Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Approach to the infant and child with interstitial lung disease

Lisa R Young, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD


Interstitial lung disease (ILD) consists of a diverse group of disorders that involve the pulmonary parenchyma and interfere with gas exchange. Although some of the conditions that cause ILD in children and adults are similar, they occur in different proportions in each population. In addition, certain diseases are unique to infants [1-6].

Children with ILD may present with respiratory failure, or with more indolent or chronic symptoms including tachypnea, hypoxemia, retractions, cough, exercise intolerance, failure to thrive, gastroesophageal reflux, or other nonspecific symptoms. Thus, the differential diagnosis is broad, and the first approach is to exclude more common causes for this presentation, including infection, immunodeficiency, structural airway abnormalities, congenital heart disease, and cystic fibrosis [7]. Once more common explanations are excluded, a child with unexplained pulmonary symptoms and diffuse pulmonary infiltrates may be considered to have childhood ILD syndrome, and further investigations to determine a specific cause of childhood ILD are warranted [7]. Establishing a definitive diagnosis may inform prognosis, genetic counseling for families, and in some cases may alter treatment decisions. However, for many forms of ILD, treatment options are limited and often include drugs of unproven efficacy with substantial side effects. Thus, ILD presents a diagnostic and therapeutic challenge, even to the most experienced pediatric pulmonologist.

This topic review provides an approach to the diagnosis and management of ILD in infants and children. Other topic reviews with related content include:

(See "Classification of diffuse lung disease (interstitial lung disease) in infants and children".)

(See "Genetic disorders of surfactant dysfunction".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: May 20, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Fan LL, Langston C. Chronic interstitial lung disease in children. Pediatr Pulmonol 1993; 16:184.
  2. Fan LL. Evaluation and therapy of chronic interstitial pneumonitis in children. Curr Opin Pediatr 1994; 6:248.
  3. Bokulic RE, Hilman BC. Interstitial lung disease in children. Pediatr Clin North Am 1994; 41:543.
  4. Diaz, RP, Bowman, CM. Childhood interstitial lung disease. Semin Respir Med 1990; 11:253.
  5. Interstitial lung disease in children, Laraya-Cuasay LR, Hughes WT (Eds) (Eds), CRC Press, Inc, CRC Press, Inc 1988.
  6. Fan LL, Deterding RR, Langston C. Pediatric interstitial lung disease revisited. Pediatr Pulmonol 2004; 38:369.
  7. Kurland G, Deterding RR, Hagood JS, et al. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med 2013; 188:376.
  8. Dinwiddie R, Sharief N, Crawford O. Idiopathic interstitial pneumonitis in children: a national survey in the United Kingdom and Ireland. Pediatr Pulmonol 2002; 34:23.
  9. Griese M, Haug M, Brasch F, et al. Incidence and classification of pediatric diffuse parenchymal lung diseases in Germany. Orphanet J Rare Dis 2009; 4:26.
  10. Clement A, ERS Task Force. Task force on chronic interstitial lung disease in immunocompetent children. Eur Respir J 2004; 24:686.
  11. Barbato A, Panizzolo C, Cracco A, et al. Interstitial lung disease in children: a multicentre survey on diagnostic approach. Eur Respir J 2000; 16:509.
  12. Deutsch GH, Young LR, Deterding RR, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med 2007; 176:1120.
  13. Soares JJ, Deutsch GH, Moore PE, et al. Childhood interstitial lung diseases: an 18-year retrospective analysis. Pediatrics 2013; 132:684.
  14. Nathan N, Taam RA, Epaud R, et al. A national internet-linked based database for pediatric interstitial lung diseases: the French network. Orphanet J Rare Dis 2012; 7:40.
  15. Nogee LM. Genetic Basis of Children's Interstitial Lung Disease. Pediatr Allergy Immunol Pulmonol 2010; 23:15.
  16. Garmany TH, Wambach JA, Heins HB, et al. Population and disease-based prevalence of the common mutations associated with surfactant deficiency. Pediatr Res 2008; 63:645.
  17. Wambach JA, Wegner DJ, Depass K, et al. Single ABCA3 mutations increase risk for neonatal respiratory distress syndrome. Pediatrics 2012; 130:e1575.
  18. Popler J, Lesnick B, Dishop MK, Deterding RR. New coding in the International Classification of Diseases, Ninth Revision, for children's interstitial lung disease. Chest 2012; 142:774.
  19. Langston C, Fan LL. The spectrum of interstitial lung disease in childhood. Pediatr Pulmonol 2001; Suppl 23:70.
  20. Langston C, Fan LL. Diffuse interstitial lung disease in infants. Pediatr Pulmonol 2001; Suppl 23:74.
  21. Brasch F, Schimanski S, Mühlfeld C, et al. Alteration of the pulmonary surfactant system in full-term infants with hereditary ABCA3 deficiency. Am J Respir Crit Care Med 2006; 174:571.
  22. Deterding RR, Pye C, Fan LL, Langston C. Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia. Pediatr Pulmonol 2005; 40:157.
  23. Fan LL, Mullen AL, Brugman SM, et al. Clinical spectrum of chronic interstitial lung disease in children. J Pediatr 1992; 121:867.
  24. Fan LL, Kozinetz CA. Factors influencing survival in children with chronic interstitial lung disease. Am J Respir Crit Care Med 1997; 156:939.
  25. Fan LL, Kozinetz CA, Deterding RR, Brugman SM. Evaluation of a diagnostic approach to pediatric interstitial lung disease. Pediatrics 1998; 101:82.
  26. Doan ML, Guillerman RP, Dishop MK, et al. Clinical, radiological and pathological features of ABCA3 mutations in children. Thorax 2008; 63:366.
  27. Hamvas A, Deterding RR, Wert SE, et al. Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1. Chest 2013; 144:794.
  28. Zapletal A, Houstĕk J, Samánek M, et al. Lung function in children and adolescents with idiopathic interstitial pulmonary fibrosis. Pediatr Pulmonol 1985; 1:154.
  29. Steinkamp G, Müller KM, Schirg E, von der Hardt H. Fibrosing alveolitis in childhood. A long-term follow-up. Acta Paediatr Scand 1990; 79:823.
  30. Gaultier C, Chaussain M, Boulé M, et al. Lung function in interstitial lung diseases in children. Bull Eur Physiopathol Respir 1980; 16:57.
  31. Long FR, Castile RG. Technique and clinical applications of full-inflation and end-exhalation controlled-ventilation chest CT in infants and young children. Pediatr Radiol 2001; 31:413.
  32. Young LR, Brody AS, Inge TH, et al. Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders. Chest 2011; 139:1060.
  33. Kerby GS, Wagner BD, Popler J, et al. Abnormal infant pulmonary function in young children with neuroendocrine cell hyperplasia of infancy. Pediatr Pulmonol 2013; 48:1008.
  34. Lynch DA, Brasch RC, Hardy KA, Webb WR. Pediatric pulmonary disease: assessment with high-resolution ultrafast CT. Radiology 1990; 176:243.
  35. Kuhn JP. High-resolution computed tomography of pediatric pulmonary parenchymal disorders. Radiol Clin North Am 1993; 31:533.
  36. Koh DM, Hansell DM. Computed tomography of diffuse interstitial lung disease in children. Clin Radiol 2000; 55:659.
  37. Long FR, Castile RG, Brody AS, et al. Lungs in infants and young children: improved thin-section CT with a noninvasive controlled-ventilation technique--initial experience. Radiology 1999; 212:588.
  38. Lynch DA, Hay T, Newell JD Jr, et al. Pediatric diffuse lung disease: diagnosis and classification using high-resolution CT. AJR Am J Roentgenol 1999; 173:713.
  39. Copley SJ, Coren M, Nicholson AG, et al. Diagnostic accuracy of thin-section CT and chest radiography of pediatric interstitial lung disease. AJR Am J Roentgenol 2000; 174:549.
  40. Brody AS, Guillerman RP, Hay TC, et al. Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT. AJR Am J Roentgenol 2010; 194:238.
  41. Réfabert L, Rambaud C, Mamou-Mani T, et al. Cd1a-positive cells in bronchoalveolar lavage samples from children with Langerhans cell histiocytosis. J Pediatr 1996; 129:913.
  42. Mahut B, Delacourt C, Scheinmann P, et al. Pulmonary alveolar proteinosis: experience with eight pediatric cases and a review. Pediatrics 1996; 97:117.
  43. Niggemann B, Rebien W, Rahn W, Wahn U. Asymptomatic pulmonary involvement in 2 children with Niemann-Pick disease type B. Respiration 1994; 61:55.
  44. Carson KF, Williams CA, Rosenthal DL, et al. Bronchoalveolar lavage in a girl with Gaucher's disease. A case report. Acta Cytol 1994; 38:597.
  45. Chadelat K, Baculard A, Grimfeld A, et al. Pulmonary sarcoidosis in children: serial evaluation of bronchoalveolar lavage cells during corticosteroid treatment. Pediatr Pulmonol 1993; 16:41.
  46. Tessier V, Chadelat K, Baculard A, et al. BAL in children: a controlled study of differential cytology and cytokine expression profiles by alveolar cells in pediatric sarcoidosis. Chest 1996; 109:1430.
  47. Ratjen F, Costabel U, Griese M, Paul K. Bronchoalveolar lavage fluid findings in children with hypersensitivity pneumonitis. Eur Respir J 2003; 21:144.
  48. Langston C, Patterson K, Dishop MK, et al. 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.
  49. Rothenberg SS, Wagner JS, Chang JH, Fan LL. The safety and efficacy of thoracoscopic lung biopsy for diagnosis and treatment in infants and children. J Pediatr Surg 1996; 31:100.
  50. Fan LL, Kozinetz CA, Wojtczak HA, et al. Diagnostic value of transbronchial, thoracoscopic, and open lung biopsy in immunocompetent children with chronic interstitial lung disease. J Pediatr 1997; 131:565.
  51. de Blic J. Pulmonary alveolar proteinosis in children. Paediatr Respir Rev 2004; 5:316.
  52. Desmarquest P, Tamalet A, Fauroux B, et al. Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses. Pediatr Pulmonol 1998; 26:332.
  53. de Benedictis FM, Canny GJ, Levison H. The role of corticosteroids in respiratory diseases of children. Pediatr Pulmonol 1996; 22:44.
  54. Yeh TF, Lin YJ, Lin HC, et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004; 350:1304.
  55. Springer C, Maayan C, Katzir Z, et al. Chloroquine treatment in desquamative interstitial pneumonia. Arch Dis Child 1987; 62:76.
  56. Leahy F, Pasterkamp H, Tal A. Desquamative interstitial pneumonia responsive to chloroquine. Clin Pediatr 1984; 24:230.
  57. Waters KA, Bale P, Isaacs D, Mellis C. Successful chloroquine therapy in a child with lymphoid interstitial pneumonitis. J Pediatr 1991; 119:989.
  58. Campos JM, Simonetti JP. Treatment of lymphoid interstitial pneumonia with chloroquine. J Pediatr 1993; 122:503.
  59. Bush A, Sheppard MN, Warner JO. Chloroquine in idiopathic pulmonary haemosiderosis. Arch Dis Child 1992; 67:625.
  60. Abou Taam R, Jaubert F, Emond S, et al. Familial interstitial disease with I73T mutation: A mid- and long-term study. Pediatr Pulmonol 2009; 44:167.
  61. Kitazawa H, Moriya K, Niizuma H, et al. Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations. Eur J Pediatr 2013; 172:953.
  62. Rosen DM, Waltz DA. Hydroxychloroquine and surfactant protein C deficiency. N Engl J Med 2005; 352:207.
  63. Mogulkoc N, Brutsche MH, Bishop PW, et al. Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation. Am J Respir Crit Care Med 2001; 164:103.
  64. Scott JP, Whitehead B, de Leval M, et al. Paediatric incidence of acute rejection and obliterative bronchiolitis: a comparison with adults. Transpl Int 1994; 7 Suppl 1:S404.
  65. Rama JA, Fan LL, Faro A, et al. Lung transplantation for childhood diffuse lung disease. Pediatr Pulmonol 2013; 48:490.