SYLVIA COSTA LIMA FARHAT
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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- O ozônio diminui a qualidade do sêmen em pacientes com lúpus eritematoso sistêmico(2016) FARHAT, Juliana; FARHAT, Sylvia Costa Lima; BRAGA, Alfesio Luis Ferreira; COCUZZA, Marcello; BORBA, Eduardo Ferreira; BONFA, Eloisa; SILVA, Clovis ArturObjective: To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). Methods: A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. Results: Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01-89.65; p = 0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93-216.38; p = 0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80-88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8-40.0; p = 0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3-128.7; p = 0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80-88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0-53.0; p = 0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1-155.9; p = 0.044). Conclusion: Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.
conferenceObject EXPOSURE TO ENVIRONMENTAL FACTORS DURING PREGNANCY AND AFTER BIRTH TO THE BEGINNING OF JUVENILE IDIOPATHIC ARTHRITIS(2015) FRANCA, C. M. P.; SALLUM, A. M. E.; SILVA, C. A.; AIKAWA, N. E.; BRAGA, A. L. F.; FARHAT, S. C. L.- Risk Factors Associated with Juvenile Idiopathic Arthritis: Exposure to Cigarette Smoke and Air Pollution from Pregnancy to Disease Diagnosis(2018) FRANCA, Camila Maria Paiva; SALLUM, Adriana Maluf Elias; BRAGA, Alfesio Luis Ferreira; STRUFALDI, Fernando Louzada; SILVA, Clovis Artur Almeida; FARHAT, Sylvia Costa LimaObjective. To evaluate exposure to environmental factors inhaled during pregnancy and after birth until juvenile idiopathic arthritis (JIA) diagnosis among residents of a large city. Methods. This is an exploratory case-control study that consists of 66 patients with JIA and 124 healthy controls matched by age and sex, living in the Sao Paulo, Brazil, metropolitan area until JIA diagnosis, and whose mothers had resided in this region during pregnancy. A structured and reliable questionnaire (k index for test-retest was 0.80) assessed demographic data, gestational and perinatal-related factors, and exposure to inhalable environmental elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, exposure to cigarette smoke, and the presence of industrial activities or gas stations near the home, work, daycare, or school). Tropospheric pollutants included particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O-3), and carbon monoxide (CO). Results. During pregnancy, intrauterine cigarette smoke exposure (OR 3.43, 95% CI 1.45-8.12, p = 0.005) and maternal occupational exposure (OR 13.69, 95% CI 4.4-42.3, p < 0.001) were significant independent risk factors for JIA diagnosis. In contrast, maternal employment (OR 0.06, 95% CI 0.02-0.2, p < 0.001) and ideal maternal weight gain (OR 0.36, 95% CI 0.2-0.8, p = 0.017) presented negative associations. Secondhand smoke exposure from birth to JIA diagnosis (OR 3.6, 95% CI 1.8-7.3, p < 0.001) and exposure to O-3 during the second year of life (OR 2.76, 95% CI 1.20-6.37, p = 0.017) were independent and significant risk factors for the pathogenesis of JIA. Conclusion. In our study, cigarette smoke exposure (intrauterine and after birth), exposure to O-3 in the second year of life, and maternal occupational exposure were identified as potential risk factors for JIA, warranting further study.
- Exposure to Air Pollutants and Disease Activity in Juvenile-Onset Systemic Lupus Erythematosus Patients(2015) FERNANDES, Elisabeth C.; SILVA, Clovis A.; BRAGA, Alfesio L. F.; SALLUM, Adriana M. E.; CAMPOS, Lucia M. A.; FARHAT, Sylvia C. L.ObjectiveTo investigate the association between exposure to air pollutants in the Sao Paulo metropolitan area and disease activity in juvenile-onset systemic lupus erythematosus (SLE) patients. MethodsA longitudinal panel study based on 409 consecutive visits of juvenile-onset SLE patients living in the Sao Paulo metropolitan area was carried out. Disease activity was evaluated in accordance with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and the patients were divided into 2 groups: those with SLEDAI scores 8 and those with SLEDAI scores >8. Daily concentrations of inhaled particulate matter (PM10), sulfur dioxide, nitrogen dioxide (NO2), ozone, and carbon monoxide (CO) were evaluated on the 21 days preceding the medical visits. A generalized estimation equation model was used to assess the impact of these measurements on SLEDAI-2K scores, considering the fixed effects for repetitive measurements. The models were adjusted for erythrocyte sedimentation rate, corticosteroid use (daily and cumulative doses), antimalarial use, the use of immunosuppressive agents, the presence of infection 20 days preceding the medical appointment, and the minimum temperature and relative humidity outdoors. ResultsPM(10), NO2, and CO were risk factors for juvenile-onset SLE disease activity (SLEDAI-2K score >8) approximately 2 weeks after exposure. A 13.4 g/m(3) increase in the PM10 moving average (from lag 12 to lag 15) was associated with a 34% increase (95% confidence interval 7.0-68.0) in the risk of a SLEDAI-2K score >8. ConclusionThis is the first study to show that exposure to inhaled pollutants may increase the risk of disease activity in children with juvenile-onset SLE in a large urban center.
- PERSONAL EXPOSURE TO AIR POLLUTION INFLUENCED DISEASE ACTIVITY AND EXHALED BREATH BIOMARKERS: A PROSPECTIVE STUDY IN A CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS POPULATION(2016) GOULART, M. F. G.; ALVES, A. G. F.; BRAGA, A. L. F.; SALUM, A. M. E.; PEREIRA, L. A. A.; COIMBRA, A. J. F.; CARVALHO, T. D. S.; NAKAGAWA, N. K.; SILVA, C. A.; FARHAT, S. C. L.
- Anti-ribosomal P antibody: a multicenter study in childhood-onset systemic lupus erythematosus patients(2017) VALOES, C. C. M.; MOLINARI, B. C.; PITTA, A. C. G.; GORMEZANO, N. W. S.; FARHAT, S. C. L.; KOZU, K.; SALLUM, A. M. E.; APPENZELLER, S.; SAKAMOTO, A. P.; TERRERI, M. T.; PEREIRA, R. M. R.; MAGALHAES, C. S.; FERREIRA, J. C. O. A.; BARBOSA, C. M.; GOMES, F. H.; BONFA, E.; SILVA, C. A.Objectives: Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods: This was a retrospective multicenter study performed in 10 pediatric rheumatology services of Sao Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results: Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies (p = 0.780). Conclusions: The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.
- Are prematurity and environmental factors determinants for developing childhood-onset systemic lupus erythematosus?(2018) CONDE, Paola G.; FARHAT, Luis C.; BRAGA, Alfesio L. F.; SALLUM, Adriana E. M.; FARHAT, Sylvia C. L.; SILVA, Clovis A.Objective: The objective of this study is to evaluate the influence of exposure to air pollutants and inhalable environmental elements during pregnancy and after birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis. Methods: This case-control study comprised 30 cSLE patients and 86 healthy controls living in the Sao Paulo metropolitan area. A structured and reliable questionnaire (kappa index for test-retest was 0.78) assessed demographic data, gestational and perinatal-related-factors, and exposure to inhalable particles and/or volatile vapor, and/or tobacco, as well as, the presence of industrial activities or gas stations near the home/work/daycare/school). Tropospheric pollutants included: particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O-3) and carbon monoxide (CO). Results: The median current age was similar between cSLE patients and healthy controls [16.0 (5-21) versus 15.0 (4-21) years, p = .32], likewise the frequency of female gender (87% versus 78%, p = .43). The frequencies of prematurity (30% versus 6%, p = .001), maternal occupational exposure during pregnancy (59% versus 12%, p < .001), exposure to volatile vapor (48% versus 8%, p < .001) and fetal smoking (maternal and/or secondhand) (37% versus 19%, p = .008) were significantly higher in cSLE patients compared with controls. In a multivariate analysis regarding the gestation period, maternal occupational exposure (OR 13.5, 95% CI 2.5-72.4, p = .002), fetal smoking (OR 8.6, 95% CI 1.6-47, p = .013) and prematurity (OR 15.8, 95% CI 1.9-135.3, p = .012) remained risk factors for cSLE development. Furthermore, exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95% CI 1.8-42.1, p = .002) was also a risk factor for cSLE development. Conclusions: Prematurity and environmental factors were risk factors for developing cSLE.
- Air pollution influence on serum inflammatory interleukins: A prospective study in childhood-onset systemic lupus erythematous patients(2021) FARHAT, Sylvia Costa Lima; EJNISMAN, Carolina; ALVES, Andressa Guariento Ferreira; GOULART, Maria Fernanda Giacomin; LICHTENFELS, Ana Julia de Faria Coimbra; BRAGA, Alfesio Luis Ferreira; PEREIRA, Luiz Alberto Amador; ELIAS, Adriana Maluf; SILVA, Clovis A.Objective To assess the effect of individual exposure, in real-time, to traffic-related pollutants on serum interleukin levels of childhood-onset lupus erythematous systemic (c-SLE) patients. Methods A longitudinal and observational design was conducted in 12 repeated measures of serum samples and clinical evaluations (totaling 108 measurements) of c-SLE patients over 30 consecutive months. Real-time, individual exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) was measured with portable monitors. Generalized estimating equation was used to evaluate the association between exposure to PM2.5 and NO2 and the following serum cytokine levels on the 7 days preceding clinical assessment and serum collection: MCP1, IL-6, IL-8, IL-10, IL-17, IFN-alpha, and TNF-alpha. Disease activity and other risk factors were also controlled. Results An interquartile range (IQR) increase in PM2.5 daily concentration was significantly associated with increased levels of TNF-alpha on the third, fourth, and seventh day after exposure; IL-10 on the third and fourth day after exposure; IL-17 on the third and seventh day after exposure; and INF-alpha on the third day after exposure (p < 0.05). An IQR increase in 7-day moving average of PM2.5 was associated with a 6.2 pg/mL (95% CI: 0.5; 11.8; p = 0.04) increase in serum IFN-alpha level. An unexpected significant association was observed between an IQR increase in NO(2)7-day cumulative concentration and a decrease of 1.6 pg/mL (95% CI: -2.6; -0.7; p < 0.001) in serum IL-17. Conclusion Real-time exposure to PM2.5 prospectively associated with increased serum TNF-alpha, INF-alpha, IL-10, and IL-17 levels in c-SLE patients.
- Autoimmune hepatitis in 847 childhood- onset systemic lupus erythematosus population: a multicentric cohort study(2018) BALBI, Verena A.; MONTENEGRO, Barbara; PITTA, Ana C.; SCHMIDT, Ana R.; FARHAT, Sylvia C.; COELHO, Laila P.; FERREIRA, Juliana C. O.; PEREIRA, Rosa M. R.; TERRERI, Maria T.; SAAD-MAGALHAES, Claudia; AIKAWA, Nadia E.; SAKAMOTO, Ana P.; KOZU, Katia; CAMPOS, Lucia M.; SALLUM, Adriana M.; FERRIANI, Virginia P.; PIOTTO, Daniela P.; BONFA, Eloisa; SILVA, Clovis A.Objective: To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of Sao Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni's correction (p < 0.0033). Results: AIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up >= 18 months (4/7) had complete response to therapy according to lAHGC None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0-8.5) vs. 0.12 (0-8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0-26) vs. 7 (0-41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033). Conclusions: Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.
- Henoch-Schonlein purpura nephritis: initial risk factors and outcomes in a Latin American tertiary center(2018) BUSCATTI, Izabel M.; CASELLA, Beatriz B.; AIKAWA, Nadia E.; WATANABE, Andrea; FARHAT, Sylvia C. L.; CAMPOS, Lucia M. A.; SILVA, Clovis ArturThe objective of this study was to evaluate prevalence, initial risk factors, and outcomes in Henoch-Schonlein purpura nephritis (HSPN) patients in Latin America. Two hundred ninety-six patients (validated EULAR/PRINTO/PRES HSP criteria) were assessed by demographic data, clinical/laboratorial involvements, and treatments in the first 3 months after diagnosis. They were followed-up in a Latin American tertiary center and were divided in two groups: with and without nephritis. Persistent non-nephrotic proteinuria, nephrotic proteinuria, and acute/chronic kidney injury were also systematically evaluated at 1, 5, 10, and 15 years after diagnosis. HSPN was evidenced in 139/296 (47%) in the first 3 months. The median age at diagnosis was significantly higher in HSPN patients compared without renal involvement [6.6 (1.5-17.7) vs. 5.7 (0.9-13.5) years, p = 0.022]. The frequencies of persistent purpura (31 vs. 10%, p < 0.0001), recurrent abdominal pain (16 vs. 7%, p = 0.011), gastrointestinal bleeding (25 vs. 10%, p < 0.0001), and corticosteroid use (54 vs. 41%, p = 0.023) were significantly higher in the former group. Logistic regression demonstrated that the independent variables associated with HSNP were persistent purpura (OR = 3.601; 95% CI (1.605-8.079); p = 0.002) and gastrointestinal bleeding (OR = 2.991; 95% CI (1.245-7.183); p = 0.014). Further analysis of patients without HSPN in the first 3 months revealed that 29/118 (25%) had persistent non-nephrotic proteinuria and/or hematuria in 1 year, 19/61 (31%) in 5 years, 6/17 (35%) in 10 years and 4/6 (67%) in 15 years after diagnosis. None of them had chronic kidney injury or were submitted to renal replacement therapy. The present study observed HSPN in almost one half of patients in the first months of disease, and HSPN was associated with persistent purpura and gastrointestinal bleeding. One fourth of patients had nephritis only evidenced during follow-up without severe renal manifestations.