Association between serum Vitamin D levels and asthma severity and control in children and adolescents.

OBJECTIVE: To assess the association of serum Vitamin D (vitD) levels with asthma control and severity in children and adolescents in different seasons of the year. METHOD: Longitudinal, prospective study with 7- to 17-year-old children and adolescents diagnosed with asthma. All participants underwent two assessments conducted in opposite seasons of the year which included a clinical assessment, a questionnaire for classification of asthma control (Asthma Control Test), spirometry, and blood collection to measure serum vitD levels. RESULTS: In total, 141 individuals with asthma were evaluated. The mean vitD was lower in females (p = 0.006) and sunlight exposure appears not to be an influencing factor for vitD levels. We found no differences in mean vitD of patients with controlled and uncontrolled asthma (p = 0.703; p = 0.956). However, the severe asthma group had lower mean Vitamin D than the mild/moderate asthma group for both assessments (p = 0.013; p = 0.032). In the first assessment, the group with vitD insufficiency had a higher prevalence of severe asthma (p = 0.015). Vitamin D was positively correlated with FEV1 in both assessments (p = 0.008; p = 0.006) and with FEF25-75% in the first assessment (p = 0.038). CONCLUSION: In a tropical climate zone, there is no evidence of association between seasonality and serum vitD levels or between serum vitD levels and asthma control in children and adolescents. However, vitD and lung function were positively correlated and the group with vitD insufficiency had a higher prevalence of severe asthma.

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

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 (p < 0.001). Patients who achieved asthma control reported higher intervals since their last exacerbation episode (p = 0.008) and higher quality of life scores (p < 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.

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

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.

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

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 (FEV1/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.

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

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.

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

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.

Burkholderia cepacia complex in cystic fibrosis in a Brazilian reference center.

The Burkholderia cepacia complex (BCC) can cause a severe decline in lung function in cystic fibrosis (CF). Our objective was to determine the BCC prevalence and to evaluate its clinical impact on CF. Clinical and laboratory variables were determined for CF patients with BCC (Group-A = 50 patients) and without BCC (Group-B = 134 patients). The microorganisms were identified by biochemical tests, the Vitek2®Compact test, recA-PCR and recA-nested-PCR with species-specific primers and DNA sequencing. The patients were evaluated by the Shwachman-Kulczycki score (SKCS), Bhalla score (BS), spirometry and body mass index (BMI). The BCC prevalence was 22.5%. The most common species were Burkholderia multivorans (30%), Burkholderia cepacia (24%), Burkholderia cenocepacia IIIA (10%), B. cenocepacia IIIB (2%) and Burkholderia vietnamiensis (2%). There was difference between the groups in nutritional status (p = 0.02) and general activity (p = 0.026). There was difference in total BS points (p = 0.04) and the following parameters: bronchiectasis severity (p = 0.007), peribronchial thickening (p = 0.013), bronchiectasis extent (p = 0.01) and general aspects of the affected bronchial zone (p = 0.02). The respiratory disorder classifications were as follows: obstructive-4.8% (Group-A) and 23.8% (Group-B); restrictive-9.5% (Group-A and Group-B); obstructive + restrictive-19% (Group-A) and 1.6% (Group-B); and obstructive + restrictive with a decreased forced expiratory flow-47.6% (Group-A) and 30.2% (Group-B) (p = 0.02). Nutritional status was a minor contributing factor to weight, height and BMI in the Group-A (p = 0.02). The BCC prevalence, particularly the prevalence of B. multivorans, was higher in this study. The SKCS, BS, spirometry and nutritional status results showed that BCC has a negative impact on clinical status. Phenotypic methods are useful for the identification of presumptive BCC. The Vitek2®Compact test showed accuracy in BCC identification. PCR, nested-PCR, and recA sequencing showed specificity in BCC species identification.

Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in Cystic Fibrosis.

PURPOSE: The aim of this study was to compare the qualitative and semi-quantitative detection of pathogens in the airway secretions of patients with cystic fibrosis (CF) and the sputum induction capacity before and after inhalation of 7% hypertonic saline solution (HSS). METHODS: The study enrolled 64 patients with CF. Airway secretions were collected from all enrolled patients with CF before and after inhalation of 7% HSS, and the samples were screened for pathogens. RESULTS: Inhalation of 7% HSS increased the probability of producing sputum from 36 to 52% (p = 0.002) in children with CF. The effect was most in children under 11 years. Inhalation of 7% HSS improved qualitative pathogen identification (p = 0.008). Inhalation of 7% HSS increased the mucoid Pseudomonas aeruginosa (p = 0.002) and non-mucoid P. aeruginosa in the semi-quantitative analysis (p = 0.035). Four new pathogens (Aspergillus fumigatus, Achromobacter xylosoxidans, Ochrobactrum anthropi, and Elizabethkingia meningoseptica) were identified in the sputum samples collected from the airways of patients with CF following 7% HSS. CONCLUSIONS: Inhalation of 7% HSS increased sputum production and pathogen identification in children with CF. The inhalation of 7% HSS was feasible and should be implemented for routine pathogen detection in the airways of patients with CF, particularly in those patients who do not produce sputum.

IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.

The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality.

Demographic, clinical, and laboratory parameters of cystic fibrosis during the last two decades: a comparative analysis.

BACKGROUND: In recent years, patients with cystic fibrosis (CF) have tended to experience a longer life expectancy and higher quality of life. In this context, the aim of the present study was to evaluate and compare the demographic, clinical, and laboratory markers of patients with CF during the last two decades at a CF referral center. METHODS: A retrospective study of the demographic, clinical, and laboratory markers for CF treatment at a CF referral center was performed during two decades: 2000 (DI, 1990-2000, n = 104 patients) and 2010 (DII, 2000-2010, n = 181 patients). RESULTS: The following variables were less common in DI than in DII: (i) pancreatic insufficiency, (ii) meconium ileus, (iii) diabetes mellitus, (iv) Burkholderia cepacia colonization, (v) moderate and severe Shwachman-Kulczycki score (SKS), (vi) F508del mutation screening, (vii) patients without an identified CFTR mutation (class IV, V, or VI mutation), (viii) patients above the 10th percentile for weight and height, (ix) restrictive lung disease, and (x) older patients (p < 0.01). The following variables were more common in DI than in DII: (i) excellent and good SKS, (ii) F508del heterozygous status, (iii) colonization by mucoid and nonmucoid Pseudomonas aeruginosa, (iv) obstructive lung disease, and (v) minimal time for CF diagnosis (p < 0.01). CONCLUSION: Clinical outcomes differed between the two decades. Demographic, clinical, and laboratory markers in patients with CF are useful tools and should be encouraged in CF referral centers to determine the results of CF management and treatment, enabling a better understanding of this disease and its clinical evolution. Early diagnosis and management of CF will improve patients' quality of life and life expectancy until personalized drug therapy is possible for all patients with CF.

Ventilatory abnormalities in patients with cystic fibrosis undergoing the submaximal treadmill exercise test.

BACKGROUND: Exercise has been studied as a prognostic marker for patients with cystic fibrosis (CF), as well as a tool for improving their quality of life and analyzing lung disease. In this context, the aim of the present study was to evaluate and compare variables of lung functioning. Our data included: (i) volumetric capnography (VCAP) parameters: expiratory minute volume (VE), volume of exhaled carbon dioxide (VCO2), VE/VCO2, ratio of dead space to tidal volume (VD/VT), and end-tidal carbon dioxide (PetCO2); (ii) spirometry parameters: forced vital capacity (FVC), percent forced expiratory volume in the first second of the FVC (FEV1%), and FEV1/FVC%; and (iii) cardiorespiratory parameters: heart rate (HR), respiratory rate, oxygen saturation (SpO2), and Borg scale rating at rest and during exercise. The subjects comprised children, adolescents, and young adults aged 6-25 years with CF (CF group [CFG]) and without CF (control group [CG]). METHODS: This was a clinical, prospective, controlled study involving 128 male and female patients (64 with CF) of a university hospital. All patients underwent treadmill exercise tests and provided informed consent after study approval by the institutional ethics committee. Linear regression, Kruskal-Wallis test, and Mann-Whitney test were performed to compare the CFG and CG. The α value was set at 0.05. RESULTS: Patients in the CFG showed significantly different VCAP values and spirometry variables throughout the exercise test. Before, during, and after exercise, several variables were different between the two groups; statistically significant differences were seen in the spirometry parameters, SpO2, HR, VCO2, VE/VCO2, PetCO2, and Borg scale rating. VCAP variables changed at each time point analyzed during the exercise test in both groups. CONCLUSION: VCAP can be used to analyze ventilatory parameters during exercise. All cardiorespiratory, spirometry, and VCAP variables differed between patients in the CFG and CG before, during, and after exercise.

Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study.

BACKGROUND: Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity. METHODS: A cross-sectional study of 180 CF patients was carried out from 2011 to 2012. We analyzed CFTR mutations, polymorphisms (GSTM1 and GSTT1 deletions, GSTP1 + 313A > G, GCLC-129C > T, and GCLC-3506A > G) in modifier genes and CF clinical severity as assessed by 28 clinical and laboratory variables. RESULTS: Significant associations were found between modifier gene polymorphisms and particular phenotypes or genotype changes. These included GCLC-129C > T with a higher frequency of the Pseudomonas aeruginosa mucoid to CC genotype (p = 0.044), and GCLC-3506A > G with a higher frequency of the no-mucoid P. aeruginosa (NMPA) to AA genotype (p = 0.012). The GSTT1 deletion was associated with a higher frequency of the NMPA to homozygous deletion (p = 0.008), GSTP1 + 313A > G with a minor risk of osteoporosis (p = 0.036), and patient age ≤ 154 months (p = 0.044) with the AA genotype. The Bhalla score was associated with GCLC-3506A > G (p = 0.044) and GSTM1/GSTT1 deletion polymorphisms (p = 0.02), while transcutaneous hemoglobin oxygen saturation levels were associated with GSTT1 deletions (p = 0.048). CONCLUSION: CF severity is associated with polymorphisms in GSH pathways and CFTR mutations.

The relationship between physical functional capacity and lung function in obese children and adolescents.

BACKGROUND: There is no consensus regarding obesity repercussions for lung function in children and adolescents. Therefore, the aim of the study was to determine whether obesity is associated with poor physical conditioning and damaged lung function in children and adolescents, and to correlate lung function with six-minute walk test (6MWT) results. METHODS: This cross-sectional study included 38 obese subjects of both sexes, ranging between 5 and 17 years of age, as well as 56 control subjects paired by sex and age for the 6MWT, and 39 subjects for spirometry. Subjects performed spirometry according to the guidelines of the American Thoracic Society (ATS) and the European Respiratory Society. The obese group repeated spirometry after receiving bronchodilator (BD) treatments. Physical performance was evaluated via the 6MWT according to ATS guidelines. RESULTS: The obese group demonstrated lower forced expiratory volumes in the first second compared with the control group based on forced vital capacity indices (p < 0.01), findings consistent with airway obstruction in 36.8% of patients in the obese group. Walking distances were shorter in the obese group than in the control group. Changes in lung function did not correlate directly with performance on the 6MWT among obese patients. However, there was a correlation between lung function and variables indicative of effort during exercise. CONCLUSION: In the present study, the obese group walked shorter distances and demonstrated lower values in some markers of lung function. However, there is no relationship between their physical conditions and these test results. Therefore, we cannot conclusively state that poor physical performance results from damaged pulmonary function.

Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.

BACKGROUND: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. METHODS: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. RESULTS: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). CONCLUSIONS: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

Correlations between ambient air pollution and the prevalence of hospitalisations and emergency room visits for respiratory diseases in children: a systematic review.

OBJECTIVE: It is known that exposure to air pollution is associated with an increased risk for cardiovascular and respiratory diseases. This review aimed to summarise observational studies on the impact of short and long-term exposure to ambient air pollution on prevalence of hospitalisations and/or emergency department visits caused by respiratory diseases in children and adolescents. SOURCES: Pubmed, Scopus, Embase and Cochrane Library databases were searched for the years 2018 to December 2022, including studies in any language. SUMMARY OF THE FINDINGS: A total of 15 studies published between 2018 and 15 January 2022 were included in this review. PM2.5 was the most type of particulate matter studied. Short-term exposure to PM2,5, PM10, NO2, SO2 and O3, even at concentrations less than the current health-based guidelines, was significantly correlated with increased risk of outpatient/hospital visits and hospitalisations for respiratory diseases by children. CONCLUSIONS: Our findings emphasise the importance and urgency of long-term control of air pollution and pollution-related diseases, especially among children and adolescents. There is a need for further research employing more homogeneous methodologies for assessing exposure and outcome measurements, in order to enable systematic reviews with meta-analysis.

Bronchodilator response assessment through impulse oscillometry system and spirometry in children and adolescents with cystic fibrosis.

OBJECTIVE: To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis. METHODS: Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation. RESULTS: The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response. CONCLUSIONS: The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.

Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity. METHOD: A total of 180 CF's patients were included in this study, which investigated polymorphisms in GCLC and GST genes (GCLC -129C>T and -3506A>G; GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G) by PCR and PCR-RFLP associating to clinical variables of CF severity, including variables of sex, clinical scores [Shwachman-Kulczycki, Kanga e Bhalla (BS)], body mass index, patient age, age for diagnosis, first clinical symptoms, first colonization by Pseudomonas aeruginosa, sputum's microorganisms, hemoglobin oxygen saturation in the blood, spirometry and comorbidities. The CFTR genotype was investigated in all patients, and the genetic interaction was performed using MDR2.0 and MDRPT0.4.7 software. RESULTS: The analysis of multiple genes in metabolic pathways in diseases with variable clinical expression, as CF disease, enables understanding of phenotypic diversity. Our data show evidence of interaction between the GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G polymorphism with CFTR gene mutation classes, and BS (Balance testing accuracy=0.6824, p=0.008), which measures the commitment of bronchopulmonary segments by tomography. CONCLUSION: Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors.

BACKGROUND: Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. METHODS: Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. RESULTS: We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. CONCLUSIONS: Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Manual therapy for childhood respiratory disease: a systematic review.

OBJECTIVE: This study reviewed the scientific evidence available on the effects of manipulative techniques on children with respiratory diseases. METHOD: Three databases (SciELO, PEDro, and MEDLINE) were searched for clinical trials on the effects of manual therapy techniques on children and adolescents with respiratory diseases. The relevant studies were chosen by 2 independent researchers who assessed their abstracts and selected the studies that met the criteria for a complete and structured review. RESULTS: Of the 1147 relevant titles, 103 titles were selected for abstract assessment, and of these, 24 were selected for a full-text review. After critical analysis, 8 studies were included in the review and 16 were excluded for the following reasons: 1 covered only conventional therapy, 7 were not about the studied theme, and 8 included adults. Of the 8 studies included in the present review, 5 consisted of asthmatic children and the others of children with the following conditions: cystic fibrosis, bronchiolitis, recurrent respiratory infections, among others. Only 2 studies did not identify positive results with the use of manual therapy. The other 6 studies found some benefit, specifically in spirometric parameters, immunologic tests, anxiety questionnaire, or level of salivary cortisol. CONCLUSION: The use of manual techniques on children with respiratory diseases seems to be beneficial. Chiropractic, osteopathic medicine, and massage are the most common interventions. The lack of standardized procedures and limited variety of methods used evidenced the need for more studies on the subject.

Sweat conductivity diagnostic accuracy for cystic fibrosis: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of diagnostic test accuracy studies to summarise the properties of sweat conductivity (SC) to rule in/out cystic fibrosis (CF). DATA SOURCE: We searched PubMed, Embase, Web of Science, Google Scholar, SciELO and LILACS up to 13 March 2023. STUDY SELECTION: We selected prospective and retrospective diagnostic test accuracy studies which compared SC, measured through two well-established and commercially available devices, that is, Nanoduct or Sweat-Chek Analyser, to quantitative measurement of sweat chloride. MAIN OUTCOME MEASURES: Pooled sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LR), and their corresponding 95% CIs. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines were followed. Data were extracted by one reviewer and checked by another. The hierarchical summary receiver operating characteristics model was used to estimate diagnostic test accuracy. RESULTS: Ten studies involving 8286 participants were included. The pooled estimates of sensitivity, specificity, +LR and -LR were 0.97 (95% CI 0.94 to 0.98), 0.99 (95% CI 0.98 to 0.99), 171 (95% CI 58 to 500) and 0.02 (95% CI 0.01 to 0.05), respectively. Sensitivity analyses did not reveal a substantial impact of study-level factors on the results, such as study quality, cut-off values for a positive test, study sample size and participant age group. The quality of evidence was considered moderate. CONCLUSION: SC demonstrated excellent diagnostic performance. In addition, its accuracy parameters suggest its role as an alternative to the sweat test for CF diagnosis. PROSPERO REGISTRATION NUMBER: CRD42022284504.