INTRODUCTION:
Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. Recent estimates of disease prevalence range from 0.15 to 4.6 cases per 100,000 children, depending on the definitions and ascertainment methods utilized.1-3Despite increasing clinician awareness of chILD and improved diagnostic tools, the prevalence of these disorders is likely significantly underestimated.
While some types of chILD overlap with adult forms of interstitial lung disease, pediatric conditions have important differences in etiology, phenotype, and natural history.4-6 Many diverse causes of chILD are known, whereas mechanistic understanding remains unknown for many cases.6-8 The investigation of suspected chILD cases requires analysis of combinations of clinical presentation, imaging, lung biopsy pathology, and genetic testing. Disease severity at initial presentation varies widely both within and between disorders from birth to adolescence, encompassing a range of respiratory symptoms such as cough, dyspnea, exercise intolerance, recurrent lung infections, hemoptysis, and respiratory failure. Physical findings include tachypnea, crackles, wheezing, hypoxemia, and pneumothorax. Diagnosis may occur through lung imaging and/or pulmonary function testing (PFTs) in asymptomatic patients by family screening or screening of high-risk groups, such as children with connective tissue or immune-mediated disorders, oncologic disorders, or post-stem cell transplantation. Overall, chILD is associated with high healthcare costs and a heavy burden of care both chronically and with acute exacerbations.9,10
The Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN) was established in 2004 in the U.S.11 In addition to producing disease-specific reports, this network conducted two foundational studies. The first study applied a new classification scheme to lung biopsies from 187 infants with diffuse lung disease from eleven centers.4 A subsequent manuscript reported 191 lung biopsies in older children from ten institutions.5 These studies were crucial in defining the pathologic spectrum of chILD, but were retrospective studies limited by lung biopsy ascertainment. While there have been several registry reports from Europe, Australia, and New Zealand,2,3,12,13 there have as of yet been no prospective multicenter studies of chILD in North America.
Strategies to accelerate progress in this field were the focus of a workshop sponsored by the National Heart, Lung, and Blood Institute in 2015. The priority areas identified were to: (1) establish an interactive, data-driven, research community, (2) define the clinical phenotypes, epidemiology, and natural history, (3) identify pathogenic mechanisms, biomarkers, and pharmacotherapeutic targets, and (4) define, measure, and improve clinical outcomes.14
To provide a framework to address these unmet needs, we established a longitudinal observational study using single-IRB reliance agreements. The objectives are to advance knowledge concerning clinical features, management, and outcomes of infants and children with chILD disorders, while developing infrastructure to facilitate scientific advancement and clinical trials in this field. Here we provide a report on the development and study design of this registry and the characteristics of the initial enrollment cohort. Some of the results of this study have been previously reported in the form of an abstract.15