1. بسم الله الرحمن الرحيم ” بلي إن تصبروا و تتقوا ويأتوكم من فورهم هذا يمددكم ربكم بخمسة الآف من الملآكة مسومين * وما جعله الله إلا بشري لكم و لتطمئن قلوبكم به وما النصر إلا من عند الله العزيز الحكيم“ صدق الله العظيم آل عمران الأيه 125& 126

2. Childhood Interstitial lung Disease (chILD) Dr. Malak Shaheen (PhD Pediatrics, MSc Critical Medicine) Journey to solve the Mystery

3. What is chILD Syndrom? Alveoli & perialveolar tissues Impaired gas exchange “Pneumonitis”

4. What are common features of chILD? Persistent 3 of the following 4 ≥1 month: 1- Respiratory symptoms (cough, distress, exercise intolerence) 2- Evidence of impaired gas exchange (hypoxia &/or hypercapnia) 3- Diffuse/Patchy radiological chest abnormality (CXR or CTscan) 4- Adventitious sounds on auscultation (crepitation/wheeze)

5. Fan Staging of chILD 1. Asymptomatic 2. Symptomatic with normal oxyhemoglobin saturation 3. Symptomatic with nocturnal or exercise-induced desaturation 4. Desaturation at rest 5. Pulmonary hypertension

6. Causes of chILD Infectious Aspiration (GORD) Environmental (hypersensitivity pneumonitis) Drug-induced Neoplastic diseases (&LCH) Lymphoproliferative disorders (including HIV) Metabolic disorders Surfactant disorders Neurocutaneous syndromes Idiopathic pulm hemosidrosis

7. Causes of chILD cont…. Collagen vascular disease Pulmonary vasculitis syndromes Radiation-induced Amyloidosis Graft-versus-host disease ARDS (recovering phase) Hypereosinophilic syndromes Pulmonary veno- occlusive disease Sarcoidosis With chronic liver, kidney, bowel diseases

8. DD to rule out include: Cystic fibrosis Asthma Cardiac (heart) disease Primary ciliary dyskinesia Scoliosis and chest wall abnormalities Neuro-muscular disease/Neurocut dis Immune deficiency TB Developmental abnormalities (BPD - Alveolar capillary dysplasia- Pulm hypoplasia)

9. Does chILD differ from adILD? 1. Differences in the immune system responces, cytokine and growth factors 2. Histologic classification differs significantly 3. Specific types presented at children not adults 4. Rarer and less stereotyped than adult ILD 5. More difficult to treat than adults. ChildrenAdult

10. Is there one test to diagnose chILD? First round investigations: 1. Imaging (HRCT + ventilation control) 2. Lung functions (DLCO) 3. Oxygen saturation (rest /exercise) 4. Blood tests (CBC, ESR, Immune, Serology and PCR, RAST, ACE, HIV) 5. Resp secretions cultures/PCR 6. Sweat chloride test. 7. pH study/Contrast swallow 8. ECG and ECHO 9. Ciliary Brush Biopsy 10. Urine for CMV PCR

12. Is there one test to diagnose chILD? Second round investigations: 1. Bronchoscopy and BAL for cytology (LCH, iron laden macrophages, PAP) and cultures 2. Prone Oesophagram for H type fistula 3. Videofluroscopy for aspiration evidence 4. Cardiac Cath 5. Detailed lymphocyte function tests 6. TB –Elispot test

13. Is there one test to diagnose chILD? Third round investigations: 1. Lung biopsy (Transbronchial, percutaneous, thoracoscopic, open lung) CT guided from affected patch and unaffected patch.  Special stains (eg. Bompesin or PAS)  Immunoblotting for sufactant proteins at lung biopsy  Electron microscopy study of biopsy  DNA for mutations in SPB, SPC and ABCA3

14. Desquamative interstitial pneumonitisDIP Chronic pneumonitisof infancyCIP Non-specific interstitial pneumonitisNSIP Follicular bronchiolitis /lymphoid Interstitial Pneumonia FB/LIP Organizing pneumonia (old BOOP)OP Pulmonary interstitial glycogenosisPIG Neuroendocrine cell hyperplasia of infancyNEHI * UIP: Usual interstitial pneuminitis (rare for children) Histologic Classification of chILD

15. Pulmonary Interstitial Glycogenosis

17. DIP CIP Nonspecific interstitial pneumonitis

18. Follicular bronchiolitis BOOP

19. Surfactant Metabolism Dysfunction Surfactant is a complex mixture of phospholipids and proteins (SP-A, -B, -C and -D)& ABCA3. ABCA3 an ATP-binding transporter Of lipids. (chILD) due to ABCA3 gene mutations

21. Further Readings …. First edition - 2008

22. Further Readings …. www.childfoundation.info/chILD

23. Keep the hat on! Thank You