Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme

Abstract

Rationale: Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age.

Objectives: This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed.

Methods: Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality.

Measurements and main results: A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients.

Conclusions: In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

Keywords: interstitial lung disease; pathology; rare pediatric lung disease.

Figure 1.

Study cohort and clinical–pathologic classification in children 2 to 18 years of age with diffuse lung disease. ABCA = ATP-binding cassette, subfamily A, member 3; GVHD = graft versus host disease; ICM = immunocompromised; ICT = immunocompetent; ILD = interstitial lung disease; NEHI = Neuroendocrine Cell Hyperplasia of Infancy; PTLD = post-transplant lymphoproliferative disorder.

Figure 2.

Representative pathology findings in immunocompetent patients. (A) Pulmonary capillaritis demonstrating interstitial and alveolar neutrophils, admixed with acute hemorrhage and hemosiderin-laden macrophages, in a 4-year-old girl with anemia and hematuria (hematoxylin and eosin [H&E] stain; original magnification: ×50). (B) Nonspecific interstitial pneumonia pattern in a 10-year-old girl with systemic sclerosis (H&E stain; original magnification: ×50). (C) Pleural fibrosis and pleuritis with subpleural interstitial inflammation, fibrosis, and cholesterol clefts (endogenous lipoid pneumonia) in a patient with systemic sclerosis (Movat pentachrome stain; original magnification: ×50). (D) Mild interstitial fibrosis and severe pulmonary arterial disease in a 10-year-old girl with juvenile idiopathic arthritis (H&E; original magnification: ×10). (E) Severe pulmonary arteriopathy with medial hypertrophy and intimal proliferation in a patient with juvenile idiopathic arthritis (Movat pentachrome; original magnification: ×50).

Figure 3.

Representative pathology findings in immunocompromised patients. (A) Diffuse alveolar damage and organizing pneumonia pattern secondary to respiratory syncytial virus infection in a 16-year-old girl with myelodysplastic syndrome and aplastic anemia, status after bone marrow transplant (hematoxylin and eosin [H&E] stain; original magnification: ×50). (B) Severe postinfectious constrictive bronchiolitis associated with organizing pneumonia in an 11-year-old boy on therapy for acute myeloid leukemia (H&E stain; original magnification: ×25). (C) Zygomycete infection with invasive fungal hyphae in a 14-year-old girl on therapy for Burkitt lymphoma (H&E stain; original magnification: ×50). (D) Acquired pulmonary alveolar proteinosis and reactive changes consistent with drug toxicity in a 4-year-old girl on therapy for acute myeloid leukemia (periodic acid Schiff stain; original magnification: ×50). (E) Epstein-Barr virus–associated lymphoproliferative disorder, polymorphous type, in a 10-year-old girl status after liver transplant (H&E stain; original magnification: ×25).