RONALDO ADIB KAIRALLA

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Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina

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Autor: CARVALHO, Carlos Roberto Ribeiro ×

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  • article 37 Citação(ões) na Scopus
    Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade
    (2011) PIMENTA, Suzana Pinheiro; BALDI, Bruno Guedes; ACENCIO, Milena Marques Pagliarelli; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro
    Objective: Lymphangioleiomyomatosis (LAM) is characterized by lung cysts, whose development is associated with matrix metalloproteinase (MMP) hyperactivity, principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients and controls in terms of the levels of these MMPs, as well as to determine the safety and efficacy of treatment with doxycycline, a potent MMP inhibitor. Methods: Prospective clinical study involving female LAM patients who received doxycycline (100 mg/day) for six months. Urine and blood samples were collected for the quantification of MMP-2 and MMP-9 before and after the treatment period. Samples from 10 healthy women were also collected. Results: Of the 41 LAM patients who started the treatment, 34 completed the protocol. Serum and urinary MMP-9 levels were significantly lower in the controls than in the LAM patients (p < 0.0001). Comparing pre- and post-treatment values, we found that the median level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05), whereas that of MMP-9 in urine decreased from 11,558 pg/mL to 7,315 pg/mL (p = 0.10). After treatment, the median level of MMP-2 in serum was significantly lower (p = 0.04) and urinary MMP-2 levels were undetectable. Nausea, diarrhea, and epigastric pain were the most prevalent adverse affects and were often self-limiting. There was only one case in which the patient discontinued the treatment because of side effects. Conclusions: We have demonstrated, for the first time, a decrease in serum and urine levels of MMPs in LAM patients treated with doxycycline, which proved to be a safe medication, with mild and well-tolerated side effects.
  • article 9 Citação(ões) na Scopus
    Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis
    (2020) HEIDEN, Glaucia Itamaro; SOBRAL, Juliana Barbosa; FREITAS, Carolina Salim Goncalves; ALBUQUERQUE, Andre Luis Pereira de; SALGE, Joao Marcos; KAIRALLA, Ronaldo Adib; FERNANDES, Caio Julio Cesar dos Santos; CARVALHO, Carlos Roberto Ribeiro; SOUZA, Rogerio; BALDI, Bruno Guedes
    BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH). RESEARCH QUESTION: What are the mechanisms of exercise limitation, the exercise capacity , and the prevalence of dynamic hyperinflation (DH) and PH in PLCH? STUDY DESIGN AND METHODS: In a cross-sectional study, patients with PLCH underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (D-LCO) < 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity > 2.5 m/s and/or with indirect PH signs underwent right heart catheterization. RESULTS: Thirty-five patients were included (68% women; mean age, 47 +/- 11 years). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. FEV1 and D-LCO were 64 +/- 22% predicted and 56 +/- 21% predicted. Reduction in D-LCO, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients. FEV1 and D-LCO were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with a precapillary pattern, and mean pulmonary artery pressure correlated best with FEV1 and tricuspid regurgitation velocity. INTERPRETATION: PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms are ventilatory, cardiocirculatory, and suggestive of PH limitations.
  • article 14 Citação(ões) na Scopus
    Colagenose pulmão dominante em pacientes com doença pulmonar intersticial: prevalência, estabilidade funcional e manifestações extratorácicas comuns
    (2015) PEREIRA, Daniel Antunes Silva; DIAS, Olivia Meira; ALMEIDA, Guilherme Eler de; ARAUJO, Mariana Sponholz; KAWANO-DOURADO, Leticia Barbosa; BALDI, Bruno Guedes; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro
    Objective: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). Methods: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (>= 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CO). Results: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. Conclusions: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.
  • article 24 Citação(ões) na Scopus
    Highlights of the Brazilian Thoracic Association Guidelines for Interstitial Lung Diseases
    (2012) BALDI, Bruno Guedes; PEREIRA, Carlos Alberto de Castro; RUBIN, Adalberto Sperb; SANTANA, Alfredo Nicodemos da Cruz; COSTA, Andre Nathan; CARVALHO, Carlos Roberto Ribeiro; ALGRANTI, Eduardo; CAPITANI, Eduardo Mello de; BETHLEM, Eduardo Pamplona; COLETTA, Ester Nei Aparecida Martins; ARAKAKI, Jaquelina Sonoe Ota; MARTINEZ, Jose Antonio Baddini; CARVALHO, Jozelio Freire de; STEIDLE, Leila John Marques; ROCHA, Marcelo Jorge Jaco; LIMA, Mariana Silva; SOARES, Maria Raquel; CARAMORI, Marlova Luzzi; AIDE, Miguel Abidon; FERREIRA, Rimarcs Gomes; KAIRALLA, Ronaldo Adib; OLIVEIRA, Rudolf Krawczenko Feitoza de; JEZLER, Sergio; RODRIGUES, Silvia Carla Sousa; PIMENTA, Suzana Pinheiro
    Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.
  • conferenceObject
    Prevalence of pulmonary hypertension among outpatients with sarcoidosis: An echocardiographic and pulmonary catheterization study
    (2012) MEDEIROS-NETO, Agostinho Hermes; RODRIGUES, Fabiola Gomes; TSUTSUI, Jean Mike; SOUZA, Rogerio; CARVALHO, Carlos Roberto Ribeiro; KAIRALLA, Ronaldo Adib
  • conferenceObject
    Sarcoidosis in Sao Paulo, Brazil: Clinical, tomographic and lung functions data from 72 patients
    (2012) MEDEIROS-NETO, Agostinho Hermes; RODRIGUES, Fabiola Gomes; CARVALHO, Carlos Roberto Ribeiro; KAIRALLA, Ronaldo Adib
  • article 1 Citação(ões) na Scopus
    Idiopathic pulmonary fibrosis can be a transient diagnosis
    (2016) OLIVEIRA, Martina Rodrigues de; PEREIRA, Daniel Antunes Silva; DIAS, Olivia Meira; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro; BALDI, Bruno Guedes
  • article 6 Citação(ões) na Scopus
    Association between pulmonary artery to aorta diameter ratio with pulmonary hypertension and outcomes in diffuse cystic lung diseases
    (2021) BALDI, Bruno Guedes; FERNANDES, Caio Julio Cesar dos Santos; HEIDEN, Glaucia Itamaro; FREITAS, Carolina Salim Goncalves; SOBRAL, Juliana Barbosa; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro; SOUZA, Rogerio
    To investigate the importance of pulmonary vascular measurements on computed tomography (CT) in predicting pulmonary hypertension (PH) and worse outcomes in diffuse cystic lung diseases (DCLDs). We conducted a cross-sectional study of patients with DCLDs. Patients underwent pulmonary function tests, a six-minute walk test (6MWT), chest CT, transthoracic echocardiography, and right heart catheterization. Pulmonary artery (PA) diameter and PA-ascending aorta ratio (PA-Ao ratio) were obtained from CT. Mean pulmonary artery pressure (mPAP) from right heart catheterization was correlated with tomographic, functional, and echocardiographic variables. The association between the PA-Ao ratio with outcomes was determined by Kaplan-Meier curves. Thirty-four patients were included (18 with pulmonary Langerhans cell histiocytosis and 16 with lymphangioleiomyomatosis, mean age 46 +/- 9 years). Forced expiratory volume in the first second and lung diffusing capacity for carbon monoxide were 47 +/- 20% and 38 +/- 21% predicted, respectively. PA diameter and PA-Ao ratio were 29 +/- 6 mm and 0.95 +/- 0.24, respectively. PA-Ao ratio > 1 occurred in 38.2% of patients. PA-Ao ratio was a good predictor of PH. mPAP correlated best with PA-Ao ratio, PA diameter, oxygen desaturation during six-minute walk test, and echocardiographic variables. Patients with PA-Ao ratio > 1 had greater mPAP, and a higher risk of death or lung transplantation (log-rank, P < .001) than those with PA-Ao ratio <= 1. The PA-Ao ratio measured on CT scan has a potential role as a non-invasive tool to predict the presence of PH and as a prognostic parameter in patients with DCLDs.
  • article 25 Citação(ões) na Scopus
    Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations
    (2015) FREITAS, Carolina Salim Gonçalves; BALDI, Bruno Guedes; ARAÚJO, Mariana Sponholz; HEIDEN, Glaucia Itamaro; KAIRALLA, Ronaldo Adib; CARVALHO, Carlos Roberto Ribeiro
    OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). METHODS: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. RESULTS: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. CONCLUSIONS: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.
  • article 13 Citação(ões) na Scopus
    Immunohistological features related to functional impairment in lymphangioleiomyomatosis
    (2018) NASCIMENTO, Ellen Caroline Toledo do; BALDI, Bruno Guedes; MARIANI, Alessandro Wasum; ANNONI, Raquel; KAIRALLA, Ronaldo Adib; PIMENTA, Suzana Pinheiro; SILVA, Luiz Fernando Ferraz da; CARVALHO, Carlos Roberto Ribeiro; DOLHNIKOFF, Marisa
    Background: Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients. Methods: We analyzed morphological and functional parameters of thirty-three patients. Two groups of disease severity were identified according to FEV1 values. Lung tissue from open biopsies or lung transplants was immunostained for SMA, HMB-45, mTOR, VEGF-D, MMP-9 and D2-40. Density of cysts, density of nodules and protein expression were measured by image analysis and correlated with PFT parameters. Results: There was no difference in the expression of D2-40 between the more severe and the less severe groups. All other immunohistological parameters showed significantly higher values in the more severe group (p <= 0.002). The expression of VEGF-D, MMP-9 and mTOR in LAM cells was associated with the density of both cysts and nodules. The density of cysts and nodules as well as the expression of MMP-9 and VEGF-D were associated with the impairment of PFT parameters. Conclusions: Severe LAM represents an active phase of the disease with high expression of VEGF-D, mTOR, and MMP-9, as well as LAM cell infiltration. Our findings suggest that the tissue expression levels of VEGF-D and MMP-9 are important parameters associated with the loss of pulmonary function and could be considered as potential severity markers in open lung biopsies of LAM patients.