Pediatric interstitial lung disease

Abstract

Interstitial lung disease in children (chILD) is rare and encompasses more than 200 entities, with new especially genetic causes being discovered. Several classifications have been proposed, and there is considerable overlap with entities which present in adult life. Presentation may be shortly after birth with acute respiratory distress and in infancy and childhood either with a primary respiratory presentation or with systemic symptoms such as poor feeding and failure to thrive. Newborn acute presentations are usually due either to a mutation in one of the surfactant protein (Sp) genes or the alveolar capillary dysplasia (ACD)-congenital alveolar dysplasia (CAD) spectrum. The latter usually progress rapidly to extracorporeal membrane oxygenation, and early lung biopsy is advisable to prevent prolonged futile treatment being offered. Outside the newborn period, a staged protocol for investigation is proposed. This starts with a computed tomography scan, which confirms or otherwise the presence of chILD, and occasionally can lead to a specific diagnosis. In particular in settings where there is a high burden of infection, infective mimics of chILD need to be excluded. The next investigations aim to try to move from pattern recognition to specific diagnoses, both genetic and environmental. The speed of progression to lung biopsy will depend on the clinical state of the child, and the biopsy itself may suggest a hunt for a new underlying cause, such as immunodeficiency. Specific genetic causing chILD includes mutations in SpB and SpC and processing genes (thyroid transcription factor-1 [TTF-1] and adenosine triphosphate-binding cassette subfamily A) (the last three can present at any time in the life course); genes involved in Sp catabolism (granulocyte-macrophage colony factor receptor A and B genes), an increasing number implicated in the ACD-CAD spectrum, and other non-Sp related genes such as Filamin-A and integrin genes. Environmental causes are also important and vary across the world. Vaping has been implicated as causing a large number of chILDs, and a vaping history is essential in any young person with an unusual respiratory illness. Medications, both prescribed and over-the-counter such as oily laxatives, are also causes of chILD. There are important conditions of unknown cause presenting in early childhood. Neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis generally have a good prognosis, and are probably best considered as part of a spectrum of pulmonary dysmaturity syndromes, in some of which underlying gene mutations have been detected, for example, TTF-1 for NEHI. Pulmonary alveolar proteinosis is an example of an umbrella description, which may present at any age, and has a number of underlying causes with different specific treatments, underscoring the need to move from pattern recognition to specific diagnoses. chILDs have important implications for adult physicians; there may be late as yet poorly described sequelae of the disease or its treatment in adult life; there may be genetic implications for the wider family; and there may be late chILD relapses. Smooth transition to adult services is essential for all chILD survivors, with pediatric and adult chest physicians working closely together.