Papers by Jose Dirceu Ribeiro
Genes
Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical ... more Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) h...
Jornal Brasileiro de Pneumologia, 2020
Objective: To assess the agreement among asthma control measures and functional exercise capacity... more Objective: To assess the agreement among asthma control measures and functional exercise capacity in children and adolescents with uncontrolled and controlled asthma. Methods: Children and adolescents with asthma from 7-17 years old were selected, and they were attended in the "Pediatric Pulmonology Outpatient Clinic of State University of Campinas", in Brazil. All patients had asthma control level assessed by Global Initiative for Asthma questionnaire (GINAq), Asthma Control Test (ACT), spirometry and six-minute-walk-test (6MWT). Patients were classified as uncontrolled or controlled asthma in each test and agreement among measures was assessed by kappa statistics. The ROC curve was calculated for the 6MWT. The spirometric index obtained from spirometry was composed by FEV1, FEV1/FVC and FEF25-75%. Spirometry and 6MWT results were compared between uncontrolled and controlled asthma group by GINAq. Results: Of the 138 subjects included, 78 (56.5%) were male with median age of 11 (7-17) years old. GINAq detected 68.8% of patients with uncontrolled asthma. Moderate agreement (p < 0.001; k = 0.56) and high specificity (100%) was observed between GINAq and ACT. In 6MWT, the cutoff point of 82.03% of predicted distance was able to distinguish patients with controlled and uncontrolled asthma. Spirometric index presented 73.4% of sensitivity according to GINAq. The results for 6MWT in patients with uncontrolled asthma were the worst of all. Conclusion: This study highlights the importance of assessing more than one measure to differentiate asthma control level. GINAq identified more patients with uncontrolled asthma and presented moderate agreement with ACT. Spirometric index was associated with uncontrolled asthma according to GINAq. 6MWT was a suitable measure to distinguish patients with controlled and uncontrolled asthma.
Jornal de Pediatria, 2020
Objective: Systematically assess studies that have analyzed the psychometric properties of multic... more Objective: Systematically assess studies that have analyzed the psychometric properties of multichannel intraluminal impedance-pH for the diagnosis of gastroesophageal reflux. Systematically verify studies that have analyzed the psychometric properties of multichannel intraluminal impedance-pH regarding the diagnosis of gastroesophageal reflux disease in pediatric patients. Methods: Systematic review considering specific descriptors (children and adolescents, gastroesophageal reflux disease and multichannel intraluminal impedance-pH) and their synonyms. The systematic search was carried out in the MEDLINE/Ovid, Scopus, and Embase databases, considering the period from October 2017 to December 2018. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), which was used for study selection. The psychometric properties described in the studies were: sensitivity, specificity, accuracy, and reproducibility. Results: Sensitivity was discussed in most studies, with a result of more than 70% in four of them. Specificity was assessed only in conjunction with sensitivity, with values from 23% to 25% in two studies, and it reached 80% in a single study. Accuracy was assessed higher than 76% in one of the selected articles. The methodological quality of the studies demonstrated low risk of bias, and there was no significant concern related to applicability of the studies.
Clinical Drug Investigation, 2019
Background Among the many consequences of loss of CFTR protein function, a significant reduction ... more Background Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO 3 −) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO 3 − leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO 3 inhalation may be a low-cost, easily accessible therapy for CF. Objective To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO 3 solutions (4.2% and 8.4%). Methods An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18 years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels. Results Sputum pH increased immediately after inhalation of NaHCO 3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G′ (elasticity of the mucus) = − 0.241; G″ (viscosity of the mucus) = − 0.287; G* (viscoelasticity of the mucus) = − 0.275]. G* and G′ were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV 1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO 2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO 2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed. Conclusion Nebulized NaHCO 3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO 3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.
Pulmonology, 2019
Background: The phenotypic variability in cystic fibrosis (CF) is widely recognized and modulated... more Background: The phenotypic variability in cystic fibrosis (CF) is widely recognized and modulated by environmental and genetic factors, including CFTR pathogenic variants and modifier genes genetic variants. In this context, determining the presence of variants in genes involved in immune response may allow a better understanding of CF variability, mainly in lung disease. Thus, ADIPOQ and S TAT H genes were selected and the analysis of exons and exon/intron junctions was performed for the determination of variations in its sequence, to determine the possible genetic modulation. Methods: A total of 49 patients with CF, diagnosed for showing abnormal [chloride] levels in the sweat test, and identification of two pathogenic variants in CFTR categorized as class I and II were included. Genetic sequencing was performed for the identification of variants in the modifier genes. Results: In our analysis, there was absence of rare genetic variants in S TAT H and ADIPOQ genes associated with the clinical variability. Thus, we are not able to establish an association between the disease severity and rare genetic variants in S TAT H and ADIPOQ genes, considering exons and exon/intron junctions.
Jornal de Pediatria, 2018
Objective: To compare the values of the markers for volumetric capnography and spirometry and the... more Objective: To compare the values of the markers for volumetric capnography and spirometry and their ability to classify children and adolescents with asthma, cystic fibrosis (CF), and healthy controls. Methods: This was a cross-sectional study that included 103 patients with controlled persistent allergic asthma, 53 with CF and a healthy control group with 40 volunteers (aged 6-15 years), of both sexes. The individuals underwent volumetric capnography and spirometry. Results: Phase III slope (SIII), SIII standardized by exhaled tidal volume (SIII/TV) and capnographic index (SIII/SII) × 100 (KPIv) were different among the three groups assessed, with highest values for CF. The relation between the forced expiratory volume in one second and the forced vital capacity (FEV 1 /FVC) was the only spirometric marker that presented difference on the three groups. On individuals with normal spirometry, KPIv and FEV 1 /FVC were different among the three groups. The ROC curve identified the individuals with asthma or CF from the DOI se refere ao artigo:
Journal of Genetic Syndromes & Gene Therapy, 2016
Physical exercise, including games and other modalities are essential for children and adolescent... more Physical exercise, including games and other modalities are essential for children and adolescents. These activities allow numerous and unquestioned benefits, maximizing physical, psychological and social development. Tools that assess the response of the body to exercise activities have been sought in numerous clinical situations [1]. Chronic obstructive pulmonary diseases such as cystic fibrosis (CF), asthma, and bronchiolitis obliterans may lead to reduction or limitation in exercise performance by ventilatory factors. Consequently, a reduction in lung function can be observed, characterized by decreased respiratory reserve and dynamic hyperinflation during exercise [1-4]. Various instruments have been developed and studied in the pediatric population in order to evaluate the functional capacity (physical and ventilation functional tests) during exercise, being grouped into maximal tests and submaximal tests. The difference between maximal and submaximal tests depends on whether the test is performed in an open area or laboratory, with ergometers (treadmill) or not. In the maximal test, the individual performs the activity to achieve voluntary exhaustion, leading the participant to the fullest of their oxygen uptake and/or estimated (more than 90%) heart rate (HR). In the submaximal tests, the HR is located around 75% to 90% of the maximum estimated HR [3,5]. The maximal test requires well-defined methodological conditions regarding aspects related to the health expert staff, physical space and adequate equipment, and materials and medications for use in an emergency. The responsible professional must have experience with the test and be able to act in emergencies, so the team must include a medical doctor [5].
Jornal brasileiro de pneumologia : publicaça̋o oficial da Sociedade Brasileira de Pneumologia e Tisilogia, 2015
To evaluate quality of life according to the level of asthma control and degree of asthma severit... more To evaluate quality of life according to the level of asthma control and degree of asthma severity in children and adolescents. We selected children and adolescents with asthma (7-17 years of age) from the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. Asthma control and asthma severity were assessed by the Asthma Control Test and by the questionnaire based on the Global Initiative for Asthma, respectively. The patients also completed the Paediatric Asthma Quality of Life Questionnaire (PAQLQ), validated for use in Brazil, in order to evaluate their quality of life. The mean age of the patients was 11.22 ± 2.91 years, with a median of 11.20 (7.00-17.60) years. We selected 100 patients, of whom 27, 33, and 40 were classified as having controlled asthma (CA), partially controlled asthma (PCA), and uncontrolled asthma (UA), respectively. As for asthma severity, 34, 19, and 47 were classified as ...
ConScientiae Saúde, 2015
Objetivos: Avaliar e comparar o efeito do Flutter VRP1® e do Shaker® referente à quantidade de se... more Objetivos: Avaliar e comparar o efeito do Flutter VRP1® e do Shaker® referente à quantidade de secreção pulmonar expectorada e aos parâmetros cardiorrespiratórios de frequência cardíaca (fc) e de saturação periférica de oxigênio (SpO2). Método: Neste estudo randomizado do tipo intervencional, 16 pacientes, com idades entre 7 e 21 anos (12 anos ±4,11), realizaram sessões de fisioterapia em dois dias diferentes com ambos os dispositivos. Na primeira sessão, os participantes utilizaram um dos dispositivos, conforme o resultado da randomização. E, após sete dias sem intervenção, na segunda sessão, usaram o outro dispositivo. Verificaram-se os parâmetros cardiorrespiratórios de fc e SpO2 e registraram-se tais valores antes e ao final de cada coleta em cada dia de terapia. Colheu-se secreção pulmonar durante e após a terapia para determinação dos pesos seco e úmido. Resultados: Não houve diferença entre os dispositivos quanto a peso úmido (p=0,589) e seco (p=0,719) e parâmetros cardiorres...
Journal of Cystic Fibrosis, 2014
Objectives: Autoantibodies to bactericidal/permeability increasing protein (BPI-ANCA) has been pr... more Objectives: Autoantibodies to bactericidal/permeability increasing protein (BPI-ANCA) has been proposed as a biomarker for disease severity in PsA colonized CF patients. PsA serology on the other hand is used to support a diagnosis of PsA colonization. In this study we compare the performance of BPI-ANCA with three different serological tests for PsA with respect to reduced lung function and colonization, as well as their ability to predict future colonization. Methods: All non-transplanted CF patients (n = 117) at the CF centre in Lund, Sweden, were included. Bacterial colonization was classified according to Leeds criteria. IgA BPI-ANCA was measured with ELISA and results were compared with assays for anti-PsA antigens Exotoxin A (Exo), Alkaline protease (Alp) and Elastase (Ela). Results: Among PsA colonized patients (Leeds I) IgA BPI-ANCA showed the best correlation with reduced lung function (r = 0.45 and AUC 0.799) followed by Alp (r = 0.39, AUC 0.689), while Ela and Exo were not informative (r= 0.24, AUC 0.596 and r = 0.08, AUC 0.516). All four tests were useful to identify patients with chronic PsA colonization with AUC ranging from 0.822 (Ela) to 0.929 (Exo). None of the tests was able to predict chronic PsA colonization within three years (change from Leeds III/IV to I, (n = 9). Conclusion: PsA serology as well as BPI-ANCA is useful for the identification of patients with chronic PsA colonization, but BPI-ANCA is better than at least Ela and Exo to detect lung function impairment. The results are in line with the notion that BPI-ANCA is marker of an unfavourable host-pathogen interaction.
Journal of Cystic Fibrosis, 2006
Journal of Cystic Fibrosis, 2011
Journal of Cystic Fibrosis, 2013
Objectives: Neonatal screening for CF has been continuous in New Zealand (NZ) for 30 years. Initi... more Objectives: Neonatal screening for CF has been continuous in New Zealand (NZ) for 30 years. Initially this was by two blood immunoreactive trypsin (IRT) levels until 1996 when a three gene detection replaced the second IRT measurement. Aim: To determine the number of children with a late diagnosis and why they were not detected despite our long term newborn screening programme. Methods: Retrospective review of all children with CF under full care at Starship Children's Hospital, Auckland, NZ from 2003-2012 which includes patients up to 18 years of age to therefore determine missed on screening from 1985-2012 in the greater Auckland region with a general population of 800,000 to 1.2 million over this time. Results: In the last decade 100 children with CF were in this clinic of whom 18 had a late diagnosis, mean age 14 months (range 6 weeks to 11 years). Eight of them were born overseas in regions without a newborn screening programme at that time. Ten were born in NZ; 4 were pancreatic sufficient and 6 were pancreatic insufficient. Nine were missed as the IRT level was not in the highest 1% and therefore the gene determination was not undertaken, or they had "uncommon" gene, undetectable on screening. One child's parents refused newborn screening. All ten had recurrent pneumonias, 2 had established bronchiectasis, 4 FTT and 1 had severe liver disease leading to the diagnosis. Conclusion: Even with an established newborn screening programme in place, cystic fibrosis should be considered in the appropriate clinical setting.
Journal of Cystic Fibrosis, 2013
Objectives: To compare Cystic Fibrosis (CF) severity with NOS-1 polymorphisms (pol.) (AAT, TG1 an... more Objectives: To compare Cystic Fibrosis (CF) severity with NOS-1 polymorphisms (pol.) (AAT, TG1 and TG2) and CFTR interaction. Methods: 181 patients included. The NOS-1 pol. was analyzed by Megabace1000 ® sequencer. Variables: sex, race, scores [Shwachman-Kulczycki, Kanga and Bhalla (EB)], BMI, age, diagnosis age, first symptoms (digestive and pulmonary), first P. aeruginosa, microorganisms (P. aeruginosa mucoid and non-mucoid, A. xylosoxidans, S. aureus, B. cepacia), SaO2, spirometry and comorbidities (nasal polyps, osteoporosis, meconium ileus, pancreatic insufficiency, diabetes mellitus). Statistical analysis: MDR2.0 and MDRPT0.4.7 software. Numerical data: classified by the median. Categorical data: presence or absence (bacteria and comorbidities). Multiple genes analysis in disease with clinical variation, like CF, allows greater understanding of phenotypic diversity. The analysis of all alleles for NOS-1 and CFTR did not show association. The same was observed to alleles with more repetitions in NOS-1. However, alleles with minor repetitions in NOS-1 and CFTR showed association with the race and age. For race, the ratio between Caucasian and non-Caucasian was not similar and the p-value becomes irrelevant. Regarding age, only the CFTR was associated. Finally, there was association of minor repetitions to the TG1 and TG2 pol. in NOS-1, along with CFTR, with BS (measures the degree of impairment of structure bronchopulmonary) (Ratio: 0.954; Ball Test. Acc: 0.643, p: 0.033). The BS is a marker of early lung disease and is associated with the clinical severity, being considered an important factor in clinical prediction. Conclusion: NOS-1 and CFTR interaction influence BS value in CF. WS20.6 High throughput screening as a source for novel cystic fibrosis therapeutic targets
Journal of Cystic Fibrosis, 2013
BMC Gastroenterology, 2013
Background Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis ... more Background Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort, invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the patients perspective to assess its feasibility as an outcome measure in clinical trials. Methods We compared three bowel preparation solutions (NaCl 0.9%, glycerol 12%, mannitol), and two biopsy forceps (standard and jumbo) in 580 rectal specimens from 132 individuals (CF and non-CF). Assessment of the overall rectal biopsy procedure (obtained by biopsy forceps) by patients was carried out by telephone surveys to 75 individuals who underwent the sigmoidoscopy procedure. Results Integrity and friability of the tissue specimens correlat...
Respiratory Care, 2019
BACKGROUND: Lung ultrasound is an examination that allows the assessment of pulmonary involvement... more BACKGROUND: Lung ultrasound is an examination that allows the assessment of pulmonary involvement by analyzing artifacts. Our primary aim was to correlate our lung ultrasound findings with pulmonary function and the modified Bhalla score in patients with cystic fibrosis. METHODS: Subjects with cystic fibrosis were evaluated based on the results of lung ultrasound, pulmonary function exams (ie, spirometry before and after the use of a bronchodilator and S pO 2), and the modified Bhalla score. The partial correlation set by age between lung ultrasound, pulmonary function, and modified Bhalla score was carried out. Lung ultrasound was graded according to a new score, ranging from 0 to 36, with a higher score being associated with a greater degree of involvement. We performed Bland-Altman and linear regression analysis to identify bias between lung ultrasound and modified Bhalla score. Alpha ؍ 0.05. RESULTS: 18 subjects with cystic fibrosis were included. In partial correlation controlled by age, we observed significant ultrasound score values with weight (partial correlation ؍ ؊0.579), body mass index (partial correlation ؍ ؊0.609), S pO 2 (partial correlation ؍ ؊0.728), FVC% (pre-bronchodilator: partial correlation ؍ ؊0.538; post-bronchodilator: partial correlation ؍ ؊0.560), FEV 1 % (pre-bronchodilator: partial correlation ؍ ؊0.536; post-bronchodilator: partial correlation ؍ ؊0.546), and modified Bhalla score (partial correlation ؍ 0.607). We did not identify bias between lung ultrasound and modified Bhalla score measured by z-score. CONCLUSIONS: Lung ultrasound seems to be effective and corroborates with high-resolution computed tomography when evaluated by the modified Bhalla score. At the same time, lung ultrasound had significant correlation with pulmonary function and nutritional status.
Jornal brasileiro de pneumologia : publicaça̋o oficial da Sociedade Brasileira de Pneumologia e Tisilogia
To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmemb... more To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients w...
International Journal of Molecular Epidemiology and Genetics, May 29, 2014
Modifier genes, as the TNF-α gene, can modulate the cystic fibrosis (CF) severity. Thus, -238G>... more Modifier genes, as the TNF-α gene, can modulate the cystic fibrosis (CF) severity. Thus, -238G>A and -308G>A polymorphisms of TNF-α gene were analyzed as modifiers of CF. In this context, the present study enrolled 49 CF patients (diagnosis performed by sweat test and complete CFTR screening). The -238G>A polymorphism analysis was performed by ARMS-PCR, and -308G>A, by PCR-RFLP. In our data, the -238G>A polymorphism was not associated with clinical variability. The AA genotype for -308G>A polymorphism was a risk factor for early gastrointestinal symptoms (OR=5.98, 95%CI=1.06-49.68) and protection for the first Pseudomonas aeruginosa (OR=0.05, 95%CI=0.0003-0.007). For the first P. aeruginosa, GA genotype was a risk factor (OR=10.2, 95%CI=1.86-84.09); for the same genotype, the diagnosis was made in minor time than the AA genotype (p=0.031). Considering the -308G>A polymorphism alleles, the G allele was a risk factor for early pulmonary symptoms (OR=3.81, 95%CI=1....
Uploads
Papers by Jose Dirceu Ribeiro