Low Expression of Human Epithelial Sodium Channel in Airway Epithelium of Preterm Infants With Respiratory Distress
Bibliographic record
Abstract
OBJECTIVE: Active ion transport is critical to postnatal clearance of lung fluid. The importance of epithelial sodium channel (ENaC) in this clearance has been demonstrated in animal studies in which alpha-ENaC knockout mice died postnatally as a result of respiratory insufficiency. In animals, the expression of alpha-ENaC in respiratory epithelium is dependent on gestational age, but when assessed by in situ hybridization in the human (h), the mRNA is present from the earliest stages of pulmonary development. Therefore, the purpose of the present investigation was to quantify mRNA of the alpha-, beta-, and gamma-hENaC subunits of newborn preterm infants with respiratory distress and compare the gene expression data against those detected in healthy term infants. In addition, the effect of systemic dexamethasone therapy on the 3 hENaC subunits was studied in 4 preterm infants who received prolonged assisted ventilation. METHODS: The expression of subunits of hENaC was determined in samples taken from nasal respiratory epithelium of 7 healthy term infants (gestation age: 39.3 +/- 0.9 weeks [mean +/- standard deviation) and 5 preterm infants (gestational age: 27.2 +/- 0.9 weeks) with respiratory distress syndrome within 5 hours of birth. Betamethasone had been given to all mothers of preterm infants. In 4 additional preterm infants who still required assisted ventilation at 43 +/- 6 days postnatal age, the expression of alpha-hENaC was determined in samples taken before and during treatment with dexamethasone. RESULTS: Preterm infants with respiratory distress syndrome had low expression of all hENaC subunits relative to healthy term infants (alpha-hENaC: 5.38 +/- 2.01 [amol/fmol cytokeratin 18] vs 9.13 +/- 2.26; beta-hENaC: 2.44 +/- 1.43 vs 4.25 +/- 1.10; gamma-hENaC: 2.43 +/- 0.11 vs 6.81 +/- 3.24). Each of the 4 preterm infants who were treated with dexamethasone at approximately 1 month of age showed an increase in expression of alpha-hENaC and beta-hENaC subunit normalized to cytokeratin 18. CONCLUSION: All 3 subunits of the hENaC are low in preterm relative to full-term infants. alpha-hENaC mRNA in respiratory epithelium is increased by therapeutic doses of glucocorticosteroid. Low expression of alpha-hENaC in human respiratory epithelium may play a role in the pathogenesis of respiratory distress in preterm infants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".