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Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease
Open accessAbstract
BACKGROUND: The acute chest syndrome is the leading cause of death among patients with sickle cell disease. Since its cause is largely unknown, therapy is supportive. Pilot studies with improved diagnostic techniques suggest that infection and fat embolism are underdiagnosed in patients with the syndrome. METHODS: In a 30-center study, we analyzed 671 episodes of the acute chest syndrome in 538 patients with sickle cell disease to determine the cause, outcome, and response to therapy. We evaluated a treatment protocol that included matched transfusions, bronchodilators, and bronchoscopy. Samples of blood and respiratory tract secretions were sent to central laboratories for antibody testing, culture, DNA testing, and histopathological analyses. RESULTS: Nearly half the patients were initially admitted for another reason, mainly pain. When the acute chest syndrome was diagnosed, patients had hypoxia, decreasing hemoglobin values, and progressive multilobar pneumonia. The mean length of hospitalization was 10.5 days. Thirteen percent of patients required mechanical ventilation, and 3 percent died. Patients who were 20 or more years of age had a more severe course than those who were younger. Neurologic events occurred in 11 percent of patients, among whom 46 percent had respiratory failure. Treatment with phenotypically matched transfusions improved oxygenation, with a 1 percent rate of alloimmunization. One fifth of the patients who were treated with bronchodilators had clinical improvement. Eighty-one percent of patients who required mechanical ventilation recovered. A specific cause of the acute chest syndrome was identified in 38 percent of all episodes and 70 percent of episodes with complete data. Among the specific causes were pulmonary fat embolism and 27 different infectious pathogens. Eighteen patients died, and the most common causes of death were pulmonary emboli and infectious bronchopneumonia. Infection was a contributing factor in 56 percent of the deaths. CONCLUSIONS: Among patients with sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and infection, especially community-acquired pneumonia. Among older patients and those with neurologic symptoms, the syndrome often progresses to respiratory failure. Treatment with transfusions and bronchodilators improves oxygenation, and with aggressive treatment, most patients who have respiratory failure recover.
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“Epidemiologically, ACS is a complication of VOC, based on its typical development 2–3 days after the onset of vaso-occlusive pain (111)”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [111]
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“it is more common in children and, if untreated, has a high mortality [9% in adults (111)].”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [111]
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Metadata
- Authors
- Vichinsky, E. P., Neumayr, L. D., Earles, A. N., Williams, R., Lennette, E. T., Dean, D., Nickerson, B., Orringer, E., McKie, V., Bellevue, R., Daeschner, C., Abboud, M., Moncino, M., Ballas, S., Ware, R., & Manci, E. A.
- Affiliations
- University of California, San Francisco (US)
- Children's Hospital of Orange County (US)
- University of North Carolina at Chapel Hill (US)
- Augusta University (US)
- NewYork–Presbyterian Brooklyn Methodist Hospital (US)
- East Carolina University (US)
- Duke Medical Center (US)
- University of South Alabama Medical Center (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-06-22
- Volume
- 342
- Issue
- 25
- Pages
- 1855-1865
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2332642667
- Cited by
- 1,234
- References
- 44
- Citations by year
- 2026: 35 · 2025: 55 · 2024: 52 · 2023: 62 · 2022: 59 · 2021: 67 · 2020: 75 · 2019: 44 · 2018: 48 · 2017: 38 · 2016: 63 · 2015: 51 · 2014: 57 · 2013: 59 · 2012: 51
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- University of Southern California
- University of Miami
- Emory University
- University of South Alabama
- National Institutes of Health (5p60hl020985-25)
- National Heart, Lung, and Blood Institute (HL20985, HL 99016)
- National Center for Research Resources (M01 RR 01271)
- Children's Hospital of Pittsburgh
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood transfusion and management
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Keywords
- acute chest syndrome, sickle cell disease, pulmonary fat embolism, infection, community-acquired pneumonia, bronchodilators, bronchoscopy, mechanical ventilation, respiratory failure, neurological complications, mortality, hypoxia
- MeSH terms
- Acute Disease, Adolescent, Adult, Anemia, Sickle Cell, Blood Transfusion, Bronchodilator Agents, Chest Pain, Child, Child, Preschool, Embolism, Fat, Female, Humans, Infections, Lung Diseases, Male, Prospective Studies, Pulmonary Embolism, Respiration, Artificial, Respiratory Insufficiency, Proportional Hazards Models, Community-Acquired Infections
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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