Immediate Postnatal Concentrations of Metalloproteinase-8 in the Tracheal Aspirates and the Development of Atypical Chronic Lung Disease of Prematurity

PURPOSE: Matrix metalloproteinase-8 (MMP-8) is an endoproteinase which degrades extracellular matrix and basement membrane. As early pulmonary inflammation is known to play a key role in the development of chronic lung disease (CLD), we tested the hypothesis that preterm infants who develop CLD have higher concentrations of MMP-8 in the tracheobronchial aspirates (TA) within 24 hours after birth than those who do not develop CLD. METHODS: A retrospective cohort study was done in 70 preterm infants delivered and admitted to the neonatal intensive care unit of Seoul National University Children's Hospital. TA MMP-8 concentrations were measured by ELISA. All patients were categorized into two groups according to the presence of respiratory distress syndrome (RDS). Multiple logistic regression analysis was done to assess the risk factors of CLD. RESULTS: CLD was diagnosed in 46 patients (65.7%). There were no statistically significant differences in the TA MMP-8 concentrations between CLD (+) and CLD (-)group among whole and RDS (+) groups. But in RDS (-)group, TA MMP-8 higher in CLD (+) group than in CLD (-)group. These differences persisted significantly after adjustments for the effects of gestational age at birth and histologic chorioamnionitis [P<0.050, Odds ratio: 4.720, 95% CI: 1.004-22.196]. The diagnostic indices of MMP-8 concentrations (cutoff, 7.94 ng/mL) as a predictor of development of CLD in RDS (-)group were: sensitivity of 82.4%, specificity of 77.8%, positive predictive value of 87.5%, and negative predictive value of 70.0%. CONCLUSION: There was a strong association between increased levels of TA MMP-8 and development of CLD in RDS (-)group. We propose that TA MMP-8 concentrations within 24 hours after birth may be a significant predictor of later development ofatypical CLD.

Clinical Characteristics of Premature Infants with Atypical Chronic Lung Disease

PURPOSE: To compare the incidence and clinical characteristics of infants with atypical CLD and those with classic BPD among premature infants less than 32 weeks' gestation. METHODS: Clinical data was collected retrospectively from the 256 premature infants less than 32 weeks' gestation and their mothers during 3-year study period. RESULTS: Among 212 preterm infants less than 32 weeks' gestation who survived to 28 days of life, 19 (9%) had atypical CLD and 38 (17.9%) had classic BPD. Atypical CLD infants were significantly heavier and more mature than classic BPD infants (mean birth weights, 1,100+/-294 g vs 915+/-225 g; and mean gestational age, 26.9+/-1.6 weeks vs 21.1+/-1.3 weeks). Duration of ventilator therapy and oxygen inhalation within 28 days of age were shorter in atypical CLD infants than in classic BPD infants (mean duration of ventilator therapy, 16.3+/-6.9 days vs 27+/-6.8 days; and mean duration of oxygen inhalation, 25.5+/-13.5 days vs 53.8+/-39 days). Oxygen dependency in atypical CLD infants showed bimodal pattern, decreasing gradually to 3-week after birth and upturning to peak at about 5-week after birth. Comparing the respiratory indices between classic BPD and aypical CLD, FiO2 at day 2,7, and 10, and oxygen index at day 2, and 10 were significant in classic BPD, but MAP were not. Considering the birth weight, MAP per birth weight, and modified oxygen index showed more apparent differencies between the two groups. CONCLUSION: 35.5% of total CLD were atypical CLD and showed bimodal pattern in oxygen dependency. Atypical CLD infants were significantly heavier and more mature than classic BPD infants.

Classification and Risk Factors for Chronic Lung Disease(CLD) of Prematurity: Classical CLD Versus Atypical CLD

PURPOSE: We tried to classify the different type of CLD and assess the risk factors for classical CLD and atypical CLD. METHODS: Retrospective cohort analysis was done in 120 preterm infants with birth weights less than 1,500 g who were admitted to NICU in Seoul National University Children's Hospital between Jan. 1993 and Dec. 1998 and survived more than 28 days of life. RESULTS: CLD occurred in 44 of all infants(37%). The total subjects were classified into severe respiratory distress syndrome(RDS) group, mild RDS group, and non-RDS group. Multivariative logistic regression analysis was done for the assessment of risk factors for CLD in each groups. The analysis revealed that in severe RDS group, the significant risk factors for CLD were short gestational duration[OR 3.1(per 1 week decrement), 95% CI 1.4-7.0], male sex(OR 11, 95% CI 1.0-121), and poor response to surfactant(initial poor response to surfactant or relapse of RDS after initial good response to surfactant, OR 15, 95% CI 1.3-168). In non-RDS group, the significant risk factors for CLD were male sex(OR 8.9, 95% CI 1.5-51), chorioamnionitis(OR 7.5, 95% CI 1.4-38), and high mean airway pressure during the first 72 hours of life[OR 2.1(per 1 cmH2O increment), 95% CI 1.3-3.3]. CONCLUSIONS: It could be suggested that the poor response to surfactant of RDS might be one of the etiologic factors of classical CLD which occurs following severe RDS, and chorioamnionits might be one of the etiologic factors of atypical CLD which occurs without a history of RDS. Therefore CLD might be an etiologically heterogeneous disease entity.