FREDERICO LEON ARRABAL FERNANDES

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico

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  • article 10 Citação(ões) na Scopus
    Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses
    (2021) LOURENCO, Juliana D.; TEODORO, Walcy R.; BARBEIRO, Denise F.; VELOSA, Ana Paula P.; SILVA, Larissa E. F.; KOHLER, Julia B.; MOREIRA, Alyne R.; V, Marcelo Aun; SILVA, Isadora C. da; FERNANDES, Frederico L. A.; NEGRI, Elnara M.; GROSS, Jefferson L.; TIBERIO, Iolanda F. L. C.; ITO, Juliana T.; LOPES, Fernanda D. T. Q. S.
    Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, ROR gamma t, Foxp3, interleukin (IL)-6, -17, -10, and TGF-beta was assessed by RT-qPCR. IL-6, -17, -10, and TGF-beta levels were determined by ELISA. We observed increased STAT3, ROR gamma t, Foxp3, IL-6, and TGF-beta gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, ROR gamma t, IL-6, and TGF-beta gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.
  • article 47 Citação(ões) na Scopus
    Comparação entre medidas objetivas do tabagismo e tabagismo autodeclarado em pacientes com asma ou DPOC: será que nossos pacientes dizem a verdade?
    (2015) STELMACH, Rafael; FERNANDES, Frederico Leon Arrabal; CARVALHO-PINTO, Regina Maria; ATHANAZIO, Rodrigo Abensur; RACHED, Samia Zahi; PRADO, Gustavo Faibischew; CUKIER, Alberto
    Objective: Smoking prevalence is frequently estimated on the basis of self-reported smoking status. That can lead to an underestimation of smoking rates. The aim of this study was to evaluate the difference between self-reported smoking status and that determined through the use of objective measures of smoking at a pulmonary outpatient clinic. Methods: This was a cross-sectional study involving 144 individuals: 51 asthma patients, 53 COPD patients, 20 current smokers, and 20 never-smokers. Smoking status was determined on the basis of self-reports obtained in interviews, as well as through tests of exhaled carbon monoxide (eCO) and urinary cotinine. Results: All of the asthma patients and COPD patients declared they were not current smokers. In the COPD and asthma patients, the median urinary cotinine concentration was 167 ng/mL (range, 2-5,348 ng/mL) and 47 ng/mL (range, 5-2,735 ng/mL), respectively (p < 0.0001), whereas the median eCO level was 8 ppm (range, 0-31 ppm) and 5 ppm (range, 2-45 ppm), respectively (p < 0.05). In 40 (38%) of the patients with asthma or COPD (n = 104), there was disagreement between the self-reported smoking status and that determined on the basis of the urinary cotinine concentration, a concentration > 200 ng/mL being considered indicative of current smoking. In 48 (46%) of those 104 patients, the self-reported non-smoking status was refuted by an eCO level > 6 ppm, which is also considered indicative of current smoking. In 30 (29%) of the patients with asthma or COPD, the urinary cotinine concentration and the eCO level both belied the patient claims of not being current smokers. Conclusions: Our findings suggest that high proportions of smoking pulmonary patients with lung disease falsely declare themselves to be nonsmokers. The accurate classification of smoking status is pivotal to the treatment of lung diseases. Objective measures of smoking could be helpful in improving clinical management and counseling.
  • article 12 Citação(ões) na Scopus
    Recommendations for the pharmacological treatment of COPD: questions and answers
    (2017) FERNANDES, Frederico Leon Arrabal; CUKIER, Alberto; CAMELIER, Aquiles Assuncao; FRITSCHER, Carlos Cezar; COSTA, Claudia Henrique da; PEREIRA, Eanes Delgado Barros; GODOY, Irma; CANCADO, Jose Eduardo Delfini; ROMALDINI, Jose Gustavo; CHATKIN, Jose Miguel; JARDIM, Jose Roberto; RABAHI, Marcelo Fouad; NUCCI, Maria Cecilia Nieves Maiorano de; SALES, Maria da Penha Uchoa; CASTELLANO, Maria Vera Cruz de Oliveira; AIDE, Miguel Abidon; TEIXEIRA, Paulo Jose Zimermann; MACIEL, Renato; CORREA, Ricardo de Amorim; STIRBULOV, Roberto; ATHANAZIO, Rodrigo Abensur; RUSSO, Rodrigo; MINAMOTO, Suzana Tanni; LUNDGREN, Fernando Luiz Cavalcanti
    O tratamento da DPOC vem se tornando cada vez mais eficaz. Medidas que envolvem desde mudanças comportamentais, redução de exposições a fatores de risco, educação sobre a doença e seu curso, reabilitação, oxigenoterapia, manejo de comorbidades, tratamentos cirúrgicos e farmacológicos até os cuidados de fim de vida permitem ao profissional oferecer uma terapêutica personalizada e efetiva. O tratamento farmacológico da DPOC constitui um dos principais pilares desse manejo, e muitos avanços têm sido atingidos na área nos últimos anos. Com a maior disponibilidade de medicações e combinações terapêuticas fica cada vez mais desafiador conhecer as indicações, limitações, potenciais riscos e benefícios de cada tratamento. Com o intuito de avaliar criticamente a evidência recente e sistematizar as principais dúvidas referentes ao tratamento farmacológico da DPOC, foram reunidos 24 especialistas de todo o Brasil para elaborar a presente recomendação. Foi elaborado um guia visual para a classificação e tratamento adaptados à nossa realidade. Dez perguntas foram selecionadas pela relevância na prática clínica. Abordam a classificação, definições, tratamento e evidências disponíveis para cada medicação ou combinação. Cada pergunta foi respondida por dois especialistas e depois consolidadas em duas fases: revisão e consenso entre todos os participantes. As questões respondidas são dúvidas práticas e ajudam a selecionar qual o melhor tratamento, entre as muitas opções, para cada paciente com suas particularidades.
  • article 2 Citação(ões) na Scopus
    The patient profile of individuals with Alpha-1 antitrypsine gene mutations at a referral center in Brazil
    (2018) FELISBINO, Manuela Brisot; FERNANDES, Frederico Leon Arrabal; NUCCI, Maria Cecilia Nieves Maiorano de; PINTO, Regina Maria de Carvalho; PIZZICHINI, Emilio; CUKIER, Alberto
  • article 8 Citação(ões) na Scopus
    The Mini-Balance Evaluation System Test Can Predict Falls in Clinically Stable Outpatients With COPD A 12-MO PROSPECTIVE COHORT STUDY
    (2019) PEREIRA, Ana Carolina A. C.; XAVIER, Rafaella F.; LOPES, Aline C.; SILVA, Cibele C. B. M. da; OLIVEIRA, Cristino C.; FERNANDES, Frederico L. A.; STELMACH, Rafael; CARVALHO, Celso R. F.
    Purpose: This study evaluated the accuracy of the Mini-Balance Evaluation System Test (Mini-BESTest) for predicting falls in patients with chronic obstructive pulmonary disease (COPD) and investigated whether postural balance is a risk factor for falls. Methods: Postural balance was evaluated by the Mini-BESTest at baseline, and the incidence of falls over a 12-mo period was prospectively measured by a self-reported falls diary and confirmed by telephone calls. A discriminative power analysis was performed using receiver operating characteristic (ROC) curve and logistic regression analysis. Results: Sixty-seven outpatients with COPD (mean age SD = 67 +/- 9.3 yr) were included. Twenty-five patients (37.3%) experienced 1 fall, and 28.2% of the falls resulted in injuries. The Mini-BESTest predicted falls in patients with COPD at the 6- and 12-mo follow-ups with a cut-off score of 22.5 (area under the curve = 0.85 and 0.87) with good sensitivity and specificity (85.7% and 66.7%; 84% and 73.8%, respectively). Higher scores on the Mini-BESTest were associated with a lower risk of falls at 12 mo (OR = 0.50; 95% CI, 0.36-0.70; P < .001). Conclusions: Postural balance assessed by the Mini-BESTest is a good predictor of falls in patients with COPD. Our results imply that impaired balance contributes to the risk of falling and that balance training and fall prevention programs may be required for this population.
  • article 31 Citação(ões) na Scopus
    Impaired Pulmonary Function is an Additional Potential Mechanism for the Reduction of Functional Capacity in Clinically Stable Fontan Patients
    (2017) TURQUETTO, Aida L. R.; CANEO, Luiz F.; AGOSTINHO, Daniela R.; OLIVEIRA, Patricia A.; LOPES, Maria Isabel C. S.; TREVIZAN, Patricia F.; FERNANDES, Frederico L. A.; BINOTTO, Maria A.; LIBERATO, Gabriela; TAVARES, Glaucia M. P.; NEIROTTI, Rodolfo A.; JATENE, Marcelo B.
    Central factors negatively affect the functional capacity of Fontan patients (FP), but ""non-cardiac"" factors, such as pulmonary function, may contribute to their exercise intolerance. We studied the pulmonary function in asymptomatic FP and its correlations with their functional capacity. Pulmonary function and cardiopulmonary exercise tests were performed in a prospective study of 27 FP and 27 healthy controls (HC). Cardiovascular magnetic resonance was used to evaluate the Fontan circulation. The mean age at tests, the mean age at surgery, and the median follow-up time of FP were 20(+/- 6), 8(+/- 3), and 11(8-17) years, respectively. Dominant ventricle ejection fraction was within normal range. The mean of peak VO2 expressed in absolute values (L/min), the relative values to body weight (mL/kg/min), and their predicted values were lower in FP compared with HC: 1.69 (+/- 0.56) vs 2.81 (+/- 0.77) L/min; 29.9 (+/- 6.1) vs 41.5 (+/- 9.3) mL/kg/min p < 0.001 and predicted VO2 Peak [71% (+/- 14) vs 100% (+/- 20) p < 0.001]. The absolute and predicted values of the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), inspiratory capacity (IC), total lung capacity (TLC), diffusion capacity of carbon monoxide of the lung (DLCO), maximum inspiratory pressure (MIP), and sniff nasal inspiratory pressure (SNIP) were also significantly lower in the Fontan population compared to HC. An increased risk of restrictive ventilatory pattern was found in patients with postural deviations (OD:10.0, IC:1.02-97.5, p = 0.042). There was a strong correlation between pulmonary function and absolute peak VO2 [FVC (r = 0.86, p < 0.001); FEV1 (r = 0.83, p < 0.001); IC (r = 0.84, p < 0.001); TLC (r = 0.79, p < 0.001); and DLCO (r = 0.72, p < 0.001). The strength of the inspiratory muscles in absolute and predicted values was also reduced in FP [-79(+/- 28) vs -109(+/- 44) cmH(2)O (p = 0.004) and 67(+/- 26) vs 89(+/- 36) % (p = 0.016)]. Thus, we concluded that the pulmonary function was impaired in clinically stable Fontan patients and the static and dynamic lung volumes were significantly reduced compared with HC. We also demonstrated a strong correlation between absolute Peak VO2 with the FVC, FEV1, TLC, and DLCO measured by complete pulmonary test.
  • article 6 Citação(ões) na Scopus
    Characterization of the severity of dyspnea in patients with bronchiectasis: correlation with clinical, functional, and tomographic aspects
    (2020) NUCCI, Maria Cecilia Nieves Maiorano de; FERNANDES, Frederico Leon Arrabal; SALGE, Joao Marcos; STELMACH, Rafael; CUKIER, Alberto; ATHANAZIO, Rodrigo
    Objective: To characterize a population of patients with bronchiectasis, correlating clinical, radiological, and functional aspects with the severity of dyspnea. Methods: This was a cross-sectional study involving adult patients with HRCT-confirmed bronchiectasis, categorized according to the severity of dyspnea (as being mildly or severely symptomatic, on the basis of the modified Medical Research Council scale). We correlated the severity of dyspnea with clinical parameters, functional parameters (spirometry values, lung volumes, and DLCO), and CT parameters. Results: We evaluated 114 patients, 47 (41%) of whom were men. The median age (interquartile range) was 42 years (30-55 years). The most common form was idiopathic bronchiectasis. Of the 114 patients, 20 (17.5%) were colonized with Pseudomonas aeruginosa and 59 (51.8%) were under continuous treatment with macrolides. When we applied the Exacerbation in the previous year, FEV1, Age, Colonization, Extension, and Dyspnea score, the severity of dyspnea was categorized as moderate in 54 patients (47.4%), whereas it was categorized as mild in 50 (43.9%) when we applied the Bronchiectasis Severity Index. The most common lung function pattern was one of obstruction, seen in 95 patients (83.3%), and air trapping was seen in 77 patients (68.7%). The prevalence of an obstructive pattern on spirometry was higher among the patients with dyspnea that was more severe, and most functional parameters showed reasonable accuracy in discriminating between levels of dyspnea severity. Conclusions: Patients with bronchiectasis and dyspnea that was more severe had greater functional impairment. The measurement of lung volumes complemented the spirometry data. Because bronchiectasis is a complex, heterogeneous condition, a single variable does not seem to be sufficient to provide an overall characterization of the clinical condition.
  • article 15 Citação(ões) na Scopus
    A real-life study of the effectiveness of different pharmacological approaches to the treatment of smoking cessation: re-discussing the predictors of success
    (2011) PRADO, Gustavo Faibischew; LOMBARDI, Elisa Maria Siqueira; BUSSACOS, Marco Antonio; ARRABAL-FERNANDES, Frederico Leon; TERRA-FILHO, Mario; SANTOS, Ubiratan de Paula
    OBJECTIVE: To evaluate the effectiveness of nicotine replacement therapy (NRT), bupropion, nortriptyline and combination therapy and describe factors associated with treatment success. INTRODUCTION: Clinical trials clearly demonstrate the efficacy of pharmacotherapy in smoking cessation. However, it is only after its use in real-life settings that clinical effectiveness and limitations of a treatment are fully known. METHODS: Patients attended a four-session cognitive-behavioral program and received medicines free of charge. Abstinence from smoking was assessed at each visit. RESULTS: A total of 868 smokers (68.8% women) were included. Their mean age was 49.6 years; the amount smoked was 25 cigarettes/day and the Fagerstrom Score was 6.6. Abstinence rates after 6 months and 1 year were 36.5% and 33.6%. In univariate analysis, male gender, age (> 50), higher number of cigarettes smoked, cardiovascular comorbidities, longer interval from the last cigarette and combined treatment of nortriptyline plus NRT were predictive of abstinence, while neuropsychiatric comorbidities and the answer ""yes'' to the question ""Do you smoke more often during the first hours after waking'' were correlated with failure. In a multivariate model, predictors of abstinence were neuropsychiatric comorbidities, the answer ""yes'' to the question ""Do you smoke more often during the first hours after waking'' and combined treatment of nortriptyline plus NRT. Male gender and a longer period from the last cigarette were correlated with lower abstinence rate. CONCLUSION: Satisfactory success rates were obtained in a teaching hospital. Factors such as age, daily cigarette consumption, number of pack-years and dependency score were not reliable markers of abstinence. The combination nortriptyline+NRT was independently associated with higher abstinence rates.
  • article 2 Citação(ões) na Scopus
    Exploratory analysis of requests for authorization to dispense high-cost medication to COPD patients: the Sao Paulo ""protocol""
    (2019) CARVALHO-PINTO, Regina Maria; SILVA, Ingredy Tavares da; NAVACCHIA, Lucas Yoshio Kido; GRANJA, Flavia Munhos; MARQUES, Gustavo Garcia; NERY, Telma de Cassia dos Santos; FERNANDES, Frederico Leon Arrabal; CUKIER, Alberto; STELMACH, Rafael
    Objective: A resolution passed by the government of the Brazilian state of Sao Paulo established a protocol for requesting free COPD medications, including tiotropium bromide, creating regional authorization centers to evaluate and approve such requests, given the high cost of those medications. Our objective was to analyze the requests received by an authorization center that serves cities in the greater metropolitan area of (the city of) Sao Paulo between 2011 and 2016. Methods: Data regarding the authorization, return, or rejection of the requests were compiled and analyzed in order to explain those outcomes. Subsequently, the clinical and functional data related to the patients were evaluated. Results: A total of 7,762 requests for dispensing COPD medication were analyzed. Requests related to male patients predominated. Among the corresponding patients, the mean age was 66 years, 12% were smokers, 88% had frequent exacerbations, and 84% had severe/very severe dyspnea. The mean FEV1 was 37.2% of the predicted value. The total number of requests decreased by 24.5% from 2012 to 2013 and was lowest in 2015. Most (65%) of the requests were accepted. The main reasons for the rejection/return of a request were a post-bronchodilator FEV1/FVC ratio > 0.7, a post-bronchodilator FEV1 > 50% of the predicted value, and failure to provide information regarding previous use of a long-acting beta(2) agonist. During the study period, the total number of requests returned/rejected decreased slightly, and there was improvement in the quality of the data included on the forms. Conclusions: Here, we have identified the characteristics of the requests for COPD medications and of the corresponding patients per region served by the authorization center analyzed, thus contributing to the improvement of local public health care measures.
  • article 169 Citação(ões) na Scopus
    The Role of Exercise in a Weight-Loss Program on Clinical Control in Obese Adults with Asthma A Randomized Controlled Trial
    (2017) FREITAS, Patricia D.; FERREIRA, Palmira G.; SILVA, Aline G.; STELMACH, Rafael; CARVALHO-PINTO, Regina M.; FERNANDES, Frederico L. A.; MANCINI, Marcia C.; SATO, Maria N.; MARTINS, Milton A.; CARVALHO, Celso R. F.
    Rationale: Clinical control is difficult to achieve in obese patients with asthma. Bariatric surgery has been recommended for weight loss and to improve asthma control; however, the benefits of nonsurgical interventions have been poorly investigated. Objectives: To examine the effect of exercise training in a weight loss program on asthma control, quality of life, inflammatory biomarkers, and lung function. Methods: Fifty-five obese patients with asthma were randomly assigned to either a weight-loss program plus exercise (WL + E group, n = 28) or a weight-loss program plus sham (WL + S group, n = 27), where the weight-loss program included nutrition (caloric restriction) and psychological therapies. The WL + E group incorporated aerobic and resistance muscle training, whereas the WL + S group incorporated breathing and stretching exercises. Measurements and Main Results: The primary outcome was clinical improvement in asthma control over 3 months. Secondary outcomes included quality of life, lung function, body composition, aerobic capacity, muscle strength, and inflammatory/antiinflammatory biomarkers. After 3 months, 51 patients were analyzed. Compared with the WL + S group, the WL + E group demonstrated improved clinical control scores (median [25th to 75th percentile],-0.7 [-1.3 to -0.3] vs. -0.3 [-0.9 to 0.4]; P = 0.01) and greater weight loss (mean +/- SD, -6.8% +/- 3.5 vs. -3.1% +/- 2.6; P < 0.001) and aerobic capacity (median [25th to 75th percentile], 3.0 [2.4 to 4.0] vs. 0.9 [-0.3 to 1.3] ml O-2 X kg(-1) X min(-1); P < 0.001). These improvements in the WL + E group were also accompanied by improvements in lung function, antiinflammatory biomarkers, and vitamin D levels, as well as reductions in airway and systemic inflammation. Conclusions: Adding exercise to a short-term weight-loss program should be considered as a useful strategy for achieving clinical control of asthma in obese patients.