Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray. The spectrum of clinical manifestations can range from mild respiratory illness to acute respiratory distress syndrome. The presence of severe hypoxemia is a useful predictor of severity and outcome. The etiology of ACS is often multifactorial. One of the proposed mechanisms involves increased adhesion of sickle red cells to pulmonary microvasculature in the presence of hypoxia. Other commonly associated etiologies include infection, pulmonary fat embolism, and infarction. Infection is a common cause in children, whereas adults usually present with pain crises. Several risk factors have been identified in children to be associated with increased incidence of ACS. These include younger age, severe SCD genotypes (SS or Sβ0 thalassemia), lower fetal hemoglobin concentrations, higher steady-state hemoglobin levels, higher steady-state white blood cell counts, history of asthma, and tobacco smoke exposure. Opiate overdose and resulting hypoventilation can also trigger ACS. Prompt diagnosis and management with intravenous fluids, analgesics, aggressive incentive spirometry, supplemental oxygen or respiratory support, antibiotics, and transfusion therapy, are key to the prevention of clinical deterioration. Bronchodilators should be considered if there is history of asthma or in the presence of acute bronchospasm. Treatment with hydroxyurea should be considered for prevention of recurrent episodes. This review evaluates the etiology, pathophysiology, risk factors, clinical presentation of ACS, and preventive and treatment strategies for effective management of ACS.
We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of Busulfan (13.2 mg/kg), Fludarabine (175 mg/m2) and Thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17–36) were enrolled at 8 centers. Seventeen patients received marrow from an HLA-identical sibling donor and 5 patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grade II-III acute GVHD (18%) and 6 developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68–98%) and 86% (95% CI, 63–95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).
Key Points Question Are concerns about the opioid epidemic in the United States and the heightened oversight and restrictions on prescribing opioids associated with changes in the management of acute and chronic pain for patients with sickle cell disease? Findings This qualitative study interviewed 15 adults with sickle cell disease. Participants reported that they face increased barriers to the use of opioids for pain management, that their physicians exclusively focus on opioid dosage without establishing a multimodality pain management plan, and that they lack access to nonopioid therapies. Meaning Adult patients with sickle cell disease should be included in establishing goals for managing pain and improving functionality using multimodality approaches.
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