1. Ward Hagar USCF Benioff Children’s Hospital Oakland 9/10/2016

2.  Review of Causes and Effects of Lung Damage  What’s New in 2016 Signs and Symptoms  Diagnosis  Treatment  Take Home Messages

3. Ballas,S. with permission

4. Clinical Subphenotypes of SCD Gladwin M and Vichinsky E N Engl J Med 2008;359:2254

5. Gladwin M and Vichinsky E. N Engl J Med 2008;359:2254

6.  ACS has been the leading cause of death in persons with sickle cell  Occurs in the majority of sickle cell patients at least once in their lives  Second most common cause of admissions after painful vaso-occlusive crises.  Dramatic lowered rate in patients on hydroxyurea (49%)

7.  Research Definition New pulmonary infiltrate involving at least one complete lung segment Clinical findings (one of the following) chest pain temperature > 38.5 C tachypnea Wheezing/fremitus cough  Clinical Definition any new infiltrate with a fever (early on may be afebrile)

8. Courtesy of Richard Lottenberg, MD

9. American Journal of Hematology, Vol. 90, No. 5, May 2015

10.  Infection ◦ Initial fever, URI or chest symptoms  Bone marrow emboli ◦ Severe extremity pain without chest symptoms  Thromboembolism ◦ Sudden onset of chest pain and dyspnea ◦ Acute hemodynamic collapse (esp with PTH)  Atelectasis ◦ Chest paints with splinting from rib pain and infarcts, hypoventilation, fluid overload, and opioid treatment

11. Cause # of episodes (percent) Fat embolism59 (8.8) Chlamydia48 (7.2) Mycoplasma44 (6.6) Virus43 (6.4) Bacteria 30 (4.5) Mixed infections25 (3.7) Legionella 4 (0.6) Miscellaneous infections 3 (0.4) Infarction 108 (16.1) Unknown 306 (45.7) Vichinsky et al., NEJM 2000

12. Medicine Volume 94, Number 18, May 2015

13. RESPIRATORY CARE APRIL 2015 VOL 60 NO 4

14.  9% of episodes of acute chest syndrome  Lower mean oxygen saturations  Upper-Lobe infiltrates during hospitalizations

15. Medoff BD et al. Case 17-2005: A 22-Year-Old Woman with Back and Leg Pain and Respiratory Failure. NEJM 2005;352(23):2425-34. Bone Marrow Emboli in Lung

16. Am. J. Hematol. 91:173–178, 2016

17.  Half of patients admitted for another diagnosis (usually pain)  Radiographic and clinical findings appeared a mean of 2.5 days after admission

18.  Severe Extremity pain (marrow infarcts)  May not have lung or chest symptoms at presentation  Initial CXR often normal of basilar “hazy”  Decline may be rapid ◦ Drops in oxygen saturation ◦ Need to cough, dyspnea ◦ Develops rales, tachypnea

19. Medoff BD et al. Case 17-2005: A 22-Year-Old Woman with Back and Leg Pain and Respiratory Failure. 2005;352(23):2425-34.

20.  Fluid management: 1 - 1.5 times daily requirement (intravenous plus oral)  Pain management – minimize chest splinting, avoid narcosis  Incentive Spirometry and bronchodilator therapy (check pre and post peak flows)  Red blood cell transfusion or exchange if PaO2 compromised or clinical deterioration  Empiric antimicrobial treatment with a cephalosporin and a macrolide

21.  Often able to use simple transfusions as hemoglobin levels often fall 1 gm/day, and continue to fall  Would like to monitor %S, but often is a send out, target being less than 30%  Simple transfusions have the danger of increasing viscosity and reducing oxygenation unless prior hemoglobin S is low  Transfusion reactions, especially sickle cell hyperhemolytic transfusion reactions, may be hard to distinguish from hemolytic crises

22.  Potential misleading diagnostic considerations in the patient with progressive hypoxemia ̵ Increasing pulmonary infiltrates → pulmonary edema ̵ Lack of response to antibiotics → inadequate coverage ̵ Altered mental status → narcosis  Avoid delays in transfusion therapy Fawibe, AE Tr Royal Soc Trop Med Hyg 2008; 102: 526

23. Annals ATS Volume 12 Number 7| July 2015 13 year old with Acute Chest Syndrome

24.  Potent pulmonary vasodilator  Distributed to areas with most ventilation, should lead to preferential blood flow to these areas, improving ventilation-to- perfusion matching  Helps oxygenation, but unclear if effects mortality or ventilator-free days  Increases oxygen affinity for hemoglobin S, making sickling less likely to occur

25.  Often Severe Acute chest occurs in someone previously doing well, even for years  Incidence seems to be changing  Do steroid really help?  Use of IV arginine, nitric oxide, glutamate  Role of secretory phospholipase A 2 ?

26.  Pain, especially limb, may be an acute chest prodrome ◦ If trouble breathing and not know to be in rib or muscles, go to ED ◦ Incentive spirometry ◦ Daily monitoring for lung disease  Transfuse Early ◦ Watch for hemoglobin and platelets dropping ◦ Dropping oxygen saturation ◦ Pheresis for severe Acute Chest  Antibiotics for Infection even if cultures are negative ◦ Levofloxicin and ceftriaxone  Steroids may be helpful, but need to be tapered  Consultation with a sickle cell center early if not improving

27.  TAKE YOUR HYDROXYUREA