RESUMO
OBJECTIVE: To establish a method for measuring nasal transepithelial potential difference (PD) in infants. STUDY DESIGN: A modified infant method (smaller catheter size, reduced flow rates, and shorter protocol time) was compared with an established adult nasal PD method in 10 adult volunteers (4 with cystic fibrosis [CF]). Nasal PD was measured in 13 infants with a possible diagnosis of CF. RESULTS: Recordings were similar for the established and the modified methods in adult volunteers. An amiloride concentration of 10(-4) mol/L was necessary for full inhibition of amiloride-sensitive sodium ion (Na(+)) transport. Of the 13 infants, 2 had PD values suggestive of CF (mean baseline PD, -50.1 mV and -31.4 mV; maximum baseline PD, -61 mV and -49 mV; change in PD after perfusion with zero chloride solution with isoprenaline and amiloride [DeltazeroCl(-)/Iso], -1 mV and +3.5 mV), and 11 had normal values (mean +/- SEM baseline PD, -13.2 +/- 1.0 mV; maximum baseline PD, -21.4 +/- 2.0; DeltazeroCl(-)/Iso, -15.3 +/- 1.9 mV). These results correlated with subsequent sweat test data, mutation analysis, and clinical outcome. CONCLUSION: Nasal PD measured with this modified method is comparable to that measured with an established adult method. The measurements were well tolerated in 13 infants and discriminated bioelectric profiles characteristic of normal and CF respiratory epithelium. This study supports the use of this modified nasal PD technique as a diagnostic test for CF in newborn infants.
Assuntos
Fibrose Cística/diagnóstico , Mucosa Nasal , Adulto , Amilorida , Fibrose Cística/genética , Limiar Diferencial , Diuréticos , Genótipo , Humanos , Lactente , Recém-NascidoRESUMO
The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.
Assuntos
Fibrose Cística/diagnóstico , Mucosa Nasal/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Insuficiência Pancreática Exócrina/diagnóstico , Feminino , Heterozigoto , Humanos , Masculino , Potenciais da Membrana/fisiologia , Mutação , Fenótipo , Suor/químicaRESUMO
No large-scale studies of the incidence or disease severity of cystic fibrosis (CF) in black patients have been reported to date. In this study, the CF Foundation National Patient Registry was used to establish new incidence figures and to compare the clinical status of U.S. black (n = 601) and white patients (n = 17,755) with CE Results indicate that the incidence of CF is approximately 1 in 3,200 white and 1 in 15,000 black live births in the United States. Black patients with CF are currently, and were at diagnosis, younger and have poorer nutritional status and pulmonary function than white patients with CF. Fewer have meconium ileus, but more have distal intestinal obstruction syndrome. To control for genotype, each black deltaF508 homozygote (n = 47) was compared with four age- and sex-matched white deltaF508 homozygotes. Only the difference in nutritional status remained. The deltaF508 mutation is associated with higher levels of meconium ileus than other genotypes, independent of race. In conclusion, the clinical manifestations of CF are similar in black and white patients except for poorer nutritional status in black patients, which appears to be independent of age and genotype.
Assuntos
População Negra , Fibrose Cística/etnologia , População Branca , População Negra/genética , Criança , Pré-Escolar , Estudos Transversais , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Feminino , Genótipo , Humanos , Incidência , Lactente , Masculino , Estado Nutricional , Fenótipo , Testes de Função Respiratória , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
OBJECTIVE AND STUDY DESIGN: Successful adaptation to air breathing at birth depends on rapid absorption of fetal lung liquid that is mediated by activation of amiloride-sensitive sodium ion channels. To test the relationship between respiratory epithelial Na+ transport and development of respiratory distress syndrome (RDS), we measured nasal transepithelial potential difference (PD) in 31 very premature (< or = 30 weeks of gestation) newborn infants. Infants were retrospectively assigned to RDS (22 infants) and non-RDS (9 infants) groups on the basis of clinical and chest x-ray criteria. RESULTS: Maximal nasal epithelial PD increased with birth weight (-1.2 mV/100 gm) and was lower in infants with RDS (-16.5 +/- 0.6 mV) than in those without RDS (-22.0 +/- 1.3 mV). Infants without RDS had PD values similar to normal fullterm infants. Amiloride inhibition of PD, an index of Na+ absorption, was significantly lower, within the first 24 hours of life, in infants in whom RDS developed (3.8 +/- 0.2 mV; 29.5% +/- 0.8% inhibition) than in those without RDS (6.1 +/- 0.6 mV; 38.6% +/- 0.5% inhibition). Maximal and amiloride-sensitive PD returned to normal during the recovery phase of RDS. CONCLUSIONS: We conclude that Na+ absorption across nasal epithelium increases with increasing birth weight and that impairment of Na+ absorption across the respiratory epithelia of very premature infants may contribute to the pathogenesis of RDS.
Assuntos
Mucosa Nasal/metabolismo , Síndrome do Desconforto Respiratório do Recém-Nascido/metabolismo , Sódio/metabolismo , Amilorida/farmacologia , Transporte Biológico Ativo , Peso ao Nascer , Estudos de Casos e Controles , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Bloqueadores dos Canais de Sódio , Canais de Sódio/metabolismoAssuntos
Amilorida/farmacocinética , Fibrose Cística/metabolismo , Absorção Intestinal/fisiologia , Mucosa Intestinal/metabolismo , Reto/metabolismo , Amilorida/farmacologia , Cloretos/análise , Fibrose Cística/fisiopatologia , Humanos , Lactente , Recém-Nascido , Obstrução Intestinal/metabolismo , Mecônio/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Mucosa Nasal/metabolismo , Suor/químicaRESUMO
We studied the change in ion transport function by measuring the basal transepithelial potential difference (PD) across the ciliated epithelium of the nose in 85 term neonates during the first 72 hours of life. Differences in PD associated with the mode of delivery or the presence of respiratory disease and differences in the PD response to the superfusion of amiloride (10(-5) mol/L) were assessed. We also studied term neonates with transient tachypnea of the newborn (TTN) and acute respiratory insufficiency. Basal PDs during the first 24 hours of life were higher in neonates delivered by cesarean section without prior labor (-29.7 +/- 2.5 mV) and in those with TTN (-38.5 +/- 6.0 mV) than in neonates born during normal spontaneous vaginal delivery (-23.0 +/- 2.9 mV) or cesarean section with prior labor (-23.7 +/- 0.7 mV) or in those with respiratory insufficiency (-22.4 +/- 2.3 mV). The percentage inhibition of PD by amiloride superfusion (less than 24 hours) was significantly lower in infants with TTN (30.9 +/- 4.9%) and after cesarean section without prior labor (31.8 +/- 2.2%) than in other groups (37.6 +/- 1.6%). By 48 hours, nasal PDs after cesarean section without prior labor and in neonates with TTN had declined; and by 72 hours, values were similar to those in other groups; respiratory rate paralleled the decline in PD. The respiratory rate of neonates with respiratory insufficiency remained high and paralleled the persistence of respiratory distress. Amiloride sensitivity was similar for all groups by 72 hours. These findings indicate (1) that PDs vary with the mode of delivery and support a role for labor in the normal transition of respiratory epithelial ion transport and (2) that TTN is associated with abnormal epithelial ion transport.
Assuntos
Parto Obstétrico , Mucosa Nasal/fisiologia , Respiração , Transporte Biológico , Contagem de Células , Células Epiteliais , Epitélio/fisiologia , Feminino , Humanos , Recém-Nascido , Trabalho de Parto/fisiologia , Potenciais da Membrana , Mucosa Nasal/citologia , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologiaRESUMO
Patients with cystic fibrosis (CF) have an increased nasal transepithelial potential difference (PD) which reflects increased sodium absorption across epithelium relatively impermeable to chloride. To evaluate nasal epithelial function in neonates with CF, the PD was recorded and the voltage response to superfusion of 10(-5M) amiloride, an inhibitor of sodium transport, measured between a Ringer perfused bridge on the nasal mucosa and a reference electrode in the subcutaneous space. We studied three neonates with CF with meconium ileus and compared the results with those in 24 term healthy neonates, including one obligate heterozygote for CF, and 27 control neonates with disease. All three CF neonates had raised sweat chloride values (mean 100 mEq/L) at 2 months. The CF neonates had higher PDs (-64.0 +/- 8.4 mV) than those in normal (-24.4 +/- 2.0 mV) or control (-25.8 +/- 2.0 mV) neonates. Superfusion with amiloride induced a 72% reduction in PD in the CF neonates as compared with healthy (37.5 +/- 1.0%) and diseased (36.0 +/- 1.3%) neonates. The PD and amiloride response in CF neonates are similar to those in CF infants (2.24 months), older CF children (greater than 6 years), and CF adults (-64.9 +/- 9.3 mV; 77.7 +/- 1.8%, n = 51). These results suggest that (1) nasal epithelial dysfunction is present in patients with CF shortly after birth, and (2) the nasal PD may be a diagnostic adjunct to the sweat test in the early diagnosis of CF.