RESUMO
BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Obesidade Mórbida/genética , Proteínas Repressoras , Adolescente , Adulto , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Criança , Análise Mutacional de DNA , Genes Reporter , Estudos de Associação Genética , Humanos , Camundongos , Fenótipo , Proteínas Repressoras/genética , Ativação TranscricionalRESUMO
BACKGROUND: Asthma is a complex clinical disease characterized by airway inflammation. Recently, various studies reported on the analysis of exhaled breath condensate (EBC) in the search for potential biomarkers for asthma. However, in a complex disease such as asthma, one biomarker might not be enough for early diagnosis or follow-up. OBJECTIVE: The use of proteome analysis may reveal disease-specific proteolytic peptide or protein patterns, and may lead to the identification of novel proteins for the detection of asthma. METHODS: Liquid chromatography and mass spectrometry were used to separate and detect proteins (proteolytic peptides) present in EBC samples from 30 healthy children and 40 children with asthma in the age group of 6-12 years. RESULTS: Support vector machine analysis resulted in differentiating profiles based on asthma status. These proteolytic peptide patterns were not correlated to some well known (spirometry, exhaled nitric oxide) and more recently described exhaled markers (EBC pH, LTB4). The more abundant proteins in EBC were identified as cytokeratins, albumin, actin, haemoglobin, lysozyme, dermcidin, and calgranulin B. CONCLUSION: Although the exact role in the disease development or physiological state of the airways of the proteins described in the presented pattern is not clear at this moment, this is an important step in the search for exhaled biomarkers for asthma. This study shows that EBC contains proteins that are of interest for future non-invasive asthma diagnosis or follow-up.
Assuntos
Asma/diagnóstico , Biomarcadores/análise , Testes Respiratórios/métodos , Proteômica/métodos , Criança , Cromatografia Líquida , Expiração , Feminino , Humanos , Masculino , Espectrometria de MassasRESUMO
Persistent wheeze is a common chronic disease in early childhood and later may progress to asthma. However, the association between pre- and post-bronchodilator lung function and the wheezing phenotype in preschool children is not known. Children 4 yrs of age involved in a prospective birth cohort study (in Antwerp, Belgium) concerning perinatal factors and the occurrence of asthma and allergies, were invited to participate in lung function measurements with the forced oscillation technique. The wheezing phenotype was assessed via (bi)annual questionnaires. Wheezing phenotype and baseline respiratory impedance data were available for 325 children, 96% of whom underwent bronchodilation tests. The baseline resistance at 4 Hz was higher in children with early transient (11.0 hPa x s x L(-1), n = 127) or persistent wheeze (11.9 hPa x s x L(-1), n = 54) than in children who never wheezed (10.3 hPa x s x L(-1), n = 144). After bronchodilation, the resistance decreased on average by 22%. The decrease was greater among the persistent wheezers than among those who never wheezed (3.4 versus 2.3 hPa x s x L( -1)). The baseline lung function was poorer and the bronchodilator response was greater in 4-yr-old children with persistent wheeze than in those who never wheeze or who had early transient wheeze, implying a higher bronchomotor tone in the former group.
Assuntos
Asma/diagnóstico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Testes de Função Respiratória , Inquéritos e Questionários , Corticosteroides/uso terapêutico , Asma/fisiopatologia , Bélgica , Pré-Escolar , Impedância Elétrica , Feminino , Humanos , Masculino , Fenótipo , Sons RespiratóriosRESUMO
Sleep-disordered breathing is highly prevalent in childhood obesity. Two recent cross-sectional studies have demonstrated an independent association between the severity of sleep-disordered breathing and the metabolic syndrome. A limited number of studies have also addressed the correlation between sleep-disordered breathing and insulin resistance, the core factor of the metabolic syndrome. Cross-sectional reports in modestly obese children are in favor of an association between sleep apnea and insulin resistance. However, these findings were not confirmed in studies of normal-weight children and of morbidly obese children. Only one out of three treatment studies before and after adenotonsillectomy confirmed the association between sleep apnea and insulin resistance, but only in obese children. Although statistical power issues and differences in patient characteristics might partially explain these contradicting results, the evidence to date is far from establishing a causal link between sleep-disordered breathing and insulin resistance. Longitudinal studies and randomized control trials are therefore warranted to investigate a possible causal link between sleep-disordered breathing and insulin resistance.
Assuntos
Síndrome Metabólica/etiologia , Obesidade/complicações , Síndromes da Apneia do Sono/complicações , Adolescente , Criança , Estudos Transversais , Humanos , Resistência à Insulina , Fatores de RiscoRESUMO
BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.
Assuntos
Fibrose Cística/terapia , Encaminhamento e Consulta , Adolescente , Bélgica , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/microbiologia , Progressão da Doença , Humanos , Avaliação de Resultados em Cuidados de Saúde , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Capacidade VitalRESUMO
OBJECTIVES: To assess whether sleep-disordered breathing (SDB) in overweight children and adolescents has an additional effect on the spectrum of urinary albumin to protein loss, as markers of early kidney dysfunction. METHODS: Prospective study in a clinical sample of overweight children and adolescents. Each subject underwent anthropometry, blood sampling, oral glucose tolerance test and polysomnography. From a 24-hour urine collection, albumin excretion rate and total urinary protein to creatinine ratio (UPCR) were calculated. RESULTS: 94 nondiabetic subjects were included (mean age = 11.0 +/- 2.5, 42 boys). Average BMI z-score was 2.25 +/- 0.47 (26 overweight subjects and 68 obese subjects). There was no difference in albumin excretion rate or UPCR between subjects with and without SDB. None of the SDB parameters correlated with the transformed albumin excretion rate or UPCR. Albumin excretion rate significantly correlated with fasting insulin and C-peptide and with post-challenge glucose, insulin and C-peptide levels, while UPCR correlated with fasting and post-challenge C-peptide levels. Multiple regression indicated that post-challenge glucose levels were the most important predictors of albumin excretion rate. CONCLUSION: Insulin resistance, and not SDB, was associated with increased levels of albuminuria, indicating early renal dysfunction, in this clinical sample of overweight children and adolescents.
Assuntos
Albuminúria/urina , Resistência à Insulina , Obesidade/urina , Síndromes da Apneia do Sono/urina , Adolescente , Albuminúria/fisiopatologia , Biomarcadores/urina , Criança , Estudos de Coortes , Creatinina/urina , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Nefropatias/etiologia , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , Obesidade/complicações , Obesidade/fisiopatologia , Polissonografia/métodos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologiaRESUMO
OBJECTIVE: To assess whether sleep-disordered breathing (SDB) is a risk factor of the metabolic syndrome (MS) in children and adolescents who are overweight and to examine whether the severity of SDB was independently associated with glucose intolerance, insulin resistance, and/or dyslipidemia. STUDY DESIGN: Consecutive subjects who were overweight or obese underwent polysomnography, fasting blood sample, and oral glucose tolerance test (for calculation of area under the curve [AUC]). SDB was defined as a respiratory disturbance index > or = 2. MS was present when > or = 3 of these factors were present: waist circumference > or = 90th percentile; fasting glucose level > or = 110 mg/dL; triglyceride level > or = 110 mg/dL; high-density lipoprotein cholesterol level < or = 40 mg/dL; blood pressure > or = 90th percentile. RESULTS: A total of 104 subjects were included in the study (44% boys; 58% prepubertal; mean age, 11.1 +/- 2.6 years; 69% obese). Mean SaO2 (odds ratio, 0.54) and SaO2nadir (odds ratio, 0.89) were independent, significant predictors of the presence of MS. Multiple regression showed significant associations between SaO2nadir and high-density lipoprotein cholesterol level, mean SaO2 and both AUC glucose and triglyceride levels, and between the percentage of total sleep time with SaO2 > or = 95% and cholesterol level, while controlling for adiposity and sex, puberty, or both. CONCLUSION: This study supports the hypothesis of an interaction between SDB and metabolic abnormalities, independent of estimates of body fat distribution, in children and adolescents who are overweight and obese.
Assuntos
Síndrome Metabólica/epidemiologia , Sobrepeso , Síndromes da Apneia do Sono/epidemiologia , Adolescente , Área Sob a Curva , Glicemia/análise , Criança , Comorbidade , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Sobrepeso/fisiologia , Polissonografia , Fatores de RiscoRESUMO
AIM: Only a limited number of studies, designed to establish normal values for sleep-related respiratory variables in children, have been reported, and all are non-European. The aim of this study was to expand the knowledge on normative data in children. METHODS: Subjects ranging from 6 to 16 years were recruited and underwent full polysomnography. Only subjects without sleep disordered breathing or other sleep problems as assessed by clinical history were included. RESULTS: Sixty subjects were studied (
Assuntos
Oximetria , Polissonografia , Apneia do Sono Tipo Central/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico , Sono/fisiologia , Adolescente , Índice de Massa Corporal , Criança , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Sobrepeso/fisiologia , Valores de Referência , Fatores Sexuais , Ronco , População BrancaRESUMO
AIM: To investigate the association between wheezing and impaired sleep in Sri Lankan children, aged 6-12 years; and, to report the prevalence of asthma-related symptoms in these subjects. METHODS: The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed. RESULTS: Of 800 originally distributed questionnaires, 652 were analyzed. Wheezing was present in 89 children (14%). Within this group, 66% reported wheezing in the last 12 months. Wheezing children had a significantly higher presence of snoring, restless sleep, nocturnal awakenings and daytime tiredness. Wheezing was found to be independently associated with restless sleep (odds ratio (OR) = 2.4). There was no association between wheezing and difficulties falling asleep, nocturnal awakenings, apneas, and daytime sleepiness and tiredness. After adjusting for possible confounders, the following significant associations were present: snoring and apneas (OR = 1.6), chronic rhinitis and apneas (OR = 1.6), snoring and restless sleep (OR = 3.2), chronic rhinitis and restless sleep (OR = 2.1), and hayfever and daytime tiredness (OR = 4.3). Wheezing was related to an increased risk of snoring (OR = 2.8) and subjects with chronic rhinitis had also an increased risk of snoring (OR = 1.7), adjusting for possible confounders. CONCLUSION: The sleep of wheezing children was impaired compared with their non-wheezing peers, resulting in an increased prevalence of daytime tiredness. Upper airway symptoms, such as chronic rhinitis or hayfever, should be carefully considered in these children, as they might be responsible for these sleep problems.
Assuntos
Sons Respiratórios/fisiopatologia , Sono , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Sri Lanka , Inquéritos e QuestionáriosRESUMO
Collection of exhaled breath condensate (EBC) is a simple and noninvasive method to obtain information on the respiratory system. Different mediators can be determined in EBC. However, determinants of variability are not well described. The aim of this study was to evaluate variability of pH, volume and protein concentration of EBC between individuals and between sampling times. Therefore, EBC was collected from 20 healthy volunteers on two different days. Median pH for all samples, measured 5 min after collection without deaeration, was 6.17. Median volume was 1.70 ml and median total protein concentration was 1.02 microg/ml. Coefficients of variation were 5.17%, 21.84% and 37.93%, respectively. No intra- or interday variability could be found, except for the first collection time. Between individuals, significant differences were observed for all three mediators. Age, height and gender can explain part of this variation. In conclusion, no significant difference between sampling times on the same day or on different days was obtained for pH, volume and total protein concentration, provided that subjects are experienced in collecting EBC.
Assuntos
Testes Respiratórios/métodos , Proteínas/análise , Adolescente , Adulto , Envelhecimento/fisiologia , Estatura/fisiologia , Expiração , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Manejo de Espécimes/métodosRESUMO
When input impedance is determined by means of the forced oscillation technique, part of the oscillatory flow measured at the mouth is lost in the motion of the upper airway wall acting as a shunt. This is avoided by applying the oscillations around the subject's head (head generator) rather than at the mouth (conventional technique). In seven wheezing infants, we compared both techniques to estimate the importance of the upper airway wall shunt impedance (Zuaw) for the interpretation of the conventional technique results. Computation of Zuaw required, in addition, estimation of nasal impedance values, which were drawn from previous measurements (K. N. Desager, M. Willemen, H. P. Van Bever, W. De Backer, and P. A. Vermeire. Pediatr. Pulmonol. 11: 1-7, 1991). Upper airway resistance and reactance at 12 Hz ranged from 40 to 120 and from 0 to -150 hPa. l(-1). s, respectively. Varying nasal impedance within the range observed in infants did not result in major changes in the estimates of Zuaw or lung impedance (ZL), the impedance of the respiratory system in parallel with Zuaw. The conventional technique underestimated ZL, depending on the value of Zuaw. The head generator technique slightly overestimated ZL, probably because the pressure gradient across the upper airway was not completely suppressed. Because of the need to enclose the head in a box (which is not required with the conventional technique), the head generator technique is difficult to perform in infants.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Sistema Respiratório/anatomia & histologia , Algoritmos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Modelos Biológicos , Pletismografia , Reprodutibilidade dos TestesRESUMO
The forced oscillation technique according to Làndsér et al. (J. Appl. Physiol. 41:101-106, 1976) was modified for use in infants. Adaptations, including a flexible tube to connect the infant to the measuring system and a bias flow to avoid rebreathing, did not influence impedance values. The linearity of the respiratory system was assessed and confirmed by 1) applying pseudo-random noise oscillations at three different amplitudes to 7 infants and 2) comparing in 12 infants impedance values obtained with pseudo-random noise and with sinusoidal oscillations at 12 and 32 Hz. Intersubject variability, averaged for all frequencies, was 6%. In 17 infants the relative error (+/- SD) between two series of five measurements within a time interval of 15 min was 0.5 +/- 5.7%. No statistically significant difference was found between impedance values before and after repositioning of the infant's head, whereas rotation resulted in a decrease in resistance and no effect on reactance. Our results indicate that the infant-adapted forced pseudo-random noise oscillation technique has the potential to give valuable information about ventilatory lung function in infants.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Testes de Função Respiratória/instrumentação , Asma/fisiopatologia , Cabeça , Humanos , Lactente , Recém-Nascido , Recidiva , Reprodutibilidade dos TestesRESUMO
By applying oscillations to the respiratory system through a rigid face mask, the infant-adapted Lándsér forced oscillation technique measures impedance of the total respiratory system including the nose, at frequencies from 4 to 52 Hz. The present study was aimed at evaluating nasal impedance in infants from consecutive forced oscillation measurements through both nostrils and each nostril separately, using a simple electrical model. In 30 asthmatic infants with varying degrees of nasal obstruction, aged 1-16 months, calculated nasal resistance (Rn) at 24 Hz ranged from 1 to 16 cm H2O.L-1.s. The ratio of Rn to total respiratory system resistance varied between 1 and 48% (mean: 16%). In seven non-asthmatic infants, aged 0-12 months, Rn was between 1 and 11 cm H2O.L-1.s. Nasal patency (evaluated clinically) was correlated with the calculated Rn (P less than 0.05). Rn showed almost no frequency dependence between 24 and 48 Hz as demonstrated by a mean slope of -0.09 +/- 0.08 cm H2O.s2/L for the asthmatic and of -0.08 +/- 0.07 for the non-asthmatic infants. In seven of the asthmatic infants the differences between two Rn determinations at a 45 min interval ranged from -1.7 to 3.8 cm H2O.L-1.s-1 at 24 Hz and from -3.6 to 1.0 at 48 Hz. Changes in Rn did not correlate with changes in total respiratory system resistance (P greater than 0.05). In conclusion, nasal impedance can be approximated from three consecutive measurements through both nostrils and through each nostril separately.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Cavidade Nasal/fisiologia , Asma/fisiopatologia , Humanos , Lactente , Recém-Nascido , Modelos Biológicos , Obstrução Nasal/diagnóstico , Ruído , Oscilometria/métodos , Fenômenos Fisiológicos RespiratóriosRESUMO
Airways obstruction has been demonstrated in acutely wheezing infants. The aim of the present study was to assess functional abnormalities as detected by measurement of total respiratory system resistance (Rrs) and functional residual capacity (FRC) in infants with a history of recurrent episodes of wheezing, while not acutely ill. In 30 such infants (mean age, 10 months; range, 4-17) and in 10 healthy infants (mean age, 6 months; range, 0-14) four Rrs measurements, performed with the forced pseudo-random noise (PRN) oscillation technique, and three FRC determinations, using the closed-circuit helium dilution technique, were averaged. A lower than predicted FRC was demonstrated in 20/30 (66%) patients. At 16 Hz, Rrs was significantly above predicted in 3/30 (10%) patients. Specific Rrs (Rrs x FRC) at 16 Hz was increased in 5/30 (17%) patients. In conclusion, the PRN oscillation technique combined with FRC measurement by helium dilution detects lung function abnormalities in a minority of wheezing infants during symptom-free intervals.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Capacidade Residual Funcional/fisiologia , Pulmão/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Estudos de Casos e Controles , Hidrato de Cloral , Hélio , Humanos , Lactente , Recém-Nascido , Pulmão/fisiopatologia , Oscilometria , Pico do Fluxo Expiratório , Pletismografia Total , Ventilação Pulmonar , Análise de Regressão , Reprodutibilidade dos Testes , Sons Respiratórios , EspirometriaRESUMO
We investigated the effects of 10 mg aerosolized furosemide on clinical score in 28 acutely wheezing infants (Part A) and in a second group of 20 intermittently wheezing babies on airway resistance and functional residual capacity during a symptomfree period (Part B), using a double-blind, placebo-controlled design. In both parts of the study no therapeutic effects were observed during and following aerosol inhalation of 10 mg furosemide.
Assuntos
Antiasmáticos/administração & dosagem , Bronquiolite/tratamento farmacológico , Furosemida/administração & dosagem , Sons Respiratórios/efeitos dos fármacos , Administração por Inalação , Aerossóis , Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/fisiologia , Bronquiolite/fisiopatologia , Método Duplo-Cego , Feminino , Capacidade Residual Funcional/efeitos dos fármacos , Capacidade Residual Funcional/fisiologia , Humanos , Lactente , Masculino , Sons Respiratórios/fisiopatologia , Falha de TratamentoRESUMO
In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height). Mean adult height was the same in subjects who took ICs during childhood as compared to those who had never received ICs (boys: 179.3cm+/-6.8 vs. 180.4 cm+/-5.6; girls: 165.8 cm+/-7.5 vs. 167.7 cm+/-7.2). SDS of adult height was also not different between the two groups: in subjects who did not take ICs it was 0.89+/-1.00, while in those who took ICs it was 0.66+/-1.10 (P = 0.31). SDS of target height was also not different between the two groups: in subjects not taking ICs it was 0.95+/-0.86, while in those who took ICs it was 0.28+/-0.76 (P = 0.30). However, subjects who took ICs during childhood showed a statistically significant lower value of adult height minus target height than those who never took ICs (whole group: -0.003+/-5.9 vs. 2.54 +/-4.8, P = 0.03 ; boys: 0.004+/-5.8 vs. 3.09+/-4.5, P = 0.04 ; girls: -0.075+/-6.3 vs. 1.91+/-5.2, P = 0.31). Patients on ICs during childhood who had ever been hospitalized for asthma showed a lower value for adult height minus target height than those who took ICs but were never hospitalized (-3.08+/-7.8 vs. 1.06+/-4.8, P = 0.046). A logistic regression analysis predicting growth impairment showed that the best-fitting model was one that used only ICs as a dependent variable (crude odds ratio, 3.3; 95% CI, 1.3-8.4). Patients who were treated with ICs in combination with intranasal corticosteroids (treatment for rhinitis) tended to have a lower value of adult height minus target height than the other children, but the difference was not statistically significant (P = 0.07). We conclude that although adult height was the same in young adults who were treated with ICs during childhood compared to those who were not treated with ICs during childhood, there was a statistically significant difference between the two groups for adult height minus target height, suggesting mild growth retardation in patients who took ICs during childhood. These findings may be explained by the use of ICs, but it seems more likely that a difference in asthma severity between both groups was responsible for it.
Assuntos
Antiasmáticos/farmacologia , Asma/fisiopatologia , Estatura/efeitos dos fármacos , Glucocorticoides/farmacologia , Adolescente , Adulto , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Beclometasona/farmacologia , Beclometasona/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The forced oscillation technique is usually calibrated by loading the measuring device with a known impedance. A correction function is calculated, relating the measured and reference impedances at each frequency. However, this one point calibration procedure does not account for transducer asymmetry. A procedure has previously been presented to circumvent this problem: in addition to one known reference impedance, the calibration was repeated with the system occluded (infinite impedance). The aim of the present study was to evaluate a variant of this procedure, in which instead of resorting to an extreme condition imposing high requirements on the flow measuring system, two reference loads of 4 and 50 hPal-1 s were measured, thus covering the range of impedances observed in children and infants (a two-point procedure). The calibration procedure was performed with these two impedances and evaluated with a third impedance of approximately 17 hPal-1 s. The results of three calibration procedures were compared: one-point, two-point and a previously reported calibration procedure. Impedances consisted of sintered glass and mesh wire screens mounted in glass or polyvinyl tubes. For low impedance values, in the range of 4 to 17 hPal-1 s, measured and predicted values were similar for the three calibration procedures at frequencies from 4-52 Hz, although with the one point calibration procedure there was some underestimation above 44 Hz. With the highest load, especially above 32 Hz, marked discrepancies between measured and predicted values were observed with the one-point calibration procedure and the previously reported calibration procedure. Under these circumstances the two-point procedure is preferred.
Assuntos
Testes de Função Respiratória/métodos , Mecânica Respiratória , Transdutores de Pressão , Calibragem , HumanosRESUMO
UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Testes Genéticos , Obesidade Infantil/genética , Mutação Puntual , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Variação Genética , Humanos , Masculino , Obesidade Infantil/diagnóstico , FenótipoRESUMO
OBJECTIVE: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation (