Publications by authors named "Jose Dirceu Ribeiro"

109 Publications

The Sun also rises.

J Bras Pneumol 2022 Jan 5;47(6):e20210473. Epub 2022 Jan 5.

. Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil.

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http://dx.doi.org/10.36416/1806-3756/e20210473DOI Listing
January 2022

Impact of rapid maxillary expansion on mouth-breathing children and adolescents: A systematic review.

J Clin Exp Dent 2021 Dec 1;13(12):e1258-e1270. Epub 2021 Dec 1.

Universidade Estadual de Campinas, Hospital das Clínicas, Departamento de Otorrinolaringologia, Campinas, SP, Brazil.

Background: Rapid maxillary expansion (RME) is an orthodontic procedure used to correct transverse maxillary deficiency. Due to the anatomical relationship between the palate and the nasal cavity, RME promotes an increase in nasal dimensions, which should hypothetically improve nasal respiratory function. Objective: This review aimed to systematically verify studies that assessed the effects of RME on nasal patency in mouth-breathing children and adolescents.

Material And Methods: An electronic search was performed in the MEDLINE databases via OVID, Scopus and EMBASE. The terms were: "children and adolescents", "rapid maxillary expansion" and "mouth breathing". The search was conducted in October 2019, according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The assessment of the quality of the studies was conducted by two evaluators, using the Fowkes & Fulton´s guidelines for critical appraisal of medical research.

Results: 475 titles were identified and 18 articles were selected. All of them showed high methodological quality, but without randomized clinical trials. The instruments evaluated were: teleradiography, frontal postero-anterior radiography, computed tomography, acoustic rhinometry and computed rhinomanometry.

Conclusions: This review shows that RME promotes the enlargement of dental arches and of the nasal and maxillary structures, with improved mouth breathing in the short term. However, its long-term benefits could not be proved so far. More robust results of the effectiveness of RME in mouth breathing can be achieved with meta-analysis studies, with a consensual definition of the long-term follow-up period after RME. Child, adolescent, maxillary expansion, palatal expansion, mouth breathing.
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http://dx.doi.org/10.4317/jced.58932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715551PMC
December 2021

Rhinoviruses as critical agents in severe bronchiolitis in infants.

J Pediatr (Rio J) 2021 Dec 20. Epub 2021 Dec 20.

Universidade Estadual de Campinas (UNICAMP), Instituto de Biologia, Departamento de Genética, Evolução, Microbiologia e Imunologia, Laboratório de Virologia Animal, Campinas, SP, Brazil. Electronic address:

Objectives: To detect RSV or other thirteen respiratory viruses as possible causer agent of bronchiolitis in infants.

Method: This is an epidemiological analytical study, conducted using a nasopharyngeal aspirate of 173 hospitalized children younger than two years old with severe bronchiolitis in three hospitals in the Campinas Metropolitan Region (CMR) during 2013-14. The data was statically evaluated by Pearson's chi-squared test with statistical significance of 0.05 and 95% confidence level.

Results: As expected, the most prevalent viruses detected were RSV A and B in 47% and 16% of the samples, respectively. However, almost a third of severe bronchiolitis cases there were no detection of RSV, and the viruses more commonly detected were rhinoviruses, which were identified in almost a quarter of all positive samples for at least a viral agent.

Conclusions: Although nothing could be concluded from the disease severity and clinical-epidemiological data, the present study's results indicate that severe bronchiolitis is not always related to RSV infections in children younger than two years old, and the rhinoviruses were more prevalent in these cases. These findings reinforce the need to carry out a viral diagnosis in the hospital emergency would be very appropriate for all cases of respiratory infections in children, even for diseases in which the primary etiological agent seems to be well known.
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http://dx.doi.org/10.1016/j.jped.2021.11.006DOI Listing
December 2021

Risk factors for recurrent wheezing in preterm infants who received prophylaxis with palivizumab.

J Bras Pneumol 2021 15;47(5):e20210157. Epub 2021 Oct 15.

. Laboratório de Fisiologia Pulmonar, Centro de Investigação em Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas - UNICAMP - Campinas (SP) Brasil.

Objective: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW.

Methods: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians.

Results: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions.

Conclusions: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.
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http://dx.doi.org/10.36416/1806-3756/e20210157DOI Listing
October 2021

Differences between patients who achieved asthma control and those who remain uncontrolled after standardized severe asthma care strategy.

J Asthma 2020 Dec 2:1-13. Epub 2020 Dec 2.

Faculty of Medical Sciences, Laboratory of Pulmonary Physiology, Center for Investigation in Pediatrics, State University of Campinas, Campinas, São Paulo, Brazil.

Objective: To assess clinical, functional, and inflammatory patterns of children and adolescents with severe uncontrolled asthma, and investigate the differences between patients who achieved asthma control and those who remain uncontrolled after standardized asthma care strategy.

Methods: Screening all children and adolescents with asthma from the Pediatric Pulmonology Outpatient Clinic of Unicamp, Brazil, and included those with severe uncontrolled asthma according to GINA guidelines criteria. Patients were assessed at baseline and after by demographic and medication data, questionnaires (Asthma Control Test and Pediatric Asthma Quality of Life Questionnaire), Six-Minute Walk Test, skin prick test, spirometry, induced sputum, and blood collection (total immunoglobulin E and eosinophil count). Cytokine dosage was analyzed in sputum supernatant and serum by Cytometric Bead Array.

Results: Thirty-three patients with severe uncontrolled asthma were included (median age 10.9 [7.00-17.60] years). All patients presented satisfactory adherence to treatment and 50% of them achieved good asthma control after six-month follow-up ( < 0.001). Patients who achieved asthma control reported higher intervals since their last exacerbation episode ( = 0.008) and higher quality of life scores ( < 0.001) as compared to patients who remained uncontrolled. We found no changes in lung function markers, inflammatory biomarkers, or cytokine levels between patients with uncontrolled and controlled asthma.

Conclusion: Participation of six months in a structured outpatient clinic for children with severe asthma had a notable improvement in control and quality of life of patients. This demonstrates the importance of a global assessment, focused on peculiarities presented by patients with severe uncontrolled asthma.
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http://dx.doi.org/10.1080/02770903.2020.1852415DOI Listing
December 2020

Lung function in obese children and adolescents without respiratory disease: a systematic review.

BMC Pulm Med 2020 Oct 28;20(1):281. Epub 2020 Oct 28.

Department of Pediatrics, School of Medical Sciences, Unicamp, Rua Tessália Vieira de Camargo, Cidade Universitária Zeferino Vaz - Barão Geraldo, 126, Campinas, 13083-887, São Paulo, Brazil.

Background: Obesity in children and adolescents is associated with increased morbidity and mortality due to multisystemic impairment, including deleterious changes in lung function, which are poorly understood.

Objectives: To perform a systematic review to assess lung function in children and adolescents affected by obesity and to verify the presence of pulmonary changes due to obesity in individuals without previous or current respiratory diseases.

Methods: A systematic search was performed in the MEDLINE-PubMed (Medical Literature Analysis and Retrieval System Online), Embase (Excerpta Medica Database) and VHL (Virtual Health Library/Brazil) databases using the terms "Lung Function" and "Pediatric Obesity" and their corresponding synonyms in each database. A period of 10 years was considered, starting in February/2008. After the application of the filters, 33 articles were selected. Using the PICOS strategy, the following information was achieved: (Patient) children and adolescents; (Intervention/exposure) obesity; (Control) healthy children and adolescents; (Outcome) pulmonary function alterations; (Studies) randomized controlled trial, longitudinal studies (prospective and retrospective studies), cross-over studies and cross-sectional studies.

Results: Articles from 18 countries were included. Spirometry was the most widely used tool to assess lung function. There was high variability in lung function values, with a trend towards reduced lung function markers (FEV/FVC, FRC, ERV and RV) in obese children and adolescents.

Conclusion: Lung function, measured by several tools, shows numerous markers with contradictory alterations. Differences concerning the reported results of lung function do not allow us to reach a consensus on lung function changes in children and adolescents with obesity, highlighting the need for more publications on this topic with a standardized methodology.
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http://dx.doi.org/10.1186/s12890-020-01306-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594270PMC
October 2020

Reliability of impulse oscillometry parameters in healthy children and in children with cystic fibrosis.

Int J Clin Pract 2021 Apr 31;75(4):e13715. Epub 2020 Dec 31.

UDESC, Florianopolis, Brazil.

Introduction & Aims: Impulse oscillometry system (IOS) is an instrument developed to evaluate the mechanical lung properties. It has been reported that to analyse the exam in a proper way it is necessary to carry out more than one measure. However, studies addressing the standardisation are still scarce. The objective was to determine within trial reliability of three measures in IOS parameters in healthy children and children with cystic fibrosis (CF).

Method: Weight, height, body mass index, forced spirometric and the oscillometric parameters (resistance, respiratory impedance, respiratory reactance and resonance frequency) data were collected, in a way that all participants performed three IOS measures. To evaluate, the reproducibility was used the intraclass correlation coefficient [two-way mixed model, absolute agreement definition, ICC]. The response stability was appraised using the standard error of measurements (SEM) in three repetitions of the IOS in the healthy children group (HCG) and in the cystic fibrosis group (CFG).

Results: About 95 subjects participated, in each group with a mean age of 10.89 ± 2.21 years old in the HCG and 9.73 ± 2.43 years old in the CFG, having been 41 and 43 boys and 54 and 52 girls, in the respectively group. In both groups, all IOS parameters evaluated in the three measures presented an ICC of 0.9, which is a high reproducibility.

Conclusion: The IOS parameters are reproducible for healthy children and CF children in three measures. However, according to the population studied, the performance of only one measure is sufficient to assess respiratory mechanics, whereas the SEM were low, except for Fres, in both groups.
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http://dx.doi.org/10.1111/ijcp.13715DOI Listing
April 2021

Are there differences in the physical activity level and functional capacity among children and adolescents with and without asthma?

J Pediatr (Rio J) 2021 May-Jun;97(3):295-301. Epub 2020 Jun 7.

Universidade Estadual de Campinas (Unicamp), Laboratório de Fisiologia Pulmonar, Campinas, SP, Brazil; Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil. Electronic address:

Objective: The aim of this study was to analyze the physical activity level, using two tools, and the functional capacity of children and adolescents with asthma and with different levels of disease control, and to compare them to those of individuals without asthma.

Methods: Cross-sectional study with children and adolescents with (asthma group, AG) and without asthma (WAG), aged from 7 to 17 years. All participants performed the six-minute walk test (6MWT), the Glittre Activities of Daily Living test (Glittre-ADL), the International Physical Activity Questionnaire (IPAQ), and daily record of steps on a pedometer.

Results: The study included 145 individuals with asthma and 173 individuals without asthma. The WAG walked a greater distance in the 6MWT and performed the Glittre-ADL in less time than the AG. Individuals with uncontrolled, partially controlled, and controlled asthma presented the same functional capacity. A difference was observed in the IPAQ classification, with 13.9% of participants from the WAG being sedentary, compared with 26.2% in the AG. The mean quantity of steps measured by the pedometer was higher in the WAG.

Conclusion: There was a difference in the performance of individuals with and without asthma in the physical activity and functional capacity tests. The AG presented worse performance in the physical activity tests and, regardless of the level of asthma control, presented worse functional capacity.
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http://dx.doi.org/10.1016/j.jped.2020.04.004DOI Listing
May 2021

Assessment of asthma control among different measures and evaluation of functional exercise capacity in children and adolescents with asthma.

J Bras Pneumol 2020;46(3):e20190102. Epub 2020 Mar 13.

Laboratório de Fisiologia Pulmonar, Universidade Estadual de Campinas, Campinas, SP, Brasil.

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 cut-off 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.
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http://dx.doi.org/10.36416/1806-3756/e20190102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650812PMC
September 2020

Multichannel intraluminal impedance-pH and psychometric properties in gastroesophageal reflux: systematic review.

J Pediatr (Rio J) 2020 Nov - Dec;96(6):673-685. Epub 2020 Feb 28.

Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil.

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.

Conclusions: According to the selected studies, multichannel intraluminal impedance-pH was considered a safe and effective tool, presenting higher sensitivity values than pHmetry regarding the diagnosis of gastroesophageal reflux disease.
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http://dx.doi.org/10.1016/j.jped.2020.01.005DOI Listing
January 2021

Lung ultrasound assessment of response to antibiotic therapy in cystic fibrosis exacerbations: a study of two cases.

J Bras Pneumol 2019 11 25;45(6):e20190128. Epub 2019 Nov 25.

. Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas (SP) Brasil.

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http://dx.doi.org/10.1590/1806-3713/e20190128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447551PMC
November 2019

Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis.

Clin Drug Investig 2020 Feb;40(2):105-117

Center for Investigation in Pediatrics, Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 126, Tessália Vieira de Camargo, Campinas, São Paulo, 13083-887, Brazil.

Background: Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO inhalation may be a low-cost, easily accessible therapy for CF.

Objective: To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO 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 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), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO) 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), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed.

Conclusion: Nebulized NaHCO inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.
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http://dx.doi.org/10.1007/s40261-019-00861-xDOI Listing
February 2020

Concordance between whole- and half-body scans to evaluate body composition in dual-energy X-ray absorptiometry in children and adolescents with different nutritional and pubertal conditions.

Nutrition 2019 10 26;66:78-86. Epub 2019 Apr 26.

Department of Pediatrics, University of Campinas (Unicamp), Faculty of Medical Sciences, Campinas, São Paulo, Brazil.

Objectives: Evaluation of body composition is a relevant clinical instrument for the follow-up assessments of children and adolescents, and dual-energy X-ray absorptiometry (DXA) is an accurate method for the pediatric population. However, DXA has limited scan area for the obese population. Thus, half-body scans emerged as an alternative to evaluate individuals with obesity. The aim of this study was to compare the body composition of children and adolescents with whole- and half-body DXA scans, considering nutritional status, pubertal development, sex, and age.

Methods: This was a cross-sectional, analytical, and diagnostic intervention study with a sample of 82 participants of both sexes between 4 and 20 y of age. Body composition was evaluated by DXA using an iDXA bone densitometer (GE Healthcare Lunar, Madison, WI, USA). Two evaluations were performed: whole-body and half-body scans. The Bland-Altman correlation and linear regression tests were applied to identify the presence of association bias between the techniques. α = 0.05 was set.

Results: Of the 82 participants, 20 were excluded. A high correlation was observed between the data (correlation coefficient ∼0.999). Bland-Altman plots and regression analyses demonstrated correlation and randomness bias between whole- and half-body scan techniques in obese or normal weight participants for all DXA markers.

Conclusions: The use of half-body scans was feasible and accurate to evaluate whole-body composition. The difference bias between techniques occurred randomly and was clinically irrelevant. A high correlation was observed between half- and whole-body analysis techniques.
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http://dx.doi.org/10.1016/j.nut.2019.03.018DOI Listing
October 2019

Severe pulmonary disease in an adult primary ciliary dyskinesia population in Brazil.

Sci Rep 2019 06 18;9(1):8693. Epub 2019 Jun 18.

Department of Pathology, São Paulo University Medical School, São Paulo, SP, 01246-903, Brazil.

Primary Ciliary Dyskinesia (PCD) is underdiagnosed in Brazil. We enrolled patients from an adult service of Bronchiectasis over a two-year period in a cross-sectional study. The inclusion criteria were laterality disorders (LD), cough with recurrent infections and the exclusion of other causes of bronchiectasis. Patients underwent at least two of the following tests: nasal nitric oxide, ciliary movement and analysis of ciliary immunofluorescence, and genetic tests (31 PCD genes + CFTR gene). The clinical characterization included the PICADAR and bronchiectasis scores, pulmonary function, chronic Pseudomonas aeruginosa (cPA) colonization, exhaled breath condensate (EBC) and mucus rheology (MR). Forty-nine of the 500 patients were diagnosed with definite (42/49), probable (5/49), and clinical (2/49) PCD. Twenty-four patients (24/47) presented bi-allelic pathogenic variants in a total of 31 screened PCD genes. A PICADAR score > 5 was found in 37/49 patients, consanguinity in 27/49, LD in 28/49, and eight PCD sibling groups. FACED diagnosed 23/49 patients with moderate or severe bronchiectasis; FEV ≤ 50% in 25/49 patients, eight patients had undergone lung transplantation, four had been lobectomized and cPA+ was determined in 20/49. The EBC and MR were altered in all patients. This adult PCD population was characterized by consanguinity, severe lung impairment, genetic variability, altered EBC and MR.
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http://dx.doi.org/10.1038/s41598-019-45017-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582273PMC
June 2019

Microbiological contamination of nebulizers used by cystic fibrosis patients: an underestimated problem.

J Bras Pneumol 2019 May 30;45(3):e20170351. Epub 2019 May 30.

. Laboratório de Fisiologia Pulmonar, Centro de Investigação em Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas (SP), Brasil.

Objective: Home nebulizers are routinely used in the treatment of patients with cystic fibrosis (CF). This study aims to evaluate the contamination of nebulizers used for CF patients, that are chronically colonized by Pseudomonas aeruginosa, and the association of nebulizer contamination with cleaning, decontamination and drying practices.

Methods: A cross-sectional, observational, multicenter study was conducted in seven CF reference centers in Brazil to obtain data from medical records, structured interviews with patients/caregivers were performed, and nebulizer's parts (interface and cup) were collected for microbiological culture.

Results: overall, 77 CF patients were included. The frequency of nebulizer contamination was 71.6%. Candida spp. (52.9%), Stenotrophomonas maltophilia (11.9%), non-mucoid P. aeruginosa (4.8%), Staphylococcus aureus (4.8%) and Burkholderia cepacia complex (2.4%) were the most common isolated pathogens. The frequency of nebulizers' hygiene was 97.4%, and 70.3% of patients reported cleaning, disinfection and drying the nebulizers. The use of tap water in cleaning method and outdoor drying of the parts significantly increased (9.10 times) the chance of nebulizers' contamination.

Conclusion: Despite the high frequency hygiene of the nebulizers reported, the cleaning and disinfection methods used were often inadequate. A significant proportion of nebulizers was contaminated with potentially pathogenic microorganisms for CF patients. These findings support the need to include patients/caregivers in educational programs and / or new strategies for delivering inhaled antibiotics.
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http://dx.doi.org/10.1590/1806-3713/e20170351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715035PMC
May 2019

Novel, rare and common pathogenic variants in the CFTR gene screened by high-throughput sequencing technology and predicted by in silico tools.

Sci Rep 2019 04 17;9(1):6234. Epub 2019 Apr 17.

Department of Medical Genetics and Genomic Medicine, School of Medical Sciences, University of Campinas. Tessália Vieira de Camargo, 126, Barão Geraldo, Cidade Universitária Zeferino Vaz, CEP: 13083-887, Campinas, São Paulo, Brazil.

Cystic fibrosis (CF) is caused by ~300 pathogenic CFTR variants. The heterogeneity of which, challenges molecular diagnosis and precision medicine approaches in CF. Our objective was to identify CFTR variants through high-throughput sequencing (HTS) and to predict the pathogenicity of novel variants through in 8 silico tools. Two guidelines were followed to deduce the pathogenicity. A total of 169 CF patients had genomic DNA submitted to a Targeted Gene Sequencing and we identified 63 variants (three patients had three variants). The most frequent alleles were: F508del (n = 192), G542* (n = 26), N1303K (n = 11), R1162* and R334W (n = 9). The screened variants were classified as follows: 41 - pathogenic variants [classified as (I) n = 23, (II) n = 6, (III) n = 1, (IV) n = 6, (IV/V) n = 1 and (VI) n = 4]; 14 - variants of uncertain significance; and seven novel variants. To the novel variants we suggested the classification of 6b-16 exon duplication, G646* and 3557delA as Class I. There was concordance among the predictors as likely pathogenic for L935Q, cDNA.5808T>A and I1427I. Also, Y325F presented two discordant results among the predictors. HTS and in silico analysis can identify pathogenic CFTR variants and will open the door to integration of precision medicine into routine clinical practice in the near future.
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http://dx.doi.org/10.1038/s41598-019-42404-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470152PMC
April 2019

Extent of rescue of F508del-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del Cystic Fibrosis patients.

Biochim Biophys Acta Mol Basis Dis 2019 06 1;1865(6):1323-1331. Epub 2019 Feb 1.

University of Lisboa, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Portugal. Electronic address:

Background: We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508del/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM: 608481) gene.

Methods: The I measurements of primary nasal epithelial cells from F508del/F508del patients (n = 12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (n = 2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR.

Results: The CRC-HNE cells from F508del/F508del patients evidenced high variability in the basal levels of CFTR function. Also, the rs7512462*C allele showed an increased basal CFTR function and higher responses to VX-809 + VX-770. The rs7512462*CC + CT genotypes together evidenced CFTR function levels of 14.89% relatively to wt/wt (rs7512462*CT alone-15.29%) i.e., almost double of rs7512462*TT (7.13%). Furthermore, sweat [Cl] and body mass index of patients also evidenced an association with the rs7512462 genotype.

Conclusion: The CFTR function can be performed in F508del/F508del patient-derived CRC-HNEs and its function and responses to VX-809 + VX-770 combination as well as clinical data, are all associated with the rs7512462 variant, which partially sheds light on the generally inter-individual phenotypic variability and in personalized responses to CFTR modulator drugs.
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http://dx.doi.org/10.1016/j.bbadis.2019.01.029DOI Listing
June 2019

Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients.

Med Microbiol Immunol 2019 Apr 31;208(2):205-213. Epub 2019 Jan 31.

Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Rua Vital Brasil 251, 2nd floor, Cidade Universitária, Barão Geraldo, Campinas, SP, 13083-888, Brazil.

Pseudomonas aeruginosa (Pa) detection in the paranasal sinuses may help to prevent or postpone bacterial aspiration to the lower airways (LAW) and chronic lung infection in cystic fibrosis (CF). We assessed the ability of an ELISA test for measurement of specific Pa secretory IgA (sIgA) in saliva (a potential marker of sinus colonization) to early detect changes in the Pa LAW status (indicated by microbiological sputum or cough swab culture and specific serum IgG levels) of 65 patients for three years, in different investigation scenarios. Increased sIgA levels were detected in saliva up to 22 months before changes in culture/serology. Patients who remained Pa-positive had significantly increased sIgA levels than patients who remained Pa-negative, both at the baseline (39.6 U/mL vs. 19.2 U/mL; p = 0.02) and at the end of the follow-up (119.4 U/mL vs. 25.2 U/mL; p < 0.001). No association was found between sIgA levels in saliva and emergence or recurrence of Pa in the LAW. A positive median sIgA result in the first year of follow-up implied up to 12.5-fold increased risk of subsequent Pa exposure in the LAW. Our test detected early changes in the P. aeruginosa LAW status and risk of exposure to P. aeruginosa in the LAW with two years in advance. Comparison with sinus culture is needed to assess the test's ability to identify CF patients in need of a sinus approach for Pa investigation, which could provide opportunities of Pa eradication before its aspiration to the lungs.
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http://dx.doi.org/10.1007/s00430-019-00578-wDOI Listing
April 2019

Lung disease and vitamin D levels in cystic fibrosis infants and preschoolers.

Pediatr Pulmonol 2019 05 20;54(5):563-574. Epub 2019 Jan 20.

School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Introduction: Vitamin D acts on the immune system and lung response. Patients with cystic fibrosis (CF) may be deficient in this vitamin. The aims of the study were to evaluate vitamin D levels and severity of lung disease in infants and preschoolers diagnosed with CF, and to compare them to a group of children without pancreatic insufficiency (PI).

Methods: Patients with CF up to 4 years old were included, and compared to an age-matched group of children without diagnosis of CF. CF group had medical records and High Resolution Thorax Computed Tomography (HRCCT) evaluated in order to verify the severity of lung disease. Information on demographic data, sun exposure habits, supplemental vitamin D therapy, and on the season at the time of vitamin D sampling were collected for both groups.

Results: This study included 45 patients in the CF group and 102 in the non-CF group, with no differences in age (P = 0.327) between them. There was no association between vitamin D levels and markers of lung disease in the CF group. The non-CF group had lower daily sun exposure (P = 0.034), and lower supplementation than the CF group (P < 0.001). Supplementation and seasonality were the determinant variables for vitamin D levels, which were lower for non-supplemented children and for assessments during fall/winter.

Conclusion: There was no association between lung disease severity and vitamin D levels in CF group. Supplementation and seasonality were associated to higher vitamin levels.
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http://dx.doi.org/10.1002/ppul.24260DOI Listing
May 2019

Analysis of motor and respiratory function in Duchenne muscular dystrophy patients.

Respir Physiol Neurobiol 2019 04 17;262:1-11. Epub 2019 Jan 17.

Department of Pediatrics, School of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111 Campinas, São Paulo, Brazil; Laboratory of Pulmonary Physiology, Center for Pediatrics Investigation, School of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111 Campinas, São Paulo, Brazil. Electronic address:

Introduction: Duchenne muscular dystrophy(DMD) shows motor and respiratory impairment.

Methods: 19 DMD patients (DMDG) (nine ambulatory and 10 non-ambulatory) were evaluated through motor function measure (MFM), 6-minute walk test (6MWT), respiratory muscle strength, cough peak flow, spirometry and volumetric capnography (VCap) tools. Control group that performed spirometry and VCap (CG1-n = 17) were different from those that performed the 6MWT (CG2-n = 8).

Results: The follow tools were assessed (p < 0.05): (i) MFM: Ambulatory patients showed higher values than non-ambulatory patients; (ii) 6MWT: DMDG walked a shorter distance and showed higher respiratory rate at rest and heart rate (HR) at rest than CG2; (iii) Spirometry: DMDG and non-ambulatory patients had minor values achieved in spirometry when compared with CG1 and ambulatory patients, respectively; (iv) VCap: DMDG when compared with CG1 showed: (<11 years-old) lower values in VCap parameters; (>11 years-old): higher HR and lower slope 2. There was correlation between spirometry, mainly for zFEV/FVC, and MFM.

Conclusion: DMDG showed motor (MFM/6MWT) and respiratory (spirometry/VCap) deterioration when compared with CG. Non-ambulatory condition was associated with worse MFM and spirometry.
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http://dx.doi.org/10.1016/j.resp.2019.01.009DOI Listing
April 2019

Volumetric capnography versus spirometry for the evaluation of pulmonary function in cystic fibrosis and allergic asthma.

J Pediatr (Rio J) 2020 Mar - Apr;96(2):255-264. Epub 2018 Dec 7.

Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil; Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Laboratório de Fisiologia Pulmonar (LAFIP), Centro de Investigação em Pediatria (CIPED), Campinas, SP, Brazil. Electronic address:

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 to 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/FVC) was the only spirometric marker that presented difference on the three groups. On individuals with normal spirometry, KPIv and FEV/FVC were different among the three groups. The ROC curve identified the individuals with asthma or CF from the control group, both through volumetric capnography (better to identify CF in relation to the control using KPIv) and through spirometry (better to identify asthma in relation to the control). KPIv was the best parameter to distinguish asthma from CF, even in individuals with normal spirometry.

Conclusion: Volumetric capnography and spirometry identified different alterations in lung function on asthma, CF, and healthy controls, allowing the three groups to be distinguished.
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http://dx.doi.org/10.1016/j.jped.2018.10.008DOI Listing
October 2020

IMPULSE OSCILLOMETRY AND SPIROMETRY IN SCHOOLERS SUBMITTED TO THE SIX-MINUTE WALK TEST.

Rev Paul Pediatr 2018 Oct-Dec;36(4):474-481. Epub 2018 Oct 29.

Universidade do Estado de Santa Catarina, Florianópolis, SC, Brasil.

Objective: To verify repercussions of submaximal exercise testing on respiratory mechanics and pulmonary function in schoolchildren.

Methods: Cross-sectional study, with children aged 7 to 14 years, who had their respiratory mechanics assessed by impulse oscillometry (IOS), and pulmonary function by spirometry. They performed the six-minute walk test (6MWT), as per the standards by the American Thoracic Society. The 6MWT was performed twice with a 30-minute interval. IOS and spirometry were performed before the first 6MWT (Pre-6MWT) and immediately after the first (Post-6MWT1) and second walking tests (Post-6MWT2). The results in these three phases were compared by analysis of variance for repeated measures (post-hoc Bonferroni test) or by the Friedman's test, with p≤0.05 considered significant.

Results: Twenty-one subjects participated in the study: 53% were males and mean age was 10.9±2.3 years. There were differences between total resistance (R5) and central airway resistance (R20) at the three phases of assessment (p=0.025 and p=0.041, respectively). Post-hoc analysis indicated increase in R5 when Pre-6MWT and Post-6MWT1 were compared (R5=0.540±0.100 versus 0.590±0.150 kPa/L/s, p=0.013; and R20=0.440±0.800 versus 0.470±0.100 kPa/L/s, p=0.038). Forced expiratory flow 25-75% (FEF25-75%) changed over time (p=0.003).

Conclusions: Repercussions were: increase in central and total airway resistance and reduction of FEF25-75% after 6MWT in schoolchildren, suggesting that greater attention should be given to submaximal tests in children with predisposition to airways alterations.
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http://dx.doi.org/10.1590/1984-0462/;2018;36;4;00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322806PMC
June 2019

Evaluation of continuous constant current and continuous pulsed current in sweat induction for cystic fibrosis diagnosis.

BMC Pulm Med 2018 Sep 14;18(1):153. Epub 2018 Sep 14.

Center for Biomedical Engineering, University of Campinas, Cidade Universitária Zeferino Vaz, Barão Geraldo, Campinas, São Paulo, 13083-970, Brazil.

Background: The sweat test (ST) is the gold standard for the diagnosis of cystic fibrosis (CF). However, little is known about sweat induction using different types of currents and waves. In this context, our objective was to develop a device to induce sweat and compare the use of continuous constant current (CCC) and continuous pulsed current (CPC) in individuals with CF and healthy controls.

Methods: A prospective cross-sectional study with experimental intervention. The variables of gender, ethnicity, age, and body mass index (BMI) were considered. The method of Gibson and Cooke was used, and the following markers were evaluated: sweat weight, electrical impedance, sufficient sweat amount, and CF diagnosis. Triangular (TPC) or sinusoidal (SPC) pulsed current was applied to the right arm, and CCC was applied to the left arm.

Results: The study analyzed 260 individuals, 141/213 (54.2%) were female participants, 135/260 (51.9%) were Caucasians. The distribution of individuals by concentration of chloride at the ST was: (CF) 26/260 (10%); (borderlines) 109/260 (41.9%); (healthy) 97/260 (37.3%); (insufficient weight in sweat) 28/260 (10.8%). No association was observed between the sufficient sweat amount to perform the ST when we compared the currents. However, the SPC showed a higher amount of sweat weight. Using Bland and Altman plot considering the agreement between the sweat chloride values achieved from CPC [SPC and TPC] and CCC, there was no proportional bias and mean values are unrelated and only explain less than 8% of the variation. Moreover, TPC presented higher electrical impedance when compared with SPC and CCC. SPC presented lower electrical impedance and higher sweat weight than CCC. Male participants presented lower electrical impedance and higher sweat weight with CCC and TPC, and higher sweat weight with SPC.

Conclusions: The evaluated currents are safe and able to induce and produce sweat in sufficient quantities for the ST. SPC presented lower electrical impedance when compared with other currents. The use of SPC is recommended to induce sweat in patients with sweat problems. Finally, ethnicity, gender, age and BMI did not influence sweat induction at the ST, and no side effect was observed in our study.
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http://dx.doi.org/10.1186/s12890-018-0696-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137935PMC
September 2018

Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.

J Pediatr (Rio J) 2019 Jul - Aug;95(4):443-450. Epub 2018 May 19.

Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Patologia Clínica, Campinas, SP, Brasil. Electronic address:

Objective: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥60mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis.

Methods: There were 160 subjects enrolled: 57/160 (35.70%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.40%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer equipment and, sweat chloride concentration and sweat sodium concentration, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann-Whitney test, and Spearman's correlation. Alpha=0.05.

Results: Patients with cystic fibrosis showed higher values of sweat chloride concentration, sweat sodium concentration, saliva chloride concentration, and saliva sodium concentration than healthy controls subjects (p-value<0.001). The correlation between saliva chloride concentration and sweat chloride concentration showed a positive Spearman's Rho (correlation coefficient)=0.475 (95% CI=0.346 to 0.587). Also, the correlation between saliva sodium concentration and sweat sodium concentration showed a positive Spearman's Rho=0.306 (95% CI=0.158 to 0.440).

Conclusions: Saliva chloride concentration and saliva sodium concentration are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by the general population.
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http://dx.doi.org/10.1016/j.jped.2018.04.005DOI Listing
May 2020

Continuous glucose monitoring to evaluate glycaemic abnormalities in cystic fibrosis.

Arch Dis Child 2018 06 29;103(6):592-596. Epub 2018 Jan 29.

Department of Pediatrics, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.

Objective: This study aimed to determine the glycaemic profile of patients with cystic fibrosis using a continuous glucose monitoring system (CGMS), and to evaluate the associations of glycaemic abnormalities with sex, age, pubertal stage, gene mutations, nutritional status, lung function, oral glucose tolerance test, glycated haemoglobin concentrations, fasting insulin concentrations, C peptide concentrations and exocrine pancreatic function.

Study Design: This observational study evaluated CGMS data from 39 patients with cystic fibrosis who were treated at a referral centre. The patients were 10-19.9 years old, and were categorised according to whether they had normal results (27 patients) or glucose intolerance (12 patients) during the oral glucose tolerance test.

Results: The maximum interstitial glucose concentration among individuals with normal oral glucose tolerance test results was 174.9±65.1 mg/dL (9.7-3.61 mmol/L), compared with 170.4±40.9 mg/dL (9.46-2.27 mmol/L) among individuals with glucose intolerance. The CGMS revealed that 18 of the 27 patients with normal oral glucose tolerance test results had peak interstitial glucose concentrations of >140 mg/dL (7.8 mmol/L), and that 4 of these individuals had peak levels of >200 mg/dL (11.1 mmol/L). None of the analysed clinical or laboratory characteristics predicted the occurrence of hyperglycaemic peaks on CGMS.

Conclusions: The present study revealed that CGMS could detect hyperglycaemia among patients with cystic fibrosis and 'normal' oral glucose tolerance test results, and that their clinical and laboratory characteristics were not useful in discerning between patients who did and did not exhibit these excursions.
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http://dx.doi.org/10.1136/archdischild-2017-314250DOI Listing
June 2018

Skin Biomarkers for Cystic Fibrosis: A Potential Non-Invasive Approach for Patient Screening.

Front Pediatr 2017 10;5:290. Epub 2018 Jan 10.

Innovare Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, Brazil.

Background: Cystic fibrosis (CF) is a disabling genetic disease with an increased prevalence in European heritage populations. Currently, the most used technique for collection of CF samples and diagnosis is provided through uncomfortable tests, with uncertain results, mostly based on chloride concentration in sweat. Since CF mutation induces many metabolic changes in patients, exploring these alterations might be an alternative to visualize potential biomarkers that could be used as interesting tools for further diagnostic upgrade, prioritizing simplicity, low cost, and quickness.

Methods: This contribution describes an accurate strategy to provide potential biomarkers related to CF, which may be understood as a potential tool for new diagnostic approaches and/or for monitoring disease evolution. Therefore, the present proposal consists of using skin imprints on silica plates as a way of sample collection, followed by direct-infusion high-resolution mass spectrometry and multivariate data analysis, intending to identify metabolic changes in skin composition of CF patients.

Results: Metabolomics analysis allowed identifying chemical markers that can be traced back to CF in patients' skin imprints, differently from control subjects. Seven chemical markers from several molecular classes were elected, represented by bile acids, a glutaric acid derivative, thyrotropin-releasing hormone, an inflammatory mediator, a phosphatidic acid, and diacylglycerol isomers, all reflecting metabolic disturbances that occur due to of CF.

Conclusion: The comfortable method of sample collection combined with the identified set of biomarkers represent potential tools that open the range of possibilities to manage CF and follow the disease evolution. This exploratory approach points to new perspectives about the development of diagnostic assay using biomarkers and the management CF.
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http://dx.doi.org/10.3389/fped.2017.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767587PMC
January 2018

Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis.

Gene 2018 Mar 15;645:7-17. Epub 2017 Dec 15.

Department of Pediatrics, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, Campinas CEP 13083-887, São Paulo, Brazil.

Background: Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis.

Methods: We prospectively evaluated 181 infants with severe bronchiolitis admitted at three hospitals over a 2-year period, who required oxygen therapy. The control group consisted of 536 healthy adults. Patients were evaluated for the presence of comorbidities (premature birth, chronic respiratory disease, and congenital heart disease), underwent nasopharyngeal aspirate testing for virus detection by multiplex-PCR, and SNPs identification in immune response genes. Patient outcomes were assessed.

Results: We observed association between SNP rs2107538*CCL5 and bronchiolitis caused by respiratory syncytial virus(RSV) and RSV-subtype-A, and between rs1060826*NOS2 and bronchiolitis caused by rhinovirus. SNPs rs4986790*TLR4, rs1898830*TLR2, and rs2228570*VDR were associated with progression to death. SNP rs7656411*TLR2 was associated with length of oxygen use; SNPs rs352162*TLR9, rs187084*TLR9, and rs2280788*CCL5 were associated with requirement for intensive care unit admission; while SNPs rs1927911*TLR4, rs352162*TLR9, and rs2107538*CCL5 were associated with the need for mechanical ventilation.

Conclusions: Our findings provide some evidence that SNPs in CCL5 and NOS2 are associated with presence of bronchiolitis and SNPs in TLR4, TLR2, TLR9, VDR and CCL5 are associated with severity of bronchiolitis.
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http://dx.doi.org/10.1016/j.gene.2017.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127094PMC
March 2018

Respiratory syncytial virus in Brazilian infants - Ten years, two cohorts.

J Clin Virol 2018 01 6;98:33-36. Epub 2017 Dec 6.

Department of Pediatrics, Faculty of Medical Sciences, University of Campinas - Unicamp, São Paulo, Brazil. Electronic address:

Background: Each year, a considerable amount of children will experience at least one episode of acute viral bronchiolitis (AVB) during their first year of life. About 10% of them will be hospitalized, with significant physical and economic burdens.

Objectives: To compare two cohorts of infants with AVB, from same region, in a ten-year interval, regarding epidemiologic factors and viral etiology.

Study Design: Cohorts: 142 (2004) and 172 (2014) infants at ages zero to 12 months; clinical diagnosis of AVB; medical care in hospital and genetic screening of nasopharyngeal secretion for respiratory viruses.

Results: The comparative analysis showed a difference in the percentage of respiratory syncytial virus (RSV) positive patients [2004 (33.1%); 2014 (70.3%)] (p<0.01). No differences were noted regarding gender, breastfeeding, tobacco exposure, crowding and maternal education. There was a difference as to the month of incidence (seasonality) of AVB (higher in April 2014). There was a higher age at attendance in the first cohort, and lower birth weight and gestational age ratios in the second cohort (p<0.05). There were no differences in hospitalization time, need of mechanical ventilation and number of deaths, however a difference regarding co-morbidities was noted (higher in 2004) (p<0.001).

Conclusion: None of the analyzed variables had an impact on severity features. Virology and immunology must be considered in this kind of situation, by studying genetic variants and the maturation of the immune system in AVB by RSV or other viruses.
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http://dx.doi.org/10.1016/j.jcv.2017.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106499PMC
January 2018

Pancreatic Insufficiency in Cystic Fibrosis: Influence of Inflammatory Response Genes.

Pancreas 2018 01;47(1):99-109

Objective: Pancreatic insufficiency (PI) in cystic fibrosis (CF) patients is a crucial clinical marker for severity and disease progression. In our study, 125 modifier genes and their SNPs were associated between CF patients with PI or pancreatic sufficiency.

Methods: We prospectively evaluated 214 CF patients admitted at 1 hospital for a 2-year period. The PI status was associated with clinical variables and SNPs related with inflammatory response considering CFTR mutations. Open Array technique was used to perform the SNPs identification.

Results: For PI risk, after correction by multiple test, in CF patients and 2 CFTR mutations class I, II, and/or III, there were 6 SNPs with positive association (P < 0.005). The odds ratio amplitude was 0.087 (95% confidence interval [CI], 0.004-0.544) for rs9870255*CG (CTNNB1 gene) to 11.06 (95% CI, 1.746-252.3) for rs729302*AA (IRF5 gene). For all CF patients at the same time, 9 SNPs showed positive association. The odds ratio amplitude was 0.144 (95% CI, 0.028-0.602) for rs2348071*AA (PSMA3 gene) to 5.809 (95% CI, 1.536-37.54) for rs11702779*AA (RUNX1 gene). In our data, we observed the interaction between CFTR mutations, rs9870255*CTNNB1, rs9378805*IRF4, and rs7664617*KCNIP4 to PI status.

Conclusions: Multiple SNPs in inflammatory response genes showed association with PI considering the CFTR mutations screening.
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http://dx.doi.org/10.1097/MPA.0000000000000963DOI Listing
January 2018
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