- Human pathology

Home > E. Pathology by systems > Respiratory system > pediatric interstitial lung diseases

pediatric interstitial lung diseases

Thursday 31 July 2008

Interstitial lung disease is much rarer in children than in adults, and there are many more variants.

The literature, with occasional exceptions, consists of case reports and case series.

The chILD (Children’s Interstitial Lung Disease) network has published what is without doubt the most significant article in the field, in which a comprehensive classification, based on independent pathologic review of nearly 200 open-lung biopsies in children younger than 2 years, categorized 88% of 187 biopsies.

This classification consigns the practice of "lumping" of children into "fibrosing alveolitis of children" into the obscurity from which it previously emerged.

The categories that are proposed are as follows:
- diffuse developmental disorders (the alveolar-capillary dysplasia–acinar dysplasia spectrum),
- lung growth abnormalities (pulmonary hypoplasia from a variety of causes),
- pulmonary interstitial glycogenosis,
- surfactant protein (SP) dysfunction (SpB, SpC, and ABCA3 deficiency),
- disorders of the normal host (mainly infectious or postinfectious, aspiration, or allergic alveolitis),
- disorders resulting from systemic disease processes (very few cases, mainly pulmonary hemorrhagic syndromes),
- disorders of the immunocompromised host (infectious and postinfectious predominant, and iatrogenic complications),
- disorders masquerading as chILD (mainly pulmonary vascular and lymphatic disorders).

Although the final version of this classification may be modified, there is no doubt that this is a major and important review.

If an open-lung biopsy is to be performed for suspected chILD, a careful protocol should be used to ensure tissue is stored for all relevant tests, including electron microscopy.

Such children should have clinical data carefully and systematically recorded, and CT scans performed using standard protocols for evaluation by more than one radiologist.

Biopsies from patients with chILD should be seen by more than one pathologist who has extensive experience with such disorders.

These conditions are so rare that only by international collaboration, using standard protocols, are we likely to obtain large enough groups of patients for clinical trials, in particular of expensive, potentially toxic, anticytokine therapies.

See also



- Barbato A, Panizzolo C, Cracco A, de Blic J, Dinwiddie R, Zach M. Interstitial lung disease in children: a multicentre survey on diagnostic approach. Eur Respir J 2000;16:509–513.

- Clement A; European Respiratory Society Task Force. Task force on chronic interstitial lung disease in immunocompetent children. Eur Respir J 2004;24:686–697.

- Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean JA, Bush A, Wade A, Carr S, Castle R, Dinwiddie R, Hoo AF, Lum S, et al.; ChILD Research Co-operative. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med 2007;176:1120–1128.

- Nicholson AG, Bush A. Classification of diffuse lung disease in infants: the reality of groups. Am J Respir Crit Care Med 2007;176:1060–1061.

- Deterding RR, Young LR, Dishop M, Fan L, Dell S, Sweet S, Hagood J, Redding G, Castile R, Kurland G, et al. Diffuse lung disease in older children: report of the chILD network review. Am J Respir Crit Care Med 2007;175:A148.

- Langston C, Patterson K, Dishop MK; chILD Pathology Co-operative Group. A protocol for the handling of tissue obtained by operative lung biopsy: recommendations of the chILD pathology co-operative group. Pediatr Dev Pathol 2006;9:173–180.

- Diffuse lung disease in young children: application of a novel classification scheme. Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean JA, Brody AS, Nogee LM, Trapnell BC, Langston C; Pathology Cooperative Group, Albright EA, Askin FB, Baker P, Chou PM, Cool CM, Coventry SC, Cutz E, Davis MM, Dishop MK, Galambos C, Patterson K, Travis WD, Wert SE, White FV; ChILD Research Co-operative. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1120-8. PMID: 17885266 (Free)

- New surfactant protein C gene mutations associated with diffuse lung disease. Guillot L, Epaud R, Thouvenin G, Jonard L, Mohsni A, Couderc R, Counil F, de Blic J, Taam RA, Le Bourgeois M, Reix P, Flamein F, Clement A, Feldmann D. J Med Genet. 2009 Jul;46(7):490-4. PMID: 19443464 (Free)

- Allam JS, Limper AH. Idiopathic pulmonary fibrosis: is it a familial disease? Curr Opin Pulm Med. 2006 Sep;12(5):312-7. PMID: 16926644

- Nogee LM. Genetics of pediatric interstitial lung disease. Curr Opin Pediatr. 2006 Jun;18(3):287-92. PMID: 16721150

- Agostini C, Siviero M, Semenzato G. Immune effector cells in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 1997 Sep;3(5):348-55. PMID: 9331536

- Bruder E, Hofmeister J, Aslanidis C, Hammer J, Bubendorf L, Schmitz G, Rufle A, Bührer C. Ultrastructural and molecular analysis in fatal neonatal interstitial pneumonia caused by a novel ABCA3 mutation. Mod Pathol 2007;20:1009–1018.

- Thomas H, Risma KA, Graham TB, Brody AS, Deutsch GH, Young LR, Joseph PM. A kindred of children with interstitial lung disease. Chest 2007;132:221–230.

- Becker ML, Martin TM, Doyle TM, Rosé CD. Interstitial pneumonitis in Blau syndrome with documented mutation in CARD15. Arthritis Rheum 2007;56:1292–1294.

- Markart P, Ruppert C, Wygrecka M, Schmidt R, Korfei M, Harbach H, Theruvath I, Pison U, Seeger W, Guenther A, et al. Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias. Eur Respir J 2007;29:134–137.

- Somaschini M, Nogee LM, Sassi I, Danhaive O, Presi S, Boldrini R, Montrasio C, Ferrari M, Wert SE, Carrera P. Unexplained neonatal respiratory distress due to congenital surfactant deficiency. J Pediatr 2007;150:649–653.

- Bullard JE, Nogee LM. Heterozygosity for ABCA3 mutations modifies the severity of lung disease associated with a surfactant protein C gene (SFTPC) mutation. Pediatr Res 2007;62:176–179.