Diffuse lung disease in young children: application of a novel classification scheme.
BACKGROUND
Considerable confusion exists regarding nomenclature, classification, and management of pediatric diffuse lung diseases due to the relative rarity and differences in the spectrum of disease between adults and young children.


OBJECTIVE
A multidisciplinary working group was formed to: (1) apply consensus terminology and diagnostic criteria for disorders presenting with diffuse lung disease in infancy; and (2) describe the distribution of disease entities, clinical features, and outcome in young children who currently undergo lung biopsy in North America.


METHODS
Eleven centers provided pathologic material, clinical data, and imaging from all children less than 2 years of age who underwent lung biopsy for diffuse lung disease from 1999 to 2004.


RESULTS
Multidisciplinary review categorized 88% of 187 cases. Disorders more prevalent in infancy, including primary developmental and lung growth abnormalities, neuroendocrine cell hyperplasia of infancy, and surfactant-dysfunction disorders, constituted the majority of cases (60%). Lung growth disorders were often unsuspected clinically and under-recognized histologically. Cases with known surfactant mutations had characteristic pathologic features. Age at biopsy and clinical presentation varied among categories. Pulmonary hypertension, presence of a primary developmental abnormality, or ABCA3 mutation was associated with high mortality, while no deaths occurred in cases of pulmonary interstitial glycogenosis, or neuroendocrine cell hyperplasia of infancy.


CONCLUSIONS
This retrospective cohort study identifies a diverse spectrum of lung disorders, largely unique to young children. Application of a classification scheme grouped clinically distinct patients with variable age of biopsy and mortality. Standardized terminology and classification will enhance accurate description and diagnosis of these disorders.
Deutsch
Gail H
GH
Divisions of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Young
Lisa R
LR
Deterding
Robin R
RR
Fan
Leland L
LL
Dell
Sharon D
SD
Bean
Judy A
JA
Brody
Alan S
AS
Nogee
Lawrence M
LM
Trapnell
Bruce C
BC
Langston
Claire
C
Albright
Eric A
EA
Askin
Frederic B
FB
Baker
Peter
P
Chou
Pauline M
PM
Cool
Carlyne M
CM
Coventry
Susan C
SC
Cutz
Ernest
E
Davis
Mary M
MM
Dishop
Megan K
MK
Galambos
Csaba
C
Patterson
Kathleen
K
Travis
William D
WD
Wert
Susan E
SE
White
Frances V
FV
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D015331:Cohort Studies; D004700:Endocrine System Diseases / Q000145:classification; D006130:Growth Disorders / Q000145:classification; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000254:growth & development / Q000473:pathology; D008171:Lung Diseases / Q000145:classification* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D009154:Mutation; D009422:Nervous System Diseases / Q000145:classification; D011663:Pulmonary Surfactants; D012189:Retrospective Studies; D012720:Severity of Illness Index; D009626:Terminology as Topic
C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D011663:Pulmonary Surfactants