Interstitial Lung Disease in Children: “Specific Conditions of Undefined Etiology” Becoming Clearer

Abstract

Background: Children’s interstitial lung disease (chILD) is a rare group of pediatric lung diseases affecting the lung interstitium diffusely. In this work, we focused our attention on a specific infant group of chILD, also known as “specific conditions of undefined aetiology”, including pulmonary interstitial glycogenosis (PIG) and neuroendocrine cell hyperplasia of infancy (NEHI). Methods: PubMed was searched to conduct this narrative review. We searched for articles in English using the following keywords: (1) neuroendocrine cell hyperplasia of infancy; (2) NEHI; (3) pulmonary interstitial glycogenosis; (4) PIG; (5) chILD. Results: An increasing interest and insight into these two conditions have been reported. The updated literature suggests that it is possible to look at these disorders as a continuum of diseases, rather than two different entities, since they share a pulmonary dysmaturity. Conclusions: NEHI and PIG are featured by dysmaturity of airway development and consequent respiratory distress. Understanding the underlying pathogenic mechanisms would lead to identifying new targeted therapies to ameliorate the mortality and morbidity of these rare conditions.

Lung biopsies in infants and children in critical care situation

“…1,10,[35][36][37] Furthermore, a certain vagueness persists regarding the significance of certain patterns, such as pulmonary interstitial glycogenosis: while current chILD classifications include it as a separate entity, other authors consider pulmonary interstitial glycogenosis a marker of impaired lung maturity. 38 When discussing a lung biopsy, it is crucial to consider its expected value:…”

“…This could be attributed to the diversity and rarity of diseases observed in older children, but also to progressive fibrosing evolution of lung diseases with age that may contribute to less typical histological findings in older compared to conditions that are more commonly seen in neonates 1,10,35–37 . Furthermore, a certain vagueness persists regarding the significance of certain patterns, such as pulmonary interstitial glycogenosis: while current chILD classifications include it as a separate entity, other authors consider pulmonary interstitial glycogenosis a marker of impaired lung maturity 38 . When discussing a lung biopsy, it is crucial to consider its expected value: not reaching an etiologic diagnosis can still have a significant therapeutic impact.…”

Emerging Treatments for Childhood Interstitial Lung Disease

“…Synthetic gene transfer vectors have been tested in experimental models both in vitro and in vivo in patients with chILDs, including those related to dysfunctional SFTPC , SFTPB , and ABCA3 . Viral vectors (i.e., retroviral vectors, lentiviral vectors, adeno-associated viral [AAV] vectors, or adenoviral [Ad]-based vectors) have shown great potential in gene modulation, particularly for SP-B deficiency [ 99 – 101 ]. Nuclease-encoding, chemically modified mRNA is able to deliver site-specific nucleases in a mouse model of SP-B deficiency and improve survival of the animals.…”