General Information about chILD
Children’s Interstitial Lung Diseases (CHILD) are a group of rare heterogeneous diffuse lung diseases that can present from infancy through adolescence. Despite the rarity of these diseases, new knowledge has improved diagnosis, knowledge of the natural history, and access to expert consultation that allows meaningful research to continue. This article will review the "new" diseases, and acknowledge that these disorders need further characterization.
Although rare, a large number of adult interstitial lung diseases (ILD) can present in children. Hypersensitivity pneumonitis, lymphangioleiomyomatosis (LAM), Langerhans cell Histiocytosis (LCH), Hermansky-Pudlak syndrome, sarcoidosis, and a few of the idiopathic interstitial pneumonias such as lymphocytic interstitial pneumonia (LIP), and non-specific interstitial pneumonia (NSIP) have been described in children. Aspiration syndromes are prominent in infancy. Connective tissue diseases can present in children (dermatomyositis, systemic lupus erythematosis, and juvenile rheumatoid arthritis) and involve the lung in presentations similar to adult patients.
However, some new diagnoses seen almost exclusively in children emerged from the most recent collaborative endeavors of the European Respiratory Society Task Force on Interstitial Lung Disease in Children and the North American Children's Interstitial Lung Disease Group of the NHLBI Rare Lung Disease Consortium. Because rare diseases often provide insight into the biology of other more common lung diseases, these new diseases are being carefully characterized to better understand their pathogenesis and optimal treatment.
Unfortunately, most of these diseases require an open lung biopsy (OLB) for diagnosis and significant barriers to OLB exist in pulmonary pediatric practice. Therefore, many cases have a diagnostic delay to exclude self-limiting or infectious causes of cough, tachypnea, or respiratory failure. However, prolonged hypoxemia and diffuse infiltrates on radiographic imaging often lead to the OLB in described cases. The duration of symptoms in all of these diseases is variable with some rapidly progressive and others with more prolonged presentations.
Neuroendocrine cell hyperplasia of infancy (NEHI) is usually seen before the age of two with neuroendocrine cell hyperplasia in the distal airways, revealed by bombesin-like immunoreactivity. Although many pulmonary disorders including asthma and cystic fibrosis can have some neuroendocrine cell hyperplasia or dysfunction, these infants are diagnosed with NEHI in the absence of other pulmonary diseases. Therefore, the diagnosis requires a correlation among clinical, histological and radiological findings.
Pulmonary interstitial glycogenosis (PIG) is a rare neonatal disease with uniform interstitial thickening with immature mesenchymal cells showing abundant cytoplasmic glycogen detected by electron microscopy. The prognosis of NEHI and PIG is generally good.
Interstitial disease caused by genetic alterations in the surfactant proteins (SP-A, -B, -C and -D) has been seen in children and adults. Surfactant protein metabolism involves other molecules, such as ABCA3 and thyroid transcription factor-1 (TTF-1). The mechanism by which accumulation of abnormal proteins in the endoplasmic reticulum activates the inflammatory cascade and interferes with normal protein synthesis and cellular injury is an active area of study. Mutations in the ABCA3 gene can be fatal in neonates or present as an ILD in older children and adults.
Diffuse Diseases of Development have been described due to both alveolar and vascular abnormalities. Acinar dysplasia and congenital alveolar dysplasia are usually seen in infancy. Alveolar capillary dysplasia with misalignment of pulmonary veins produce diffuse shadowing on imaging studies.
Therapeutic options for these diseases have historically included anti-inflammatory and immunosuppressive drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy. As individual diseases are more uniformly characterized, similar to what has happened in adult ILD, treatment trials will be better designed and focused. Meaningful comparisons of different patient populations, radiologic-pathologic correlation, and development of disease-specific therapeutic strategies will hopefully emerge.
Charlie Strange, MD
Medical University of South Carolina
Chair, ATS Assembly on Clinical Problems
Four Facts About chILD