Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies.
Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Sachiko
S
Seo
Department of Microbiology and Immunology, University of Montreal, Montreal, Canada;
Christian
C
Renaud
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, University of Washington, Seattle, WA;
Jane M
JM
Kuypers
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;
Charles Y
CY
Chiu
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, University of Washington, Seattle, WA;
Meei-Li
ML
Huang
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;
Erik
E
Samayoa
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Hu
H
Xie
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;
Guixia
G
Yu
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, and.
Cynthia E
CE
Fisher
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
Ted A
TA
Gooley
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;
Steven
S
Miller
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, University of Washington, Seattle, WA; Department of Pathology, University of Washington, Seattle, WA;
Robert C
RC
Hackman
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Pathology, University of Washington, Seattle, WA;
David
D
Myerson
Department of Laboratory Medicine, University of Washington, Seattle, WA;
Ruth H
RH
Sedlak
Department of Pediatrics, Samsung Medical Center, Sungkyungkwan University, School of Medicine, Seoul, Korea; and.
Yae-Jean
YJ
Kim
Hematopoietic Stem Cell Transplantation Division, National Cancer Research Center Hospital, Tokyo, Japan.
Takahiro
T
Fukuda
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, and.
David N
DN
Fredricks
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, and.
David K
DK
Madtes
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Laboratory Medicine, University of Washington, Seattle, WA;
Keith R
KR
Jerome
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, and.
Michael
http://orcid.org/0000-0003-1538-7984
M
Boeckh
D000293:Adolescent; D000328:Adult; D001228:Aspergillosis / Q000175:diagnosis / Q000209:etiology / Q000382:microbiology; D001230:Aspergillus / Q000302:isolation & purification; D001424:Bacterial Infections / Q000175:diagnosis / Q000209:etiology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology / Q000821:virology; D002648:Child; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000821:virology; D055370:Lung Injury / Q000209:etiology / Q000382:microbiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014777:Virus Diseases / Q000175:diagnosis / Q000209:etiology / Q000821:virology; D055815:Young Adult