The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort

Abstract

Introduction: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders.

Methods: This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform.

Results: We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%).

Conclusion: This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

Keywords: NEHI; interstitial lung disease; rare lung disease.

FIGURE 1

Subjects enrolled by registry site. Total n = 683 from May 2016, to December 1, 2022. Site enrollment is represented above, numbered by the order in which site activation occurred. Subjects have been enrolled from the following participating centers (listed alphabetically): Boston Children’s Hospital (Boston, MA), Children’s Hospital of Colorado (Aurora, CO), Children’s Hospital Los Angeles (Los Angeles, CA), Children’s Hospital at Montefiore (Bronx, NY), Children’s Hospital of Philadelphia (Philadelphia, PA), Children’s Hospital of Pittsburgh (Pittsburgh, PA), Children’s Mercy (Kansas City, MO), Johns Hopkins Children’s Center (Baltimore, MD), Cohen Children’s Medical Center Northwell Health (North New Hyde Park, NY), Lucile Packard Children’s Hospital at Stanford (Palo Alto, CA), Lurie Children’s Hospital (Chicago, IL), Monroe Carell Jr. Children’s Hospital at Vanderbilt (Nashville, TN), North Carolina Children’s Hospital at UNC (Chapel Hill, NC), Oregon Health and Science University (Portland, OR), Rady Children’s Hospital of San Diego/UC San Diego (San Diego, CA), Rainbow Babies and Children’s Hospital (Cleveland, OH), Riley Children’s Hospital (Indianapolis, IN), Seattle Children’s Hospital (Seattle, WA), University of California San Francisco Benioff Children’s Hospitals (San Francisco, CA), University of Michigan C.S. Mott Children’s Hospital (Ann Arbor, MI), University of Missouri Children’s Hospital (Columbia, MO), Washington University School of Medicine/St. Louis Children’s Hospital (St. Louis, MO), Weill Cornell Medical Center (New York, NY).

FIGURE 2

Distribution of ChILD diagnoses. Primary diagnoses and classification categories in the Registry as reported by site investigators. Note that 11% of cases were designated as unclassified chILD. *Other category includes groupings with small numbers of cases, including environmental/toxic/drug related, pulmonary interstitial glycogenosis, lung developmental dysplasia, pulmonary alveolar proteinosis, and specific multisystem disorders.

FIGURE 3

Genetic testing and lung biopsy. Data are shown for the total registry cohort and the most frequent diagnoses or diagnostic categories. (A) The rate of genetic testing utilization differs among diagnostic categories (p < 0.0001) (B) The rate of lung biopsy differs among diagnostic categories (p = 0.0028).