Childhood Interstitial Lung Diseases: An 18-year Retrospective Analysis

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Childhood interstitial lung diseases occur in a variety of clinical contexts and are associated with high morbidity and mortality. Advances in the understanding of disease pathogenesis and use of standardized terminology have facilitated increased case ascertainment. WHAT THIS STUDY ADDS:This study demonstrates that cases of newly described forms of childhood interstitial lung diseases likely occur at all children' s hospitals. With advances in genetic testing and recognition of imaging patterns, a significant portion of cases are identifiable with noninvasive evaluations. abstract OBJECTIVE: Childhood interstitial lung diseases (ILD) occur in a variety of clinical contexts. Advances in the understanding of disease pathogenesis and use of standardized terminology have facilitated increased case ascertainment. However, as all studies have been performed at specialized referral centers, the applicability of these findings to general pulmonary practice has been uncertain. The objective of this study was to determine the historical occurrence of childhood ILD to provide information reflecting general pediatric pulmonary practice patterns. METHODS:Childhood ILD cases seen at Vanderbilt Children' s Hospital from 1994 to 2011 were retrospectively reviewed and classified according to the current pediatric diffuse lung disease histopathologic classification system. RESULTS:A total of 93 cases were identified, of which 91.4% were classifiable. A total of 68.8% (64/93) of subjects underwent lung biopsy in their evaluations. The largest classification categories were disorders related to systemic disease processes (24.7%), disorders of the immunocompromised host (24.7%), and disorders more prevalent in infancy (22.6%). Eight cases of neuroendocrine cell hyperplasia of infancy (NEHI) were identified, including 5 that were previously unrecognized before this review.CONCLUSIONS: Our findings demonstrate the general scope of childhood ILD and that these cases present within a variety of pediatric subspecialties. Retrospective review was valuable in recognizing more recently described forms of childhood ILD. As a significant portion of cases were classifiable based on clinical, genetic, and/or radiographic criteria, we urge greater consideration to noninvasive diagnostic approaches and suggest modification to the current childhood ILD classification scheme to accommodate the increasing number of cases diagnosed without lung biopsy. Pediatrics 2013;132:684-691

Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme

“…In the Royal Brompton series, one case of UIP was found post mortem in an 18-year-old man before the availability of testing for surfactant mutations and with no clinical information (13). Similar to our study, no IPF/UIP cases were found in the Vanderbilt series (16). Therefore, IPF with UIP phenotype has not been convincingly demonstrated in a child.…”

“…We propose two factors that explain these differences: (1) our study included only biopsied children and (2) our study included both ICM and ICT patients. In the 18-year retrospective review of 93 chILD cases from Vanderbilt Children's Hospital, Soares and colleagues found that, with newer noninvasive techniques, almost one third could be diagnosed without lung biopsy (16). Compared with the Vanderbilt study, which included biopsied and nonbiopsied children of all ages, the mortality of biopsied children in our combined studies (,2 and 2-18) was twice as high (16.1 vs. 32.3%).…”

“…In contrast to the single-center Brompton study, which was strictly a pathologic review, our multicenter study included clinical and outcome information that was correlated with pathologic findings. Patients included in our study had higher mortality than that of previously reported studies in which mortality ranged from 5.9 to 16.1% (12,(14)(15)(16). We propose two factors that explain these differences: (1) our study included only biopsied children and (2) our study included both ICM and ICT patients.…”

Update on Diffuse Lung Disease in Children

“…The need for multicenter collaboration to improve approaches to diagnosis and treatment of children with these disorders has resulted in the formation of research networks, including the Children's Interstitial Lung Disease Research Network in North America and the Children's Interstitial Lung DiseaseEuropean Union. Several recent studies suggest that childhood interstitial lung disease is often underrecognized 3,4 and associated with high health-care resource utilization. 1 One primary area of progress is recognition that the forms of diffuse lung disease affecting children aged < 2 years are often distinct from the forms most common in adults.…”

Persistent Lung Disease in Adults with NKX2.1 Mutation and Familial Neuroendocrine Cell Hyperplasia of Infancy

“…These imaging findings, in conjunction with an appropriate clinical context, are now considered sufficient for NEHI diagnosis, per American Thoracic Society clinical guidelines (8). Although these radiologic findings are believed to be specific for NEHI when observed and have been used to retrospectively identify cases (9), atypical imaging is present in some cases subsequently diagnosed by biopsy (7). Chest CT patterns in adults with NEHI have not been characterized to date.…”