Biomedical subjects

ACCESS Research Group

Publications and source records attributed to ACCESS Research Group.

9 recordsLinked to original sources

PubMed2006

Robust trend tests for genetic association using matched case-control design.

Trend tests for genetic association using a matched case-control design are studied, which allows for a variable number of controls per case. However, the tests depend on the scores based on the underlying genetic model, thus it may result in substantial loss of power when the model is misspecified. Since the mode of inheritance may be unknown for complex diseases, robust trend tests in matched case-control studies are developed. Simulation is conducted to compare the trend tests and the robust trend tests under various genetic models. The results are applied to detect candidate-gene association using an example from a case-control aetiologic study of sarcoidosis.

Black People↗

PubMed2005

The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites.

The BTNL2 gene is a member of the B7 receptor family that probably functions as a T-cell costimulatory molecule. It resides in the class II major histocompatibility complex (MHC) region of chromosome 6p and has recently been associated with sarcoidosis susceptibility in a white German population. We sought to replicate the BTNL2 association in an African American family-based study population (n=219 nuclear families) and two case-control populations--one African American (n=295 pairs) and one white (n=366 pairs). Ten SNPs were detected within a 490-bp region spanning exon/intron 5 of BTNL2. Haplotype variation within this region was significantly associated with sarcoidosis in all three study populations but more so in whites (P=.0006) than in the African American case-control (P=.02) or family-based (P=.03) samples. The previously reported BTNL2 SNP with the strongest sarcoidosis association, rs2076530, was also the SNP with the strongest association in our white population (P<.0001). The A allele of rs2076530 results in a premature exon-splice site and increases risk for sarcoidosis (odds ratio=2.03; 95% confidence interval 1.32-3.12). Although rs2076530 was not associated with sarcoidosis in either African American sample, a three-locus haplotype that included rs2076530 was associated with sarcoidosis across all three study samples. Multivariable logistic regression analyses showed that BTNL2 effects are independent of human leukocyte antigen class II genes in whites but may interact antagonistically in African Americans. Our results underscore the complexity of genetic risk for sarcoidosis emanating from the MHC region.

Black or African American↗

PubMed2005

Job and industry classifications associated with sarcoidosis in A Case-Control Etiologic Study of Sarcoidosis (ACCESS).

OBJECTIVES: To determine whether specific occupations and industries may be associated with sarcoidosis. METHODS: A Case Control Etiologic Study of Sarcoidosis (ACCESS) obtained occupational and environmental histories on 706 newly diagnosed sarcoidosis cases and matched controls. We used Standard Industrial Classification (SIC) and Standard Occupational Classification (SOC) to assess occupational contributions to sarcoidosis risk. RESULTS: Univariable analysis identified elevated risk of sarcoidosis for workers with industrial organic dust exposures, especially in Caucasian workers. Workers for suppliers of building materials, hardware, and gardening materials were at an increased risk of sarcoidosis as were educators. Work providing childcare was negatively associated with sarcoidosis risk. Jobs with metal dust or metal fume exposures were negatively associated with sarcoidosis risk, especially in Caucasian workers. CONCLUSIONS: In this study, we found that exposures in particular occupational settings may contribute to sarcoidosis risk.

Adolescent↗

PubMed2005

Pulmonary and psychosocial findings at enrollment in the ACCESS study.

AIM: To assess lung involvement and the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis at enrollment in A Case Control Etiologic Study of Sarcoidosis (ACCESS). METHODS: 736 patients with biopsy diagnosis of sarcoidosis within 6 months of enrollment were studied at 10 US centers. Lung involvement was evaluated by chest radiography, spirometry and dyspnea questionnaire. Demographics, number of involved extrathoracic organ systems, comorbidities, and health-related quality of life (HRQL) were assessed. RESULTS: 95% of patients had lung involvement. 8% were Scadding Stage 0, 40% I, 37% II, 10% III, and 5% IV 51% reported dyspnea. Increasing radiographic lung stage was associated with decreasing Forced Vital Capacity (FVC) (p < 0.01). Patients with higher stages had more airways obstruction and dyspnea. 46% of cases and 27% of controls had Center for Epidemiologic Studies Depression Scale (CES-D) scores of 9 or greater, (p < 0.001). Age > or = 40, African-American race, body mass index > or = 30kg/m2, and CES-D scores > 9 were associated with decreased FVC and greater dyspnea. Impaired spirometry and greater dyspnea were associated with poorer quality of life. CONCLUSION: A "global" approach to the sarcoidosis patient, including careful assessment of dyspnea and health related quality of life, as well as of lung function and radiographic changes, and any extrathoracic involvement, is important, not only in management of the individual patient, but should also prove beneficial in assessing outcomes in clinical trials in the future.

Adult↗

PubMed2004

A case control etiologic study of sarcoidosis: environmental and occupational risk factors.

Past research suggests that environmental factors may be associated with sarcoidosis risk. We conducted a case control study to test a priori hypotheses that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of age-, race-, and sex-matched control subjects. Interviewers administered questionnaires containing questions regarding occupational and nonoccupational exposures that we assessed in univariable and multivariable analyses. We observed positive associations between sarcoidosis and specific occupations (e.g., agricultural employment, odds ratio [OR] 1.46, confidence interval [CI] 1.13-1.89), exposures (e.g., insecticides at work, OR 1.52, CI 1.14-2.04, and work environments with mold/mildew exposures [environments with possible exposures to microbial bioaerosols], OR 1.61, CI 1.13-2.31). A history of ever smoking cigarettes was less frequent among cases than control subjects (OR 0.62, CI 0.50-0.77). In multivariable modeling, we observed elevated ORs for work in areas with musty odors (OR 1.62, CI 1.24-2.11) and with occupational exposure to insecticides (OR 1.61, CI 1.13-2.28), and a decreased OR related to ever smoking cigarettes (OR 0.65, CI 0.51-0.82). The study did not identify a single, predominant cause of sarcoidosis. We identified several exposures associated with sarcoidosis risk, including insecticides, agricultural employment, and microbial bioaerosols.

Adolescent↗

PubMed2003

The diagnostic pathway to sarcoidosis.

PURPOSE: To examine the time from the first physician visit to the diagnosis of sarcoidosis. HYPOTHESES: The time required to diagnose sarcoidosis is dependent on the initial symptoms, socioeconomic status, referral to a specialist, race, and severity of pulmonary involvement. METHODS: Patients were recruited from the Case Control Etiology of Sarcoidosis Study (ACCESS) and had biopsy-confirmed sarcoidosis. Subjects were asked to recall the date of onset of symptoms of sarcoidosis, their first physician visit, number of physician visits, and types of physicians seen. RESULTS: One hundred eighty-nine patients were enrolled. The diagnosis of sarcoidosis was made on the first physician visit in only 15.3% of cases. The presence of pulmonary symptoms was associated with prolonged time (> 6 months vs < or = 6 months, p = 0.02) until diagnosis, and the presence of skin symptoms with a shorter time (< or = 6 months vs > 6 months, p = 0.02) until diagnosis. Patients with pulmonary symptoms had more physician visits (mean +/- SEM) until the diagnosis was made compared to those without pulmonary symptoms (4.84 +/- 0.38 visits vs 3.15 +/- 0.24 visits, p = 0.0002). The mean baseline FEV(1) was greater in those diagnosed < or = 6 months from the first physician visit than those diagnosed > 6 months (87.3 +/- 1.52% predicted vs 81.2 +/- 2.5% predicted, p = 0.04). There was a significant delay in diagnosis (> 6 months vs < or = 6 months) from first physician visit with higher Scadding stages (stage 4 vs stage 2, or stage 3 vs stage 0 or 1, p = 0.04). CONCLUSIONS: The diagnosis of sarcoidosis is often delayed and seems to be more a factor of disease presentation than patient or physician characteristics. The presence of pulmonary symptoms or higher radiographic stages is associated with a prolonged time until diagnosis. The presence of skin symptoms is associated with less delay in diagnosis. It is likely that the delay in diagnosis of pulmonary sarcoidosis relates to the fact that pulmonary symptoms and parenchymal involvement are nonspecific and are often regarded as manifestations of other pulmonary diseases.

Adult↗

PubMed2003

Recovery of cell wall-deficient organisms from blood does not distinguish between patients with sarcoidosis and control subjects.

STUDY OBJECTIVE: To determine if cell wall-deficient forms (CWDF) of mycobacteria can be grown in culture of blood from subjects with sarcoidosis. DESIGN: A special multicenter study of sarcoidosis (A Case Control Etiologic Study of Sarcoidosis), supported by the National Heart, Lung, and Blood Institute. PATIENTS AND CONTROL SUBJECTS: PATIENTS AND CONTROL SUBJECTS were recruited at 10 institutions in the United States. Control subjects (controls) were of the same gender and race, and within 5 years of age as matching patients with sarcoidosis (cases). RESULTS: Cultures were incubated from 347 blood specimens (197 cases, 150 controls). Two investigators trained to recognize CWDF mycobacteria examined material obtained from culture tubes after 3 weeks. Structures thought to be CWDF were seen with equal frequency in cases (38%) and controls (41%). Thirty-nine percent of cases and 37% of controls were read as negative for CWDF. CONCLUSION: This study fails to confirm earlier reports that CWDF mycobacteria can be grown from the blood of patients with sarcoidosis, but not from control subjects.

Bacteriological Techniques↗

PubMed2003

Two year prognosis of sarcoidosis: the ACCESS experience.

A cohort of 215 sarcoidosis patients from the ACCESS study underwent a clinical evaluation at study enrollment and two years later. Approximately 80% of subjects had an improved or stable FVC, FEV1, chest radiograph determined by Scadding stage, and dyspnea scale. African-Americans had less improvement in FVC than Caucasians (p = 0.04). Patients with erythema nodosum at presentation were more likely to have improvement in the chest radiograph at two-year follow-up (p = 0.007). Patients with a lower annual family income were more likely to worsen with respect to dyspnea (p = 0.01) and more likely to have new organ involvement at two-year follow-up (p = 0.045). The development of new organ involvement over the two year follow-up period was more common in African-Americans compared to Caucasians (p = 0.002) and more likely in those with extrapulmonary involvement at study entry (p = 0.003). There was an excellent concordance between changes in FVC and FEV1 over the two-year period. However, changes in FVC alone were inadequate to describe the change in pulmonary status of the patients, as changes in chest radiographic findings or the level of dyspnea did often but not always move in the same direction as FVC. In conclusion, data from this heterogeneous United States sarcoidosis population indicate that sarcoidosis tends to improve or remain stable over two years in the majority of patients. Several factors associated with improved or worse outcome over two years were identified.

Adult↗

PubMed2001

Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS).

Despite reports of familial clustering of sarcoidosis, little empirical evidence exists that disease risk in family members of sarcoidosis cases is greater than that in the general population. To address this question, we estimated sarcoidosis familial relative risk using data on disease occurrence in 10,862 first- and 17,047 second-degree relatives of 706 age, sex, race, and geographically matched cases and controls who participated in the multicenter ACCESS (A Case-Control Etiology Study of Sarcoidosis) study from 1996 to 1999. Familial relative risk estimates were calculated using a logistic regression technique that accounted for the dependence between relatives. Sibs had the highest relative risk (odds ratio [OR] = 5.8; 95% confidence interval [CI] = 2.1-15.9), followed by avuncular relationships (OR = 5.7; 95% CI = 1.6-20.7), grandparents (OR = 5.2; 95% CI = 1.5-18.0), and then parents (OR = 3.8; 95% CI = 1.2-11.3). In a multivariate model fit to the parents and sibs data, the familial relative risk adjusted for age, sex, relative class, and shared environment was 4.7 (95% CI = 2.3-9.7). White cases had a markedly higher familial relative risk compared with African-American cases (18.0 versus 2.8; p = 0.098). In summary, a significant elevated risk of sarcoidosis was observed among first- and second-degree relatives of sarcoidosis cases compared with relatives of matched control subjects.

Adolescent↗