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Diffuse Lung Disease in Young Children

Application of a Novel Classification Scheme

Gail H. Deutsch^1,*, Lisa R. Young^2,*, Robin R. Deterding³, Leland L. Fan⁴, Sharon D. Dell⁵, Judy A. Bean⁶, Alan S. Brody⁷, Lawrence M. Nogee⁸, Bruce C. Trapnell⁹, Claire Langston¹⁰, and the Pathology Cooperative Group:, Eric A. Albright¹¹, Frederic B. Askin¹², Peter Baker¹¹, Pauline M. Chou¹³, Carlyne M. Cool¹⁴, Susan C. Coventry¹⁵, Ernest Cutz¹⁶, Mary M. Davis¹⁷, Megan K. Dishop¹⁰, Csaba Galambos¹⁸, Kathleen Patterson¹⁹, William D. Travis²⁰, Susan E. Wert⁹, Frances V. White²¹ and on behalf of the ChILD Research Co-operative

Divisions of ¹ Pathology, ² Pulmonary Medicine, ⁶ Epidemiology, and ⁹ Pulmonary Biology, and ⁷ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; ³ Department of Pediatrics, Children's Hospital, Denver, Colorado; Departments of ⁴ Pediatrics and ¹⁰ Pathology, Texas Children's Hospital, Houston, Texas; Divisions of ⁵ Respiratory Medicine and ¹⁶ Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada; Departments of ⁸ Pediatrics and ¹² Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; ¹¹ Department of Anatomic Pathology, Children's Hospital, Columbus, Ohio; ¹³ Department of Pathology, Children's Memorial Hospital, Chicago, Illinois; ¹⁴ Department of Pathology, University of Colorado Health Science Center, Denver, Colorado; ¹⁵ Department of Pathology, Kosair Children's Hospital, Louisville, Kentucky; ¹⁷ Division of Pediatric Pathology, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana; ¹⁸ Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania; ¹⁹ Department of Laboratories, Children's Hospital and Regional Medical Center, Seattle, Washington; ²⁰ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; and ²¹ Division of Surgical Pathology, Washington University School of Medicine, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Claire Langston, M.D., Department of Pathology, Texas Children's Hospital, 6621 Fannin Street, Houston, TX 77030. E-mail: cxlangst{at}texaschildrenshospital.org

Rationale: 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.

Objectives: 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.

Measurements and Main 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.

Key Words: infant • pulmonary • interstitial lung disease • surfactant • neuroendocrine hyperplasia

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject There are only limited studies of diffuse lung disease in infants. Progress has been hindered by the rarity of these disorders and the use of adult terminology and classification systems that do not adequately address pediatric or genetic entities. What This Study Adds to the Field This multicenter study of diffuse lung disease in infants employs a new classification system emphasizing infant disorders. Its use in a large cohort of infants with lung biopsy provides new information on disease frequency, clinical settings, and outcome.

 

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