The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mortality in sickle cell disease. Life expectancy and risk factors for early death
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P. (1994) · New England Journal of Medicine · doi:10.1056/nejm199406093302303 · Cited by 3,320
Rickinson, A. B. (2002) · PubMed · doi:10.1016/s0168-1702(01)00436-1 · Cited by 2,182
Cerebrovascular accidents in sickle cell disease: rates and risk factors.
(1998) · PubMed · doi:10.1182/blood.v91.1.288 · Cited by 1,694
Incidence of and Risk Factors for Ventilator-Associated Pneumonia in Critically Ill Patients
Cook, D. J., Walter, S. D., Cook, R. J., Griffith, L. E., Guyatt, G. H., Leasa, D., Jaeschke, R. Z., & Brun‐Buisson, C. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-6-199809150-00002 · Cited by 1,108
Castro, O. L., Brambilla, D. J., Thorington, B. D., Reindorf, C. A., Scott, R., GILLETTE, P. N., Vera, J., & Levy, P. S. (1994) · Blood · doi:10.1182/blood.v84.2.643.643 · Cited by 805
Vichinsky, E. P., Haberkern, C. M., Neumayr, L., Earles, A. N., Black, D. M., Koshy, M., Pegelow, C. H., Abboud, M. R., Ohene‐Frempong, K., & Iyer, R. V. (1995) · New England Journal of Medicine · doi:10.1056/nejm199507273330402 · Cited by 644
Self-citationCastro, O. L., Brambilla, D. J., Thorington, B. D., et al. (1994) · Blood · doi:10.1182/blood.v84.2.643.bloodjournal842643 · Cited by 615
Acute Chest Syndrome in Sickle Cell Disease: Clinical Presentation and Course
Vichinsky, E. P., Styles, L. A., Colangelo, L. H., Wright, E. C., Castro, O., Nickerson, B., & Disease, T. C. S. O. S. C. (1997) · Blood · doi:10.1182/blood.v89.5.1787 · Cited by 573
Self-citationSickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure.
Powars, D., WEIDMAN, J. A., Odom‐Maryon, T., Niland, J. C., & Johnson, C. M. (1988) · PubMed · Cited by 329
Sickle Cell Chronic Lung Disease
Powars, D. R., WEIDMAN, J. A., ODOM-MARYON, T., Niland, J. C., & Johnson, C. S. (1988) · Medicine · doi:10.1097/00005792-198801000-00005 · Cited by 283
Incentive Spirometry to Prevent Acute Pulmonary Complications in Sickle Cell Diseases
Bellet, P. S., Kalinyak, K. A., Shukla, R., Gelfand, M. J., & Rucknagel, D. L. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509143331104 · Cited by 278
Pulmonary fat embolism: a distinct cause of severe acute chest syndrome in sickle cell anemia
Vichinsky, E., Williams, R., Das, M., Earles, A., Lewis, N., Adler, A., & McQuitty, J. (1994) · Blood · doi:10.1182/blood.v83.11.3107.3107 · Cited by 261
Self-citationMicrobial Etiology of Acute Pneumonia in Hospitalized Patients
Bates, J. H., Campbell, G. D., Barton, A. L., Gh, M., Morgan, P. N., Moses, E. B., & Davis, C. M. (1992) · CHEST Journal · doi:10.1378/chest.101.4.1005 · Cited by 255
Bernini, J. C., Rogers, Z. R., Sandler, E. S., REISCH, J. S., Quinn, C. T., & Buchanan, G. R. (1998) · Blood · doi:10.1182/blood.v92.9.3082 · Cited by 228
Phospholipase A2 levels in acute chest syndrome of sickle cell disease
Styles, L., Schalkwijk, C., Aarsman, A. J., Vichinsky, E. P., Lubin, B. H., & Kuypers, F. A. (1996) · Blood · doi:10.1182/blood.v87.6.2573.bloodjournal8762573 · Cited by 196
Self-citationCook, P. J., Honeybourne, D., Lip, G. Y. H., Beevers, D. G., Wise, R., & Davies, P. (1998) · Stroke · doi:10.1161/01.str.29.2.404 · Cited by 182
Comprehensive care in sickle cell disease: its impact on morbidity and mortality.
Vichinsky, E. P. (1991) · PubMed · Cited by 163
Self-citationAdult Respiratory Distress Syndrome
Bone, R. C., BALK, R. A., Slotman, G. J., Maunder, R., SILVERMAN, H. J., Hyers, T. M., & Kerstein, M. D. (1992) · CHEST Journal · doi:10.1378/chest.101.2.320 · Cited by 158
Cerebral hyperemia, stroke, and transfusion in sickle cell disease
Prohovnik, I., Pavlakis, S. G., Piomelli, S., Bello, J., Mohr, J. P., Hilal, S., & De Vivo, D. C. (1989) · Neurology · doi:10.1212/wnl.39.3.344 · Cited by 153
Effect of transfusion in acute chest syndrome of sickle cell disease
Emre, U., Miller, S. T., Gutierez, M., Steiner, P., Rao, S. P., & Rao, M. (1995) · The Journal of Pediatrics · doi:10.1016/s0022-3476(95)70025-0 · Cited by 151
Acute chest syndrome in sickle cell disease: Etiology and clinical correlates
Poncz, M., Kane, E., & Gill, F. M. (1985) · The Journal of Pediatrics · doi:10.1016/s0022-3476(85)80176-1 · Cited by 140
Infection with Chlamydia pneumoniae in Brooklyn
Chirgwin, K., Roblin, P. M., Gelling, M., Hammerschlag, M. R., & Schachter, J. (1991) · The Journal of Infectious Diseases · doi:10.1093/infdis/163.4.757 · Cited by 139
Bronchoalveolar Lavage for Rapid Diagnosis of the Fat Embolism Syndrome in Trauma Patients
Chastre, J. E., Fagon, J.-Y., Soler, P., Fichelle, A., Dombret, M.-C., Huten, D., Hance, A. J., & Gibert, C. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-8-583 · Cited by 128
SYSTEMIC FAT EMBOLISM AND PULMONARY HYPERTENSION IN SICKLE CELL DISEASE
Castro, O. (1996) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70401-9 · Cited by 122
Godeau, B., Schaeffer, A., Bachir, D., Fleury-Feith, J., Galacteros, F., Verra, F., Escudier, E., Vaillant, J. N., Brun-Buisson, C., Rahmouni, A., et al. (1996) · American journal of respiratory and critical care medicine · doi:10.1164/ajrccm.153.5.8630622 · Cited by 116
Sprinkle, R. H., Cole, T., Smith, S., & Buchanan, G. R. (1986) · PubMed · Cited by 109
Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis.
Tohgi, H., Suzuki, H., Tamura, K., & Kimura, B. (1991) · Stroke · doi:10.1161/01.str.22.1.17 · Cited by 103
Acute respiratory distress syndrome
Wyncoll, D. L. A., & Evans, T. W. (1999) · The Lancet · doi:10.1016/s0140-6736(98)08129-x · Cited by 100
A genetically engineered cell line that produces empty capsids of B19 (human) parvovirus.
Kajigaya, S., Shimada, T., Fujita, S., & Young, N. S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7601 · Cited by 99
Gladwin, M. T., Schechter, A. N., Shelhamer, J. H., & Ognibene, F. P. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.159.5.9810094 · Cited by 96
Role of Chlamydia pneumoniae in acute chest syndrome of sickle cell disease
Miller, S. T., Hammerschlag, M. R., Chirgwin, K. D., Rao, S. P., Roblin, P. M., Gelling, M., Stilerman, T., Schachter, J., & Cassell, G. H. (1991) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)81839-6 · Cited by 82
DNA Diagnosis of Central Nervous System Infection by Mycoplasma pneumoniae
Narita, M., Matsuzono, Y., Togashi, T., & Kajii, N. (1992) · PEDIATRICS · doi:10.1542/peds.90.2.250 · Cited by 81
Beneficial Effect of Blood Transfusion in Children With Sickle Cell Chest Syndrome
Mallouh, A. A. (1988) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1988.02150020080034 · Cited by 81
Chronic Follicular Conjunctivitis Associated withChlamydia psittaciorChlamydia pneumoniae
Lietman, T. M., Brooks, D. G., Moncada, J., Schachter, J., Dawson, C. R., & Dean, D. (1998) · Clinical Infectious Diseases · doi:10.1086/516373 · Cited by 73
Self-citationBronchoalveolar Lavage for Diagnosis of Pneumonia in the Immunocompromised Child
Frankel, L. R., Smith, D. W., & Lewiston, N. J. (1988) · PEDIATRICS · doi:10.1542/peds.81.6.785 · Cited by 62
Fat embolism in sickle cell disease
Hutchinson, R. M., Merrick, M. V., & White, J. M. L. (1973) · Journal of Clinical Pathology · doi:10.1136/jcp.26.8.620 · Cited by 60
Pulmonary entrapment of sickle cells: the role of regional alveolar hypoxia
Aldrich, T. K., Dhuper, S., Patwa, N. S., Makolo, E., Suzuka, S. M., Najeebi, S. A., Santhanakrishnan, S., Nagel, R. L., & Fabry, M. E. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.80.2.531 · Cited by 58
Kirkpatrick, M. B., Haynes, J., & Bass, J. B. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)80161-e · Cited by 40
Smolinski, P. A., Offermann, M. K., Eckman, J., & Wick, T. M. (1995) · Blood · doi:10.1182/blood.v85.10.2945.bloodjournal85102945 · Cited by 33
Potentiated adherence of sickle erythrocytes to endothelium infected by virus.
Hebbel, R. P., Visser, M. R., Goodman, J. L., Jacob, H., & Vercellotti, G. M. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113233 · Cited by 32
Clinical Indicators in Sepsis and Septic Adult Respiratory Distress Syndrome
Jacobs, E. R., & Bone, R. C. (1986) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30932-4 · Cited by 29
Reduced Platelet Counts in Neonatal Respiratory Distress Syndrome
Kohelet, D., Perlman, M., Hanna, G., & Ballin, A. (2009) · Biology of the Neonate · doi:10.1159/000243210 · Cited by 15
Sickle erythrocytes induce prostacyclin and thromboxane synthesis by isolated perfused rat lungs
Ibe, B. O., Morris, J., Kurantsin‐Mills, J., & Raj, J. U. (1997) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1997.272.4.l597 · Cited by 11
Stoeckert, C. J., & Cheng, H. (1996) · American Journal of Hematology · doi:10.1002/(sici)1096-8652(199603)51:3 · Cited by 4
Research works printed but not linked: 9
- Vichinsky E, 1991, Semin Hematol, 28, 220
- Sprinkle RH, 1986, Am J Pediatr Hematol Oncol, 8, 105
- Landry ML, Hsiung GD. Primary isolation of viruses. In: Specter S, Lancz G, eds. Clinical virology manual. 2nd ed. New York: Elsevier Science Publishing, 1992:43-69.
- Waites KB, Taylor-Robinson D. Mycoplasma and Ureaplasma. In: Murray PR, ed. Manual of clinical microbiology. 7th ed. Washington, D.C.: ASM Press, 1999:782-806.
- 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.
- 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.
- Ohene-Frempong K, 1998, Blood, 91, 288
- Mallouh AA, 1988, Am J Dis Child, 142, 178
- Ibe BO, 1997, Am J Physiol, 272, L597
Cited by
Sorted by citations
Rees, D. C., Williams, T. N., & Gladwin, M. T. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61029-x · Cited by 2,504
Padmanabhan, A., Connelly‐Smith, L. S., Aqui, N. A., Balogun, R. A., Klingel, R., Meyer, E., Pham, H. P., Schneiderman, J., Witt, V., Wu, Y., et al. (2019) · Journal of Clinical Apheresis · doi:10.1002/jca.21705 · Cited by 2,245
Piel, F. B., Steinberg, M. H., & Rees, D. C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1510865 · Cited by 1,488
Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members
Yawn, B. P., Buchanan, G. R., Afenyi-Annan, A. N., Ballas, S. K., Hassell, K. L., James, A. H., Jordan, L., Lanzkron, S. M., Lottenberg, R., Savage, W. J., et al. (2014) · JAMA · doi:10.1001/jama.2014.10517 · Cited by 1,599
Self-citationKato, G. J., Piel, F. B., Reid, C. D., Gaston, M. H., Ohene-Frempong, K., Krishnamurti, L., Smith, W. R., Panepinto, J. A., Weatherall, D. J., Costa, F. F., et al. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.10 · Cited by 1,501
Self-citation
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
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
