Physical activity and asthma control level in children and adolescents.

BACKGROUND AND OBJECTIVE: Physical activity is defined as any bodily movement produced by a muscle contraction with increased energy expenditure. The aim of this study was to assess the physical activity, asthma control level, spirometric measurements and quality of life in children and adolescents with asthma. METHODS: We included all children and adolescents aged 7-17 years who had a diagnosis of atopic asthma and who attended the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas, Brazil. Asthma control levels were evaluated by the Asthma Control Test (ACT). Physical activity was measured using the long version of the International Physical Activity Questionnaire (IPAQ) and by other questions about daily activities at school and at home over the last week. Lung function was assessed by spirometry, both pre- and post-bronchodilator (BD). Quality of life was evaluated using the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). RESULTS: Out of 100 patients, 60 were classified as presenting with controlled asthma (CA) and 40 as presenting with uncontrolled asthma (UA). In the IPAQ, 29% were classified as sedentary, 17% as active and 54% as very active. There was no significant association between physical activity and the level of asthma control. We found no differences between active and sedentary children and adolescents with asthma in spirometric variables or quality of life. CONCLUSION: No associations were observed between physical activity and asthma control level, spirometric measurements and quality of life in children and adolescents with asthma.

Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility.

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 correlate with their transepithelial resistance (r = -0.438 and -0.305, respectively) and are influenced by the bowel preparation solution and biopsy forceps used, being NaCl and jumbo forceps the most compatible methods with the electrophysiological analysis. The great majority of the individuals (76%) did not report major discomfort due to the short procedure time (max 15 min) and considered it relatively painless (79%). Importantly, most (88%) accept repeating it at least for one more time and 53% for more than 4 times. CONCLUSIONS: Obtaining rectal biopsies with a flexible endoscope and jumbo forceps after bowel preparation with NaCl solution is a safe procedure that can be adopted for both adults and children of any age, yielding viable specimens for CFTR bioelectrical/biochemical analyses. The procedure is well tolerated by patients, demonstrating its feasibility as an outcome measure in clinical trials.

Obesity increases eosinophil activity in asthmatic children and adolescents.

BACKGROUND: A clear relationship between asthma and obesity has been reported, but the mechanisms remain unclear. The aim of this study was to evaluate the influence of obesity on eosinophil activity (chemotaxis and adhesion) in asthmatic children and adolescents compared with cells from healthy volunteers. METHODS: Asthmatic obese (AO), asthmatic non-obese (ANO), non-asthmatic obese (NAO) and non-asthmatic non-obese (NANO) individuals were included in the present study. The chemotaxis of eosinophils after stimulation with eotaxin (300 ng/ml), platelet-activating factor (10 µM; PAF) and RANTES (100 ng/ml) was performed using a microchemotaxis chamber. The eosinophil peroxidase activity was measured to determine the adhesion activity of eosinophils cultivated on fibronectin-coated plates. The serum leptin, adiponectin, TNF-α and IgE levels were quantified using ELISA assays. RESULTS: The serum IgE levels and eosinophil counts were significantly higher in asthmatic (obese and non-obese) individuals compared with non-asthmatic individuals (obese and non-obese). Spontaneous eosinophil chemotaxis was greater in the AO group compared with either the ANO or NANO groups. The activation of eosinophils using eotaxin and PAF increased eosinophil chemotaxis in the AO group. RANTES treatment increased eosinophil chemotaxis in the NAO group compared with the NANO or ANO groups. The activation of eosinophils using eotaxin significantly increased eosinophil adhesion in the AO group compared with other groups. The serum leptin and TNF-α levels were higher in obese subjects (asthmatic and non-asthmatic), whereas the levels of adiponectin did not significantly differ among these groups. CONCLUSION: This study is the first to show increased eosinophilic activity (chemotaxis and adhesion) associated with high serum leptin and TNF-α levels in atopic asthmatic obese children and adolescents compared with non-obese healthy volunteers.

Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis.

BACKGROUND: The most common cystic fibrosis (CF) manifestation is the progressive chronic obstructive pulmonary disease caused by deficiency, dysfunction, or absence of the CFTR (Cystic Fibrosis Transmembrane Regulator) protein on the apical surface of the cells in the respiratory tract. The use of bronchodilators (BD), and inhaled corticosteroids (IC) have been suggested for the management of airway inflammation in CF. The effectiveness of BD and IC have been verified, proven in laboratory and in the clinical treatment for asthma patients. However, in CF, the effectiveness of these drugs is controversial. The extent of asthma's response to BD depends on the presence of polymorphisms in the ADRB2 gene. In contrast, in CF, little is known about the response to the BD and the association of CF´s severity with the different polymorphisms in ADRB2 gene. In this context, our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene are associated with severity and with the bronchodilator response in CF patients. METHOD: Cross-sectional study of 122 CF patients subjected to analysis of mutations in the CFTR gene, polymorphisms in ADRB2 gene, along with clinical and laboratorial characteristics of severity. RESULT: The Arg16Gly polymorphism in ADRB2 gene was associated with pancreatic insufficiency(p:0.009), Bhalla score(p:0.039), forced expiratory volume in the first second[FEV1(%)](p:0.003), forced expiratory flow between 25 and 75% of the forced vital capacity-FVC[FEF25-75(%)](p:0.008) and lower age at the first isolation of the Pseudomonas aeruginosa(p:0.012). The response to the BD spirometry was associated with clinical severity markers, FEV1(%)(p:0.011) and FEF25-75(%)(p:0.019), for the Arg16Gly polymorphism in the ADRB2 gene. The haplotype analysis showed association with the FEV1/FVC marker from the spirometry test, before and after using the BD, with higher values in the group with Gly/Gly and Glu/Glu, respectively, for the Arg16Gly and Gln27Glu polymorphisms. The analysis by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly was respondent by 17.35% and Gln27Glu by 6.8% in variation found. CONCLUSION: There was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.

The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is a monogenic disease with complex expression because of the action of genetic and environmental factors. We investigated whether the ACE gene D/I polymorphism is associated with severity of CF. METHODS: A cross-sectional study was performed, from 2009 to 2011, at University of Campinas - UNICAMP. We analyzed 180 patients for the most frequent mutations in the CFTR gene, presence of the ACE gene D/I polymorphism and clinical characteristics of CF. RESULTS: There was an association of the D/D genotype with early initiation of clinical manifestations (OR: 1.519, CI: 1.074 to 2.146), bacterium Burkholderia cepacia colonization (OR: 3.309, CI: 1.476 to 6.256) and Bhalla score (BS) (p = 0.015). The association was observed in subgroups of patients which were defined by their CFTR mutation genotype (all patients; subgroup I: no mutation detected; subgroup II: one CFTR allele identified to mutation class I, II or III; subgroup III: both CFTR alleles identified to mutation class I, II and/or III). CONCLUSION: An association between the D allele in the ACE gene and the severity of CF was found in our study.

Prevalence of constipation in cystic fibrosis patients: a systematic review of observational studies.

OBJECTIVE: To systematically revise the literature in search of data about the prevalence of constipation in patients with cystic fibrosis according to the publications in this field, which partly refer to guidelines defined in 2010 by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. SOURCES: Systematic review selecting articles based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, including Cystic Fibrosis patients of all ages. Sources of information were selected to identify the articles without period limitation: CADTH - Canadian Agency for Drugs and Technologies in Health, CINAHL Complete, Clinical Trials US NIH, Cochrane Library, Embase, MEDLINE via Ovid, Scopus, Web Of Science, PubMed, SciELO, MEDLINE and LILACS , Health Systems Evidence, PDQ Evidence, CRD Canadian Agency for Drugs and Technologies in Health, INAHTA - International Network of Agencies for Health Technology Assessment, and PEDro. FINDINGS: The prevalence of constipation was reported in eight observational studies. Only two studies assessed the frequency of constipation as a primary objective; in the others, constipation was quoted along with the prevalence of the spectrum of gastrointestinal manifestations. Altogether, the publications included 2,018 patients, the reported prevalence varied from 10% to 57%. Only two of the six articles published after 2010 followed the definition recommended by the European Society. CONCLUSIONS: Constipation is a frequent but still insufficiently assessed complaint of Cystic Fibrosis patients. The use of diverse diagnostic criteria restricts comparison and epidemiological conclusions, future studies should compulsorily apply the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition definition.

Lymphocyte responses to Mycobacterium tuberculosis and Mycobacterium bovis are similar between BCG-vaccinated patients with cystic fibrosis and healthy controls.

BACKGROUND: The low rate of nontuberculous mycobacteria (NTM) among Brazilian patients with cystic fibrosis (CF) may be due to cross-reactive Bacille Calmette-Guérin (BCG) vaccination. In the present pilot study, we aimed to compare the lymphocyte responses against Mycobacterium tuberculosis(Mtb) and Mycobacterium bovis (BCG) in BCG-vaccinated CF patients and healthy controls. METHODS: The lymphocyte responses of CF patients (n = 10) and healthy controls (n = 10) were assessed in terms of lymphocyte proliferation index (LPI), using flow cytometry. Median rates of each cell subtype - CD4, CD8, γδ T cells and CD19 (B) cells - were also determined. RESULTS: Median LPIs (CF vs. controls) were 22.9% vs. 13.0% (p = 0.481) and 23.1% vs. 17.6% (p = 0.481), upon stimulation with Mtb and BCG, respectively. Both groups had a predominant CD4 T cell response to Mtb (median rate = 82.5% vs. 79.7%; p = 0.796) and BCG (LPI = 84.3% vs. 83.0%; p = 0.853), which were significantly higher than the CD8, CD19 and γδ responses within both groups. CF patients tended to have a higher CD8 T cell response upon stimulation with the phytohemagglutinin mitogen than healthy controls (median rate = 42.8% vs. 31.7%, p = 0.075). CONCLUSION: The responses of BCG-vaccinated CF patients to Mtb and BCG are at least similar to those of healthy individuals. These are probably memory responses elicited by the BCG vaccination, which can cross-react with NTM and may explain the low frequency of NTM lung infection in our CF center.

The Use of Ultrasound as a Tool to Evaluate Pulmonary Disease in Cystic Fibrosis.

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 SpO2 ), 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), SpO2 (partial correlation = -0.728), FVC% (pre-bronchodilator: partial correlation = -0.538; post-bronchodilator: partial correlation = -0.560), FEV1% (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.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis.

OBJECTIVE: To evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. METHODS: Case series of ten patients (median age 13.2 years), followed-up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow-up. RESULTS: All patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. CONCLUSION: In this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients.

OBJECTIVES: Volumetric capnography provides the standard CO2 elimination by the volume expired per respiratory cycle and is a measure to assess pulmonary involvement. Thus, the objective of this study was to evaluate the respiratory dynamics of healthy control subjects and those with cystic fibrosis in a submaximal exercise protocol for six minutes on the treadmill, using volumetric capnography parameters (slope 3 [Slp3], Slp3/tidal volume [Slp3/TV], and slope 2 [Slp2]). METHODS: This was a cross-sectional study with 128 subjects (cystic fibrosis, 64 subjects; controls, 64 subjects]. Participants underwent volumetric capnography before, during, and after six minutes on the treadmill. Statistical analysis was performed using the Friedman, Mann-Whitney, and Kruskal-Wallis tests, considering age and sex. An alpha=0.05 was considered. RESULTS: Six minutes on the treadmill evaluation: in cystic fibrosis, volumetric capnography parameters were different before, during, and after six minutes on the treadmill; the same was observed for the controls, except for Slp2. Regarding age, an Slp3 difference was observed in cystic fibrosis patients regardless of age, at all moments, and in controls for age≥12 years; a difference in Slp3/TV was observed in cystic fibrosis and controls, regardless of age; and an Slp2 difference in the cystic fibrosis, regardless of age. Regarding sex, Slp3 and Slp3/TV differences were observed in cystic fibrosis regardless of sex, and in controls in male participants; an Slp2 difference was observed in the cystic fibrosis and female participants. The analysis between groups (cystic fibrosis and controls) indicated that Slp3 and Slp3/TV has identified the CF, regardless of age and sex, while the Slp2 showed the CF considering age. CONCLUSIONS: Cystic fibrosis showed greater values of the parameters before, during, and after exercise, even when stratified by age and sex, which may indicate ventilation inhomogeneity in the peripheral pathways in the cystic fibrosis.

Recurrent wheezing in preterm infants: Prevalence and risk factors.

OBJECTIVE: To evaluate the prevalence and risk factors associated with progression to recurrent wheezing in preterm infants. METHODS: The cross-sectional study was carried out in 2014 and 2015 and analyzed preterm infants born between 2011 and 2012. The search for these children was performed in a university maternity hospital and a Special Immunobiological Reference Center. The evaluation was performed through a questionnaire applied during a telephone interview. RESULTS: The study included 445 children aged 39 (18-54) months. In the univariate analysis, the risk factors with the greatest chance of recurrent wheezing were birth weight <1000g, gestational age <28 weeks, living with two or more siblings, food allergy, and atopic dermatitis in the child, as well as food allergy and asthma in the parents. In the multivariate analysis, there was a significant association between recurrent wheezing and gestational age at birth <28 weeks, food allergy and atopic dermatitis in the child, and living with two or more children. Of the 445 analyzed subjects, 194 received passive immunization against the respiratory syncytial virus, and 251 preterm infants were not immunized. There was a difference between the gestational age of these subgroups (p<0.001). The overall prevalence of recurrent wheezing was 27.4% (95% CI: 23.42-31.70), whereas in the children who received passive immunization it was 36.1% (95% CI: 29.55-43.03). CONCLUSIONS: Personal history of atopy, lower gestational age, and living with two or more children had a significant association with recurrent wheezing. Children with lower gestational age who received passive immunization against the respiratory syncytial virus had a higher prevalence of recurrent wheezing than the group with higher gestational age.

Interaction among variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1, and SLC9A3) and CFTR mutations with clinical markers of cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is due to dysfunction of the CFTR channel and function of this channel is, in turn, affected by modifier genes that can impact the clinical phenotype. In this context, we analyzed the interaction among rs3788766*SLC6A14, rs7512462*SLC26A9, rs17235416*SLC11A1, and rs17563161*SLC9A3 variants, CFTR mutations and 40 CF severity markers by the Multifactor Dimensionality Reduction (MDR) model. METHODS: A total of 164 patients with CF were included in the study. The variants in the modifier genes were identified by real-time PCR and the genotype of the CFTR gene in the diagnostic routine. Analysis of interaction between variants, CFTR mutations groupings and demographic, clinical and laboratory data were performed by the MDR. RESULTS: There were interaction between the rs3788766, rs7512462, rs17235416, and rs17563161 variants, and CFTR mutations with pancreatic insufficiency (PI), onset of digestive symptoms, and presence of mucoid Pseudomonas aeruginosa. Regarding PI, the interaction was observed for CFTR*rs17563161 (P-value = 0.015). Also, for onset of digestive symptoms the interaction was observed for CFTR*rs3788766*rs7512462*rs17235416*rs17563161 (P-value = 0.036). Considering the presence of mucoid P. aeruginosa, the interaction occurred for CFTR*rs3788766*rs7512462*rs17563161 (P-value = 0.035). CONCLUSION: Interaction between variants in the SLC family genes and the grouping for CFTR mutations were associated with PI, onset of digestive symptoms and mucoid P. aeruginosa, being important to determine one of the factors that may cause the diversity among the patients with CF.

Impulse oscillometry and obesity in children.

OBJECTIVE: To compare impulse oscillometry system parameters of normal-weight children with overweight and obese children. METHOD: All participants were submitted to the evaluation of lung function (spirometry and impulse oscillometry) following the American Thoracic Society standards. The evaluation of respiratory mechanics was performed using the Jaeger™ MasterScreen™ Impulse Oscillometry System (Erich Jaeger, Germany), three tests were recorded, with acquisition for at least 20seconds. RESULTS: The study included 81 children (30 in the control group, 21 in the overweight group, and 30 the in obesity group), matched for age and sex. Regarding spirometry data, obesity group showed higher numerical values in relation to the control group; however, there were no significant differences among the three groups. For impulse oscillometry parameters, there was a difference between control group and obesity group for respiratory impedance (p=0.036), resistance at 5hertz (p=0.026), resonant frequency (p=0.029), and reactance area (p=0.014). For the parameters expressed in percentage of predicted, there were differences in resistance at 5 hertz, resonant frequency, and reactance area between control group and obesity group. CONCLUSIONS: Obese children showed increased oscillometry parameters values representative of airway obstruction, compared to normal-weight children. Changes in some oscillometry parameters can already be observed in overweight school-aged children.

Prevalence and clinical outcomes of nontuberculous mycobacteria in a Brazilian cystic fibrosis reference center.

Nontuberculous mycobacteria (NTM) have been well established as an opportunistic pathogenic bacterial group for cystic fibrosis (CF) patients, with a prevalence ranging from 3% to 23% worldwide. A myriad of factors can bias the prevalence rate in different CF centers, especially misdiagnosis as systematic screening for NTM are still lacking in a number of centers. Here, we evaluated the presence and clinical outcomes of NTM isolation in microbiological respiratory cultures from CF patients attending a Brazilian reference center after setting up a systematic diagnostic protocol. Of 117 patients with respiratory samples cultured for NTM research, we found seven patients (6%) with at least one positive result for NTM [four males (57.1%), median age = 21 years (9-58)]. These cases are reported one-by-one. Median FEV1 was 40%, all patients showed signs of lung deterioration, with a median number of pulmonary exacerbations of three per patient/year. However, the impact of NTM isolation remains unclear in our center as all patients were coinfected with other CF respiratory pathogens. Our NTM prevalence assimilates to the lowest levels reported in literature, which is possibly influenced by the routinely applied Bacille Calmette-Guérin vaccine.

Relationship between physiologic deadspace/tidal volume ratio and gas exchange in infants with acute bronchiolitis on invasive mechanical ventilation.

OBJECTIVES: To evaluate the association between deadspace/tidal volume ratio (Vd/Vt) and gas exchange variables: Pao2, Paco2, Pao2/Fio2, arterial/alveolar oxygen tension ratio (Pao2/PAo2), alveolar-arterial oxygen tension difference/arterial oxygen tension ratio (P(A-a)o2/Pao2), carbon dioxide production (Vco2), ventilation index ([Paco2 x peak inspiratory pressure x mechanical respiratory rate]/1000), and oxygenation index ([mean airway pressure x Fio2 x 100]/Pao2), all measured at an early stage in children with obstructive acute respiratory failure. DESIGN: Prospective, cross-sectional, observational study. SETTING: Pediatric intensive care unit, university hospital. PATIENTS: Twenty-nine infants with acute bronchiolitis, defined according to clinical and radiologic criteria. Children with chronic pulmonary disease, neuromuscular disease, congenital cardiopathies, or hemodynamic instability were excluded. INTERVENTIONS: Measurements were made between 24 and 72 hrs of mechanical ventilation using volumetric capnography and arterial blood gas analysis. MEASUREMENTS AND MAIN RESULTS: The following variables significantly correlated with Vd/Vt, calculated using Spearman's correlation coefficient (rs): Pao2 (rs = -0.63, p < .001), Pao2/Fio2 (rs = -0.56, p = .002), Pao2/PAo2 (rs = -0.46, p = .012), P(A-a)o2/Pao2 (rs = -0.46, p = .012), Paco2 (rs = 0.51, p = .005), Vco2 (rs = -0,62, p < .01), oxygenation index (rs = 0.48, p = .009), and ventilation index (rs = -0.53, p = .003). A statistically significant association was found between an increase in Vd/Vt and severity of lung injury, defined as Pao2/Fio2 <200 (p = .03, Mann-Whitney). CONCLUSIONS: In the study population, Vd/Vt not only reflected ventilatory disorders, as is well recognized, but also was associated with disturbances of oxygenation. These results warrant further evaluation of the usefulness of serial measurement of Vd/Vt as a marker of disease severity in severe acute bronchiolitis and other causes of respiratory failure.

Nasal and paranasal sinus endoscopy, computed tomography and microbiology of upper airways and the correlations with genotype and severity of cystic fibrosis.

OBJECTIVE: Many studies have assessed clinical and functional aspects of lower airway affections in cystic fibrosis. Conversely, few studies have been performed to assess the clinical and functional affections of upper airways. The objective of the present study was to correlate the variables obtained by nasal and paranasal sinuses endoscopy, paranasal sinus laboratory and computed tomography (CT) scan findings, and to check the association with severity and genotype of cystic fibrosis patients. METHODS: Clinical and laboratory study of 50 patients with cystic fibrosis at a university center. All patients were submitted to CT scan, nasal and paranasal endoscopy and bacterioscopy of maxillary sinus, trachea and oropharynx secretion. Severity of cystic fibrosis was assessed by Shwachman score and the most frequent genetic mutations were identified. RESULTS: The prevalence of polyposis in the studied population was 36% and it was greater among homozygote for DeltaF 508. Shwachman score was correlated with age (p=0.003). The genotype was correlated with presence of nasal polyposis (p=0.006). There was no association between affections in CT scan and severity of cystic fibrosis (CF). Patients presented high prevalence of early colonization of Pseudomonas aeruginosa. CONCLUSIONS: Sinus disease in CF patients presents several clinical, endoscopic and tomographic affections. Although most of them are not correlated with severity and disease genotype, severity of CF is correlated with age and presence of polyposis is genotype-dependent.

Personalized or Precision Medicine? The Example of Cystic Fibrosis.

The advent of the knowledge on human genetics, by the identification of disease-associated variants, culminated in the understanding of human variability. With the genetic knowledge, the specificity of the clinical phenotype and the drug response of each individual were understood. Using the cystic fibrosis (CF) as an example, the new terms that emerged such as personalized medicine and precision medicine can be characterized. The genetic knowledge in CF is broad and the presence of a monogenic disease caused by mutations in the CFTR gene enables the phenotype-genotype association studies (including the response to drugs), considering the wide clinical and laboratory spectrum dependent on the mutual action of genotype, environment, and lifestyle. Regarding the CF disease, personalized medicine is the treatment directed at the symptoms, and this treatment is adjusted depending on the patient's phenotype. However, more recently, the term precision medicine began to be widely used, although its correct application and understanding are still vague and poorly characterized. In precision medicine, we understand the individual as a response to the interrelation between environment, lifestyle, and genetic factors, which enabled the advent of new therapeutic models, such as conventional drugs adjustment by individual patient dosage and drug type and response, development of new drugs (read through, broker, enhancer, stabilizer, and amplifier compounds), genome editing by homologous recombination, zinc finger nucleases, TALEN (transcription activator-like effector nuclease), CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated endonuclease 9), and gene therapy. Thus, we introduced the terms personalized medicine and precision medicine based on the CF.

Secretory IgA response against Pseudomonas aeruginosa in the upper airways and the link with chronic lung infection in cystic fibrosis.

We assessed the diagnostic ability of an enzyme-linked immunosorbent assay test for measurement of specific secretory IgA (sIgA) in saliva to identify cystic fibrosis (CF) patients with Pseudomonas aeruginosa chronic lung infection and intermittent lung colonization. A total of 102 Brazilian CF patients and 53 healthy controls were included. Specific serum IgG response was used as a surrogate to distinguish CF patients according to their P. aeruginosa colonization/infection status. The rate of sIgA positivity was 87.1% in CF chronically infected patients (median value = 181.5 U/mL), 48.7% in intermittently colonized patients (median value = 45.8 U/mL) and 21.8% in free of infection patients (median value = 22.1 U/mL). sIgA levels in saliva were significantly associated with serum P. aeruginosa IgG and microbiological culture results. The sensitivity, specificity, PPV and NPV for differentiation between presence and absence of chronic lung infection were 87%, 63%, 51% and 92%, respectively. Measurement of sIgA in saliva may be used for screening patients in risk of developing P. aeruginosa chronic lung infection in CF and possibly also for paranasal sinusitis, and, most importantly, to efficiently rule out chronic P. aeruginosa lung infection.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

OBJECTIVE: To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. METHODS: Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. RESULTS: At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV1/FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p<0.05). Volumetric capnography showed that obese individuals had a higher volume of produced carbon dioxide and alveolar tidal volume (p<0.05). Additionally, the associations between dead space volume and tidal volume, as well as phase-3 slope normalized by tidal volume, were lower in healthy subjects (p<0.05). These data suggest that obesity does not alter ventilation homogeneity, but flow homogeneity. After subdividing the groups by age, a greater difference in lung function was observed in obese and healthy individuals aged >11 years (p<0.05). CONCLUSION: Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV1/FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes.

Effect of expiratory flow increase technique on pulmonary function of infants on mechanical ventilation.

BACKGROUND AND PURPOSE: Although chest physiotherapy techniques are commonly used in the treatment of respiratory diseases, there are, however, few studies in the literature on the effectiveness of these techniques in paediatric patients. The purpose of the present study was to evaluate the effect of the expiratory flow increase technique (EFIT) on the pulmonary function of infants on invasive mechanical pulmonary ventilation. METHOD: A prospective, non-randomized study design was used, with consecutive enrolment conducted in the paediatric intensive care unit (PICU) of a university hospital. All infants with acute obstructive respiratory failure who were on invasive mechanical pulmonary ventilation between April 2001 and April 2003 were included in this study. Respiratory rate, PaO2, PaCO2, SatO2, PaO2/FiO2, P(A-a)O2/PaO2, PaO2/PAO2, VD/VT, dynamic compliance, inspiratory and expiratory resistance values were compared before and after application of the EFIT. RESULTS: Blood gas and pulmonary function measurements were recorded before and after EFIT. Repeated-measures analysis of variance (ANOVA) was used. The results were considered statistically significant when p values were < 0.05. Twenty-two infants were enrolled. There was a significant increase in respiratory rate, SatO2 and PaO2/PAO2 and a significant decrease in P(A-a)O2/PaO2 after application of the EFIT. CONCLUSION: There was a short-term improvement in the oxygenation of infants who were submitted to the EFIT. Additional studies are necessary to establish the efficacy and effectiveness of this technique.