Morphometric Analysis of the Lung in Prolonged Bronchopulmonary Dysplasia

Abstract

Summary Speculation MATERIALS AND METHODSSevere neonatal lung injury, with persistent oxygen dependency throughout infancy might result in inhibition or marked slowing of lung growth. Because development of conducting airways is completed early during intrauterine life and because most alveolar development takes place postnatally, one might expect disturbances in alveolar growth to overshadow residual airway injury in survivors of bronchopulmonary dysplasia.Morphometric analysis of the lungs and heart of a male infant who died at 33 months of age of bronchopulmonary dysplasia after prematurity and respiratory distress syndrome and its treatment is presented. Alveolar internal surface area was 8.4 m 2 compared to 15.3-27.8 for age-matched controls. The number of alveoli was 19 X 10 6 (123.3-172.5 X 10 6 for controls); however, the mean small airway diameter, 0.44 mm was normal, and small airway abnormalities were minimal. There was marked muscular hypertrophy of the right ventricle.The growth and development of the lungs follow a continuous course, beginning with conception and finishing when somatic growth ceases. Conducting airways are fully formed by the sixteenth wk of gestational age, whereas multiplication of alveoli continues throughout gestation, infancy, and early childhood (21).In the premature infants with mild hyaline membrane disease, pulmonary function tests after the first year of life seem to indicate that such infants subsequently progress toward normal lung development (4, II,19,23). On the other hand, little is known of the nature and degree of "catch-Up" lung growth during early childhood in premature infants who are survivors of severe respiratory distress syndrome and its sequel, bronchopulmonary dysplasia (BPO). In this group of older infants with BPO, pulmonary function studies during the first year of life (4, 19) have shown marked abnormalities, including hypoxemia, increased lung volume, maldistribution of ventilation, and increased airway resistance. These findings have been attributed mostly to the presence of interstitial edema (13, 22) and/or increased bronchiolar secretions (3, 18). Obliterative airway disease and simplified alveoli with interstitial fibrosis have been described in infants with BPO,(3,16,18), but, to our knowledge, quantitative anatomic studies have not been done. required continuous positive airway pressure (CPAP) with 100% oxygen mask-bag because of bradycardia and cyanosis. He was admitted to the intensive care nursery and had a gestational age of 31 wk by Oubowitz criteria (weight, 1500 g; length, 41 cm; and head circumference, 27.5 cm). Despite CPAP and 100% inspired oxygen the child developed immediate and severe respiratory distress with apneic spells. At 35 min of age he was intubated and mechanically ventilated with an inspired oxygen concentration (FI02) of 80% and positive end-expiratory pressure (PEEP) of 8 cm H20. The peak pressure remained between 40-50 cm of H 2 0 during the first wk; the oxygen requirement diminished rapidly to 60% at 12 hand 40% at...

Protection against Acute and Chronic Hyperoxic Inhibition of Neonatal Rat Lung Development with the 21-Aminosteroid Drug U74389F

“…We suggest this because: I ) very low birth weight premature infants may require elevated F102 therapy for periods of months; and, 2) this hyperoxic treatment is occurring at a time when the fetal lung should normally be entering its most rapid phase of lung development and surface-area expansion (with the normal formation of an estimated 40 x lo6 alveoli between 26 wk gestation and term) (45,46). In recent years, several morphometric studies of the lungs of human infants who died with chronic lung disease (bronchopulmonary dysplasia) have clearly illustrated much-enlarged terminal air spaces, markedly reduced total number of alveoli, and proportionately reduced lung internal surface area (47)(48)(49). These changes indeed appear quite similar to the findings of morphometric studies in the hyperoxiaexposed newborn animal.…”

“…These changes indeed appear quite similar to the findings of morphometric studies in the hyperoxiaexposed newborn animal. The recent pathologic study by Margraf et al (47) also demonstrates the reduced elastin fiber deposition and altered (frayed) appearance of the elastin fibers in the lungs from premature infants who died from chronic lung disease after long-term O2 treatment. The degree of inhibition of normal lung development in these 02-requiring infants with bronchopulmonary dysplasia is dramatic, with a total lung alveoli complement of only 20 to 40 x lo6 versus 60 to 200 x lo6 for agematched control infants and internal respiratory exchange surface areas totaling (1.0 m2 versus the normal values of 2 to 6 m2 (49).…”

Oxygen Toxicity in Neonatal Rats: The Effect of Endotoxin Treatment on Survival during and post-O2 Exposure

“…Several recent reports, including that by Sobonya, et a/. (43) would seem to support the contention (42-45) that inhibited alveolarization and reduced surface area for respiratory exchange can be a serious consequence of prolonged respiratory support for BPD.…”

Effects of Retinoic Acid on Airspace Development and Lung Collagen in Hyperoxia-Exposed Newborn Rats

“…Dexamethasone treatment resulted in fewer alveoli and a smaller gas-exchange surface area, similar to that seen in premature infants with BPD (11)(12)(13). In a subsequent study, Massaro and Massaro (14) demonstrated that the inhibition of alveolarization produced by dexamethasone treatment of newborn rats could be attenuated by the administration of retinoic acid.…”