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Children’s Interstitial Lung
Disease (ChILD):
Clinical Overview
Leland L. Fan, MD
2/7/15
Disclosures
• I receive royalties for writing
topics for UpToDate
Interstitial Lung Disease (ILD),
also known as diffuse lung disease, includes
large, heterogeneous group of rare pulmonary...
Alveolar Wall
• Epithelial lining cells
• Closely apposed
capillary network
• Delicate fibroelastic
matrix
• Prevalence 0.13*
67-81#
• Dominant Form None UIP
• Unique Entities
– Growth Abnormalilties Yes No
– NEHI Yes No
– PIG Ye...
Idiopathic Pulmonary Fibrosis (IPF)/
Usual Interstitial Pneumonitis (UIP)
• Temporal
Heterogeneity
• Fibroblastic foci
Hig...
UIP Pattern in Non-IPF Patients
• Immune-mediated Disorders
• Hypersensitivity Pneumonitis
• Inborn Errors of Surfactant
M...
Desquamative Interstitial Pneumonia
(DIP)
• Benign form of adult ILD
• Linked to smoking
• Very responsive to steroids
• Nothing known at the time
• Pediatricians assumed these were
pediatric examples of ILD types
described in adults
• Numer...
Mortality
DIP 39%*
5%+
UIP 4%#
50-80%+
Children Adults
#
Zapletel. Pediatr Pulmonol 1985;1:154
#
Hewitt. Arch Dis Child 19...
Pediatr Pulmonol 1993;16:184
UIP in Children
1
AJRCCM 2007;176:1120
2
Histopathol 2013 EPUP
3
Pediatrics 2013;132:684
# Cases # UIP
ChILDRN1
378 0
Brom...
What we now know
• True IPF/UIP probably does
not exist in children
• Most cases of pediatric DIP
are related to inborn er...
ChILD
can be very difficult to diagnose
and treat, and is associated
with significant morbidity and
mortality.
ChildRN Classification
• Disorders more prevalent in infancy
• Disorders of the immunocompetent host
• Disorders related t...
ChildRN Classification
• Disorders more prevalent in infants
–Diffuse developmental disorders
–Growth abnormality
–PIG
–NE...
Growth
PIG
SP-C
NEHI
Growth
ABCA3
Deutsch. AJRCCM 2007;176:1120
Inborn Errors of Surfactant Metabolism
(IESM)
• Abnormal production
– SP-B
– SP-C
– ABCA3
– TTF-1 (NKX2-1)
• Abnormal cata...
SP-B SP-C ABCA3 TTF-1 CSF2RA
CSF2RB
Pathology PAP, DIP
Abnormal
lamellar
bodies on
EM
PAP, DIP,
CPI, NSIP.
UIP
PAP, DIP,
C...
An Official American Thoracic Society Clinical Practice
Guideline: Classification, Evaluation, and Management of
Childhood...
6%
26%
9%
3%
10%
12%
15%
3%
5%
11% Diffuse developmental
Growth abnormality
NEHI
PIG
Surfactant dysfunction
Normal host
Im...
6%
26%
9%
3%
10%
12%
15%
3%
5%
11% Diffuse developmental
Growth abnormality
NEHI
PIG
Surfactant dysfunction
Normal host
Im...
• Systemic Disease 48 (12.7%)
–Immune-mediated 39 (10.3%)
•JIA 5 (1.3%)
–NSIP 2
–Capillaritis 1
–Multicompartment disease ...
a systematic approach is essential
to the evaluation of ChILD.
With such a huge
differential diagnosis,
Diagnostic Tools
Infant PFTs
HRCT VATS
BAL
• Hct 7
• ANA neg
• ANCA neg
• AGMBA neg
• UA neg
3 YO Girl
Alveolar Hemorrhage Syndromes
2010-2013
44 Pediatric Cases
2222
1414
88
1970
1990
2000
1980
BAL
VATS
HRCT
Molecular Genetics
PFTs
Infant PFTs
CVCT
OLB
Progress
In ChILD Biomarkers
2010
Diagnosti...
1970
1990
2000
DIP, UIP, CFA
1980
BAL
VATS
HRCTSP-B
Molecular Genetics
PFTs
Infant PFTs
PIG
ABCA3
SP-C
LIP
CVCT
OLB
Progre...
1970
1990
2000
DIP, UIP, CFA
1980
SP-B
PIG
ABCA3
PC, NEHI
SP-C
LIP
2010Growth
CSF2RA, CSF2RB
DNA repair defects
TTF1
Progr...
1970
1990
2000
DIP, UIP, CFA
1980
SP-B
PIG
ABCA3
PC, NEHI
SP-C
LIP
2010Growth
CSF2RA, CSF2RB
DNA repair defects
TTF1
pulse...
1970
1990
2000
DIP, UIP, CFA
1980
SP-B
PIG
ABCA3
SP-C
LIP
2010Growth
CSF2RA, CSF2RB
DNA repair defects
TTF1
Progress
In Ch...
2020
ChILD
The Future
?
2030
2010
Regenerative medicine
Gene sequencing
We’ve come a long way, Baby!
It’s IPF.It’s IPF.
Childrens Interstitial Lung Disease Clinical Overview
Childrens Interstitial Lung Disease Clinical Overview
Childrens Interstitial Lung Disease Clinical Overview
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Childrens Interstitial Lung Disease Clinical Overview

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Childrens Interstitial Lung Disease Clinical Overview

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Childrens Interstitial Lung Disease Clinical Overview

  1. 1. Children’s Interstitial Lung Disease (ChILD): Clinical Overview Leland L. Fan, MD 2/7/15
  2. 2. Disclosures • I receive royalties for writing topics for UpToDate
  3. 3. Interstitial Lung Disease (ILD), also known as diffuse lung disease, includes large, heterogeneous group of rare pulmonary disorders that cause derangements of the alveolar wall and disordered gas exchange
  4. 4. Alveolar Wall • Epithelial lining cells • Closely apposed capillary network • Delicate fibroelastic matrix
  5. 5. • Prevalence 0.13* 67-81# • Dominant Form None UIP • Unique Entities – Growth Abnormalilties Yes No – NEHI Yes No – PIG Yes No – SP-B Mutations Yes No ChILD vs Adult ILD Children Adults *OJRD. 2009;4:26 #AJRCCM 1994;150:967
  6. 6. Idiopathic Pulmonary Fibrosis (IPF)/ Usual Interstitial Pneumonitis (UIP) • Temporal Heterogeneity • Fibroblastic foci Highly lethal disease of older adults
  7. 7. UIP Pattern in Non-IPF Patients • Immune-mediated Disorders • Hypersensitivity Pneumonitis • Inborn Errors of Surfactant Metabolism
  8. 8. Desquamative Interstitial Pneumonia (DIP) • Benign form of adult ILD • Linked to smoking • Very responsive to steroids
  9. 9. • Nothing known at the time • Pediatricians assumed these were pediatric examples of ILD types described in adults • Numerous cases reported as DIP, UIP, IPF, and CFA Early Cases of ChILD
  10. 10. Mortality DIP 39%* 5%+ UIP 4%# 50-80%+ Children Adults # Zapletel. Pediatr Pulmonol 1985;1:154 # Hewitt. Arch Dis Child 1977;52:22 # Chetty. Ann Allergy 1987;58:336 # Steinkamp. Acta Paediatr Scand 1990;79:823 *Stillwell. Chest 1980;77:165 + King. AJRCCM 2005;172:268
  11. 11. Pediatr Pulmonol 1993;16:184
  12. 12. UIP in Children 1 AJRCCM 2007;176:1120 2 Histopathol 2013 EPUP 3 Pediatrics 2013;132:684 # Cases # UIP ChILDRN1 378 0 Brompton2 203 1 Vanderbilt3 64 0
  13. 13. What we now know • True IPF/UIP probably does not exist in children • Most cases of pediatric DIP are related to inborn errors of surfactant metabolism
  14. 14. ChILD can be very difficult to diagnose and treat, and is associated with significant morbidity and mortality.
  15. 15. ChildRN Classification • Disorders more prevalent in infancy • Disorders of the immunocompetent host • Disorders related to systemic disease • Disorders of the immunocompromised host • Disorders masquerading as ILD • Unclassified Paediatr Respir Rev 2011;12:230
  16. 16. ChildRN Classification • Disorders more prevalent in infants –Diffuse developmental disorders –Growth abnormality –PIG –NEHI –Inborn error of surfactant metabolism
  17. 17. Growth PIG SP-C NEHI Growth ABCA3 Deutsch. AJRCCM 2007;176:1120
  18. 18. Inborn Errors of Surfactant Metabolism (IESM) • Abnormal production – SP-B – SP-C – ABCA3 – TTF-1 (NKX2-1) • Abnormal catabolism – CSF2RA – CSF2RB
  19. 19. SP-B SP-C ABCA3 TTF-1 CSF2RA CSF2RB Pathology PAP, DIP Abnormal lamellar bodies on EM PAP, DIP, CPI, NSIP. UIP PAP, DIP, CPI, NSIP, UIP Abnormal lamellar bodies on EM Alveolar simplification, DIP PAP Lethality +++++ +-++ +++ +-++ + IESM
  20. 20. An Official American Thoracic Society Clinical Practice Guideline: Classification, Evaluation, and Management of Childhood Interstitial Lung Disease in Infancy Geoffrey Kurland, Robin R. Deterding, James S. Hagood, Lisa R. Young, Alan S. Brody, Robert G. Castile, Sharon Dell, Leland L. Fan, Aaron Hamvas, Bettina C. Hilman, Claire Langston, Lawrence M. Nogee, and Gregory J. Redding; on behalf of the American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network Am J Respir Crit Care Med 2013;188:376
  21. 21. 6% 26% 9% 3% 10% 12% 15% 3% 5% 11% Diffuse developmental Growth abnormality NEHI PIG Surfactant dysfunction Normal host Immunocompromised Systemic Vascular Unclassified Infants (0-2)
  22. 22. 6% 26% 9% 3% 10% 12% 15% 3% 5% 11% Diffuse developmental Growth abnormality NEHI PIG Surfactant dysfunction Normal host Immunocompromised Systemic Vascular Unclassified 40% 22% 16% 1% 0% 2% 0% 7% 9% 3% Diffuse developmental Growth abnormality NEHI PIG Surfactant dysfunction Normal host Immunocompromised Systemic Masqueraders Unclassified Infants (0-2) Older Children (2-18)
  23. 23. • Systemic Disease 48 (12.7%) –Immune-mediated 39 (10.3%) •JIA 5 (1.3%) –NSIP 2 –Capillaritis 1 –Multicompartment disease 1 –Granulomatous pneumonia, likely infection 1
  24. 24. a systematic approach is essential to the evaluation of ChILD. With such a huge differential diagnosis,
  25. 25. Diagnostic Tools Infant PFTs HRCT VATS BAL
  26. 26. • Hct 7 • ANA neg • ANCA neg • AGMBA neg • UA neg 3 YO Girl
  27. 27. Alveolar Hemorrhage Syndromes 2010-2013 44 Pediatric Cases 2222 1414 88
  28. 28. 1970 1990 2000 1980 BAL VATS HRCT Molecular Genetics PFTs Infant PFTs CVCT OLB Progress In ChILD Biomarkers 2010 Diagnostic Tools
  29. 29. 1970 1990 2000 DIP, UIP, CFA 1980 BAL VATS HRCTSP-B Molecular Genetics PFTs Infant PFTs PIG ABCA3 SP-C LIP CVCT OLB Progress In ChILD Biomarkers 2010Growth CSF2RA, CSF2RB DNA repair defects TTF1 Diagnostic Tools PC, NEHI IPH
  30. 30. 1970 1990 2000 DIP, UIP, CFA 1980 SP-B PIG ABCA3 PC, NEHI SP-C LIP 2010Growth CSF2RA, CSF2RB DNA repair defects TTF1 Progress In ChILD IPH
  31. 31. 1970 1990 2000 DIP, UIP, CFA 1980 SP-B PIG ABCA3 PC, NEHI SP-C LIP 2010Growth CSF2RA, CSF2RB DNA repair defects TTF1 pulse steroids corticosteroids, hydroxychloroquine, azathioprine, cyclophosphamide IVIG cyclosporine lung transplant biologic agents tacrolimus, MMF macrolides Progress In ChILD Treatment plasmapheresis IPH
  32. 32. 1970 1990 2000 DIP, UIP, CFA 1980 SP-B PIG ABCA3 SP-C LIP 2010Growth CSF2RA, CSF2RB DNA repair defects TTF1 Progress In ChILD Controlled Clinical Trials PC, NEHI IPH
  33. 33. 2020 ChILD The Future ? 2030 2010 Regenerative medicine Gene sequencing
  34. 34. We’ve come a long way, Baby! It’s IPF.It’s IPF.

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