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Abstract: We aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels. In this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood. All CF/MABSC patients had increased CD3+ and CD19+ lymphoblast formation upon PBMC stimulation with MABSC lysate. There was a higher rate of CD3+ than CD19+ lymphoblasts, predominance of CD4+ over CD8+ lymphoblasts, IFN-y, TNF-a and IL-2 production, low production of the Th17-associated IL-17, and discrete or no production of Th2/B cell-associated cytokines soluble CD40 ligand (CD40L), IL-4 and IL-5, indicating a Th1-dominated phenotype and infection restricted to the lungs. A similar pattern was seen in C/BCG+ controls, and CF/MAC patients, pointing to cross-reactivity. MABSC-IgG levels were higher in CF/MABSC patients than in both control groups, but not CF/NTM- patients, most of whom also had CD3+ and/or CD19+ lymphoblast formation upon PBMC stimulation, indicating previous exposure, subclinical or latent infection with MABSC or other NTM. The anti-MABSC immune response is Th1-skewed and underlines the cross-reactivity in the anti-mycobacterial immune response. The results, together with published clinical observations, indicate that BCG vaccination may cross-react against NTM in CF patients, and this should be investigated. Due to cross-reactivity, it would also be interesting to investigate whether a combination of MABSC-induced cytokine production by blood cells and anti-MABSC IgG measurement can be useful for identifying latent or subclinical infection both with MABSC and other NTM in CF patients

Abstract: This study sought to estimate body composition values by disease severity in patients recovered from COVID-19. This was an observational, analytical, prospective cross-sectional study involving patients recovered from COVID-19 and employing the following assessment bioelectrical impedance analysis, dualenergy X-ray absorptiometry, and air displacement plethysmography. A total of 210 volunteers were included. Demographic characteristics, comorbidities, and body composition values highlighted significant differences between men and women across disease severity levels. Sex differences influence the severity of COVID-19. Our results provide a cross-sectional analysis of the impact of body composition on COVID-19 patients, showing risk factors and parameters that can contribute to the treatment, health recovery, and quality of life of this population

Abstract: Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis. We prospectively evaluated 181 infants with severe bronchiolitis admitted at three hospitals over a 2-year period, who required oxygen therapy. The control group consisted of 536 healthy adults. Patients were evaluated for the presence of comorbidities (premature birth, chronic respiratory disease, and congenital heart disease), underwent nasopharyngeal aspirate testing for virus detection by multiplex-PCR, and SNPs identification in immune response genes. Patient outcomes were assessed. We observed association between SNP rs2107538*CCL5 and bronchiolitis caused by respiratory syncytial virus(RSV) and RSV-subtype-A, and between rs1060826*NOS2 and bronchiolitis caused by rhinovirus. SNPs rs4986790*TLR4, rs1898830*TLR2, and rs2228570*VDR were associated with progression to death. SNP rs7656411*TLR2 was associated with length of oxygen use; SNPs rs352162*TLR9, rs187084*TLR9, and rs2280788*CCL5 were associated with requirement for intensive care unit admission; while SNPs rs1927911*TLR4, rs352162*TLR9, and rs2107538*CCL5 were associated with the need for mechanical ventilation. Our findings provide some evidence that SNPs in CCL5 and NOS2 are associated with presence of bronchiolitis and SNPs in TLR4, TLR2, TLR9, VDR and CCL5 are associated with severity of bronchiolitis

Abstract: To investigate the pulmonary response to exercise of non-morbidly obese adolescents, considering the gender. A prospective cross-sectional study was conducted with 92 adolescents (47 obese and 45 eutrophic), divided in four groups according to obesity and gender. Anthropometric parameters, pulmonary function (spirometry and oxygen saturation [SatO2]), heart rate (HR), blood pressure (BP), respiratory rate (RR), and respiratory muscle strength were measured. Pulmonary function parameters were measured before, during, and after the exercise test. BP and HR were higher in obese individuals during the exercise test (p = 0.0001). SatO2 values decreased during exercise in obese adolescents (p = 0.0001). Obese males had higher levels of maximum inspiratory and expiratory pressures (p = 0.0002) when compared to obese and eutrophic females. Obese males showed lower values of maximum voluntary ventilation, forced vital capacity, and forced expiratory volume in the first second when compared to eutrophic males, before and after exercise (p = 0.0005). Obese females had greater inspiratory capacity compared to eutrophic females (p = 0.0001). Expiratory reserve volume was lower in obese subjects when compared to controls (p = 0,05). Obese adolescents presented changes in pulmonary function at rest and these changes remained present during exercise. The spirometric and cardiorespiratory values were different in the four study groups. The present data demonstrated that, in spite of differences in lung growth, the model of fat distribution alters pulmonary function differently in obese female and male adolescents

Resumo: Analisar e comparar as repercussões clínicas dos acidentes com saneantes de uso domiciliar de origem legal e ilegal (clandestina) em crianças menores de 7 anos. Estudo descritivo de corte transversal, com dados obtidos dos prontuários eletrônicos do Centro de Informações e Assistência Toxicológica de referência regional, no período de um ano completo. Foram realizadas análises estatísticas descritivas não paramétricas e de testes de associação. Resultados: A amostra foi constituída de 737 casos. A maioria das exposições ocorreu em crianças menores de 3 anos (mediana: 1 ano, intervalo interquartil: 1–3 anos) na residência habitual(92,9%) e por ingestão (97,2%). Os produtos envolvidos foram saneantes de baixa toxicidade sem efeito cáustico (38,9%), com efeito cáustico (24,1%), hidrocarbonetos (19,3%), inseticidas/raticidas (16,6%), e outros produtos (1,1%). Setenta casos decorreram de exposições a produtos clandestinos, principalmente cáusticos (n=47) e raticidas (n=15). Entre as 337 crianças que apresentaram manifestações clínicas pós-exposição, as ocorrências mais frequentes foram vômitos (n=125), queimaduras orais (n=74), tosse (n=35), salivação (n=26) e dor abdominal (n=25), significativamente mais comum com produtos clandestinos (55/70 versus 282/667; p<0,01). Dezenove crianças foram hospitalizadas (cáusticos, n=17; produtos clandestinos, n=12; mediana do tempo de internação: 2 dias), e 22 foram submetidas à endoscopia digestiva alta (hidróxido de sódio, n=14; produtos clandestinos, n=14), com alterações em 12 casos (grave=2). Não houve óbitos. Conclusões: Exposições tóxicas a saneantes de uso domiciliar de origem clandestina estão associadas com maior morbidade
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Abstract: Since patients with cystic fibrosis with different Cystic Fibrosis Transmembrane Regulator (CFTR) genotypes present a wide response variability for modulator drugs such as Orkambi®, it is important to screen variants in candidate genes with an impact on precision and personalized medicine, such as Solute Carrier Family 26, member 9 (SLC26A9) gene. Sanger sequencing for the exons and intron-exon boundary junctions of the SLC26A9 gene was employed in nine individuals with p.Phe508del homozygous genotype for the CFTR gene who were not under CFTR modulators therapy. The sequencing variants were evaluated by in silico prediction tools. The CFTR function was measured by cAMP-stimulated current (?Isc-eq-FSK) in polarized CFTR of human nasal epithelial cells cultured in micro-Ussing chambers with Orkambi®. We found 24 intronic variants, three in the coding region (missense variants - rs74146719 and rs16856462 and synonymous - rs33943971), and three in the three prime untranslated region (3' UTR) region in the SLC26A9 gene. Twenty variants were considered benign according to American College of Medical Genetics and Genomics guidelines, and ten were classified as uncertain significance. Although some variants had deleterious predictions or possible alterations in splicing, the majority of predictions were benign or neutral. When we analyzed the ?Isc-eq-FSK response to Orkambi®, there were no significant differences within the genotypes and alleles for all 30 variants in the SLC26A9 gene. Among the nine individuals with p.Phe508del homozygous genotype for the CFTR gene, no pathogenic SLC26A9 variants were found, and we did not detect associations from the 30 SLC26A9 variants and the response to the Orkambi® in vitro

Abstract: To detect RSV or other thirteen respiratory viruses as possible causer agent of bronchiolitis in infants. This is an epidemiological analytical study, conducted using a nasopharyngeal aspirate of 173 hospitalized children younger than two years old with severe bronchiolitis in three hospitals in the Campinas Metropolitan Region (CMR) during 2013-14. The data was statically evaluated by Pearson's chi-squared test with statistical significance of 0.05 and 95% confidence level. As expected, the most prevalent viruses detected were RSV A and B in 47% and 16% of the samples, respectively. However, almost a third of severe bronchiolitis cases there were no detection of RSV, and the viruses more commonly detected were rhinoviruses, which were identified in almost a quarter of all positive samples for at least a viral agent. Although nothing could be concluded from the disease severity and clinical-epidemiological data, the present study's results indicate that severe bronchiolitis is not always related to RSV infections in children younger than two years old, and the rhinoviruses were more prevalent in these cases. These findings reinforce the need to carry out a viral diagnosis in the hospital emergency would be very appropriate for all cases of respiratory infections in children, even for diseases in which the primary etiological agent seems to be well known

Abstract: To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. 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. 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). 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

Abstract: Chronic rhinosinusitis with nasal polyps (CRSwNP) is usuallytreated with corticosteroids, given their anti-inflammatory effects. Unlike thenasal administration, the oral and ocular use of tretinoin, an immunoregulatorydrug, is well established. Therefore, tretinoin was thought to act on nasal polyps,and possible adverse and/or therapeutic effects were investigated.Methods:A first-in-human open-label trial was conducted enrolling patientswith CRSwNP randomized into: a control group (CTR, n=15), treated withbudesonide for 24 weeks; and an intervention group (TRT, n=15), who receivedbudesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint includedhistopathological analysis and tissue immunoassay (Multiplex) for tumor necro-sis factor?(TNF-?), interleukin (IL)-1?, IL-4, IL-5, IL-13, and matrix metallo-proteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverseevents report, endoscopy (modified Lund-Kennedy scoring system [LKS]), qual-ity of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Con-necticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24weeks.Results:TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%];p=0.044) as well as no increase in cytokines levels. All adverse events were catego-rized as "grade 1" (asymptomatic; mild). The most interesting part of this studywas the improvement in smell between baseline (T0) and week 24 (T2) in TRTonly (p=0.041).Conclusion:Transnasal tretinoin associated with budesonide was safe and welltolerated, and it should be investigated as a treatment option for some CRSwNP endotypes

Crohn's disease (CD) is a chronic transmural inflammation of the gastrointestinal tract of unknown cause. Malnutrition associated with active CD has been reduced although obesity has increased. Dietary strategies such as those with high-protein have been proposed to reduce body fat. This study compares the effects of two supplements on the nutritional status of CD patients. Materials and Methods: 68 CD patients were randomized in two groups: whey protein group (WP) and soy protein group (SP). Using bioimpedance analysis, anthropometry and albumin and pre-albumin dosages the nutritional status was measured before starting the intervention and after 8 and 16 weeks. The disease activity was determined by Crohn's Disease Activity Index and serum C-reactive protein dosage and dietary intake by 24h dietary recalls. Results: Forty-one patients concluded the study and both supplements changed body composition similarly. Triceps skin fold thickness (p<0.001) and body fat percentage (p=0.001) decreased, whereas mid-arm muscle circumference (p=0.004), corrected arm muscle area (p=0.005) and body lean percentage (p=0.001) increased. Conclusions: For Crohn's disease patients undergoing anti TNF-alpha and azatioprine therapies, supplementation with whey and soy proteins changes body composition through reduction of body fat and thus contributes to control inflammation