Childhood Interstitial lung Disease ch ILD Prof Malak

Childhood Interstitial lung Disease (ch. ILD) Prof. Malak Shaheen (Ph. D Pediatrics, MSc Critical Medicine)

What is ch. ILD Syndrom? “Pneumonitis” Alveoli & perialveolar tissues Impaired gas exchange

What are common features of ch. ILD? Persistent 3 of the following 4 ≥ 1 month: 1 - Respiratory symptoms 2 - Impaired gas exchange 3 - Diffuse/Patchy radiological chest abnormality 4 - Adventitious sounds

Fan Staging of ch. ILD Asymptomatic Symptomatic with normal Sa. O 2 Symptomatic with nocturnal or exercise-induced ↓Sa. O 2 4. ↓Sa. O 2 at rest 5. Pulmonary hypertension 1. 2. 3.

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

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

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)

Does ch. ILD differ from ad. ILD? 1. 2. 3. 4. 5. Immune system responces, cytokines and growth factors Histologic classification Specific types Rarer and less stereotyped More difficult to manage Children Adult

Is there one test to diagnose ch. ILD? 1. 2. 3. 4. First round investigations: Imaging Lung functions Sa. O 2 Blood tests (CBC, ESR, Immune, Serology, PCR, RAST, ACE, HIV) 5. 6. 7. 8. 9. 10. C&S /PCR Sweat chloride test. p. H study/Contrast swallow ECG and ECHO Ciliary Brush Biopsy Urine for CMV PCR

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

Is there one test to diagnose ch. ILD? 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 2. DNA for mutations in SPB, SPC and ABCA 3

Histologic Classification of ch. ILD DIP Desquamative interstitial pneumonitis CIP Chronic pneumonitisof infancy NSIP Non-specific interstitial pneumonitis FB/LIP OP Follicular bronchiolitis /lymphoid Interstitial Pneumonia Organizing pneumonia (old BOOP) PIG Pulmonary interstitial glycogenosis NEHI Neuroendocrine cell hyperplasia of infancy * UIP: Usual interstitial pneuminitis (rare for children)

Pulmonary Interstitial Glycogenosis

Neuroendocrine cell hyperplasia of infancy (NEHI)

DIP CIP Nonspecific interstitial pneumonitis

Follicular bronchiolitis BOOP

Surfactant Metabolism Dysfunction • Surfactant is a complex mixture of phospholipids and proteins (SP-A, -B, -C and -D)& ABCA 3. • ABCA 3 an ATP-binding transporter Of lipids. (ch. ILD) due to ABCA 3 gene mutations

ILD IN CHILDREN Building a diagnostic algorythm BAL Biopsy + Chest Radiogr. + Laboratory Tests BAL PFTs Phys. Exam. PFTs HRCT History HRCT Phys. Exam. Biopsy ? Definitive Diagnosis Chest Radiogr History

ILD IN CHILDREN Treatment ILD with specific cause: • Treatment against underlying disease • Avoidance of triggers ILD of unknown etiology: • Anti-inflammatory medication • Anti-fibrogenic medication • 02 • Supportive care

ILD IN CHILDREN Treatment Anti-inflammatory medication: • Pulsed intravenous methylprednisolone (10 mg/kg/day for 3 days each month) • Oral prednisolone (1 -2 mg/kg/day – taper with response to alternate day regimen)

ILD IN CHILDREN Treatment Anti-fibrogenic medication: • Hydroxychloroquine (6 -10 mg/kg/day in 2 divided doses)

ILD IN CHILDREN Treatment Other (experimental) treatment strategies: • Azathioprine • Cyclophosphamide • Ciclosporin • Methotrexate • Lung/heart-lung transplantation

ILD IN CHILDREN Treatment Monitoring of therapy: • • • Resting respiratory rate Exercise tolerance Oxygen saturation Growth/weight assessment PFTs • Chest radiograph • HRCT

ILD IN CHILDREN Outcome Mortality: • All types of chronic ILD: 11% • ILD of unknown etiology: 43% Morbidity: • Poor quality of life: >50% Redding and Fan In Taussig/Landau 1999

ILD IN CHILDREN Directions Areas for future research/collaboration: • Improving histologic classification of paediatric ILD • Searching for alternative concepts for classification • Exploring the genetic background of ILD • Exploring mechanisms of fibrogenesis • Studying new therapeutic concepts in paediatric patients

Download resources Prof Malak Shaheen Lectures

ch. ILD review article Vol 5 (1) 2011 – pp 55 -79

Pediatric Respiratory Medicine Handbook 2013

Further Readings …. https: //drive. google. com/drive/folders/0 B 11 rw. R 2 Kbmu. SEhhc. Et 5 Rjl. ZYW 8? usp=sharing

Further Readings …. www. childfoundation. info/ch. ILD

Good luck!