Abstract
Interstitial lung disease (ILD) is defined as a rare, heterogeneous group of parenchymal lung conditions that develop primarily because of underlying developmental or genetic disorders. Affected infants typically present with clinical syndromes characterized by dyspnea, tachypnea, crackles and hypoxemia. Until recently, the understanding of ILD in infants has been limited largely owing to a lack of evidence-based information of underlying pathogenesis, natural history, imaging findings and histopathological features. However, ILD in infants is now better understood and managed because of (1) advances in imaging methods that result in rapid and accurate detection, (2) improved thoracoscopic techniques for lung biopsy, (3) a consensus regarding the pathological criteria for these particular lung conditions and (4) a new classification system based on the underlying etiology of ILD. This article reviews the new classification system, imaging technique, clinical presentation and imaging findings of ILD in infants. Specialized knowledge of this new classification system in conjunction with recognition of characteristic imaging findings of ILD in infants has great potential for early and accurate diagnosis, which in turn can lead to optimal patient management.
Similar content being viewed by others
References
Lee EY, Cleveland RH, Langston C (2012) Interstitial lung disease in infants and children: new classification system with emphasis on clinical, imaging, and pathological correlation. In: Cleveland RH (ed) Imaging in pediatric pulmonology. Springer Science + Business Media, Dordrecht, The Netherlands, pp 156–183
Deterding RR (2010) Infants and young children with children’s interstitial lung disease. Pediatr Allergy Immunol Pulmonol 23:25–31
Vece TJ, Fan LL (2011) Diagnosis and management of diffuse lung disease in children. Paediatr Respir Rev 12:238–242
Das S, Langston C, Fan LL (2011) Interstitial lung disease in children. Curr Opin Pediatr 23:325–331
Deterding RR (2010) Expanding our understanding of children’s interstitial lung disease. Pediatr Allergy Immunol Pulmonol 23:3–4
Prestridge A, Deterding RR (2010) Diffuse lung disease in children. Pediatr Ann 39:777–783
Guillerman RP, Brody AS (2011) Contemporary perspective on pediatric diffuse lung disease. Radiol Clin North Am 49:847–868
Deterding R (2007) Evaluating infants and children with interstitial lung disease. Semin Respir Crit Care Med 28:333–341
Deutsch GH, Young LR, Deterding RR et al (2007) Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med 176:1120–1128
Ponsky TA, Rothenberg SS, Tsao K et al (2009) Thoracoscopy in children: is a chest tube necessary? J Laparoendosc Adv Surg Tech A 19(Suppl 1):S23–S25
Ponsky TA, Rothenberg SS (2008) Thoracoscopic lung biopsy in infants and children with endoloops allows smaller trocar sites and discreet biopsies. J Laparoendosc Adv Surg Tech A 18:120–122
Fan LL, Langston C (2002) Pediatric interstitial lung disease: children are not small adults. Am J Respir Crit Care Med 165:1466–1467
Langston C, Dishop MK (2004) Infant lung biopsy: clarifying the pathologic spectrum. Pathol Int 54:S419–S421
Guillerman RP (2010) Imaging of childhood interstitial lung disease. Pediatr Allergy Immunol Pulmonol 23:43–68
Clement A, Task Force ERS (2004) Task force on chronic interstitial lung disease in immunocompetent children. Eur Respir J 24:686–697
Furlow B (2011) Radiation protection in pediatric imaging. Radiol Technol 82:421–439
Seely JM, Effmann EL, Muller NL (1997) High-resolution CT of pediatric lung disease: imaging findings. AJR 168:1269–1275
Garcia-Pena P, Lucaya J (2004) HRCT in children: technique and indications. Eur Radiol 14(Suppl 4):L13–L30
Garcia-Pena P, Boixadera H, Barber I et al (2011) Thoracic findings of systemic diseases at high-resolution CT in children. Radiographics 31:465–482
Kazerooni EA (2001) High-resolution CT of the lungs. AJR 177:501–519
Bastos M, Lee EY, Strauss KJ et al (2009) Motion artifact on high-resolution CT images of pediatric patients: comparison of volumetric and axial CT methods. AJR 193:1414–1418
Sumikawa H, Johkoh T, Koyama M et al (2005) Image quality of high-resolution CT with 16-channel multidetector-row CT: comparison between helical scan and conventional step-shoot scan. Radiat Med 23:539–544
Mayo JR (2009) CT evaluation of diffuse infiltrative lung disease: dose considerations and optimal technique. J Thorac Imag 24:252–259
Lucaya J, Garcia-Pena P, Herrera L et al (2000) Expiratory chest CT in children. AJR 174:235–241
Long FR, Castile RG, Brody AS (1999) Lungs in infants and young children: improved thin-section CT with a noninvasive controlled-ventilation technique—initial experience. Radiology 212:588–593
Long FR, Castile RG (2001) Technique and clinical applications of full-inflation and end-exhalation controlled-ventilation chest CT in infants and young children. Pediatr Radiol 31:413–422
Lee EY, Mason KP, Zurakowski D et al (2008) MDCT assessment of tracheomalacia in symptomatic infants with mediastinal aortic vascular anomalies: preliminary technical experience. Pediatr Radiol 38:82–88
Lee EY, Boiselle PM (2009) Tracheobronchomalacia in infants and children: multidetector CT evaluation. Radiology 252:7–22
Lee EY, Strauss KJ, Tracy DA et al (2010) Comparison of standard-dose and reduced-dose expiratory MDCT techniques for assessment of tracheomalacia in children. Acad Radiol 17:504–510
Rutledge JC, Jensen P (1986) Acinar dysplasia: a new form of pulmonary maldevelopment. Hum Pathol 17:1290–1293
Gillespie LM, Fenton AC, Wright C (2004) Acinar dysplasia: a rare cause of neonatal respiratory failure. Acta Paediatr 93:712–713
Hugosson CO, Salama HM, Al-Dayel F et al (2005) Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study. Pediatr Radiol 35:311–316
Michalsky MP, Arca MJ, Groenman F et al (2005) Alveolar capillary dysplasia: a logical approach to a fatal disease. J Pediatr Surg 40:1100–1105
Haraida S, Lochbuhler H, Heger A et al (1997) Congenital alveolar capillary dysplasia: rare cause of persistent pulmonary hypertension. Pediatr Pathol Lab Med 17:959–975
Eulmesekian P, Cutz E, Parvez B et al (2005) Alveolar capillary dysplasia: a six-year single center experience. J Perinat Med 33:347–352
Bishop NB, Stankiewicz P, Steinhorn RH (2011) Alveolar capillary dysplasia. Am J Respir Crit Care Med 184:172–179
Hung SP, Hung SH, Wu CH et al (2011) Misalignment of lung vessels and alveolar capillary dysplasia: a case report with autopsy. Pediatri Neonatal 52:232–236
Sen P, Choudhury T, Smith EO et al (2010) Expression of angiogenic and vasculogenic proteins in the lung in alveolar capillary dysplasia/misalignment of pulmonary veins: an immunohistochemical study. Pediatr Dev Pathol 13:354–361
Sihoe AD, Lee AT, To KF et al (2005) Alveolar capillary dysplasia with congenital misalignment of pulmonary vessels. Asian Cardiovasc Thorac Ann 13:82–84
Nogee LM (2010) Genetic basis of children’s interstitial lung disease. Pediatr Allergy Immunol Pulmonol 23:15–24
Stankiewicz P, Sen P, Bhatt SS et al (2009) Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 84:780–791
Gamillscheg A, Zobel G, Spuller E et al (2008) Aortic coarctation associated with alveolar capillary dysplasia and misalignment of the pulmonary veins. Pediatr Cardiol 29:191–194
Taborosi B, Todt-Pingel I, Kayser G et al (2007) A rare case of aortic coarctation and ventricular septal defect combined with alveolar capillary dysplasia. Pediatr Cardiol 28:319–323
Roth W, Bucsenez D, Blaker H et al (2006) Misalignment of pulmonary vessels with alveolar capillary dysplasia: association with atrioventricular septal defect and quadricuspid pulmonary valve. Virchows Arch 448:375–378
Ahmed S, Ackerman V, Faught P et al (2008) Profound hypoxemia and pulmonary hypertension in a 7-month-old infant: late presentation of alveolar capillary dysplasia. Pediatr Crit Care Med 9:e43–e46
Roy PG, Patel P, Vayalakkad A et al (2007) Alveolar capillary dysplasia presenting as pneumothorax: a case report and review of literature. Pediatr Surg Int 23:915–917
Mahut B, De Blic J, Emond S et al (2007) Chest computed tomography findings in bronchopulmonary dysplasia and correlation with lung function. Arch Dis Child Fetal Neonatal Ed 92:F459–F464
Aukland SM, Halvorsen T, Fosse KR et al (2006) High-resolution CT of the chest in children and young adults who were born prematurely: findings in a population-based study. AJR 187:1012–1018
Biko DM, Schwartz M, Anupindi SA et al (2008) Subpleural lung cysts in Down syndrome: prevalence and association with coexisting diagnoses. Pediatr Radiol 38:280–284
Taylor PA, Dishop MK, Lotze TE et al (2009) Congenital multilobar emphysema: a characteristic lung growth disorder attributable to filamin A gene mutations. Pediatr Radiol 39(Suppl 3):S516
De Wit MC, Tiddens HA, de Coo IF et al (2011) Lung disease in FLAN mutation: confirmatory report. Eur J Med Genet 54:299–300
Masurel-Paulet A, Haan E, Thompson EM et al (2011) Lung disease associated with periventricular nodular heterotopia and an FLNA mutation. Eur J Med Genet 54:25–28
Epaud R, Jonard L, Ducou-le-Pointe H et al (2012) Genetic disorders of surfactant. Arch Pediatr 19:212–219
Wert SE, Whitsett JA, Nogee LM (2009) Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 12:253–274
Somaschini M, Nogee LM, Sassi I et al (2007) Unexplained neonatal respiratory distress due to congenital surfactant deficiency. J Pediatr 150:649–653
Wilder MA (2004) Surfactant protein B deficiency in infants with respiratory failure. J Perinat Neonatal Nurs 18:61–67
Garmany TH, Moxley MA, White FV et al (2006) Surfactant composition and function in patients with ABCA3 mutations. Pediatr Res 59:801–805
Somaschini M, Wert S, Mangili G et al (2000) Hereditary surfactant protein B deficiency resulting from a novel mutation. Intensive Care Med 26:97–100
Hamvas A (2006) Inherited surfactant protein-B deficiency and surfactant protein-C associated disease: clinical features and evaluation. Semin Perinatol 30:316–326
Matsumura Y, Ban N, Ueda K et al (2006) Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency. J Bio Chem 281:34503–34514
Doan ML, Guillerman RP, Dishop MK et al (2008) Clinical, radiological and pathological features of ABCA3 mutations in children. Thorax 63:366–373
Newman B, Kuhn JP, Kramer SS et al (2001) Congenital surfactant protein B deficiency—emphasis on imaging. Pediatr Radiol 31:327–331
Galambos C, Levy H, Cannon CL et al (2010) Pulmonary pathology in thyroid transcription factor-1 deficiency syndrome. Am J Respir Crit Care Med 182:549–554
Parto K, Svedstrom E, Majurin ML et al (1993) Pulmonary manifestations in lysinuric protein intolerance. Chest 104:1176–1182
Santamaria F, Parenti G, Guidi G et al (1996) Early detection of lung involvement in lysinuric protein intolerance: role of high-resolution computed tomography and radioisotopic methods. Am J Respir Crit Care Med 153:731–735
Rossi SE, Erasmus JJ, Volpacchio M et al (2003) ‘Crazy-paving’ pattern at thin-section CT of the lungs: radiologic-pathologic overview. Radiographics 23:1509–1519
Zontsich T, Helbich TH, Wojnarovsky C et al (1998) Pulmonary alveolar proteinosis in a child: HRCT findings before and after bronchoalveolar lavage. Eur Radiol 8:1680–1682
Cetin E, Lee EY (2007) Pneumocystis carinii pneumonia in an infant with hypogammaglobulinemia. Pediatr Radiol 37:329
Gower WA, Nogee LM (2011) Surfactant dysfunction. Paediatr Respir Rev 12:223–229
Deterding RR, Pye C, Fan LL et al (2005) Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol 40:157–165
Cutz E, Yeger H, Pan J (2007) Pulmonary neuroendocrine cell system in pediatric lung disease—recent advances. Pediatr Dev Pathol 10:419–435
Popler J, Gower WA, Mogayzel PJ Jr et al (2010) Familial neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 45:749–755
Brody AS, Guillerman RP, Hay TC et al (2010) Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT. AJR 194:238–244
Young LR, Brody AS, Inge TH et al (2011) Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders. Chest 139:1060–1071
Canakis AM, Cutz E, Monson D et al (2002) Pulmonary interstitial glycogenosis: a new variant of neonatal interstitial lung disease. Am J Respir Crit Care Med 165:1557–1565
Smets K, Dhaene K, Schelstraete P et al (2004) Neonatal pulmonary interstitial glycogen accumulation disorder. Eur J Pediatr 163:408–409
Deutsch GH, Young LR (2009) Histologic resolution of pulmonary interstitial glycogenosis. Pediatr Dev Pathol 12:475–480
Lanfranchi M, Allbery SM, Wheelock L et al (2010) Pulmonary interstitial glycogenosis. Pediatr Radiol 40:361–365
Castillo M, Vade A, Lim-Dunham JE et al (2010) Pulmonary interstitial glycogenosis in the setting of lung growth abnormality: radiographic and pathologic correlation. Pediatr Radiol 40:1562–1565
Disclosure
The author has indicated he has no relevant financial relationships or potential conflicts of interest related to the material.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article has been selected as the CME activity for the current month. Please visit the SPR Web site at www.pedrad.org on the Education page and follow the instructions to complete this CME activity.
Rights and permissions
About this article
Cite this article
Lee, E.Y. Interstitial lung disease in infants: new classification system, imaging technique, clinical presentation and imaging findings. Pediatr Radiol 43, 3–13 (2013). https://doi.org/10.1007/s00247-012-2524-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00247-012-2524-x