Pulmonary Complications of Sickle Cell Disease(SCD) Olufolake Adisa, MD Assistant Professor of Pediatrics
Pulmonary Complications of Sickle Cell Disease(SCD) Olufolake Adisa, MD Assistant Professor of Pediatrics Respiratory Care Update 10/18/2014 Objectives • Brief introduction of Sickle Cell Disease • Review the literature on pulmonary complications of SCD with particular emphasis on pathophysiology • Introduce the proposed mechanisms underlying Asthma in SCD • Introduce the proposed mechanisms underlying acute chest syndrome • Review the current classification of ACS, merits and demerits and the diagnostic dilemma • Brief review of management strategies centered on proposed mechanisms Aflac Cancer and Blood Disorders Center | Emory University 2 Sickle Cell Disease • • • • • SCD is a chronic hemolytic and inflammatory disease 1:400 African Americans 1:36 000 Hispanic-American births 90-100,000 patients in US Median life expectancy in 2005 – 42 years in females, 38 years in males • Improved pediatric survival – – – – Newborn screening PCN prophylaxis Pneumococcal and HIB vaccine Parental and provider education http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhoIsAtRisk.html Aflac Cancer and Blood Disorders Center | Emory University 3 Sickle Cell Disease Pathophysiology 4 Sickle Cell Disease • Caused by a point mutation in the β-globin chain of hemoglobin, causing the amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position • The association of two wild-type α-globin subunits with two mutant β-globin subunits forms hemoglobin S (HbS). • HbS is less soluble than normal hemoglobin (HbA) when deoxygenated • Insolubility results in polymerization and aggregation of HbS which distorts red blood cells into a sickle shape and decreases their elasticity Aflac Cancer and Blood Disorders Center | Emory University 5 6 Sickle Cell Disease • Rigid, dense and sickled cells become entrapped in the microcirculation (vaso-occlusion) producing ischemia and reperfusion injury, propagating inflammatory, thrombotic and oxidant stress • Intracellular polymerization ultimately damages the membrane and depletes erythrocyte energy stores, leading to chronic and episodic extravascular and intravascular hemolytic anemia • These disease mechanisms could ultimately produce a proliferative vasculopathy affecting the brain, kidney and lung vasculature Aflac Cancer and Blood Disorders Center | Emory University 7 Complications of SCD • Phenotypic manifestations of SCD vary broadly • Vaso-Occlusion – – – – Vaso-occlusive crisis (VOC) or Events (VOE) Strokes and cerebral vasculopathy Acute Chest Syndrome Avascular necrosis • Hemolysis – – – – Priapism Splenic sequestration crisis Leg Ulcers Pulmonary Hypertension Aflac Cancer and Blood Disorders Center | Emory University 8 Pulmonary Complications of SCD • Acute – Painful (VOC) Crisis with Atelectasis – RAD/Asthma Exacerbations – Acute Chest Syndrome • Chronic – – – – Asthma Pulmonary Hypertension Cor Pulmonale Sickle cell chronic lung disease (± fibrosis) Aflac Cancer and Blood Disorders Center | Emory University 9 Painful VOE with Atelectasis Painful involvement of ribs, sternum, spine or abdomen Splinting with reduced ventilation Segmental or lobar atelectasis Increased V/Q mismatch, alveolar hypoxia and intrapulmonary shunting • ? Prelude to Acute Chest Syndrome (ACS) • Aggressive and effective pain management • Inhaled bronchodilator therapy • • • • Adapted from Leroy Graham, MD Aflac Cancer and Blood Disorders Center | Emory University 10 Asthma and Sickle Cell Disease • A physician-diagnosis of asthma is associated with increased rates of pain, ACS episodes and death in patients with SCD • Lack of objective criteria for asthma diagnosis in SCD • Significant overlap in clinical manifestations between an asthma exacerbation and an ACS episode • Patients with SCD have symptoms of wheezing, obstructive lung disease and airway hyper-responsiveness • ? Atopic Asthma or acute pulmonary manifestation of SCD Field, DeBaun, Hematology 2009; 45-53 Sylvester et al, Pediatr Pulmonol. 2007;42:272-276 Bryant et al, J Pediatr Health Care.2005;19:157-162 Boyd JH et al, Haematologica.2007;92:1115-1118 Aflac Cancer and Blood Disorders Center | Emory University 11 Asthma and Sickle Cell Disease • 291 infants with HbSS followed for a mean of 11yrs (4062 patient years) in CSSCD – 16.8% with asthma – 2X greater rate of ACS episodes (0.39 vs.0.2, p<0.001) – Increased risk for ACS during VOC pain; 4 X greater risk of ACS (95% CI, 1.7-9.5) • The OR for respiratory symptoms within 96hrs of a pain event was 4.9 (95% CI, 2.2-10.7) for children with SCD +asthma+pain vs. SCD-asthma+pain • > Number of Children with ACS taking asthma controllers compared with those without ACS Boyd JH et al, Pediatr Pulmonology.2004;38:229-232 Glassberg J et al, J Pediatr Hematol Oncol.2006;28:481-485 Sylvester et al, Pediatr Pulmonol. 2007;42:272-276 Boyd JH et al, Blood .2006;108:2923-2927 Aflac Cancer and Blood Disorders Center | Emory University 12 Asthma and Sickle Cell Disease • Prevalence of asthma in children with SCD is similar to that in AA children in the general population (~20%) • Asthma is inherited in a familial pattern in the families of children with SCD • Asthma and SCD are both chronic inflammatory diseases • PFTs in SCD patients revealed obstructive changes in 35% and restrictive changes in 8%. • Positive response to bronchodilator in 78% in obstructive group and 67% in restrictive group. Field, DeBaun, Hematology 2009; 45-53 Boyd et al, Pediatr Pulmonol. 2004;38:229-232 Koumbourlis, J Ped 2001: 138:188-192 Aflac Cancer and Blood Disorders Center | Emory University 13 Asthma and Sickle Cell Disease • Chronic airway inflammation, potentiating vascular inflammation • “Hyperreactivity” noted with a significant fall in FEV1(78% vs. 18%) • V/Q mismatch may increase the rate of pain or ACS • LT B4and CysLT levels are increased in patients with SCD at steady state and during vaso-occlusive events and increased CysLT levels correlate with asthma severity • Altered nitric oxide homeostasis in SCD and Asthma – Decreased plasma arginine – Increased arginase activity Holgate ST et al. J Allergy Clin Immunol. 2003;111:S18-34; Morris CR et al. Am J Respir Crit Care Med.2004;170;148-153 Allen, J Ped 1997; 131:278-83 CDC 2002.MMWR. 2004;53:145-148 Aflac Cancer and Blood Disorders Center | Emory University 14 Asthma in Adults with SCD • Relationship between asthma and ACS in adults with SCD is not established – Improvement in asthma symptoms with age – Recall bias and lack of rigorous evaluation for asthma – Lower incidence of ACS in adults • Obstructive pattern on PFTs common in SCD but restrictive pattern > in adults • Management is not established but patients with SCD with signs or symptoms of asthma should be treated aggressively Field, DeBaun, Hematology 2009; 45-53 Boyd et al, Pediatr Pulmonol. 2004;38:229-232 Aflac Cancer and Blood Disorders Center | Emory University 15 Sickle Cell Chronic Lung Disease (SCCLD) • Exact incidence, prevalence, natural history, and methods of diagnosis of SCCLD are not established • Prevalence of ~4% in patients with SCD • Morbidity and mortality in SCD especially SS • Begins in 2nd decade of life with death by the 4th decade • Clinically presents with progressive dyspnea, exercise intolerance, pleuritic chest pain and hypoxemia • SCCLD is presumably related to recurring episodes of infarction and infection Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Powars,D at al 1998. Medicine 1998;67:66-76 Aflac Cancer and Blood Disorders Center | Emory University 16 Sickle Cell Chronic Lung Disease • Abnormal PFT: – Lower airway obstruction, restriction, abnormal DLCO and hypoxemia – Restrictive abnormalities on PFT with increasing age • Characterized by a decrease in radiolucency of the lungs and moderate to severe impairment of pulmonary function • CXR: diffuse interstitial fibrosis, pulmonary arterial prominence and cardiomegaly • Progresses to the development of pulmonary hypertension and cor pulmonale in association with restrictive lung disease Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Powars,D at al 1998. Medicine 1998;67:66-76 Aflac Cancer and Blood Disorders Center | Emory University 17 Sickle Cell Chronic Lung Disease • The pulmonary arterial bed, which has low oxygen tension and pressure in a slow-flow system, is ideally suited to facilitate the polymerization of sickle hemoglobin, causing endothelial damage and culminating in an obstructive arteriolar vasculopathy • Post mortem studies – pulmonary vascular bed obliteration – smooth muscle hypertrophy – parenchymal fibrosis Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Powars,D at al 1998. Medicine 1998;67:66-76 Aflac Cancer and Blood Disorders Center | Emory University 18 Pulmonary Hypertension • 20-40% prevalence in SCD • Prospective study of 195 patients with SCD from the community – – – – – PFTs and transthoracic echocardiography Pulmonary HTN: TR jet velocity >2.5m/sec Pulm. artery sys pressure >30mmHg Present in 32% Predictors of high TR jet velocity included factors reflecting the presence of hemolysis, chronic anemia and the need for frequent transfusions • Another study of 60 patients with SCD • Echocardiography evidence of Pulm HTN in 17 (28%) Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Aflac Cancer and Blood Disorders Center | Emory University 19 Pulmonary Hypertension • Etiology: hemolysis, impaired NO bioavailability, chronic hypoxemia, thromboembolism, parenchymal and vascular injury, chronic liver disease and asplenia • High risk of death, resistant to hydroxyurea therapy • Sildenafil therapy – – – – – 12 patients with SCD and Pulmonary HTN 6+/-1months decrease of 9mmHg in pulmonary artery systolic pressure,(95% CI) increase in 6min walk distance diverse effects headaches 2, eye lid edema 4, Priapism in 9( 2 on CTX, 1 with ED) Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Aflac Cancer and Blood Disorders Center | Emory University 20 Pulmonary Hypertension • Recurrent vascular and parenchymal insults • Increased hemolysis resulting in increased plasma levels of cellfree hemoglobin, heme and iron which rapidly depletes NO • Increased arginase, limiting bioavailability of L-arginine, the substrate for NO synthesis – • • • • 228 patients with SCD and 36 controls, increased plasma arginase activity, highest activity in patients with secondary pulm HTN Oxidant status of SCD patients Vascular smooth muscle dysfunction Chronic hypoxemia Autosplenectomy Gladwin, et al 2004. NEJM ,350,886-895 Machado and Gladwin,2005. BJH,129,449-464 Aflac Cancer and Blood Disorders Center | Emory University 21 Case Review • Pulmonary consult for patient M.K prior to elective orthopedic surgery • M.K is an18 year old AA male with HbSS disease • Significant PMHx: – Multiple episodes of ACS preceded by VOC, about 3 episodes over the last year – ICU admission x 1, + BiPAP, no intubations – AVN Rt. Hip – Priapism • Currently on Chronic monthly PRBC Transfusions x 1 year • Body Plethysmography: Normal. ?Low FRC. Aflac Cancer and Blood Disorders Center | Emory University Case Review Day 1: CC: Pain in lower back and B/L LE PE: 36.8°C HR 122, RR 32, SPO2 98%, BP 126/81. Chest exam – Normal Day 3 : Increasing respiratory distress, hypoxia Day 6: PRBC Transfusion Aflac Cancer and Blood Disorders Center | Emory University CXR on Day 1 CXR on Day 3 Acute Chest Syndrome (ACS) The term ACS in patients with sickle cell disease (SCD) was first proposed by Charache et al in 1979 Arch Intern Med 1979;139:67 “the combination of chest pain, fever, increased leukocytosis, and appearance of a new shadow on chest radiograph” ….difficulties in determining its pathogenesis Aflac Cancer and Blood Disorders Center | Emory University Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease ELLIOTT P. VICHINSKY, M.D., LYNNE D. NEUMAYR, M.D., ANN N. EARLES, R.N., P.N.P., ROGER WILLIAMS, M.D.,EVELYNE T. LENNETTE, PH.D., DEBORAH DEAN, M.D., M.P.H., BRUCE NICKERSON, M.D., EUGENE ORRINGER, M.D.,VIRGIL MCKIE, M.D., RITA BELLEVUE, M.D., CHARLES DAESCHNER, M.D., AND ELIZABETH A. MANCI, M.D., FOR THE NATIONAL ACUTE CHEST SYNDROME STUDY GROUP N Engl J Med 2000;342:1855-65 • ACS is the leading cause of death in SCD • Etiology unknown, therefore therapy was supportive • Aim was to determine causes, incidence, clinical outcome and factors that predict prognosis • 671 episodes of ACS in 538 patients • Mean Age: 13.8 years Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Definition of ACS “The acute chest syndrome was defined ….. a new pulmonary infiltrate involving at least one complete lung segment that was consistent with the presence of alveolar consolidation, but excluding atelectasis In addition, the patients had to have chest pain, a temperature of more than 38.5°C, tachypnea, wheezing, or cough” Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Incidence of ACS ~50% admitted for non ACS, 72% for VOC ACS developed after 2.5d Mean oxygen saturation was 92% Decreasing hemoglobin values (mean 0.78g/dl from baseline) • Multilobar LL involvement common in all age groups • 55% had pleural effusion Symptoms at presentation varied with age! • • • • Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Symptoms at Presentation Age at first episode of ACS (years) All patients 0-9 10-19 ≥20 p value Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Clinical Outcome of ACS • All had antibiotics, fever resolved after 2d • No difference in extent of hypoxia but younger patients had <O2 requirement and mechanical ventilation (MV) Mean FEV1 was 53% of predicted during episode 61% treated with BD, 20% with ≥15% increase in FEV1 13% required MV for mean of 4.6d; 81% recovered 72% received PRBC transfusions (68% simple) improved oxygenation • Mean hospital stay 10.5d • Mortality 18% • • • • Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Factors that predicted severe clinical course • • • • • • • • Age >20 years History of VOC Pain in arms and legs at diagnosis Pleural Effusion Fever PRBC transfusion requirement Extensive CXR abnormalities ≥4 lobes Platelet count 0-199k Respiratory failure 13% - Neurologic events 11% Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University The NACSSG: Causes of the ACS • • • • Fat Emboli ± infection: 8.8% (n=59) Infection: 29.4% (n=197) Infarction: 16.1% (n=108) Unknown: 45.7% (n=306) Vichinsky et al, N Engl J Med 2000;342:1855-65 Aflac Cancer and Blood Disorders Center | Emory University 32 The Acute Chest Syndrome in Sickle Cell Disease: Incidence and Risk Factors Oswaldo Castro, Donald J. Brambilla, Bruce Thorington, Carl A. Reindorf, Roland B. Scott, Peter Gillette, Juan C. Vera, Paul S. Levy, and The Cooperative Study of Sickle Cell Disease Blood, 1994. 84: pp 643-649 • ACS: new infiltrate on CXR and/or a perfusion defect on a lung radioisotope scan • 2 year prospective study of 3,751 patients with SCD • 2100 ACS events in 1,085 patients • Incidence of ACS: o in HbSS, HbSβ0thal and HbSC was 12.8 , 9.4 and 5.2 per 100 patient years respectively o highest in children 2-4 years of age o lower in pts with lower steady-state Hb levels and higher fetal Hb o steady-state leukocyte count. Aflac Cancer and Blood Disorders Center | Emory University Acute Chest Syndrome in Sickle Cell Disease: Clinical Presentation and Course Elliott P. Vichinsky, Lori A. Styles, Linda H. Colangelo, Elizabeth C. Wright, Oswaldo Castro, Bruce Nickerson, and the Cooperative Study of Sickle Cell Disease Blood 1997 89:1787-1792 • To examine whether specific presentations or risk factors are predictive of clinical outcome • Prospective study of 939 SCD patients with 1,722 ACS episodes over 9 years • Ages 0-66years • ACS definition: new infiltrate on CXR and/or a perfusion defect on a lung radioisotope scan Aflac Cancer and Blood Disorders Center | Emory University 34 Acute Chest Syndrome in Sickle Cell Disease: Clinical Presentation and Course Elliott P. Vichinsky, Lori A. Styles, Linda H. Colangelo, Elizabeth C. Wright, Oswaldo Castro, Bruce Nickerson, and the Cooperative Study of Sickle Cell Disease Blood 1997 89:1787-1792 Children Adults Fever and Cough Often afebrile Negative PE SOB, chills Pain rare Severe pain Upper lobe Lower lobe and Multilobar >Bacteremia >Severe hypoxia >Cases in Winter Cases in Winter < Transfusions but earlier >Transfusions LOS 5.4d LOS 9d Preceded by fever Preceded by pain <Mortality >Mortality, X4 • Fatal cases generally developed rapid pulmonary failure and one third were associated with bacteremia Aflac Cancer and Blood Disorders Center | Emory University 35 ACS • What is consistent? – Interpretation of CXR must be reliable: ACS is a NEW radiodensity on chest radiograph – Can occur with or without fever – Is a spectrum of disease – Symptoms at presentation vary with age – Has a rapid rate of progression – Higher rate of recurrence in certain patients Aflac Cancer and Blood Disorders Center | Emory University Further studies on ACS… Other clinical events associated with development of ACS: - Intravascular sickling Davies et al, Lancet 1984;1(8367):36–38. - Microvascular in situ thrombosis Gladwin MT et al,Am J Respir Crit Care Med 1999;159(5 pt 1):1368–1376 - Acute drop in hemoglobin concentration preceding the diagnosis of ACS Gladwin MT et al,Am J Respir Crit Care Med 1999;159(5 pt 1):1368–1376 Vichinsky EP et al , Blood. 1997; 89(5):1787–1792. van Agtmael MA et al , Arch Intern Med. 1994;154(5):557–561. - Secretory phospholipase A2 Styles LA et al, Blood 1996; 87(6): 2573-2578 - Over expression of endothelial VCAM-1 Stuart and Setty, Blood 1999; 94(5 ):1555-1560 Aflac Cancer and Blood Disorders Center | Emory University Heme Catabolism and ACS • Hemin induced acute intravascular hemolysis in transgenic sickle mice and autoamplification of extracellular hemin produced an acute lung injury reminiscent of ACS Ghosh S, et al. J Clin Invest. 2013doi:10.1172/JCI64578 • Higher baseline plasma free heme is associated with increased odds of ACS Adisa OA, et al. Br J Haematol. 2013;162(5):702–705 • Polymorphism in the HMOX-1 gene (enhances expression of HO-1) was associated with lower rates of ACS incidence in children with SCD Bean CJ, et al. Blood. 2012;120(18):3822–3828 Aflac Cancer and Blood Disorders Center | Emory University Heme Catabolism in SCD Intravascular Hemolysis. Haptoglobin halts hemoglobin’s havoc Gregory J. Kato, JCI 2009 Aflac Cancer and Blood Disorders Center | Emory University 39 Extracellular Heme triggers ACS Aflac Cancer and Blood Disorders Center | Emory University 40 Hypothesis Unscavenged circulating heme is a biomarker and potential trigger for ACS Aflac Cancer and Blood Disorders Center | Emory University Association between Heme and ACS Aflac Cancer and Blood Disorders Center | Emory University Association of SCD complications with biomarkers of hemolysis Adisa OA, et al. Br J Haematol. 2013;162(5):702–705 Aflac Cancer and Blood Disorders Center | Emory University HO-1 in SCD Aflac Cancer and Blood Disorders Center | Emory University Plasma HO-1 in SCD patients HO-1 Expression: HbAA: 2.57ng/ml ± 0.8 HbSS: ± 8.2 (p<0.0001) HbSC: 12.92ng/ml ± 1.35 (p<0.0001) Adisa et al,2014. Unpublished Aflac Cancer and Blood Disorders Center | Emory University HOP-ACS Study: Genetic Heterogeneity in Heme Degradation and its Role in Acute Chest Syndrome Hypothesis: Unscavenged circulating heme is a biomarker and potential trigger for ACS Aflac Cancer and Blood Disorders Center | Emory University Definitions of the phenotypic manifestations of sickle cell disease: Acute Chest Syndrome (ACS) Samir K. Ballas, Susan Lieff, Lennette J. Benjamin, Carlton D. Dampier, Matthew M. Heeney, Carolyn Hoppe, Cage S. Johnson, Zora R. Rogers, Kim Smith-Whitley, Winfred C. Wang, and Marilyn J. Telen on Behalf of the Investigators at the Comprehensive Sickle Cell Centers American Journal of Hematology 2009 (85) vol. 1 ACS was defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray Diagnostic Criteria A new* segmental (involving at least 1 complete segment) radiographic pulmonary infiltrate AND at least one of the following: 1. 2. 3. 4. 5. 6. 7. 8. 9. Temperature ≥38.5ºC >2% decrease in SpO2 (O2 saturation) from a documented steady-state value on room air (FiO2 = 0.21) PaO2 <60 mmHg Tachypnea (per age-adjusted normal) Intercostal retractions, nasal flaring, or use of accessory muscles of respiration Chest pain Cough Wheezing Rales * Does not require a preceding radiograph or physical examination, but if either was performed then the current findings must be new. Aflac Cancer and Blood Disorders Center | Emory University Mild ACS • Meets the diagnostic criteria above AND all of the following: 1. Transcutaneous O2 saturation >90% in room air (FiO2 = 0.21) 2. Segmental or lobar infiltrates that involve no more than 1 lobe by chest radiography 3. Responsive to simple transfusion of no more than 2 units of red blood cells (or 15 cc/kg PRBC) Aflac Cancer and Blood Disorders Center | Emory University Moderate ACS • Meets the diagnostic criteria above AND all of the following: 1. Transcutaneous O2 saturation ≥85% in room air (FiO2 = 0.21) 2. Segmental or lobar infiltrates that involve no more than 2 lobes by chest radiography 3. Responsive to transfusion of ≥3 units of red blood cells (or more than 20 cc/kg PRBCs ) Aflac Cancer and Blood Disorders Center | Emory University Severe ACS • Meets the diagnostic criteria above AND 1 or more of the following: 1. Respiratory failure (PaO2 <60 mmHg or PCO2 >50 mmHg) 2. MV support required 3. Transcutaneous O2 saturation <85% in room air or ≤90% despite maximal supplementalO2 4. Segmental or lobar infiltrates that involve 3 or more lobes by chest radiography 5. Requiring transfusion or exchange transfusion of red blood cells to achieve hemoglobin A ≥70% Aflac Cancer and Blood Disorders Center | Emory University Very Severe ACS • Acute Respiratory Distress Syndrome (ARDS) or sudden, life-threatening lung failure is the most severe complication of ACS. ARDS as defined by the 3 criteria of the American-European Consensus Conference includes: 1. Acute onset of bilateral infiltrates on chest radiograph 2. Pulmonary artery wedge pressure of <19 mmHg or the absence of clinical evidence of left atrial hypertension 3. PaO2/FiO2 ≤200 regardless of positive end expiratory pressure (PEEP) level Aflac Cancer and Blood Disorders Center | Emory University ARDS • Acute onset of tachypnea, hypoxemia, and loss of compliance after a variety of stimuli; the syndrome that did not respond to usual and ordinary methods of respiratory therapy • Pathologic features were similar to infantile RDS • Etiology was a combination of insults to the lungs: viral infection, fat embolism, fluid overload, • PEEP was most helpful in oxygenation, improves alveolar ventilation • Treat underlying process but grave prognosis Ashbaugh et al.. Lancet,1967 Aflac Cancer and Blood Disorders Center | Emory University 53 Case #1 • 6 yo M with HbSC and RAD • 2-d hx of dry cough, sternal chest pain unresponsive to lortab/ibuprofen @ home, and a 1-d of tactile fever, no albuterol at home • VS: BP 89/62 | Pulse 70 | Temp 36.9 °C (Temporal) | Resp 22 | Wt 23.2 kg | SpO2 98% on room air • Local urgent care, CXR: Focal airspace disease is seen in the left lower lobe. Otherwise, the lungs are clear. The cardiac and mediastinal contours are normal. No pneumothorax or pleural effusion is seen. The bones and soft tissues are normal. IMPRESSION: Left lower lobe acute chest syndrome versus pneumonia. • Bld Cx, ceftriaxone and azithromycin Aflac Cancer and Blood Disorders Center | Emory University Case # 1 • 3/19= admit to SR. Pain is mild, pt wants to walk around. No recent sick contacts. NO URI symptoms. claf/zithro, pulm toilet • 3/20= miralax • ….On the morning of discharge , Pt is OOB at sink with grandma. Per grandma he had a good night. During the hospital course he has been afebrile, counts have been stable, blood cultures are NGTD and he had no oxygen requirement. Discharge instructions reviewed with grandma and mom via phone. • VS at Discharge: BP 97/68 | Pulse 73 | Temp 36.8 °C (Axillary) | Resp 20 | Ht 107 cm | Wt 21.1 kg | BMI 18.43 kg/m2 | SpO2 99% • Discharge Diagnosis: ? Aflac Cancer and Blood Disorders Center | Emory University 55 Case #2 • • • • • • • • • • Presented with VOC in legs On day 2, developed fever, tachypnea, hypoxia SPO2 90% CXR on day 2: RUL infiltrate Received PRBC transfusion 15ml/kg BiPAP initiated Transferred to PICU on day 3 Increasing respiratory distress CXR on day 3: LLL and RUL consolidation Repeat PRBC transfusion 10ml/kg Diagnosis ? Aflac Cancer and Blood Disorders Center | Emory University Case #3 • • • • • • • • Presented with VOC, generalized Hypoxia SPO2 90% on admission, RR 20-34 Fever on day 2 BiPAP at night due to PMHx CXR on day 3: B/L LL Consolidation with pleural effusion Received PRBC transfusion 15ml/kg Increasing respiratory distress on day 4, transferred to PICU Intubated, Exchange PRBC transfusion • Diagnosis ? Aflac Cancer and Blood Disorders Center | Emory University Our Classifications……… • Early ACS • ?ACS • Developing ACS • Mild ACS • Severe ACS ? Aflac Cancer and Blood Disorders Center | Emory University 58 Acknowledgement Solomon Ofori-Acquah, PhD Clinton Joiner, MD, PhD Michael DeBaun, MD Aflac Cancer and Blood Disorders Center SCD Team Emory University, Department of Pediatric Pulmonary, Allergy/Immunology, Cystic Fibrosis, and Sleep • Georgia Pediatric Pulmonary Associates ( Leroy Graham, MD, Jon Popler, MD and LaTresa Lang, MD) • • • • • Aflac Cancer and Blood Disorders Center | Emory University
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