PEDIATRICS Vol. 106 No. 6 December 2000, pp. 1452-1459
Lung Elastic Tissue Maturation and Perturbations During the Evolution of Chronic Lung Disease
Received Dec 8, 1999; accepted Apr 14, 2000.
,, and
From the * Department of Pediatrics, Children's Mercy Hospital;
and the University of Missouri-Kansas City School of Medicine,
Kansas City, Missouri.
Background. Infants <30 weeks' gestation have difficulty maintaining adequate functional residual capacity after the first week of life without positive end-expiratory pressure. We hypothesized that this is caused, in part, by increased lung elastic recoil. Our aims were to quantitate parenchymal elastic tissue during normal fetal development and in infants born at 23 to 30 weeks' gestation with prolonged survival at risk for chronic lung disease (CLD).
Methods. The controls were 22 to 42 weeks' gestation (n = 71), received ventilator care, and died within 48 hours of birth, plus 7 term infants who died at 43 to 50 weeks' postconceptional age from nonpulmonary causes. Infants who were 23 to 30 weeks' gestation, at risk for CLD, and who lived 5 to 59 days (n = 44), were separated into groups based on respiratory score (SCORE; The integrated area under the curve of the average daily fraction of inspired oxygen × mean airway pressure (cm H2O) over the number of days lived). The SCORE groups, <20, 21 to 69 and 70 to 200, related clinically to mild to severe lung disease. The lungs were tracheally perfused and formalin-fixed and total lung volume (TLV) was measured by water displacement. The paraffin-embedded lung blocks were stained with Miller's elastic stain. The parenchyma and parenchymal elastic tissue were point-counted. The absolute elastic tissue was calculated by multiplying TLV by the parenchymal and elastic fractions. Septal width, alveoli and alveolar duct diameters, and internal surface area (ISA) were also measured.
Results. In the controls, the volume density of
parenchymal elastic tissue and absolute quantity of elastic tissue
increased progressively from 22 to 50 weeks. In infants with CLD and
SCORE 
20, the volume density and absolute quantity of elastic tissue
increased significantly. Mean absolute elastic tissue in the 20 to 69 group was 0.76 ± 0.20 cm3 greater than in the <20
group (0.46 ± 0.10 cm3) who were similar to the
controls, and the 70 to 200 group was 1.32 ± 0.56 cm3
greater than the 20 to 69 group. Elastic tissue for infants at risk for
CLD, as a percent of predicted for same-age controls, rose linearly
with increasing SCORE (r = 0.73;
r2 = 0.55). Control TLV and ISA were
linearly related to age. Thirty-nine of the 44 CLD-risk infants had
TLVs greater than controls. However, 77% with SCORE 20 to 200 had ISAs
less than or equal to the control 95% confidence interval. Control
septal width decreased sharply from 23 to 30 weeks, then gradually
decreased to term. All infants with SCORE 70 to 200 and 80% of those
with SCORE 20 to 69 had widths more than the control 95% confidence
interval. Control alveolar and duct diameters doubled from 23 to 50 weeks and were significantly greater in infants with SCORES 20 to 200.
Discussion. Lung elastic tissue maturation is tightly
controlled during fetal development. With increasing SCORE, elastic
tissue increased >200%, accounting, in part, for the positive
end-expiratory pressure needed to maintain end-expiratory lung volume
in infants at risk for CLD. Saccule and duct diameters more than
doubled, and septa thickened significantly in CLD. We propose the
following sequence to be operative in CLD: at birth, the preterm infant
(
30 weeks) has inadequate elastic tissue and elastic recoil, but high
surface tension recoil. After surfactant treatment, surface tension
recoil markedly decreases, permitting the saccules and ducts, with very low elastic recoil, to be overstretched by volutrauma. The damaged lung
responds with elastosis, distorted acinar growth, cellular influx, and
upregulation of inflammatory and reparative proteins. This hypothesis
can be summarized by the following terms: lung immaturity,
inflammation, volutrauma, and elastic tissue
alterations.
Key words:
lung elastic tissue,
chronic lung disease.
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