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