Discussion
In this retrospective single center study, we used ICD-10 billing
diagnoses to identify patients with chILD/DLD. This strategy allowed us
to identify 306 children and adolescents with chILD/DLD who received
care at a large volume tertiary care medical center between 2019 and
2021, providing new data on the scope of chILD. Furthermore, using EMR
data collection, we provide the first report on health care utilization
and hospitalizations in chILD in the United States (U.S.).
The diagnosis of chILD/DLD is challenging and there is uncertainty about
incidence and prevalence. Published estimates are 0.13-16.2 cases per
100,000 children per year,1 acknowledging reports are
based on differing case definitions and study methodology. For example,
the 2004 European Respiratory Society task force identified 185 cases of
interstitial lung disease in children over a five-year
period13 and a 2018 study by the chILD European Union
registry identified 575 patients across 82 centers from 16 countries
over a three period.14 In the U.S., the chILD Research
Network reported 187 lung biopsy cases in children <2 years of
age from 11 centers from 1999-2004 and 191 cases in children ages 2-18
from 12 centers over a four-year period.6; 7Additionally, Soares et al. performed a retrospective review at a
mid-size single center, identifying 93 cases over an 18-year
period.15 Our study methodology did not differentiate
incident cases from prevalent cases. Our cohort size may reflect a
combination of the overall size of our children’s hospital, the study
methodology, and increased awareness and clinical suspicion for chILD in
recent years. A substantial portion of cases were seen by pulmonologists
at other centers prior to referral to our center, further limiting any
population-based estimates and volume predictions for other pediatric
centers. We do note that the size of our identified chILD cohort is very
similar to the number of patients seen at our Cystic Fibrosis Center
between 2019 and 2021.
The distribution of diagnoses of identified patients is also instructive
in considering the spectrum of chILD and the care delivery models. Our
chILD cohort highlights the large number of patients with systemic
diseases with lung involvement or pulmonary complications, particularly
those with history of oncologic, connective tissue, and immune-mediated
diseases. Immunocompromised patients accounted for approximately one
quarter of chILD cases. Disorders that typically present in infancy,
including NEHI, surfactant metabolic dysfunction, and diffuse
developmental lung diseases were less prominent in our cohort than in
prior lung-biopsy based studies. Reflecting the time period of our
study, we found a notable group of adolescent patients with e-cigarette
or vaping associated lung injury (EVALI), with either abnormalities on
chest CT or lung function. However, based on our clinical experience, we
suspect that the billing query approach underestimated the number of
patients receiving care for EVALI during this time.
We were particularly interested in examining the utilization and impact
of genetic testing in our cohort, as many prior studies have relied
heavily on lung biopsy classification. Although 51% of the cohort had
respiratory disease directed genetic testing, a molecular diagnosis was
identified in only 38 cases, reflecting 25.5% of those tested and
12.4% of the overall cohort. Despite advances in understanding the
genetic underpinnings of chILD, this data suggests opportunity for
further discovery and application of newer genomic technologies in a
more comprehensive manner. In addition to limitations in diagnostic
yield, barriers to testing may include cost and/or insurance coverage,
other access barriers, and turn-around-time for acutely ill
patients.14; 16-18 The potential value of negative
genetic testing results should also be acknowledged and further
examined. While a subset of patients at our center had both lung
biopsies and genetic testing, further prospective studies are needed to
examine how both positive and negative genetic results impact clinical
care decisions.
In addition to ambulatory medical care utilization, chILD patients were
frequently hospitalized, including in the ICU. While oncology patients
were the largest group, and our data do not allow us to delineate
whether the hospitalization was primarily attributable to lung disease,
patients with a broad representation of chILD etiologies were
hospitalized across the age spectrum. Comprehensive data were not
available on hospitalization and testing performed outside our
institution, though the frequency of second opinion referrals and
outside lung biopsies suggests that our data underestimate the overall
healthcare utilization of this cohort. A recently published prospective,
longitudinal study by Seidel et al. evaluated healthcare utilization and
medical costs in chILD among 445 patients in 10 European countries,
reporting a high health care economic burden.19 The
authors found that outpatient care, inpatient hospital admission rates
and inpatient hospital days were high, though decreased over time as
follow up was performed upwards of five years after baseline data was
obtained. Medical costs were reported to be highest in those with
diffuse developmental disorders and diffuse parenchymal lung disease of
unclear etiology in the non-neonate. While our study does not directly
consider the medical cost of chILD, our data demonstrate the impact to
patients, families, and the healthcare system in the U.S.
Our study highlights the power of EMR-derived data but also identified
some opportunities and challenges. First, historical data are limited
for older patients, as the current EMR system was implemented about 10
years ago. Because hospitalization billing diagnoses are assigned
administratively and not by medical providers at our center, chart
review would be required to determine whether lung disease was a primary
or secondary indication for hospitalization events in many cases. ILD
diagnosis benefits from multidisciplinary case review, and we suggest
development of standardized approaches to document the outcome of such
reviews, as well as other discrete data elements in the EMR that inform
individual patient care and population management. For example, although
we know that the age of symptom onset is important for the differential
diagnosis in a patient with suspected chILD, this information was not
documented in the EMR for 24.5% of our cohort. Lastly, there are
limitations in using current ICD billing codes for the purposes of case
ascertainment, due to inconsistent use and incomplete correlation with
disease categorization in some cases.
In summary, this single tertiary-care referral center report elucidates
key aspects of the scope of clinical care and healthcare utilization in
chILD, including limitation in current genetic testing and diagnostic
capabilities. Further, we demonstrate that use of an EMR approach has
the potential to provide new opportunities for cohort analysis that will
inform the feasibility of future studies in chILD. Better understanding
of these disease processes and mechanisms to monitor patients are needed
to advance clinical care delivery and improve outcomes.