Interstitial Lung Disease in Children Younger Than 2 Years

Abstract

Childhood interstitial lung disease (chILD) represents a highly heterogeneous group of rare disorders associated with substantial morbidity and mortality. Although our understanding of chILD remains limited, important advances have recently been made, the most important being probably the appreciation that disorders that present in early life are distinct from those occurring in older children and adults, albeit with some overlap. chILD manifests with diffuse pulmonary infiltrates and nonspecific respiratory signs and symptoms, making exclusion of common conditions presenting in a similar fashion an essential preliminary step. Subsequently, a systematic approach to diagnosis includes a careful history and physical examination, computed tomography of the chest, and some or all of bronchoscopy with bronchoalveolar lavage, genetic testing, and if diagnostic uncertainty persists, lung biopsy. This review focuses on chILD presenting in infants younger than 2 years of age and discusses recent advances in the classification, diagnostic approach, and management of chILD in this age range. We describe novel genetic entities, along with initiatives that aim at collecting clinical data and biologic samples from carefully characterized patients in a prospective and standardized fashion. Early referral to expert centers and timely diagnosis may have important implications for patient management and prognosis, but effective therapies are often lacking. Following massive efforts, international collaborations among the key stakeholders are finally starting to be in place. These have allowed the setting up and conducting of the first randomized controlled trial of therapeutic interventions in patients with chILD.

Respiratory distress in a 2-month-old infant: Is the primary cause cardiac, pulmonary or both?

“…ChILD represents a heterogeneous group of respiratory disorders that are mostly chronic and associated with high morbidity and mortality [ 10 ]. Typical features of ILD include the presence of diffuse opacities on chest radiography, and abnormal pulmonary function tests with evidence of a restrictive ventilatory defect (in older children) and/or impaired gas exchange [ 11 ].…”

Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

“… 8 GPAP is caused by mutations in several genes. 9 , 10 SP-B, encoded by one of the genes associated with GPAP, SFTPB (MIM: 178640 ), is required for the maturation of SP-C. SP-B deficiency (MIM: 265120 ) is an autosomal-recessive disease characterized by respiratory distress syndrome (RDS) (MIM: 267450 ) at birth, which then develops into infantile type PAP. 11 Abnormalities in SP-C (encoded by SFTPC [MIM: 178620 ]) (MIM: 610913 ) and ABCA3 (encoded by ABCA3 [MIM: 601615 ]) (MIM: 610921 ) are likely to yield manifestations of GPAP and interstitial pneumonitis.…”

Genetic basis for childhood interstitial lung disease among Japanese infants and children

“…However, some cases of respiratory failure cannot be explained by prematurity or poor adaptation. Childhood interstitial lung disease (chILD) is one such rare pathology that causes respiratory dysfunction in infants and children (1).…”