The topic is very different from the adult ILDs, majority of childhood ILDs are developmental disorders of the Lungs. We have described the common ILDs in this ppt, also discussed how to approach and management in the end.

1. CHILDHOOD INTERSTITIAL LUNG DISEASES
(chILD)

2. Introduction
Definition-
• Heterogenous group of familial or sporadic disorder
• Diffuse lung involvement
• Characterised by –
abnormal gaseous exchange (altered structure of the interstitium)
[Nelson]

3. American Thoracic Society (ATS) 2013
chILD told to be exist when-
• Common causes of mimicking diffuse lung disease (DLD) has been
excluded (Heart disease, infections, Immunodef, Cystic fibrosis, Ciliary
dyskinesia)
• 3 of the 4 criteria-
- Respiratory symptoms
- Respiratory signs
- Hypoxemia
- Diffuse abnormalities on CXR or a CT scan.

4. Epidemiology
India [J Shankar
2013]
Europe [Edward YL
2020]
Western [Teresa
liang 2019]
Prevalence 4 per 100,000
children
3.6 per 100,000 in
children
0.13-16.2 cases per
100,000 in children
M:F 1.2 1.4 1.6:1
Age of Onset ≤12months- 43.8%,
>12months- 56.2%
<2 years 30%,
>2 years 70%
<2years- 31%
>2years- 69%

5. CLASSIFICATION

6. Modified Deutsch classification
[Nelson, Deutsch et al, ATS]
Non-specific to <2years
- Disorders of normal Host
- Systemic diseases
- Immunocompromised
- Masquerading as interstitial
disease
Specific to <2years
- Diffuse Developmental
disorder
- Lung Growth abnormality
- Surfactant dysfunction
- Specific Conditions of
unknown etiology

7. Sl.
No.
Conditions Specific to
infancy (<2 years)
Diseases
1. Diffuse developmental
disorders
Acinar dysplasia
Congenital alveolar dysplasia
Alveolar capillary dysplasia
2. Lung Growth
abnormalities
Pulmonary hypoplasia
Bronchopulmonary dysplasia (BPD)
3. Surfactant dysfunction
disorders
SpB /SpC/ABCA3 genetic mutations
4. Specific conditions of
unknown etiology
Neuroendocrine cell hyperplasia of infancy (NEHI)
Pulmonary interstitial glycogenosis

8. Sl.
No.
Conditions non-Specific to
infancy
Diseases
1. Disorders of normal Host Infectious and postinfectious
Hypersensitivity pneumonitis
Aspiration pneumonia
2. Disorders related to
systemic disease
processes
Storage disorders,
Autoimmune diseases
Malignant infiltrates
3. Disorders of the
immunocompromised
host
Opportunistic infection
Disorders related to transplantation/rejection syndromes
Diffuse alveolar damage of unknown etiology

9. Prevalence of chILD
Disorders Related to Systemic Diseases
• Association of systemic illness 3.4
Immunocompromised
• Drug induced/GVHD 1.7
Sl.
No.
Diffuse Lung abnormalities %
1 NEHI 13
2 ABCA3 deficiency 7
3 Idiopathic bronchiolitis of infancy 3.4
4 Surfactant protein C deficiency 3.4
5 Nonspecific interstitial pneumonitis 3.4
6 Acinar/Alveolar capillary dysplasia 2.6
7 Surfactant Protein B deficiency 1.7
8 Chronic pneumonitis of infancy 1.7
9 Pulmonary interstitial glycogenosis 1.7
Saddi V et al 2017 (hospital based study in 10years period) N= 115
Sl.
No.
Disorders of Normal Host %
1 Pulmonary hemosiderosis 4.3
2 Post infectious and BOOP 6
3 Pulmonary vasculitis/capillaritis 1.7
4 Eosinophilic pneumonia 0.8

10. Pathogenesis

11. Cascade of Events
Developing Lung
Epithelial apoptosis
Myofibroblast proliferation
Matrix deposition
Angiogenesis
Genetic factors Injury
Disordered repair of the injured tissues
Recurrent Inflammation
Pulmonary Fibrosis
Genetic predisposition
for remodelling
Diffuse parenchymal lung disease
TGFβ, IFN γ, PDGF, IL4
etc.

12. Diseases prevalent in Infancy (<2 years age)

13. Bronchopulmonary dysplasia (BPD)
Premature infants exposed to prolonged
High-pressure mechanical ventilation
High-concentration inspired oxygen,
Airway smooth muscle hypertrophy& epithelial squamous
metaplasia
Peribronchial fibrosis & hypertensive vascular changes

14. Bronchopulmonary dysplasia (BPD)
bronchiolar and
interstitial fibrosis
CXR- interstitial
thickening, hyperinflation,
and atelectasis
CT - Interlobular septal thickening
with intermixed ground glass
opacification and overinflated lobules

15. Neuroendocrine Hyperplasia of Infancy (NEHI)
• Unknown etiology
• Prevalence 10% among all chILD
• M:F= 66:34
• Presents in early infancy (Mean age of onset 4 months)
• Persistent tachypnoea of infancy.
• Presence of Neuroendocrine cells in a term infant
• Elevated serotonin level and neuropeptide level.
• T/t- Supportive care

16. CT- the classic centrally, anteriorly
accentuated ground-glass opacities.
Biopsy- PAS positive neuroendocrine
cells

17. Pulmonary interstitial glycogenosis (PIG)
• Unknown etiology
• MC non-inflammatory type of chILD.
• Presents in neonatal period.
• Present with tachypnoea with hypoxemia
• Glycogen body accumulation in interstitial epithelium.

18. Pulmonary interstitial glycogenosis (PIG)
Biopsy- vacuolated cells from which
glycogen has been leached out during
processing.
CT- ground-glass opacities,
intralobular septal thickening,
reticularchanges, and multiple
posterior cysts

19. Surfactant Protein deficiencies
• Genetic mutations in SpB protein, SpC protein and ABCA 3 protein
genes.
Surfactant protein
deficiency
Features Age and Onset
Incidence rate
SpB Severe form with mortality at 2 month without transplant is
100%.
Radio-findings mimic HMD.
Biopsy- Eosinophilic, PAS positive lipoproteinaceous materials
Neonate- Acute <1 in million
(a bush 2020)
ABCA3 Most severe form
Progressive RD with respiratory failure.
Radio-findings mimic HMD.
Neonate- Acute
Infancy and childhood-
subacute
1 in 10000 (a bush 2020)
SpC Milder form.
Neonatal RD.
Later- Cough with hypoxemia
HRCT chest- extensive ggo
Neonate- Acute (mild)
Infancy and childhood-
subacute
Not known
NKX2.1/TTF1 Respiratory- Neonatal RD, ILD
Neurological- Hypotonia, chorea, ataxia, development delay
Hypothyroidism
Any age- Acute or chronic
Not known

20. Diffuse GGOs with interlobular septal
thickening, and distortion of the airways
H & E stain - thickening
of the alveolar septa.

21. Pulmonary alveolar proteinosis (PAP)
• Rare cause of ILD
• Mutations in proteins encoding GMCSF (CSF2RA and
CSF2RB) and methionyl-tRNA synthetase (MARS).
• Exaggerated by an acute lung infection or malignancies.
Alveolar filling with surfactant degradation products

22. CT image- diffuse ggos with septal thickening representing crazy-paving
appearance

23. Aspiration syndromes
• 26- 40% with recurrent and chronic aspirations with recurrent
chest infections develop chILD. [Thomas S]
• Risk factors- H type TEF, Neuromuscular weakness, cleft palate
and laryngeal cleft
• Chronic inflammations  Consolidation, alveolar atelectasis
and fibrosis.
• MC- RUL, post. and basal portions of both lungs.

24. Chronic aspiration severe: severe
diffuse interstitial lung disease (ILD)
with areas of atelectasis and/or fibrosis
Aspiration- Axial lung window CT
image showing mosaic distribution of
ground-glass ILD

25. Diseases prevalent in older children (>2
years age)

26. Disorders with normal immune response
• Infection and post-infection pulmonary changes
• Alveolar epithelial damage
• Biopsy- necrosis of alveolar epithelium with inflammatory cells.
• Viral infections more attributed to ILD than bacterial. [Annick C]
Organisms-
• EBV, CMV, RSV, Influenza and
HIV
• Adenovirus
• Chlamydia, Mycoplasma,
Legionella

27. Bronchiolitis obliterans organizing pneumonia (BOOP)
• In genetically susceptible children with recurrent infections can
lead to bronchial airway thickening, irregular aeration and
atelectasis.
• Development of ILD post-infectious changes causing interstitial
damage.

28. Hypersensitive pneumonitis
• Incidence rate : 0.4/100,000 in <16 years [Neil 2015]
• organic dust, bird antigens and moulds
• Mean age - 10 years
• Symptoms- dry cough, respiratory distress.
• IgG levels against specific antigen increased
• HRCT- GGOs in MUZ and nodular opacities.

29. diffuse ground glass shadowing with a
wide spread soft centrilobular nodular
pattern

30. Clinical features

31. History
• Variable presentation- age group and severity
• Symptom onset within 1 year
• Some cases are Asymptomatic
• Family history- Consanguinity (10%)
ILD in family (7%)

32. Presenting Symptoms
[vishal shaddi]
Infancy (n=66)
• Fast Breathing (91.5%)
• Chest indrawing (53%)
• Cough (47.0%)
• Unexplained fever
(14.6%)
• FTT (53.1%)
Childhood (n=37)
• Dry cough (66.7%)
• Fast breathing (55%)
• Dyspnoea on exer (72.2%)
• Dyspnoea at rest (45.9%)
• Unexplained fever (12.8%)
• Weight Loss (23.7%)

33. Signs
Infancy
• Tachypnoea & RD(91.5%)
• Inspiratory Crackles (51.8%)
• Clubbing (5.9%)
• Cyanosis (19.3%)
• Pallor (12%)
Childhood
• Tachypnoea & RD (66%)
• Inspiratory Crackles (66.7%)
• Clubbing (25.6%)
• Cyanosis (28.2%)
• Wheeze (21.6%)
• Pallor (22%)

34. Severity Of Illness score [Fan, Annick C]
Grades Symptoms Hypoxemia (SpO2
<90%) on exercise
Hypoxemia (SpO2
<90%) on Rest
Pulmonary
hypertension
1 No No No No
2 Yes No No No
3 Yes Yes No No
4 Yes Yes Yes No
5 Yes Yes Yes Yes

35. Investigations
Initial
• Oxygen saturation
• Blood investigations
• CXR/Echo
• PFT
• Immunodef. work up
• Autoantibodies
• 24 hour PH/GER scan
• Sweat chloride test
Level-II
• HRCT chest
• BAL
• Lung Biopsy

36. Pulmonary Function Tests
• Done in children above 6 years
• Useful as an add on investigation and guiding tool for
management.
• Findings :
Restrictive pattern
Reduced FEV1 and FVC and
Normal to increased FEV1/FVC
Reduced lung volumes.

37. HRCT vs CECT

38. HRCT
• More sensitive
• Thin Axial section (1.25mm)-
Fine anatomic details
• Contiguous
• Radiation exposure higher
CECT
• Less sensitive
• Thicker sections (5mm)
• IV contrast has lesser sensitive
• Non-contiguous
• Relatively lower

39. • Geographical hyperlucency- Small airway diseases, NEHI
• Septal thickening- Pulmonary hemosiderosis
• Ground glass opacities- Hypersensitive pneumonitis,
LIP
• Cysts/nodules- Langerhan cell histiocytosis
• Consolidation- Aspiration syndrome,
Bronchiolitis obliterans
HRCT chest patterns.

40. • Limited role
• lung parenchyma has poor water density- sections have poor
clarity
• RR is more in children - motion artefact.
MRI Chest

41. Bronchoalveolar Lavage
- Use of flexible bronchoscopy.
- Provides samples for cytological, microbial and molecular
analysis.
- Recommended mode where biopsy not feasible

42. Sl. No Condition BAL findings
1 Pulmonary alveolar proteinosis, PAS + milky fluid with foamy
macrophages
2 Pulmonary alveolar haemorrhage/ pul
hemosiderosis
RBC or Hemosiderin
3 Langerhans cell histiocytosis CD1a + cells
4 Lipid disorders Lipid laden molecules
5 Sarcoidosis CD4+ T cell
6 Pulmonary histiocytosis
Hypersensitivity pneumonitis
Drug-induced ILD
Collagen-vascular disease
CD8+ T cells
7 Pulmonary Eosinophilia,
Churg-Strauss syndrome
Eosinophilic infiltrates
8 Infections
Aspiration syndromes
Neutrophilic infiltrates
9. Suspected bacterial infections Positive cultures

43. - Gold standard for diagnosis of ILD.
- Open Lung biopsy
- Video assisted thoracoscopy (VATS) biopsy
- Biopsies of other tissues may be needed
Ex- Sarcoidosis
Lung Biopsy

44. Approach

45. Diagnostic Approach
Children (<2 years)
• Infant with severe rapidly
progressive disease with family
history HRCT is the initial
investigation (ATS 2013)
• Genetic testing adds on more
to the diagnosis (ABCA 3 and
SP-B)
• BAL
• Lung biopsy done early.
Children (>2 years)
• ANA and ANCA
• HRCT chest
• PFT (>6years)
• Specific antibodies for SLE,
sarcoidosis, JDM etc
• MRA for vasculitis syndromes
• Genetic testing
• BAL
• Lung biopsy

46. Clinical signs?
More common diseases excluded?
Heart diseases
Pulmonary infection
Immunodeficiency
Cystic fibrosis
Ciliary dyskinesia
chILD, not classifiable
HRCT+echocardiography
chILD, classifiable chILD unlikely
Definite diagnosis?
Genetic cause?
Consider lung biopsy
Bronchoscopy Definite diagnosis?
Definite diagnosis?
Further diagnostic work ups
Diagnosis, Treatment and Prognosis
No
No
No
Yes
Initial investigations
1
2
3
4
5
Unclassified

47. Treatment

48. General Management
• O2 suppl.
• Nutritional rehabilitation
• Immunisation (Influenza)
• Antibiotics for concurrent infection
• Prevention from exposure/drugs
pollutants/passive smoking

49. Pharmacological therapy
No specific guideline
a. Anti-inflammatory therapy-
- Can delay the progression of fibrosis
- Steroids are preferred
- IV/Oral - severity of chILD

50. ERS task force recommendation of steroid therapy for chILD
Reduce dose of MPS and space out cycles
Inj. Methylprednisolone (10-30mg/kg/dose) x 3 consecutive days at
monthly interval for a total of 3-6cycles.
After the initial disease control
Oral Prednisolone @1-2mg/kg alternate day
In children with significant advanced disease (Sore >/= 4) .

51. ERS task force recommendation of steroid therapy
Not so advanced disease- Daily Oral Prednisolone (1-2mg/kg/day)
Severe disease- IV Inj. MPS + oral prednisolone
Poor response to inhaled corticosteroid (limited studies)

52. chILD
Severe disease
Inj MPS 10-30mg/kg/day IV x
3days Monthly x 3-6cycles
+
Prednisolone P/O 1-
2mg/kg/day
Moderate
Inj MPS 10-30mg/kg/day IV
x 3days Monthly x 3-6cycles
Or
Prednisolone P/O 1-
2mg/kg/day
Mild
Prednisolone P/O
1-2mg/kg/day
Oral steroid - 2mg/kg/days x2 weeks f/b tapering dose @1mg/kg/day till 1year.
If child remained asymptomatic then discontinue.
[AIIMS pediatric Pulmonology protocol 2017]

53. ERS recommended drugs and doses for child
Sl.
No.
Drugs chILD ventilated or close
to ventilation
chILD neither ventilated nor
close to ventilation
Dose Response
duration
Dose Response
duration
1. Methylprednisolone 10-30 mg/kg IV 7days 10 mg/kg or IV 28 days
2. Prednisolone Oral 1 mg/kg used
in between pulses
of MPS
7 days Oral 2 mg/kg, as
alternative to MPS
pulses
28 days
3. Hydroxychloroquine 10 mg/kg 21-28days 10 mg/kg 3 Months
4. Azithromycin 10 mg/kg 3 days
per week
3 Months 10 mg/kg 3 days per
week
3 Months

54. Alternative drugs
1. Hydroxychloroquine- Dose 6-10mg/kg/dose
Reports have shown efficacy in steroid resistance cases.
[ Avital A et al, Balasubramnyan N et al, Dinwiddie R et al]
2. Azithromycin-
Effectivenes- anti-inflammatory and immunomodulatory action.
Benefits reported- ABCA 3, SpC deficiency, COPD and cystic fibrosis.
[Martinez F et al, Florescu D et al]

55. 3. Steroid sparing- cyclosporine, cyclophosphamide, azathioprine and
methotrexate can also be used.
[ Efficacy of these drugs in chILD not established yet]
4. Newer Drugs
- Th1 cytokine interferon-Y: act as antifibrotic agent
- Pirfenidone and Decorin : TGF- β antagonist
- Etanercept :
5. Specific therapies:
- Pulmonary alveolar proteinosis- whole lung lavage
- End stage lung diseases : Lung transplant

56. Acute exacerbation in children’s interstitial lung disease
[Mathias]
• A significant worsening of respiratory condition- necessitates a
change in regular management
• Criteria (⩾2 criteria)
- Increase in RR ⩾20% from baseline
- New or increased abnormalities on chest imaging
- Onset/increase of oxygen demand
- Need for an additional level of ventilatory support
- Decrease in spirometry (⩾10%) from baseline
- Reduced exercise tolerance (includes desaturation)

57. Prognosis
Good
• Presentation <2years
• NEHI, SpC deficiency
• Good response to
steroid
Poor
• Late childhood
• ABCA 3 and SpB
deficiency and
malformations.
• Poor response to
steroid