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
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- 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.
- 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.
- Air pollution in autoimmune rheumatic diseases: A review(2011) FARHAT, Sylvia C. L.; SILVA, Clovis A.; ORIONE, Maria Angelica M.; CAMPOS, Lucia M. A.; SALLUM, Adriana M. E.; BRAGA, Alfesio L. F.Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases.
- Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine(2021) HELITO, Alberto C.; LINDOSO, Livia; SIECZKOWSKA, Sofia M.; ASTLEY, Camilla; QUEIROZ, Ligia B.; ROSE, Natalia; SANTOS, Claudia Renata P.; BOLZAN, Thalis; PERALTA, Rita Maria I. A.; FRANCO, Ruth R.; COMINATO, Louise; PEREIRA, Rosa Maria R.; TANNURI, Uenis; CAMPOS, Lucia Maria A.; LOURENCO, Benito; TOMA, Ricardo K.; MEDEIROS, Karina; WATANABE, Andreia; GRANGEIRO, Patricia Moreno; FARHAT, Sylvia C.; CASELLA, Caio B.; V, Guilherme Polanczyk; GUALANO, Bruno; SILVA, Clovis A.OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p < 0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.
- 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.
- Pediatric chronic patients at outpatient clinics: a study in a Latin American University Hospital(2018) ALVENO, Renata A.; V, Caroline Miranda; PASSONE, Caroline G.; WAETGE, Aurora R.; HOJO, Elza S.; FARHAT, Sylvia C. L.; ODONE-FILHO, Vicente; TANNURI, Uenis; CARVALHO, Werther B.; CARNEIRO-SAMPAIO, Magda; SILVA, Clovis A.Objective: To describe the characteristics of children and adotescentes with chronic diseases of outpatient clinics at a tertiary university hospital. Methods: A cross-sectional study was performed with 16,237 patients with chronic diseases followed-up in one year. The data were collected through the electronic system, according to the number of physician appointments in 23 pediatric specialties. Patients were divided in two groups: children (0-9 years) and adolescents (10-19 years). Early (10-14 years) and late (15-19 years) adolescent groups were also analyzed. Results: Of the total sample, 56% were children and 46% were adolescents. The frequencies of following pediatric specialties were significantly higher in adolescents when compared with children: cardiology, endocrinology, hematology, nephrology/renal transplantation, neurology, nutrology, oncology, palliative and pain care, psychiatry, and rheumatology (p< 0.05). The frequencies of emergency service visits (30% vs. 17%, p < 0.001), hospitalizations (23% vs. 11%, p < 0.001), intensive care unit admissions (6% vs. 2%, p< 0.001), and deaths (1% vs. 0.6%, p=0.002) were significantly lower in adolescents than in children. However, the number of physician appointments (>= 13) per patient was also higher in the adolescent group (5% vs. 6%, p = 0.018). Further analysis comparison between early and late adolescents revealed that the first group had significantly more physician appointments (35% vs. 32%, p= 0.025), and required more than two pediatric specialties (22% vs. 21%, p = 0.047). Likewise, the frequencies of emergency service visits (19% vs. 14%, p<0.001) and hospitalizations (12% vs. 10%, p= 0.035) were higher in early adolescents. Conclusions: This study evaluated a large population in a Latin American hospital and suggested that early adolescents with chronic diseases required many appointments, multiple specialties and hospital admissions. (C) 2017 Sociedade Brasileira de Pediatria.
- Mortality in adolescents and young adults with chronic diseases during 16 years: a study in a Latin American tertiary hospital(2019) RAMOS, Gabriel F.; RIBEIRO, Vanessa P.; MERCADANTE, Mariana P.; RIBEIRO, Maira P.; DELGADO, Artur F.; FARHAT, Sylvia C. L.; LEAL, Marta M.; MARQUES, Heloisa H.; ODONE-FILHO, Vicente; TANNURI, Uenis; CARVALHO, Werther B.; GRISI, Sandra J.; CARNEIRO-SAMPAIO, Magda; SILVA, Clovis A.Objectives: To evaluate mortality in adolescents and young adult patients with chronic diseases followed in a Latin American tertiary hospital. Methods: A cross-sectional retrospective study was performed in a tertiary/academic hospital in the state of Sao Paulo, Brazil. Death occurred in 529/2850 (18.5%) adolescents and young adult patients with chronic diseases, and 25/529 (4.7%) were excluded due to incomplete medical charts. Therefore, 504 deaths were evaluated. Results: Deaths occurred in 316/504 (63%) of early adolescent patients and in 188/504 (37%) of late adolescent/young adult patients. Further comparisons between early adolescents (n=316) and late adolescent/young adult patients (n= 188) with pediatric chronic diseases at the last hospitalization showed that the median disease duration (22.0 [0-173] vs. 43.0 [0-227] months, p < 0.001) was significantly lower in early adolescents vs. late adolescent/young adult patients. The median number of previous hospitalizations was significantly lower in the former group (4.0 [1-45] vs. 6.0 [1-52], p < 0.001), whereas the last hospitalization in intensive care unit was significantly higher (60% vs. 47%, p= 0.003). Regarding supportive measures, palliative care was significantly lower in the younger group compared to the older group (33% vs. 43%, p= 0.02). The frequencies of renal replacement therapy (22% vs. 13%, p = 0.02), vasoactive agents (65% vs. 54%, p= 0.01), and transfusion of blood products (75% vs. 66%, p = 0.03) were significantly higher in the younger group. The five most important etiologies of pediatric chronic diseases were: neoplasias (54.2%), hepatic diseases/transplantation (10%), human immunodeficiency virus (5.9%), and childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis (4.9%). Autopsy was performed in 58/504 (11%), and discordance between clinical and postmortem diagnoses was evidenced in 24/58 (41.3%). Conclusions: Almost 20% of deaths occurred in adolescents and young adults with distinct supportive care and severe disease patterns. Discordance between clinical diagnosis and autopsy was frequently observed. (C) 2018 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria.
- Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic(2023) CAMPOS, Reinan T.; LINDOSO, Livia; SOUSA, Renan A. de; HELITO, Alberto C.; IHARA, Bianca P.; STRABELLI, Claudia A. A.; PARADELAS, Levi M. V.; CARNEIRO, Beatriz O. L.; CARDOSO, Maria Paula R.; SOUZA, Jean Paulo V. de; FREIRE, Marianna R. de M.; ASTLEY, Camilla; LAURENTINO, Moises F.; BUSCATTI, Izabel M.; KOZU, Katia; AIKAWA, Nadia E.; SALLUM, Adriana M. E.; FERREIRA, Juliana C. O.; SIMON, Juliana R.; VIANA, Vivianne S. L.; QUEIROZ, Ligia B.; GUALANO, Bruno; ROSCHEL, Hamilton; PEREIRA, Rosa Maria R.; TOMA, Ricardo K.; WATANABE, Andreia; GRANGEIRO, Patricia M.; CASELLA, Caio B.; FARHAT, Sylvia C.; V, Guilherme Polanczyk; CAMPOS, Lucia Maria A.; SILVA, Clovis A.Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases.Methods: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pitts-burgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0).Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inat-tention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent var-iables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00-7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08-3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12-4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93-0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95-0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16-0.77; p = 0.026) remained inversely associated with abnormal HI scores.Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppres-sive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal pro-gram to protect the mental health of adolescents with and without chronic illnesses during future pandemics.
- Risk Factors for Juvenile Dermatomyositis: Exposure to Tobacco and Air Pollutants During Pregnancy(2014) ORIONE, Maria Angelica M.; SILVA, Clovis A.; SALLUM, Adriana M. E.; CAMPOS, Lucia M. A.; OMORI, Clarissa H.; BRAGA, Alfesio L. F.; FARHAT, Sylvia C. L.Objective, To evaluate the influence of exposure to inhaled environmental factors during pregnancy on the diagnosis of juvenile dermatomyositis (DM). Methods. We performed a case control study comprising 20 juvenile DM patients and 56 healthy controls matched by age and sex who were residents in the metropolitan region of a large city. A questionnaire assessed demographic data and environmental inhalation exposure during pregnancy (occupational exposure to demolition, chalk, construction and/or quarry dust, paints, varnish, gasoline vapor, and/or battery fluids; stationary sources of inhaled pollution near the mother's home; and maternal tobacco exposure). Daily concentrations of inhaled particulate matter, SO2, NO2, O-3, and carbon monoxide (CO) were evaluated throughout the gestational period. Results. Maternal occupational exposure to school chalk dust/gasoline vapor in the juvenile DM group was significantly higher compared with controls (50% versus 4.6%; P = 0.001). Smoking mothers and secondhand smoke exposure at home during pregnancy were significantly higher in the juvenile DM group versus controls (smoking mothers: 20% versus 1.7%; P = 0.01, and secondhand smoke: 35% versus 19%; P = 0.07). In univariate logistic regression models, maternal smoking, occupational exposure to inhaled agents, and the highest tertile of tropospheric CO (3.2-5.4 parts per million) in the third trimester were significantly associated with juvenile DM (P <= 0.05). In the multivariate analysis, smoking mother (odds ratio [OR] 13.26 [95% confidence interval (95% CI) 1.21-144.291, P = 0.03), occupational exposure (OR 35.39 [95% CI 1.97-632.80], P = 0.01), and CO (third tertile) exposure in the tird rimester of gestation (OR 12.21 [95% CI 1.28-115.96], P = 0.03) remained risk factors for juvenile DM. Conclusion. Inhaled pollutants and tobacco smoking during fetal development may contribute to juvenile DM.