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Cited by 1,234Hemoglobinopathies and Related DisordersBlood transfusion and managementPneumonia and Respiratory Infections

Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease

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Vichinsky, Elliott P., Neumayr, Lynne D., Earles, Ann N., Williams, Roger, Lennette, Evelyne T., Dean, Deborah, Nickerson, Bruce, Orringer, Eugene +8 more·2000·New England Journal of Medicine
DOI 10.1056/nejm200006223422502
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Abstract

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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  • Acute chest syndrome is a complication of vaso-occlusive crisis, based on its typical development 2-3 days after the onset of vaso-occlusive pain.

    “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]

    In “Diagnosis and Symptoms of the Acute Chest Syndrome at Admission” (page unavailable), the paper reports that 72% of patients admitted for a reason other than ACS had a vaso-occlusive crisis, and ACS findings appeared a mean of 2.5 days after admission in that group. The Discussion calls pain a prodrome of ACS. These passages support the association, but the measured interval starts at admission, not at the onset of pain, and applies to a subset rather than establishing a typical interval for all ACS cases. (LLM, conf=0.87)

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  • Acute chest syndrome is more common in children and, if untreated, has a high mortality, including 9% in adults.

    “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]

    Table 1 lists more children than adults among the patients studied, and Table 2 reports 9% mortality in patients aged 20 or older. But the Hospital Course and Treatment section says patients received treatment, so the 9% figure is not an untreated mortality rate. The study's age-group counts also do not establish that acute chest syndrome is more common in children in the wider sickle cell population. (LLM, conf=0.88)

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Research works printed but not linked: 7

  1. [6]6. Lowenthal EA, Wells A, Emanuel PD, Player R, Prchal JT. Sickle cell acute chest syndrome associated with parvovirus B19 infection: case series and review. Am J Hematol 1996;51:207-13.
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  4. [16]16. Lennette ET, Lennette DA. Immune adherence hemagglutination. In: Specter S, Lancz G, eds. Clinical virology manual. 2nd ed. New York: Elsevier Science Publishing, 1992:251-61.
  5. [19]19. Schachter J. Chlamydiae. In: Balows A, Hausler WJ Jr, Hermann KL, Isenberg HD, Shadomy HJ, eds. Manual of clinical microbiology. 5th ed. Washington, D.C.: ASM Press, 1991:1045-53.
  6. [20]20. Lietman T, Brooks D, Moncada J, Schachter J, Dawson C, Dean D. Chronic follicular conjunctivitis associated with Chlamydia psittaci or Chlamydia pneumoniae. Clin Infect Dis 1998;26:1335-40.
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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
DOI
10.1056/nejm200006223422502
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
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 › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Biochemistry › 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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