A modified technique for measurement of nasal transepithelial potential difference in infants.

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.

Quantitation and localization of ENaC subunit expression in fetal, newborn, and adult mouse lung.

The newborn lung is cleared of fetal liquid by active Na+ transport. The heterotrimeric (alpha, beta, gamma) epithelial Na+ channel, ENaC, mediates this process. To understand the role of individual ENaC subunits in Na+ transport during development, we quantified murine ENaC (mENaC) subunit messenger RNA (mRNA) expression levels of fetal, neonatal, and adult mouse lung by Northern blot analysis and studied regional expression by in situ hybridization. alphamENaC and gammamENaC mRNA expression increased sharply in late fetal gestation and reached near-adult levels by Day 1 of postnatal life. betamENaC expression increased more gradually through late fetal and early postnatal life and increased progressively until adulthood. In situ hybridization studies showed similar localization patterns of alphamENaC and gammamENaC subunit expression in fetal and postnatal lung. gammamENaC and alphamENaC subunits were initially localized to fetal lung bud tubules and by late gestation both subunits were expressed in all regions (acinar and bronchiolar) of the distal lung epithelium. betamENaC was detected from 16 d gestation onward and was expressed most intensely in small airways. There was little expression of betamENaC in the alveolar region. In postnatal lung all three subunits were expressed intensely in small airways. In adult lung, alphamENaC and gammamENaC were expressed in a pattern consistent with an alveolar type II (ATII) cell distribution. The timing of quantitative changes in mENaC subunit expression is consistent with a role of Na+ transport in liquid clearance of the perinatal lung. Intense expression of mENaC subunits in medium and small airway epithelium and in ATII cells suggests that these regions are a primary location for liquid absorption in the perinatal and postnatal murine lung.

Effectiveness of home versus hospital care in the routine treatment of cystic fibrosis.

Many cystic fibrosis patients with Pseudomonas lung infections receive intravenous (IV) antibiotics and chest physiotherapy (CPT) at home. Previous studies have suggested that home care, in the setting of a clinical study, is as efficacious as hospital care. This report compares the outcomes of home care with minimal supervision to outcomes of hospital care. We compared two groups of similar age and severity of lung impairment. Patients met strict definitions for home or hospital treatment (27 home care courses/33 hospital care courses). Five patients completed six courses of both home care and hospital treatment. Treatment in both groups included intravenous antibiotics and CPT. Primary outcome measures included changes in pulmonary function between the start of treatment and after 2 weeks of therapy, duration of treatment, and intervals between antibiotic courses. In hospitalized patients, forced vital capacity (FVC) increased by 17.4 +/- 3.1% (mean +/- SEM), and forced expiratory volume in one second (FEV1) increased by 23.3 +/- 4.1%, both significant at P < 0.001. The FVC and FEV1 of patients treated at home increased by 10.2 +/- 2.0% and 13.7 +/- 2.6% respectively, neither of which was a significant improvement. Similar results were found in the five patients completing both home and hospital courses. The average duration of treatment was twice as long and time between IV antibiotic courses only two-thirds as long for those treated at home compared with the hospitalized patients. Previous reports have claimed that home care in the setting of a prospective study is as efficacious as hospital care. Our experience indicates that routine home care with minimal supervision of patients is less effective than hospital care. Furthermore, home care as delivered to patients in this report increased the overall cost of care by as much as 30% because of longer and more frequent courses of antibiotic therapy.