RESUMO
OBJECTIVE: To define longitudinal childhood wheeze phenotypes and identify their early-life risk factors. STUDY DESIGN: Current wheeze was recorded 23 times up to age 7 years in a birth cohort at high risk for allergy (n = 620). Latent class analysis of wheeze responses identified 5 classes. Multinomial logistic regression estimated associations of probability-weighted wheezing classes with early-life factors. All phenotypes were compared with never/infrequent wheezers. RESULTS: Lower respiratory tract infection (LRTI) by 1 year (relative risk [RR], 3.00; 95% CI, 1.58-5.70), childcare by 1 year (RR, 1.51; 95% CI, 1.02-2.22), and higher body mass index (RR, 2.51; 95% CI, 1.09-5.81) were associated with increased risk of early transient wheeze, whereas breastfeeding was protective (RR, 0.54; 95% CI, 0.32-0.90). LRTI (RR, 6.54; 95% CI, 2.55-16.76) and aeroallergen sensitization (RR, 4.95; 95% CI, 1.74-14.02) increased the risk of early persistent wheeze. LRTI (RR, 5.31; 95% CI, 2.71-10.41), eczema (RR, 2.77; 95% CI, 1.78-4.31), aeroallergen sensitization (RR, 5.60; 95% CI, 2.86-10.9), and food sensitization (RR, 2.77; 95% CI, 1.56-4.94) increased the risk of intermediate-onset wheeze, whereas dog exposure at baseline (RR, 0.52; 95% CI, 0.32-0.84) and first-born status (RR, 0.49; 95% CI, 0.32-0.76) were protective. Heavy parental smoking at birth (RR, 3.18; 95% CI, 1.02-9.88) increased the risk of late-onset wheeze, whereas breastfeeding reduced it (RR, 0.34; 95% CI, 0.12-0.96). All wheeze classes except early transient had greater risk of wheeze at age 12 years compared with never/infrequent wheezers. CONCLUSION: We found distinct early-life risk factor profiles for each wheeze phenotype. These findings provide insight into possible wheeze mechanisms and have implications for identifying preventive strategies and addressing clinical management of early-life wheeze.
Assuntos
Alérgenos/efeitos adversos , Hipersensibilidade/complicações , Sons Respiratórios/etiologia , Infecções Respiratórias/complicações , Poluição por Fumaça de Tabaco/efeitos adversos , Índice de Massa Corporal , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Hipersensibilidade/genética , Lactente , Masculino , Fenótipo , Prognóstico , Sons Respiratórios/genética , Infecções Respiratórias/genética , Fatores de Risco , Fatores de TempoRESUMO
The relationship between antidopaminergic drugs and glucose has not been extensively studied, even though chronic neuroleptic treatment causes hyperinsulinemia in normal subjects or is associated with diabetes in psychiatric patients. We sought to evaluate dopamine D2 receptor (D2R) participation in pancreatic function. Glucose homeostasis was studied in D2R knockout mice (Drd2(-/-)) mice and in isolated islets from wild-type and Drd2(-/-) mice, using different pharmacological tools. Pancreas immunohistochemistry was performed. Drd2(-/-) male mice exhibited an impairment of insulin response to glucose and high fasting glucose levels and were glucose intolerant. Glucose intolerance resulted from a blunted insulin secretory response, rather than insulin resistance, as shown by glucose-stimulated insulin secretion tests (GSIS) in vivo and in vitro and by a conserved insulin tolerance test in vivo. On the other hand, short-term treatment with cabergoline, a dopamine agonist, resulted in glucose intolerance and decreased insulin response to glucose in wild-type but not in Drd2(-/-) mice; this effect was partially prevented by haloperidol, a D2R antagonist. In vitro results indicated that GSIS was impaired in islets from Drd2(-/-) mice and that only in wild-type islets did dopamine inhibit GSIS, an effect that was blocked by a D2R but not a D1R antagonist. Finally, immunohistochemistry showed a diminished pancreatic beta-cell mass in Drd2(-/-) mice and decreased beta-cell replication in 2-month-old Drd2(-/-) mice. Pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops.
Assuntos
Intolerância à Glucose/metabolismo , Insulina/metabolismo , Pâncreas/metabolismo , Receptores de Dopamina D2/metabolismo , Análise de Variância , Animais , Glicemia/metabolismo , Cabergolina , Proliferação de Células/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Ergolinas/farmacologia , Feminino , Glucose/farmacologia , Intolerância à Glucose/genética , Haloperidol/farmacologia , Imuno-Histoquímica , Insulina/genética , Secreção de Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pâncreas/efeitos dos fármacos , Prolactina/sangue , Radioimunoensaio , Receptores de Dopamina D2/genética , Fatores de TempoRESUMO
OBJECTIVE: To evaluate endothelial function (EF) in a cohort of obese adolescents with impaired insulin sensitivity. STUDY DESIGN: Cardiovascular risk factors and adipocytokines, along with digital hyperemia, were evaluated by peripheral arterial tonometry (PAT) in adolescents with obesity and insulin resistance (IR) in relation to healthy, nonobese controls. RESULTS: The obese and control subjects were of similar age (13.4+/-1.7 years vs 14.0+/-1.4 years) and sex. The obese subjects had IR (mean homeostasis model of assessment [HOMA] score=5.4; 95% confidence interval=3.3-7.5) and significantly greater body mass index (BMI) (BMI z-score 2.4+/-0.2 kg/m(2) vs 0.0+/-0.8 kg/m(2)) and waist circumference (WC) measures (109.6+/-11.1cm vs 70.5+/-9.4 cm) with elevated low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-sensitivity C-reactive protein levels. The mean PAT ratio was significantly lower in obese adolescents compared with controls (1.51+/-0.4 vs 2.06+/-0.4; P=.002), indicative of impaired EF. Linear regression demonstrated associations between PAT ratio and BMI, WC, age, and LDL-C but not between PAT and leptin, resistin, or adiponectin levels or IR. CONCLUSIONS: Obese adolescents with IR exhibited significantly worse EF as assessed by PAT compared with healthy, nonobese controls, and EF showed a significant association with measures of adiposity and other cardiovascular risk factors.
Assuntos
Biomarcadores/análise , Endotélio Vascular/patologia , Resistência à Insulina , Obesidade/complicações , Doenças Vasculares/etiologia , Adolescente , Análise de Variância , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos de Casos e Controles , LDL-Colesterol/análise , Estudos de Coortes , Intervalos de Confiança , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Modelos Lineares , Masculino , Manometria , Obesidade/diagnóstico , Probabilidade , Prognóstico , Valores de Referência , Medição de Risco , Triglicerídeos/análise , Doenças Vasculares/epidemiologia , Doenças Vasculares/fisiopatologia , Circunferência da CinturaRESUMO
OBJECTIVES: Because community-based studies, which report IgE food sensitization (IgE-FS) in more than 80% of infants with moderate atopic eczema, may be influenced by referral bias, we assessed the prevalence of IgE-FS in a cohort of infants with moderate atopic eczema attending a dermatology department clinic. STUDY DESIGN: Consecutive infants (n = 51, 39 males; median age, 34 weeks; range, 20 to 51 weeks) with moderate atopic eczema referred to a university-affiliated dermatology department were studied prospectively. Clinical history and eczema severity were documented. IgE-FS was assessed by the skin prick test (SPT; n = 51) and food-specific serum IgE antibodies (CAP-FEIA test; n = 41). IgE-FS was diagnosed if the SPT or CAP-FEIA level exceeded the >95% predictive reference cutoff for positive food challenges. RESULTS: Based on SPT, 44 of 51 infants (86%; 95% confidence interval [CI] = 74% to 94%) had IgE-FS (cow's milk, 16%; egg, 73%; peanut, 51%). Using age-specific 95%-predictive cutoff values, CAP-FEIA identified 34 of 41 infants (83%; 95% CI = 68% to 93%) with IgE-FS (cow's milk, 23%; egg, 80%). Forty-six (90%) infants had IgE-FS to at least 1 food item by either SPT or CAP-FEIA. CONCLUSIONS: Atopic eczema was found to be closely associated with IgE-FS in infants attending a dermatology department.
Assuntos
Dermatite Atópica/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/sangue , Animais , Arachis/imunologia , Austrália/epidemiologia , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Humanos , Técnicas Imunoenzimáticas , Lactente , Masculino , Leite/imunologia , Óvulo/imunologia , Valor Preditivo dos Testes , Estudos Prospectivos , Testes CutâneosRESUMO
OBJECTIVES: Our purpose was to study the relation between gastroesophageal reflux (GER) and esophagitis in infants with persistent distress. STUDY DESIGN: Infants (n = 125, 79 boys; median age, 4.2 months) with persistent distress and clinical symptoms suggestive of GER and esophagitis were retrospectively studied. All had undergone esophageal 24-hour pH monitoring and had upper gastrointestinal biopsy specimens taken. RESULTS: There were 65 (48%) infants with inflammatory changes found in at least one upper gastrointestinal biopsy specimen, of whom 32 (25.6%) had esophagitis; 11 infants with esophagitis also had gastritis or duodenitis. Although infants with frequent regurgitation (n = 65) had significantly more frequent GER episodes per 24 hours (P <.03) and greater fractional reflux time (P <.001) than infants without, this was not associated with histologic esophagitis (P =.33). Of the 32 infants with esophagitis, 9 had abnormal pH monitoring and 23 had nonreflux esophagitis. A separate group of 23 infants had abnormal pH monitoring but no esophagitis. Diagnostic agreement between pH monitoring and esophageal histologic features was poor (kappa = 0.07). CONCLUSION: Esophagitis occurred in one quarter of infants with persistent distress. Abnormal esophageal pH monitoring did not reliably predict esophagitis, suggesting a nonacid peptic cause in some of these infants.