Childhood Interstitial Lung Disease (ChILD)
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1 Childhood Interstitial Lung Disease (ChILD) What the Pulmonologist Needs from the Radiologist? Winnie Chu Department of Imaging & Interventional Radiology Prince of Wales Hospital
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3 Acknowledgement Edward Y. Lee, MD, MPH Chief, Division of Thoracic Imaging Associate Professor of Radiology President, Medical Staff Organization, BCH President, International Society of Pediatric Thoracic Imaging Departments of Radiology and Medicine, Pulmonary Division Boston Children's Hospital and Harvard Medical School 300 Longwood Ave. Boston, MA 02115
4 INTRODUCTION: ChILD In the past Diagnostic challenge & confusion Paucity of information Pathogenesis Natural history Imaging findings Histopathologic features Use of adult classification system
5 INTRODUCTION: ChILD Recently True new classification system of pediatric ILDs Emphasis Combined correlations: Clinician Radiologist Pathologist Acknowledgement of the unique nature of ILD in infants Langston C, Dishop MK, Diffuse Lung Disease in Infancy: A proposed Classification, Pediatr Dev Pathol, 2009
6 Diagnosis of ChILD when 3 out of 4 criteria are met: Respiratory symptoms Cough, Increased work of breathing Exercise intolerance Respiratory signs Tachypnoea at rest Digital clubbing, crackles Failure to thrive/ respiratory failure Hypoxaemia Diffuse parenchymal abnormalities on imaging
7 Diagnosis of ChILD when 3 out of 4 criteria are met: Respiratory symptoms Cough, Increased work of breathing Exercise intolerance Respiratory signs Tachypnoea at rest Digital clubbing, crackles Failure to thrive/ respiratory failure Hypoxaemia Diffuse parenchymal abnormalities on imaging Diffuse Lung Disease DLD Common entities (e.g. CF, infection); other non-child forms of DLD Asymptomatic child diagnosis Specific child Diagnosis child Syndrome Non-ILD Masqueraders
8 Classification of child by child Research Network (childrn). 2 broad types of category nomenclature (I) More prevalent in infancy Disorders most often occurring in infancy, but that can occur in older children and even adults (2) Not specific to infancy Conditions that develop largely in older children and adults, but can manifest in infants Deutsch GH, Young LR, Deterding RR, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med 2007;176:1120 8
9 Thacker et al. Radiol Clin N Am 54 (2016) child Syndrome (respiratory signs, respiratory symptoms, hypoxemia) Rapid deterioration or progression Rule out/treat specific diseases which mimic child (appropriate cultures, chest radiograph, echocardiography) Specific for NEHI Computed Tomography Genetic Testing No specific diagnosis suggested Suggestive of Surfactant Mutation Specific Diagnosis established Negative Lung Biopsy with Electron Microscopy Diagnostic algorithm for infants and neonates with suspected ILD
10 Diffuse Developmental disorders Disorders masquerading as ILD Disorders of the normal host (immune intact) Lung growth abnormalities Surfactant dysfunction disorders Specific conditions Of undefined etiology Diffuse Lung Disease in Childhood Disorders related to systemic disease processes Disorders of the abnormal host
11 Diffuse Developmental disorders Lung growth abnormalities Surfactant dysfunction disorders Specific conditions Of undefined etiology
12 Diffuse Developmental disorders Acinar dysplasia Lung growth abnormalities Surfactant dysfunction disorders Congenital alveolar dysplasia CAD Specific conditions Of undefined etiology Alveolar capillary dysplasia with misalignment of pulmonary veins ACD MPV
13 Diffuse Developmental disorders Acinar dysplasia Growth arrest during pseudoglandular stage of lung development at 6 16 GA Key Clinical Features Usually full term neonates Progressive respiratory distress & cyanosis within 48 hours of birth Most cases are associated with extra-pulmonary anomalies Hypoplastic left heart syndrome Urinary track malformations Intestinal malrotation & atresia Congenital alveolar dysplasia CAD Alveolar capillary dysplasia with misalignment of pulmonary veins ACD MPV Growth arrest during canalicular stage of lung development at GA Abnormal lobular changes Underdevelopment Alveolar enlargement Reduced capillary density Vascular changes Prominent medial hyperplasia of small pulmonary arteries, Malposition of pulmonary veins Prominent regional or diffuse lymphangiectasis
14 Diffuse Developmental disorders Acinar dysplasia Imaging Features Various findings on initial CXRs Progressively hazy bilateral pulmonary opacification on FU CXRs Air-leak in 50% likely due to barotrauma Pneumothorax Pneumomediastinum Congenital alveolar dysplasia CAD Alveolar capillary dysplasia with misalignment of pulmonary veins ACD MPV Lee et al. Pediatr Radiol :3013
15 Diffuse Developmental disorders Teaching Points Non specific imaging features But diagnosis should be suspected in setting of: Full term neonate Severely respiratory distress resembling persistent PHTN Lack of usual predisposing features Meconium aspiration, asphyxia, prematurity, sepsis Poor prognosis with high mortality(~100%)
16 Diffuse Developmental disorders Acinar dysplasia Congenital alveolar dysplasia CAD Pneumomediastinum Role of Imaging Limited Usually CXR Barotrauma Alveolar capillary dysplasia with misalignment of pulmonary veins ACD MPV Pneumothorax Lee et al. Pediatr Radiol :3013
17 Pre-Natal Secondary pulmonary hypoplasia of varying degree Diffuse Developmental disorders Lung growth abnormalities Surfactant dysfunction disorders Post-Natal Associated chromosomal abnormalities Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) Term infants with chronic lung disease Trisomy 21 Specific conditions Of undefined etiology Associated with congenital heart disease in chromosomally normal infants Filamin A Mutation
18 Pre-Natal Secondary pulmonary hypoplasia of varying degree Lung growth abnormalities Post-Natal Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) Key Clinical Features Most common ILD in infant Both preterm & term infant Variable presentation -underlying causes of growth abnormalities Moderate mortality ( ~30%) Associated chromosomal abnormalities Associated with congenital heart disease in chromosomally normal infants Term infants with chronic lung disease Trisomy 21 Filamin A Mutation
19 Pre-Natal Secondary pulmonary hypoplasia of varying degree Oligohydramnios In utero restriction of fetal thoracic cavity Lung growth abnormalities Imaging Features: Small hemithorax, lung hypoplasia Lee et al. Pediatr Radiol :3013
20 Lung growth abnormalities Post-Natal Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) Term infants with chronic lung disease
21 Lung growth abnormalities Post-Natal Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) BPD - Most common cause - Lung injury & repair Positive pressure mechanical ventilation Oxygen toxicity Imaging Features: Coarse reticular opacities Cystic lucencies Disordered lung aeration Alveolar septal fibrosis Hyperinflated lung The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
22 Lung growth abnormalities Post-Natal Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) BPD - Most common cause - Lung injury & repair Positive pressure mechanical ventilation Oxygen toxicity Imaging Features: Coarse reticular opacities Cystic lucencies Disordered lung aeration Alveolar septal fibrosis Hyperinflated lung Department of Imaging and Lee Interventional et al. Pediatr Radiology :3013
23 Lung growth abnormalities Post-Natal Prematurity-related chronic lung disease (Bronchopulmonary dysplasia [BPD]) BPD - Most common cause - Lung injury & repair Positive pressure mechanical ventilation Oxygen toxicity Pathological Features Defective alveolarization Deficient alveolar septation Airspace enlargement Lobular simplification Normal control The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
24 Lung growth abnormalities Trisomy 21 Associated chromosomal abnormalities Filamin A Mutation
25 Trisomy 21 Associated chromosomal abnormalities Lung growth abnormalities Imaging Features: Subpleural cysts ( ~36%) along lung periphery, lung fissures, bronchovascular bundles The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
26 Associated chromosomal abnormalities Filamin A mutation (FLNA) X-linked gene Lung growth abnormalities Imaging Features: Severe multilobar hyperinflation Hyperlucent lung Peripheral pulmonary vascular attenuation Resembles emphysema/ congenital lobar overinflation Lee et al. Pediatr Radiol :3013
27 Trisomy 21 Associated chromosomal abnormalities Filamin A mutation (FLNA) X-linked gene Lung growth abnormalities Pathological Features: Lobular simplification Alveolar enlargement Normal control The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
28 SPFTB mutations Diffuse Developmental disorders SPFC mutations Lung growth abnormalities ABCA3 mutations Surfactant dysfunction disorders Specific conditions Of undefined etiology Congenital granulocytemacrophage colonystimulating factor (GMCSF) receptor deficiency Lysinuric protein intolerance
29 SPFTB mutations SPFC mutations ABCA3 mutations Pulmonary alveolar proteinosis and variant histologies Chronic pneumonitis of infancy is the dominant histological pattern PA is dominant histological pattern Surfactant dysfunction disorders Congenital granulocytemacrophage colonystimulating factor (GMCSF) receptor deficiency PAP histological pattern Lysinuric protein intolerance PAP histological pattern
30 SPFTB mutations Imaging Features: Diffuse lung disease resembling RDS of surfactant-deficient premature infants CXR diffuse hazy or granular opacity CT GGO with variable interlobular septal thickening Surfactant dysfunction disorders Ground Glass The Opacification Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
31 SPFTB mutations Pathological Features: Prominent diffuse alveolar epithelial hyperplasia Variable proteinosis material Foamy macrophages Lamellar body abnormalities on EM Surfactant dysfunction disorders Normal control The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
32 SPFC mutations ABCA3 mutations Surfactant dysfunction disorders Imaging Features: Infants Diffuse lung disease resembling RDS of surfactant-deficient premature infants CXR diffuse hazy or granular opacity CT GGO with variable interlobular septal thickening The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
33 SPFC mutations ABCA3 mutations Imaging Features: Older children CXR Coarse interstitial thickening and cystic changes Surfactant dysfunction disorders 5 Year Old Girl with Progressively Worsening Hypoxemia The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
34 SPFC mutations ABCA3 mutations Surfactant dysfunction disorders Imaging Features: Older children CT Diffuse or patchy GGO Fine or coarse septal thickening with architectural distortion Pulmonary cysts increase in number & size over time The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
35 Teaching Points Surfactant dysfunction disorders Genetic testing is required for surfactant gene mutations Routine imaging surveillance is not warranted following diagnosis Changes in the imaging findings do not correlate with lung function or outcome
36 Diffuse Developmental disorders PIG Pulmonary Interstitial Glycogenosis Lung growth abnormalities Surfactant dysfunction disorders NEHI NeuroEndocrine cell Hyperplasia of Infancy Specific conditions Of undefined etiology
37 PIG Pulmonary Interstitial Glycogenosis Previously known as - Neonatal pulmonary interstitial glycogen accumulation disorder - Infantile cellular interstitial pneumonitis Specific conditions Of undefined etiology Clinical Features Preterm or full term infants Present early neonatal period (unusual > 6 months old) Progressive hypoxemia and tachypnea Tx- Steroids Good prognosis
38 PIG Pulmonary Interstitial Glycogenosis Imaging Features: CXR progressive hyperinflation, interstitial thickening CT Hyperinflation, interlobular septal thickening, +/- centrilobular nodules, + cysts (if associated with growth disorders) Specific conditions Of undefined etiology The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
39 HRCT Ground-glass opacification Interstitial thickening Cyst-like hyperlucent disordered pulmonary lobules Courtesy Dr Paul Guillerman, USA Courtesy Dr Janice Ip Queen Mary Hospital, Hong Kong
40 PIG Pulmonary Interstitial Glycogenosis Pathological Features: Expansion of the interstitium by glycogen laden primitive mesenchymal cells Most reliable method EM for deposits of monoparticulate glycogen within mesenchymal cells Specific conditions Of undefined etiology The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
41 NEHI NeuroEndocrine cell Hyperplasia of Infancy Previously known as Persistent Tachypnea of Infancy Specific conditions Of undefined etiology Clinical Features Full term neonates Present < 2 years of age Tachypnea, hypoxia, and retractions Usually has a prolonged, slowly improving course Unresponsive to steroids Good prognosis Most patients require supplemental oxygen for many years
42 NEHI NeuroEndocrine cell Hyperplasia of Infancy Imaging Features CXR Hyperinflation with variable increased perihilar opacity Specific conditions Of undefined etiology The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
43 NEHI NeuroEndocrine cell Hyperplasia of Infancy Brody AS, et al. NEHI: Dx with HRCT, AJR 2010 Imaging Features CT Air trapping in a mosaic attenuation pattern (at least 4 lobes) with geographic GGO in the RML and Lingular Segment Sensitivity 78 83% Specificity 100% Hyperinflation may persist into adolescence Specific conditions Of undefined etiology The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
44 NEHI NeuroEndocrine cell Hyperplasia of Infancy Brody AS, et al. NEHI: Dx with HRCT, AJR 2010 Pathological Features Essentially normal lung histology Occasionally mild peri-airway lymphocytic inflammation Most reliable method Bombesin for immunopositive cells in airways and neuroepithelial bodies Specific conditions Of undefined etiology The Chinese University of Hong Courtesy Kong Dr Edward Lee, Department Boston of Imaging Children and Hospital Interventional & Harvard Radiology Medical School, USA
45 Teaching Points Learn new classification system for ILDs in infants Diffuse developmental disorders Growth abnormalities Surfactant Dysfunction Disorders & related abnormalities Specific conditions of unknown / poorly understood etiology Understand that imaging evaluation plays a pivotal role Recognize characteristic clinical presentation and imaging appearance of ILDs in infants
46 Thacker et al. Radiol Clin N Am 54 (2016) child Syndrome (respiratory signs, respiratory symptoms, hypoxemia) Rapid deterioration or progression Rule out/treat specific diseases which mimic child (appropriate cultures, chest radiograph, echocardiography) Specific for NEHI Computed Tomography Genetic Testing No specific diagnosis suggested Suggestive of Surfactant Mutation Specific Diagnosis established Negative Lung Biopsy with Electron Microscopy Diagnostic algorithm for infants and neonates with suspected ILD
47 Multidisciplinary Approach Rule out/ treat specific diseases which mimic child (Cardiac disease, Immunodeficiency, Chronic aspiration, Cystic fibrosis, Primary ciliary dyskinesia) Computed Tomography Specific for NEHI Suggestive of Surfactant Mutation Genetic Testing Electron Microscopy Bronchoscopy/ Bronchoalveolar Lavage Determine optimal area for lung biopsy if no specific diagnosis suggested CT-guided Lung Biopsy
48 Multidisciplinary Approach
49 Technical Aspect Thin Collimation HRCT 1-2mm thickness 5-7mm interval Total images 8-12 Volumetric MDCT with retrospective HR thin section reconstruction Recent Comparable image quality Bastos MD, Lee EY, et al. Motion artifact Department on HRCT in of Pediatric Imaging Patients: and Interventional Radiology Comparison of Volumetric and Axial CT Methods, AJR 2010
50 Technical Aspect Thin Collimation HRCT Non-contiguous technique ~0.2mSv (10 CXR) Volumetric MDCT with retrospective HR thin section reconstruction Contiguous technique: ~1 msv (50 CXR) Possibility of missing pulmonary abnormalities within the gaps between axial slices Underestimation of disease extent or false-negative exams + Intravenous contrast Pulmonary infection Associated vascular anomalies
51 THANK YOU
52 Typical Medical Radiation Doses: 5 year-old (msv*) * This is effective dose; organ doses (in mgy) will differ CXR Equivalents 3-view ankle view chest.02 Tc-99m radionuclide gastric emptying.06 Tc-99m radionuclide cystogram.18 Tc-99m radionuclide bone scan up to 6.2 FDG PET 15.3 Fluoroscopic cystogram <.33 Chest CT up to 3 Abdomen CT up to 5 1/
53 Risk comparison 1 CT (10 msv) equals: 140 cigarettes (lung cancer) 200 days living in NYC (air pollution) 4,000 miles drive in car (accident) 250,000 miles jet travel (accident) 300 coast to coast flights (cosmic radiation) 10 hrs. canoeing 4,000 tablespoons of peanut butter Adapted from DEO Radiation Worker Training, based on work by Cohen BL
54 One PET CT in a 5 yr old 23.3 msv 1165 chest x rays, or years of background radiation
55 pulmonary arteriole Normal secondary lobule thickened interlobular septa pulmonary veins thickened intralobular septa thickened bronchovascular core strructure traction bronchiectasis consolidation smooth nodular fissural thickening thin-walled cysts honeycombing lobular ground glass opacity centriloular Figure 17.3 HRCT Findings in Interstitial Lung Disease 1 - Interlobular (Septal) Lines 2 - Intralobular Lines 3 - Thickened Fissures 4 - Thickened Bronchovascular Structures 5 - Centrilobular (Lobular Core) Abnormalities 6 - Subpleural Lines 7 - Parenchymal Bands 8 - Honeycombing 9 - Thin-walled Cysts 10 - Irregularity of Lung Interfaces 11 - Ground-Glass or Hazy Increased Density 12 - Architectural Distortion and Traction Bronchiectasis 13 - Conglomerate Masses 14 - Consolidation Dot lik tree-in-bud Ildefined
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