Recruitment in the Cooperative Study of Sickle Cell Disease (CSSCD)

Gaston, Marilyn H.; Smith, Jeanne A.; Gallagher, Dianne; Flournoy-Gill, Zanet; West, Stewart; Bellevue, Rita; Farber, M E; Grover, Ranjeet; Koshy, Mabel; Ritchey, A. Kim; Wilimas, Judith A.; Verter, Joel

doi:10.1016/0197-2456(87)90016-x

Cited by 69 publications

(54 citation statements)

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“…PFTs were collected as part of the CSSCD, which enrolled and monitored more than 4,000 patients with SCD evaluated at 1 of 23 participating clinical centers across the United States between 1978 and 1998 (19,20). One of the primary goals of the CSSCD was to collect data on the clinical course of SCD from birth to death.…”

Section: Patient Databasementioning

confidence: 99%

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Klings

Wyszynski

Nolan

et al. 2006

Am J Respir Crit Care Med

189

166

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Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DL CO ]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DL CO , or normal. The association between laboratory data of patients with decreased DL CO Sickle cell anemia (Hb-SS) results from homozygosity for a point mutation in the ␤-globin gene (HBB; Glu6Val) causing the resultant sickle hemoglobin (Hb S) to be less soluble when deoxygenated than normal hemoglobin (1). Even with improved treatment, including the early use of prophylactic antibiotic regimens, judicious transfusions, and the administration of hydroxyurea in selected patients, mortality remains high for this population. The median age at death is 42 yr for males and 48 yr for females with Hb-SS. Pulmonary complications, including acute chest syndrome (ACS), pulmonary hypertension (PH), and pulmonary fibrosis, account for 20-30% of deaths in the Hb-SS population and are often underrecognized by the health care community (2, 3).Dyspnea is a frequent complaint amongst patients with sickle cell disease, the etiology of which is unclear and likely multifacto- 5). Studies of lung function to date in this population have been of modest size, often involving fewer than 50 patients (4, 6-11) and largely inconclusive. Their results have yielded a spectrum of abnormalities, including restrictive lung disease, abnormal diffusion capacity for carbon monoxide (Dl CO ), obstructive disease, and hypoxemia (4,6,7,9,12). No definitive profile for pulmonary function in sickle cell disease has emerged. As a result, clinicians find pulmonary function tests (PFTs) difficult to interpret in this population and their clinical utility for directing further investigation and therapy has not been well evaluated.Of growing concern is the link between obstructive lung disease and ACS, particularly in children (7,13,14). The few published studies suggest that obstructive lung disease, in some cases, plays a role in the pathogenesis of ACS (7,13,15). Moreover, obstructive lung disease could be a long-term sequela of recurrent episodes of ACS (6, 9). Larger scale studies are necessary to elucidate more clearly the interaction between lung function and ACS. In addition, certain findings on PFTs might be a marker of other complications of sickle vasculopathy. For example, isolated decreased Dl CO is a well-established finding associated with PH (16, 17). However, its role as a marker or predictor of PH in the Hb-SS population is unknown. The purpose of this study is to evalua...

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Section: Patient Databasementioning

confidence: 99%

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Klings

Wyszynski

Nolan

et al. 2006

Am J Respir Crit Care Med

189

166

View full text Add to dashboard Cite

show abstract

“…Details of the CSSCD study design with data collection at New England Research Institute (NERI, Watertown, MA) have been previously published [23,24]. Eligible patients for the current study included children with HbSS enrolled in Phase 1 of CSSCD, since this patient cohort had prospective collection of serial laboratory and clinical data related to hepatobiliary disease and genomic DNA available for analysis.…”

Section: Patient Data and Samplesmentioning

confidence: 99%

UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia

et al. 2008

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Genetic modifiers contribute to phenotypic variability in patients with sickle cell anemia (SCA). The influence of the bilirubin UDP-glucuronosyltransferase (UGT) 1A1 (TA) n TAA promoter polymorphism on bilirubin levels and gallbladder disease in SCA was examined using prospectively collected data from the Cooperative Study of Sickle Cell Disease. A total of 324 children with HbSS (median age 6.9 years) had UGT1A1 genotyping; 243 (75%) had common (TA) 6 or (TA) 7 alleles, whereas 81 (25.0%) had variant (TA) 5 or (TA) 8 alleles. The UGT1A1 genotype significantly influenced average bilirubin levels for the common alleles: 6/6 genotype 5 2.36 ± 1.13 mg/dL, 6/7 genotype 5 2.90 ± 1.54 mg/dL, and 7/7 genotype 5 4.24 ± 2.11 mg/dL (P < 0.0001). Thirty-nine percent of children with the 7/7 genotype had documented gallbladder disease, compared with 18.2% with the 6/7 genotype and only 9.9% with the wildtype 6/6 UGT1A1 genotype (P 5 0.001). To analyze the (TA) 5 and (TA) 8 variant alleles, three groups were generated, showing increasing bilirubin levels with increasing TA repeats and age. Group 3 (genotypes 6/8, 7/7, and 7/8) had a significantly greater rate of bilirubin change than Groups 1 (genotypes 5/6, 5/7, and 6/6) or 2 (genotype 6/7). These results validate previous smaller studies and confirm that the UGT1A1 promoter polymorphism exerts a powerful influence on bilirubin levels and the development of gallbladder disease in children with SCA. UGT1A1 genotyping should be considered as a screening tool for predicting children most likely to develop gallbladder disease at a young age. Am. J. Hematol. 83:800-803, 2008. V

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“…6 Objectives, eligibility requirements, enrollment procedures, and data collection methods for the CSSCD have been reported. 6,20,21 As part of this study, the CSSCD initiated a prospective infant cohort trial in 1978 into which almost 400 infants were enrolled at birth and were followed up prospectively to characterize their natural history. Children in this cohort underwent brain MRI at age 6 years and then every 2 years thereafter.…”

Section: Study Patients and Designmentioning

confidence: 99%

Distinct HLA associations by stroke subtype in children with sickle cell anemia

Hoppe¹,

Klitz²,

Noble³

et al. 2003

Blood

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Children with sickle cell anemia (SCA) carry a 200-fold increased risk for cerebral infarction. Stroke can be the result of small-vessel (SV) or large-vessel (LV) disease. However, it is unknown whether these subtypes result from the same pathophysiologic processes. Complete HLA genotyping was performed on 231 eligible children previously enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD). Cerebral infarction on magnetic resonance imaging (MRI) was documented in 71 patients, and 160 patients had negative findings on MRI. Based on MRI/magnetic resonance angiography (MRA) findings, infarct size, and location, 36 patients were classified as having LV stroke and 35 as having SV stroke. When comparing the total MRI؉ group with the MRI؊ group, HLA DPB1*0401 was associated with increased stroke risk (P ‫؍‬ .01), whereas DPB1*1701 (P ‫؍‬ .02) conferred protection from stroke. These DPB1 associations with stroke were attributed to the SV stroke group, in whom DPB1*0401 was associated with susceptibility (P ‫؍‬ .003) and DPB1*1701 with protection from stroke (P ‫؍‬ .06). In the LV stroke subgroup, HLA-A*0102 (P ‫؍‬ .02) and -A*2612 (P ‫؍‬ .007) conferred susceptibility, whereas -A*3301(P ‫؍‬ .04) protected from stroke. These results suggest that specific HLA alleles influence stroke risk and appear to contribute differently to SV and LV stroke subtypes. The distinct HLA associations with SV and LV stroke suggest that different pathologic processes may be involved in the development of stroke in children with SCA. If these results are confirmed in a larger study, HLA type may serve as a useful marker for the early identification of SCA patients at high risk for stroke. (Blood. 2003;

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Recruitment in the Cooperative Study of Sickle Cell Disease (CSSCD)

Cited by 69 publications

References 0 publications

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia

Distinct HLA associations by stroke subtype in children with sickle cell anemia

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