After Institutional Review Board approval
The aim of this study was to determine whether there are quantifiable differences in the abundance and pattern of NECs in patients with NEHI vs an age-matched disease cohort comprising patients with disorders associated with increased NECs or airway injury. Our hypothesis was that NEC prominence in NEHI would be distinct and not explained by airway injury.
Materials and Methods
Study Population
After Institutional Review Board approval, all lung biopsies performed at Cincinnati Children’s Hospital Medical Center from 1999 to 2008 for diffuse lung disease or that were reviewed in both clinical and pathology consultation (N = 138) were screened for possible study inclusion.
NEHI Group: Because a study objective was to define the histologic spectrum, stringent clinical and radiographic inclusion criteria were used for the diagnosis of NEHI. Specifically, subjects with NEHI were term or near-term infants with indolent onset of chronic tachypnea, retractions, and hypoxemia in the first year of life. Chest HRCT scan obtained nearest in time to lung biopsy was reviewed by a radiologist who was blinded to clinical information and numbers of cases in each study group. Inclusion criteria for NEHI required the HRCT scan to be rated on a 5-point Likert scale as strongly agree or agree with diagnosis of NEHI based on radiographic features previously reported. In total, 19 cases of NEHI were identified; four were excluded because either the lung biopsy specimens lacked a minimum of 10 airways for evaluation or tissue blocks were not available. Two other potential patients with NEHI were excluded because they did not meet the prespecified clinical and radiographic criteria. Thus, 13 subjects comprised the NEHI group. Independent case review was performed by two pediatric pulmonary pathologists.
Other-Diseases Comparison Group and Control Group: For the other-diseases group, comparison cases were selected to achieve a balanced sample size age matched with the NEHI cases and to include other pulmonary disorders associated with NEC hyperplasia (bronchiolitis, BPD, pulmonary hypertension). As a control group, uninvolved lung from lobectomy cases for congenital cystic adenomatoid malformations served as an additional comparison (n = 6).