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.

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.

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.

Pathophysiology of non-cystic fibrosis bronchiectasis in children and adolescents with asthma: A protocol for systematic review and meta-analysis.

BACKGROUND: The pathophysiological mechanisms by which asthma and bronchiectasis are associated are still unclear. The association of these two diseases can result in more severe symptoms and a greater number of exacerbations. OBJECTIVE: The aim of this systematic review is to collect evidence of the pathophysiology of non-cystic fibrosis bronchiectasis with associated asthma in children and adolescents, aged 6-18 years old. METHODS: A systematic and comprehensive search will be performed using eight main databases, PubMed, PubMed PMC, BVS/BIREME, Scopus, EMBASE, Cochrane Library, Scielo and Web of Science. Articles will be searched from the earliest available time to July 2023. The studied population will be composed of children and adolescents with asthma and non-cystic fibrosis bronchiectasis. From the data obtained, all articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols Checklist (PRISMA P-2015). In addition, if sufficient data are available, a meta-analysis will be conducted. Two independent reviewers will conduct the studies selection, data extraction, and risk of bias assessment. The outcome measures will be to analyze if non-cystic fibrosis bronchiectasis is related to a specific inflammatory profile. DISCUSSION: A systematic review will provide better knowledge about the etiopathogenesis and causes of the association between asthma and bronchiectasis and its role in the severity and control of asthma. Identifying, selecting and critically evaluating studies on asthma and bronchiectasis, would be possible to illuminate the characteristics of children and adolescents with associated diagnoses and provide information to help individualized treatments in order to control and prevent complications. The findings of this study will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in July 2023 (registration number CRD42023440355).

Cross-sectional evaluation of the saccharin transit time test for primary ciliary dyskinesia: did we discard this tool too soon?

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare and heterogeneous disease that is difficult to diagnose and requires complex and expensive diagnostic tools. The saccharin transit time test is a simple and inexpensive tool that may assist in screening patients with PCD. OBJECTIVES: This study aimed to compare changes in the electron microscopy findings with clinical variables and saccharin tests in individuals diagnosed with clinical PCD (cPCD) and a control group. DESIGN AND SETTING: An observational cross-sectional study was conducted in an otorhinolaryngology outpatient clinic from August 2012 to April 2021. METHOD: Patients with cPCD underwent clinical screening questionnaires, nasal endoscopy, the saccharin transit time test, and nasal biopsy for transmission electron microscopy. RESULTS: Thirty-four patients with cPCD were evaluated. The most prevalent clinical comorbidities in the cPCD group were recurrent pneumonia, bronchiectasis, and chronic rhinosinusitis. Electron microscopy confirmed the clinical diagnosis of PCD in 16 of the 34 (47.1%) patients. CONCLUSION: The saccharin test could assist in screening patients with PCD due to its association with clinical alterations related to PCD.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis.

OBJECTIVE: To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. METHODS: An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. RESULTS: A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. CONCLUSIONS: The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

The role of vitamin D in the severity and control of asthma in children and adolescents: A protocol for systematic review and meta-analysis.

BACKGROUND: Vitamin D plays an important role in the immune system and consequently in the inflammatory process of asthma. It acts directly on the regulation of helper T lymphocytes 1 (Th1) and helper T lymphocytes 2 (Th2) cells, and regulatory T lymphocytes. Evidence shows that vitamin D acts on dendritic cells, raising inflammatory mediators and increasing the imbalance between Th1, Th2, and helper T lymphocytes 17 (Th17). Evidence shows a strong association between vitamin D levels and asthma incidence, especially in patients with severe and uncontrolled asthma. METHODS: A systematic and comprehensive search will be performed using four main databases, PubMed, EMBASE, Cochrane Library, and Web of Science. Articles will be searched from the earliest available time to august 2022. The studied population will be composed of children and or adolescents with asthma. From the data obtained, all articles found will be transferred to the Rayyan platform. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist (PRISMA P-2020). In addition, if sufficient data are available, a meta-analysis will be conducted. Two independent reviewers will conduct the studies selection, data extraction, and risk of bias assessment. The outcome measures will be to analyze the serum levels of vitamin D in patients with asthma and to relate this hormone to the control and severity of the disease and its anti- inflammatory effect. RESULTS: A systematic review will provide better knowledge regarding vitamin D and its role in the severity and control of asthma. CONCLUSIONS: The findings of this study will be published in a peer-reviewed journal.

Challenges in Diagnosing Primary Ciliary Dyskinesia in a Brazilian Tertiary Hospital.

Primary ciliary dyskinesia (PCD) causes cellular cilia motility alterations, leading to clinical manifestations in the upper and lower respiratory tract and situs abnormalities. The PCD diagnosis was improved after the inclusion of diagnostic tools, such as transmission electron microscopy and genetic screening; however, the PCD screening is a challenge yet. In this context, we aimed to describe the clinical, genetic, and ultra-ciliary characteristics in individuals with clinical suspicion of PCD (cPCD) from a Brazilian Tertiary Hospital. An observational study was carried out with individuals during the follow-up between 2011 and 2021. The individuals were submitted to clinical questionnaires, transmission electron microscopy, and genetic screening for pathogenic variants in PCD-related genes. Those patients were classified according to the degree of suspicion for PCD. In our study, we enrolled thirty-seven cPCD individuals; 20/37 (54.1%) had chronic rhinosinusitis, 28/37 (75.6%) had bronchiectasis, and 29/37 (78.4%) had recurrent pneumonia. A total of 17/37 (45.9%) individuals had transmission electron microscopy or genetic confirmation of PCD; 10 individuals had at least one positive pathogenic genetic variant in the PCD-related genes; however, only seven patients presented a conclusive result according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology with two pathogenic variants in homozygous or compound heterozygous. The median age at diagnosis was 13 years, and the median time between suspicion and diagnosis was four years. Sixteen patients had class I electron microscopy alterations, seven had class II alterations, and 14 had normal transmission electron microscopy according to the international consensus guideline for reporting transmission electron microscopy results in the diagnosis of PCD (BEAT-PCD TEM Criteria). Genetic screening for pathogenic variants in PCD-related genes and transmission electron microscopy can help determine the PCD diagnosis; however, they are still unavailable to all individuals with clinical suspicion in Brazil. We described ultrastructural alterations found in our population along with the identification of pathogenic variants in PCD-related genes.

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

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.