Western States Pediatric Pulmonary Case Conference Cough, Hypoxia, and Down Syndrome

1. Western States Pediatric Pulmonary Case ConferenceCough, Hypoxia, and Down Syndrome Emily DeBoer, MD The Children’s Hospital University of Colorado September 22, 2010

2. Outline Case presentation: Cough, Hypoxia, and Down Syndrome Differential Diagnosis Multi-system complications of patients with Trisomy 21 Treatment and Monitoring

3. Chief Complaint 9 month old female with Down Syndrome referred to pulmonary clinic for initial evaluation because of cough and persistent oxygen requirement

4. History of Present Illness • Daily cough for months - day and night • No increased work of breathing • Snoring • Gags with jejunal feeds • Treated with Ranitidine • Severe oral aversion, tastes by mouth

5. Past medical/surgical history • Trisomy 21 • Born at 36 weeks in Colorado • Esophageal atresia without TEF • GT placment DOL 1 • Gastric pull-through at 4 months • On and off oxygen • Ventilated x 1 week after surgery • Discharged at 5 months on ¼ lpm O2 via nasal cannula

6. PMH/PSH PDA ligation at 5 months of age Recent echo revealed – “normal function, small left to right ASD, mild TR” Monthly esophageal dilations – tolerated well

7. Meds at visit Ranitidine Spironolactone/hydrochlorothiazide ¼ lpm oxygen No inhaled medicines No steroids

8. Review of Systems No fevers Adequate growth No hemoptysis No vomiting No steatorrhea Normal thyroid No hematuria Sitting with support

9. Family and Social History No asthma, allergies, or lung disease in the family Lives with mom, “adopted grandparents” in Denver Parents are from Senegal No known TB exposures No pets No smokers

10. Physical Exam • Vitals HR 136 | RR 28 | Ht 65 cm (43%) | Wt 7.5 kg (39%) • SaO2 88% RA | SaO2 95% ¼ lpm • General: happy baby, + drooling • HEENT: Down’s facies, small nares, +rhinorrhea • Chest: Easy work of breathing, clear to auscultation, prolonged expiratory phase • CVS: RRR, normal S1 and S2, no murmur • Abd: Soft, non-tender, no hepatosplenomegaly • Ext: No clubbing • Neuro: Decreased truncal tone

11. Chest Xray at 8 months of age

12. What should we do?

13. What should we do? Differential Diagnosis – cough, hypoxia Reflux / aspiration Pulmonary edema Airway anomaly / poor airway clearance Asthma Interstitial lung disease Pneumonia/infection

14. What should we do? Differential Diagnosis – cough, hypoxia Reflux / aspiration Pulmonary edema Airway anomaly / poor airway clearance Asthma Interstitial lung disease Pneumonia/infection Because of her Down Syndrome, she is at risk for aspiration, heart disease, tracheal anomalies, obstructive sleep apnea, pulmonary hypertension

16. Bronchoscopy COLOR COLORLESS CHARACTER HAZY NUCLEATED CELLS 910 RBC 1705 RBC MORPH NORMAL SEGS 55 LYMPHS 18 MONOCYTES 7 MACROPHAGES 17 Erythematous mucosa Copious clear secretions Mild-mod malacia of trachea and both mainstem bronchi LIPID INDEX = 0. IRON INDEX = 270. Bacterial and viral cultures: negative

18. What should we do now? Cause of increased iron index? Treatment?

20. Disorders with pulmonary capillaritis • Disorders without pulmonary capillaritis • Noncardiovascular • Cardiovascular • Chronic heart failure • Pulmary Hypertension • Pulmonary veno-occlusive disease

21. Follow-up via phone • New symptoms • Rhinorrhea • Increased cough, respiratory rate • Sleeping more • Requiring ½ - 1 lpm O2 • Intervention • 5 days of oral steroids

22. Follow-up Outpatient echocardiogram scheduled Improved for 2 weeks, then symptoms returned Treated with 5 more days oral steroids by her PCP Symptoms do not resolve – present to ED Further history – taking liquids by mouth for 6 weeks as instructed by therapy

23. Physical Exam in ED Vitals HR 180 | RR 62 | SaO2 94% 3 lpm General: Infant in moderate respiratory distress HEENT: Down’s facies, +rhinorrhea Chest: Subcostal retractions, tachypneic, coarse symmetric breath sounds CVS: Tachycardic, prominent S2, 2/6 systolic flow murmur at LLSB Abd: Soft, non-tender, Liver down 3 cm

24. 8 months of age 12 months of age in ED

25. What should we do?

26. What should we do? Differential Diagnosis – cough, hypoxemia, prominent S2, hepatomegaly Pulmonary hypertension Aspiration Heart failure Infection

27. Laboratory • CBC • 11.6 WBC 81% Segs, 8% Lymphs, 10% Monos • Hb 16.3 g/dL / Hct 51.4 % • Platelets 221 • CBG • pH 7.43 • CO2 34 mm Hg

28. Echocardiogram • Small secundum ASD with bidirectional flow. • Moderate right heart enlargement and moderate septal flattening. • Normal left ventricular size and systolic function. Low normal RV systolic function. • Systemic pulmonary hypertension (on 3 lpm NC O2). • TV jet 4.48 m/second • RV-RA grad 80 mm Hg (SBP 90/69)

29. Pulmonary Hypertension Causes?

30. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

31. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

32. Cardiac catheterization 30% FiO2 Qp/Qs = 1.25:1; Rp/Rs = 0.46 21% FiO2 Qp/Qs = 1.25:1; Rp/Rs = 0.64 100% FiO2 with 40 ppm iNO Qp/Qs = 1.14:1; Rp/Rs = 0.47

33. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

34. Chest CT

35. Chest CT - prone

36. Esophagram • Thread-like appearance of distal esophagus • Fundus of stomach superior to the diaphragm • No normal peristalsis – movement of feeds only with gravity • Swallow study • Deep laryngeal penetration with thin liquids. • No aspiration with pureeds.

37. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

38. Polysomnogram Obstructive Sleep Apnea does not explain PAH Mild sleep-disordered breathing Apnea-hypopnea index of 3 events/hour SpO2 in low 80s in RA SpO2 in mid 90s on ¼ lpm NC (≥92% for 99% of TST)

39. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

40. Further laboratories Protein C and S Prothrombin Antithrombin III Lupus Anticoagulant Factor V Leiden Homocysteine Beta 2 GP1 (antiphospholipid) antibodies Cardiolipin IgG and IgM

41. Pulmonary Hypertension • Causes of secondary PAH • Cardiac/Vascular anomaly • Chronic lung disease • Trisomy 21 • Aspiration / reflux • Overcirculation from PDA (repaired at 5 months) • Obstructive sleep apnea • Thromboembolic disease • Collagen vascular disease • Thyroid disease • HIV

42. Further laboratories ANA, ESR, CRP TSH and free T4 HIV

43. Treatment of PAH – Vasodilation and Diuretics Continuous oxygen Oral Sildenafil – started at 0.5 mg/kg/dose and titrated to 2 mg/kg/dose q6h Furosemide 1 mg/kg/dose TID

44. Thromboembolic disease can contribute to PAH Elevated Beta 2 GP1 antibodies and low antithrombin III Discussed aspirin or coumadin therapy

45. Patient’s Echo Changes with Therapy

47. Conclusions • Cause of Pulmonary Hypertension • Chronic lung disease • Primary Aspiration • Trisomy 21 • Overcirculation prior to PDA closure • ?Thromboembolic disease • Cause of increased iron index • Pulmonary Hypertension

48. Conclusions • Cause of her hypoxia • Pulmonary hypertension • Chronic lung disease • Cause of her cough • Chronic lung disease • Airway protection (aspiration/reflux) • Airway Malacia

49. Discussion • Open lung biopsy? • Repeat bronchoscopy and BAL?

50. Outline Case presentation: Cough, Hypoxia, and Down Syndrome Differential Diagnosis of Cough and Hypoxia Multi-system complications of patients with Trisomy 21 Evaluation for Elevated Iron Index and Pulmonary Hypertension Treatment and Monitoring of PAH