Childhood ILD

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General Information About Childhood ILD

chILD

Interstitial and diffuse lung diseases (ILD) in childhood are rare, heterogeneous conditions that pathologically involve the alveoli, interstitial space and pulmonary vasculature, leading to abnormal gas exchange, lung restriction and diffuse infiltrates on chest imaging. Some forms of ILD are acquired (e.g., pulmonary aspiration, infections and hypersensitivity syndromes), often presenting in childhood and adolescence. However, nearly half of cases are diagnosed in infancy, generally shortly after birth and are associated with abnormal alveolar development.

The severity and clinical course of the chILD varies. Some are self-limited and resolve without treatment after only months, while others can lead to end-stage lung disease and death. Thus, the correct diagnosis is essential.

Interstitial and diffuse lung diseases in children, especially children under two years of age, are different than those that affect adults. For instance, the most common form of pulmonary fibrosis in adults, idiopathic pulmonary fibrosis, does not occur in children. Conversely, neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis (PIG) are only found in children.

A number of the chILD disorders have been found to have a genetic basis. In particular, genetic defects in pulmonary surfactant have been shown to be responsible for some types of ILD. Surfactant is a complex mixture of phospholipids and proteins secreted into the alveoli that prevent their collapse by lowering surface tension and reducing the work of breathing. Pulmonary surfactant deficiency is common in premature babies and leads to respiratory distress syndrome (previously known as hyaline membrane disease), a cause of preterm infant morbidity and death, but inherited defects in specific surfactant proteins leads to ILD in babies born at term. Surfactant protein-B (SP-B) mutations cause fatal respiratory distress in term neonates, while defects in genes encoding surfactant protein-C (SP-C) and more recently ATP-binding cassette protein A3 (ABCA3) have been associated with ILD in both children and adults. Recently, mutations in the NKX2.1 gene have been recognized to cause ILD in infants and young children, as this gene regulates surfactant proteins such as SP-B, SP-C, and ABCA3. Children with NKX2.1 mutation may have a constellation of abnormalities called Brain, Thyroid, Lung Syndrome. Besides surfactant mutations, NEHI has also been found to exist in families and a genetic basis is proposed. As exome sequencing and new genetic strategies evolve more familial forms of chILD will be found and the chILD Foundation and chILDRN are developing strategies to incorporate these new diseases into the current chILD research and support structure. The identification of these genes and how surfactant protein mutations affect lung development and function has lead to a revolution in how we understand these diseases, but more discoveries are needed.

Links with adult interstitial disease have also been found such that surfactant mutations may cause adult disease. As novel genes are associated with idiopathic pulmonary fibrosis conversations are needed about the implications for children in these families and ways to prevent environmental insults that might alter future adult disease in children that carry these genetic risk factors. Furthermore, genetic abnormalities in the surfactant mutations have been shown to modify other disease such as respiratory distress syndrome in newborns and chronic obstructive lung disease.  Thus, understanding the genetic basis and pathophysiology of chILD for surfactant mutations and NEHI will enhance our understanding of other more common disease.

The ATS and its Public Advisory Roundtable are committed to the concept that research will lead to cures. These advances will depend on education, advocacy and research partnerships to be formed among patients, parents, clinicians and scientists. Increased research funding will allow us to uncover other causes of interstitial lung diseases, improve diagnostic testing, and develop treatments for the many patients and families we serve.


Four Facts About chILD

  • Children’s Interstitial Lung Disease (chILD) is not a single disease. It is a group of several rare disorders that affect infants and children.

  • The severity of chILD varies with the diagnosis. Most patients will require oxygen therapy, but the amount needed and duration of treatment also varies.  Some will outgrow their symptoms while others will unfortunately require lung transplants to survive.

  • Since these disorders are rare and newly recognized, very little is known about the best treatments or long term prognosis for these children.

  • The numbers of cases of chILD is not known, but doctors and researchers are working collaboratively worldwide to quantify these syndromes.