Norman J. Lewiston

Child