Interstitial lung disease in newborns

Abstract

The term 'interstitial lung disease' (ILD) refers to a group of disorders involving both the airspaces and tissue compartments of the lung, and these disorders are more accurately termed diffuse lung diseases. Although rare, they are associated with significant morbidity and mortality, with the prognosis depending upon the specific diagnosis. The major categories of ILD in children that present in the neonatal period include developmental disorders, growth disorders, surfactant dysfunction disorders, and specific conditions of unknown etiology unique to infancy. Whereas lung histopathology has been the gold standard for the diagnosis of ILD, as many of the disorders have a genetic basis, non-invasive diagnosis is feasible, and characteristic clinical and imaging features may allow for specific diagnosis in some circumstances. The underlying mechanisms, clinical, imaging, and lung pathology features and outcomes of ILD presenting in newborns are reviewed with an emphasis on genetic mechanisms and diagnosis.

Keywords: Alveolar capillary dysplasia; Genetic basis of disease; Lung development; Mutation; Neuroendocrine cell hyperplasia of infancy; Surfactant.

Fig. 1

Distribution of diagnoses of interstitial lung disease in infants aged <2 years. The chart indicates the percentage of cases in each diagnostic category collated from retrospective studies [,–5,35]. Disorders and diagnoses in bold type are those more likely to present in the newborn period. BPD, bronchopulmonary dysplasia; NEHI, neuroendocrine cell hyperplasia of infancy; PIG, pulmonary interstitial glycogenosis; PAP, pulmonary alveolar proteinosis.

Fig. 2

Evaluation of newborn with diffuse lung disease’ (DLD) and hypoxemic respiratory failure of unclear etiology. Known disorders that can cause diffuse lung disease (such as pneumonia) should first be excluded. High-resolution chest tomography (HRCT), genetic testing, and lung biopsy are all important components of the evaluation, but the sequences of evaluations is influenced by the clinical history, the severity and trajectory of the child’s lung disease, and the family history. For children whose disease is rapidly progressing, lung biopsy is likely to yield a diagnosis in the least time; as many of the conditions that result in such severe disorders have known genetic causes, genetic testing should also be pursued. Genetic testing should be prioritized in children with a positive family history of a childhood interstitial lung disease (chILD) disorder. For children with clinical features associated with growth disorders, supportive findings on HRCT may be sufficient for presumptive diagnosis, although lung biopsy is definitive. Genetic testing in these children may also be helpful primarily by excluding other known (single-gene) disorders. Next-generation sequencing panels are more cost- and time-effective than sequential single-gene panels, unless there is a family history of a known disorder. DLD, diffuse lung disease; GA, gestational age; ECMO, extracorporeal membrane oxygenation; PPHN, persistent pulmonary hypertension of the newborn.