Air Rescue for Pediatric Trauma in a Metropolitan Region of Brazil: Profiles, Outcomes, and Overtriage Rates.

Besides ensuring a quick response and transport of trauma victims, helicopter support also involves risks to patients and professionals and has higher operational costs. Studying prehospital triage criteria and their relationship with patient overtriage and outcomes is important, particularly in newly established services and in developing countries with limited health budgets. This could help improve the use of the helicopter rescue and provide better management of the costs and risks related to it. The objective of this study was to determine the epidemiologic and severity profiles of pediatric victims of trauma attended by helicopter in a Brazilian Metropolitan Area to evaluate the outcomes and overtriage rates related to pediatric air rescue in the region. We conducted an observational and retrospective study using 49 hospital and prehospital records from victims of trauma aged <18 years old (yo) assisted by helicopter and then transferred to a tertiary University Hospital. Of the 49 patients, 39 (79.6%) individuals were male, and the mean age was 11.3 yo. Vehicular collisions accounted for 15 (30.6%) of the traumas, and traumatic brain injuries occurred in 28 (57.1%) cases. A total of 29 (59.1%) individuals had severe trauma (Injury Severity Score; ISS >15), and 34 (69.4%) required admission to the intensive care unit. Overtriage varied from 18.4 to 40.8% depending on the criteria used for its definition, being more frequent in individuals aged between 1 and 5 yo. Death occurred in 10 (20.4%) patients. On prehospital evaluation, we classified 29/32 (90.6%) patients with severe trauma according to the Pediatric Trauma Score (PTS ≤8) and 18/25 (72%) according to the Revised Trauma Score (RTS ≤11). Of these, 7/29 (24.1%) and 6/18 (33.3%), respectively, presented ISS <15 at in-hospital evaluation. None of the patients with PTS >8 and 3/7 (42.8%) of those with RTS >11 presented ISS >15. In conclusion, air rescue of pediatric trauma victims was used mainly for critically ill individuals, resulting in rates of overtriage compatible with that found in the literature. PTS showed the lowest rates of overtriage within excellent rates of undertriage.

Severe Acute Respiratory Syndrome by SARS-CoV-2 Infection or Other Etiologic Agents Among Brazilian Indigenous Population: An Observational Study from the First Year of Coronavirus Disease (COVID)-19 Pandemic.

BACKGROUND: Indigenous peoples are vulnerable to pandemics, including to the coronavirus disease (COVID)-19, since it causes high mortality and specially, the loss of elderly Indigenous individuals. METHODS: The epidemiological data of severe acute respiratory syndrome (SARS) by SARS-CoV-2 infection or other etiologic agents (OEA) among Brazilian Indigenous peoples during the first year of COVID-19 pandemic was obtained from a Brazilian Ministry of Health open-access database to perform an observational study. Considering only Indigenous individuals diagnosed with SARS by COVID-19, the epidemiology data were also evaluated as risk of death. The type of sample collection for virus screening, demographic profile, clinical symptoms, comorbidities, and clinical evolution were evaluated. The primary outcome was considered the death in the Brazilian Indigenous individuals and the secondary outcome, the characteristics of Brazilian Indigenous infected by SARS-CoV-2 or OEA, as the need for intensive care unit admission or the need for mechanical ventilation support. The statistical analysis was done using Logistic Regression Model. Alpha of 0.05. FINDINGS: A total of 3,122 cases of Indigenous individuals with SARS in Brazil were reported during the first year of the COVID-19 pandemic. Of these, 1,994 were diagnosed with COVID-19 and 730/1,816 (40.2%) of them died. The death rate among individuals with SARS-CoV-2 was three-fold increased when compared to the group of individuals with OEA. Several symptoms (myalgia, loss of smell, and sore throat) and comorbidities (cardiopathy, systemic arterial hypertension, and diabetes mellitus) were more prevalent in the COVID-19 group when compared to Indigenous individuals with OEA. Similar profile was observed considering the risk of death among the Indigenous individuals with COVID-19 who presented several symptoms (oxygen saturation <95%, dyspnea, and respiratory distress) and comorbidities (renal disorders, cardiopathy, and diabetes mellitus). The multivariate analysis was significant in differentiating between the COVID-19-positive and non-COVID-19 patients [X2 (7)=65.187; P-value<0.001]. Among the patients' features, the following contributed in relation to the diagnosis of COVID-19: age [≥43 years-old [y.o.]; OR=1.984 (95%CI=1.480-2.658)]; loss of smell [OR=2.373 (95%CI=1.461-3.854)]; presence of previous respiratory disorders [OR=0.487; 95%CI=0.287-0.824)]; and fever [OR=1.445 (95%CI=1.082-1.929)]. Also, the multivariate analysis was able to predict the risk of death [X2 (9)=293.694; P-value<0.001]. Among the patients' features, the following contributed in relation to the risk of death: male gender [OR=1.507 (95%CI=1.010-2.250)]; age [≥60 y.o.; OR=3.377 (95%CI=2.292-4.974)]; the need for ventilatory support [invasive mechanical ventilation; OR=24.050 (95%CI=12.584-45.962) and non-invasive mechanical ventilation; OR=2.249 (95%CI=1.378-3.671)]; dyspnea [OR=2.053 (95%CI=1.196-3.522)]; oxygen saturation <95% [OR=1.691 (95%CI=1.050-2.723)]; myalgia [OR=0.423 (95%CI=0.191-0.937)]; and the presence of kidney disorders [OR=3.135 (95%CI=1.144-8.539)]. INTERPRETATION: The Brazilian Indigenous peoples are in a vulnerable situation during the COVID-19 pandemic and presented an increased risk of death due to COVID-19. Several factors were associated with enhanced risk of death, as male sex, older age (≥60 y.o.), and need for ventilatory support; also, other factors might help to differentiate SARS by COVID-19 or by OEA, as older age (≥43 y.o.), loss of smell, and fever. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo (Foundation for Research Support of the State of São Paulo; #2021/05810-7).

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome.

Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two patients, including 21 patients with sepsis and 21 patients with SIRS, were involved in the study. Liquid chromatography coupled to mass spectrometry and multivariate statistical methods were used to determine lipids present in patient plasma. The obtained lipid signatures revealed 355 features for the negative ion mode and 297 for the positive ion mode, which were relevant for differential diagnosis of sepsis and SIRS. These lipids were also tested as prognosis predictors. Lastly, L-octanoylcarnitine was found to be the most promising lipid signature for both the diagnosis and prognosis of critically ill patients, with accuracies of 75% for both purposes. In short, we presented the determination of lipid signatures as a potential tool for differential diagnosis of sepsis and SIRS and prognosis of these patients.

Comparative analysis of rhinologic outcomes in Cushing disease and non-functioning pituitary adenoma in patients submitted to endoscopic endonasal transsphenoidal surgery.

PURPOSE: Adrenocorticotropic hormone (ACTH) secreted by pituitary tumors lead to changes in nasal cavity anatomy and physiology. As a consequence of hormonal alteration, there is an abnormal soft tissue and an increased capillary fragility, inducting to a thinner mucosa that acts in the healing process. We compared post-operative nasal alterations in patients with Cushing's disease versus patients with non-functioning macroadenomas who underwent endoscopic endonasal transsphenoidal surgery. METHODS: A retrospective study with 14 patients with Cushing's disease who underwent initial transsphenoidal endonasal surgery for an ACTH-secreting adenoma was conducted. Forty-two patients who underwent the same surgery for non-functioning adenomas were selected as controls. The following data were collected: operative technique, endoscopic alterations in late post-operative period and post-operative nasal complaints. RESULTS: There were 13/14 (92.9%) females with Cushing disease versus 23/42 (54.8%) in the non-functioning adenoma group. Surgical approach was similar in both groups, with no differences in flap usage, turbinectomies or ethmoidectomies. No difference occurred concerning endoscopic alterations or nasal complaints in post-operative period. CONCLUSIONS: Post-operative results are similar, and healing could be expected to be equal.

Lipase C, Hepatic Type -250A/G (rs2070895) Variant Enhances Carotid Atherosclerosis in Normolipidemic and Asymptomatic Individuals from Brazil.

The common genetic variant in the promoter region of the hepatic lipase gene [LIPC -250G/A(rs2070895)] has an ambiguous association with cardiovascular disease. In this context, our study was performed to identify the relationships between the rs2070895 with carotid atherosclerosis, plasma lipids, and parameters of reverse cholesterol transport. A total of 285 normolipidemic and asymptomatic participants from an initial sample of 598,288 individuals (inclusion criteria: LDL-C ≤130 mg/dL and triglycerides ≤150 mg/dL; age: 20-75 years, both genders; confirmation of clinical, anthropometric and laboratory data; attended all visits; DNA was achieved to perform genetic analysis) were enrolled and the rs2070895 variant was genotyped by TaqMan® OpenArray® Plataform. Carotid intima-media thickness and the screening of atherosclerotic plaques were determined by B-mode ultrasonography. The rs2070895 genotype frequencies were 0.44, 0.41, and 0.15 (GG, GA, and AA, respectively). Logistic regression analysis showed that the risk of having plaques was increased in participants carrying the AA or AG genotypes (OR = 3.90; 95% CI = 1.54-10.33), despite an increase in high-density lipoprotein cholesterol levels, HDL diameter and apolipoprotein A-I, as compared to the GG genotype. Hepatic lipase and endogenous lecithin cholesterol acyl transferase activities were reduced (38% and 19%, respectively) and lipoprotein lipase was increased by 30% (AA vs GG). Our results provide evidence that the AA or AG genotypes of the rs2070895 were associated with carotid atherosclerosis in apparently healthy participants, probably as a consequence of reduced reverse cholesterol transport and accumulation of HDL subfraction 2 rich in triglycerides and depleted in cholesteryl esters that could become dysfunctional.

Assessment of Distinct Electrophysiological Parameters in Rectal Biopsies for the Choice of the Best Diagnosis/Prognosis Biomarkers for Cystic Fibrosis.

Most cases of Cystic Fibrosis (CF) are diagnosed early in life. However, people with atypical CF forms pose diagnosis dilemmas, requiring laboratory support for diagnosis confirmation/exclusion. Ex vivo analysis of fresh rectal biopsies by Ussing chamber has been the best discriminant biomarker for CF diagnosis/prognosis so far. Here we aimed to evaluate different electrophysiological parameters from Ussing chamber analysis of rectal biopsies from people with CF (PwCF) to establish the one with highest correlations with clinical features as the best CF diagnosis/prognosis biomarker. We analyzed measurements of CFTR-mediated Cl- secretion in rectal biopsies from 143 individuals (∼592 biopsies), the largest cohort so far analyzed by this approach. New parameters were analyzed and compared with the previous biomarker, i.e., the IBMX (I)/Forskolin (F)/Carbachol (C)-stimulated short-circuit current (I'sc-I/F/C). Correlations with clinical features showed that the best parameter corresponded to voltage measurements of the I/F + (I/F/CCH) response (VI/F+I/F/C), with higher correlations vs. I'sc-I/F/C for: sweat chloride (59 vs. 52%), fecal elastase (69 vs. 55%) and lung function, measured by FEV1 (27 vs. 20%). Altogether data show that VI/F+I/F/C is the most sensitive, reproducible, and robust predictive biomarker for CF diagnosis/prognosis effectively discriminating classical, atypical CF and non-CF groups.

Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients / Avaliação da dinâmica respiratória por capnografia volumétrica durante o protocolo de exercício submáximo por seis minutos em esteira em pacientes com fibrose cística

Abstract 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.

Resumo Objetivos: A capnografia volumétrica fornece o padrão de eliminação do CO2, pelo volume expirado por ciclo respiratório e avalia o comprometimento pulmonar. O objetivo do estudo foi avaliar a dinâmica respiratória de indivíduos controles saudáveis e em indivíduos com fibrose cística, em um protocolo de exercício submáximo por seis minutos em esteira, por parâmetros da capnografia volumétrica [slope 3(Slp3), Slp3/volume corrente (Slp3/TV) e slope 2(Slp2)]. Métodos: Estudo de corte transversal com 128 indivíduos [(fibrose cística) 64 indivíduos; (controles) 64 indivíduos]. Os participantes realizaram capnografia volumétrica antes, durante e após seis minutos em esteira. Análise estatística realizada pelos testes de Friedman, Mann-Whitney e Kruskal-Wallis, considerado a idade e o sexo. Alpha = 0,05. Resultados: Avaliação de seis minutos em esteira: na fibrose cística, os parâmetros da capnografia volumétrica foram diferentes antes, durante e após seis minutos em esteira, o mesmo ocorreu nos controles, exceto para o Slp2. Considerando a idade: (Slp3) diferença na FC, independentemente da idade, em todos os momentos e nos controles apenas para ≥ 12 anos; (Slp3/TV) diferença para fibrose cística e controles independentemente da idade; (Slp2) diferença apenas para o grupo fibrose cística, independentemente da idade. Considerando o sexo: (Slp3 e Slp3/TV) diferença para fibrose cística, independentemente do sexo, e controles apenas no sexo masculino; (Slp2) diferença para fibrose cística e sexo feminino. Análise entre grupos (fibrose cística versus controles): Slp3 e Slp3/TV identificou a fibrose cística, independentemente da idade e sexo, enquanto o Slp2 evidenciou a fibrose cística considerando a idade. Conclusão: A fibrose cística apresentou maiores valores dos parâmetros antes, durante e após exercício, inclusive quando se considerou idade e sexo, podendo indicar não homogeneidade da distribuição da ventilação nas vias periféricas.

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.

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.

Disease-modifying genetic factors in cystic fibrosis.

PURPOSE OF REVIEW: To compile data from the past 10 years regarding the role of modifying genes in cystic fibrosis (CF). RECENT FINDINGS: CF is a model disease for understanding of the action of modifying genes. Although it is a monogenic (CFTR) autosomal recessive disease, CF presents with wide phenotypic variability. In CF, variability occurs with different intensity among patients by each organ, being organ-specific, resulting from the mutual interaction of environmental and genetic factors, including CFTR mutations and various other genes, most of which are associated with inflammatory processes. In individuals, using precision medicine, gene modification studies have revealed individualized responses to drugs depending on particular CFTR mutations and modifying genes, most of which are alternative ion channels. SUMMARY: Studies of modifying genes in CF allow: understanding of clinical variability among patients with the same CFTR genotype; evaluation of precision medicine; understanding of environmental and genetic effects at the organ level; understanding the involvement of genetic variants in inflammatory responses; improvements in genetic counseling; understanding the involvement of genetic variants in inflammatory responses in lung diseases, such as asthma; and understanding the individuality of the person with the disease.

Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma / Espirometria e capnografia volumétrica na avaliação da função pulmonar de indivíduos obesos e eutróficos sem asma

Abstract 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.

Resumo Objetivo: Analisar e comparar a função pulmonar de crianças e adolescentes obesos e eutróficos saudáveis, sem asma, pela espirometria e capnografia volumétrica. Métodos: Estudo transversal com 77 indivíduos (38 obesos) entre cinco e 17 anos. Todos fizeram espirometria e capnografia volumétrica. Os obesos repetiram as avaliações após o uso de broncodilatador. Resultados: Na avaliação da espirometria, os indivíduos obesos, quando comparados com o grupo controle, apresentaram menores valores no volume expiratório forçado no primeiro segundo pela capacidade vital forçada (VEF1/CVF) e nos fluxos expiratórios a 75% da CVF e entre 25-75% da mesma (p < 0,05). A capnografia volumétrica demonstrou que os obesos apresentam maior volume produzido de dióxido de carbono e volume corrente alveolar (p < 0,05). Além disso, a relação entre o volume espaço morto e volume corrente, bem como o slope da fase 3 normalizado pelo volume corrente, foi menor nos indivíduos saudáveis (p < 0,05). Esses dados sugerem que a obesidade não altera a homogeneidade da ventilação, mas sim dos fluxos. Ao subdividir os grupos por idade, foi observada maior diferença na função pulmonar entre indivíduos obesos e saudáveis na faixa acima de 11 anos (p < 0,05). Conclusão: Mesmo sem o diagnóstico de asma por critérios clínicos e sem resposta ao uso de broncodilatador, os indivíduos obesos apresentaram menores valores no VEF1/CVF e nos fluxos expiratórios forçados, o que indica a presença de processo obstrutivo. A capnografia volumétrica indicou nos indivíduos obesos maior volume corrente alveolar, sem alterações na homogeneidade da ventilação, o que sugere alteração nos fluxos, sem comprometimento dos volumes pulmonares.

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.

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.

Características epidemiológicas e genéticas associadas à gravidade da bronquiolite viral aguda pelo vírus sincicial respiratório / Epidemiological and genetic characteristics associated with the severity of acute viral bronchiolitis by respiratory syncytial virus

OBJETIVO: avaliar os fatores epidemiológicos e genéticos associados à gravidade da Bronquiolite Viral Aguda (BVA) pelo Vírus Sincicial Respiratório (VSR). FONTE DOS DADOS: foram utilizados descritores "bronchiolitis", "risk factor", "genetics" e "respiratory syncytial virus" e todas as combinações entre eles, nas bases de dados PubMed, SciELO e Lilacs publicados após o ano de 2000 e que incluíram indivíduos menores de dois anos de idade. SÍNTESE DOS DADOS: foram encontrados 1.259 artigos e lidos seus respectivos resumos. Destes foram selecionados 81 que avaliaram fatores de risco para a gravidade da BVA para leitura na íntegra, e foram incluídos os 60 estudos mais relevantes. Os fatores epidemiológicos associados com a gravidade da BVA pelo VSR foram: prematuridade, tabagismo passivo, baixa idade, ausência de aleitamento materno, doença pulmonar crônica, cardiopatia congênita, sexo masculino, etnia, coinfecção viral, baixo peso na admissão hospitalar, tabagismo materno na gestação, dermatite atópica, ventilação mecânica no período neonatal, antecedente materno de atopia e/ou asma na gestação, estação do nascimento, baixo nível socioeconômico, síndrome de Down, poluição ambiental, morar em altitude acima de 2.500 metros do nível do mar e parto cesariana. Em contrapartida, algumas crianças com BVA grave não apresentam nenhum desses fatores de risco. Neste sentido, estudos recentes têm verificado a influência de fatores genéticos relacionados à gravidade da BVA pelo VSR. Polimorfismos dos genes TLRs, RANTES, JUN, IFNA5, NOS2, CX3CR1, ILs e VDR têm-se mostrado associados com a evolução mais grave da BVA pelo VSR. CONCLUSÃO: a gravidade da BVA pelo VSR é um fenômeno dependente da interação entre variáveis epidemiológicas, ambientais e genéticas em seus diferentes graus de interação.

OBJECTIVE: to assess the epidemiological and genetic factors associated with severity of acute viral bronchiolitis (AVB) by respiratory syncytial virus (RSV). DATA SOURCE: the key words ''bronchiolitis'', ''risk factor'', ''genetics'' and ''respiratory syn-cytial virus'', and all combinations among them were used to perform a search in the PubMed,SciELO, and Lilacs databases, of articles published after the year 2000 that included individualsyounger than 2 years of age. DATA SYNTHESIS: a total of 1,259 articles were found, and their respective summaries were read. Of these, 81 were selected, which assessed risk factors for the severity of AVB, and were read in full; the 60 most relevant studies were included. The epidemiologic factors associated with AVB severity by RSV were prematurity, passive smoking, young age, lack of breastfeeding, chronic lung disease, congenital heart disease, male gender, ethnicity, viral coinfection, low weight at admission, maternal smoking during pregnancy, atopic dermatitis, mechanical ventilation in the neonatal period, maternal history of atopy and/or asthma during pregnancy, season of birth, low socioeconomic status, Down syndrome, environmental pollution, living at an altitude > 2,500 meters above sea level, and cesarean section birth. Conversely, some children with severe AVB did not present any of these risk factors. In this regard, recent studies have verified the influence of genetic factors on the severity of AVB by RSV. Polymorphisms of the TLRs, RANTES, JUN, IFNA5, NOS2, CX3CR1, ILs, and VDR genes have been shown to be associated with more severe evolution of AVB by RSV. CONCLUSION: the severity of AVB by RSV is a phenomenon that depends on the varying degrees of interaction among epidemiological, environmental, and genetic variables.

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.

Generation of Nutrients and Detoxification: Possible Roles of Yeasts in Leaf-Cutting Ant Nests.

The possible roles played by yeasts in attine ant nests are mostly unknown. Here we present our investigations on the plant polysaccharide degradation profile of 82 yeasts isolated from fungus gardens of Atta and Acromyrmex species to demonstrate that yeasts found in ant nests may play the role of making nutrients readily available throughout the garden and detoxification of compounds that may be deleterious to the ants and their fungal cultivar. Among the yeasts screened, 65% exhibited cellulolytic enzymes, 44% exhibited pectinolytic activity while 27% and 17% possess enzyme systems for the degradation of protease and amylase, respectively. Galacturonic acid, which had been reported in previous work to be poorly assimilated by the ant fungus and also to have a negative effect on ants' survival, was assimilated by 64% and 79% of yeasts isolated from nests of A. texana and Acromyrmex respectively. Our results suggest that yeasts found in ant nests may participate in generation of nutrients and removal of potentially toxic compounds, thereby contributing to the stability of the complex microbiota found in the leaf-cutting ant nests.