Pediatric Interstitial Lung Disease 1_26_11

3 month old girl Full term Mild laryngomalacia 2 days of mild cough Retractions on exam ROS: no weight gain in 1 month despite feeding well

PMHx: Full term Hospitalized at 2 weeks for laryngomalacia Reflux Failure to thrive Meds: Zantac Social history: Lives with parents, grandmother Family history: Indian. Parents are first cousins.

Admission exam: tachypneic Hospital course: Progressive respiratory symptoms ENT consulted. Bronch showed larygnomalacia but was otherwise normal Over several days progressed to respiratory failure requiring intubation Lung biopsy was eventually performed Need for diagnosis as patient was deteriorating rapidly

Severe, diffuse interstitial disease

Additional Info Bronchoscopy: BAL negative for infection, including Nocardia Labs: HIV negative Quantitative Immunoglobulins are normal T and B cell subsets are normal

Lipid within the alveolus

Location of pathology is key in childrens interstitial lung disease (CHILD) V Alveolar sac A L Focus on location of pathogology rather than the name Allows you predict findings on X ray Allows you predict the cause allows Basement membrane

Airway obstruction with neuroendocrine cells1, fibrosis2 or lymph tissue3 Neuroendocrine hyperplasia of infancy Bronchiolitis obliterans Follicular bronchitis Lipid in the Alveolus4 4. Surfactant protein deficiency V Fibroblast5 Lymphocytes6 Mesenchymal cells7 Alveolar sac A L 5. Usual interstitial pneumonitis 6. Lymphocytic initerstitial pneumonitis – think HIV 7. Cellular interstitial pneumonitis (pulmonary interstitial glycogenosis)

How is chILD characterized? Diseases with increased interstitial cells Usual interstitial pneumonia - Fibroblasts Cellular interstitial pneumonitis/Pulmonary interstitial glycogen - mesenchymal cells lymphoid interstitial pneumonitis LIP Disease of the airway Persistent tachypnea of infancy/neuroendocrine cell hyperplasia of infancy (NEHI) Follicular bronchitis Bronchocentric granulomatosis Bronchiolitis obiterans Lipid in the alveolus Pulmonary alveolar proteinosis Sufactant pathway mutations Chronic pneumonitis of infancy

Chronic Pneumonitis of Infancy Type II cell hyperplasia Foam cells in the alveolus Mutation in SpB- severe, SpC- chronic and ABCA3- variable Very poor prognosis Not much works but hydroxychloroquine is your best shot

SP-B ABCA3 SP-C AR AD Loss of function Dominant negative PAP, DIP, fibrosis PAP, CIP, PAP CPI, DIP, NSIP,fibrosis Absent lamellar bodies normal lamellar bodies Fatal NB Variable prognosis Chronic

Back to the patient: Started on 10 mg/kg/day of Hydroxycloroquine Dramatic improvement within 2 days Vent settings: (SIMV-PC) Max support: 46/16 x 60, FiO2 100% Weaned to 22/5 x 18, FiO2 30%.

Marked improvement Most consistent with ABCA3 deficiency Parents are related so an autosomal recessive mutation is more likely