Prediction Of Chronic Lung Disease Research Articles

The eNAMPT/TLR4 inflammatory cascade drives the severity of intra-amniotic inflammation in pregnancy and predicts infant outcomes.

Introduction: Intra-amniotic inflammation (IAI) or chorioamnionitis is a common complication of pregnancy producing significant maternal morbidity/mortality, premature birth and neonatal risk of chronic lung diseases such as bronchopulmonary dysplasia (BPD). We examined eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a critical inflammatory DAMP and TLR4 ligand, as a potential therapeutic target to reduce IAI severity and improve adverse fetal/neonatal outcomes. Methods: Blood/tissue samples were examined in: 1) women with histologically-proven chorioamnionitis, 2) very low birth weight (VLBW) neonates, and 3) a preclinical murine pregnancy model of IAI. Groups of pregnant IAI-exposed mice and pups were treated with an eNAMPT-neutralizing mAb. Results: Human placentas from women with histologically-proven chorioamnionitis exhibited dramatic NAMPT expression compared to placentas without chorioamnionitis. Increased NAMPT expression in whole blood from VLBW neonates (day 5) significantly predicted BPD development. Compared to untreated LPS-challenged murine dams (gestational day 15), pups born to eNAMPT mAb-treated dams (gestational days 15/16) exhibited a > 3-fold improved survival, reduced neonate lung eNAMPT/cytokine levels, and reduced development and severity of BPD and pulmonary hypertension (PH) following postnatal exposure to 100% hyperoxia days 1-14. Genome-wide gene expression studies of maternal uterine and neonatal cardiac tissues corroborated eNAMPT mAb-induced reductions in inflammatory pathway genes. Discussion: The eNAMPT/TLR4 inflammatory pathway is a highly druggable contributor to IAI pathobiology during pregnancy with the eNAMPT-neutralizing mAb a novel therapeutic strategy to decrease premature delivery and improve short- and long-term neonatal outcomes. eNAMPT blood expression is a potential biomarker for early prediction of chronic lung disease among premature neonates.

MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia

Background Our aim was to evaluate the prognostic value of magnetic resonance imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) as a marker for development of chronic lung disease (CLD) in fetuses with congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were measured and the individual FLV/FBV ratio was calculated in 132 fetuses. Diagnosis of CLD was established following prespecified criteria and graded into mild/moderate/severe if present. Logistic regression analysis was used to calculate the probability of postnatal development of CLD in dependence of the FLV/FBV ratio. Receiver operating characteristic curves were analysed by calculating the area under the curve to evaluate the prognostic accuracy of this marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD was significantly associated with thoracic herniation of liver parenchyma (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001) and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV to FBV is a highly valuable prenatal parameter for development of CLD. The ratio is helpful for early therapeutic decisions by estimating the probability to develop CLD. Perinatally, gestational age at delivery and ECMO requirement are useful additional parameters to further improve prediction of CLD.

Prediction of chronic lung disease, survival and need for ECMO therapy in infants with congenital diaphragmatic hernia: Additional value of fetal MRI measurements?

The lung-to-head ratio (LHR), measured by ultrasound, and the fetal lung volume (FLV), measured by MRI, are both used to predict survival and need for extra corporeal membrane oxygenation (ECMO) in infants with congenital diaphragmatic hernia (CDH). The aim of this study is to determine whether MRI measurements of the FLV, in addition to standard ultrasound measurements of the LHR, give better prediction of chronic lung disease, mortality by day 28 and need for ECMO. Patients with unilateral isolated CDH born between January 2002 and December 2008 were eligible for inclusion. LHR and FLV were expressed as observed-to-expected values (O/E LHR and O/E FLV). Univariate and multivariate analyses were performed. Receiver operating characteristic curves were constructed and areas under the curve (AUC) were calculated to determine predictive values. 90 patients were included in the analysis. Combined measurement of the O/E LHR and O/E FLV gave a slightly better prediction of chronic lung disease (AUC=0.83 and AUC=0.87) and need for ECMO therapy (AUC=0.77 and AUC=0.81) than standard ultrasound measurements of the O/E LHR alone. Combined measurement of the O/E LHR and O/E FLV did not improve prediction of early mortality (AUC=0.90) compared to measurement of the O/E LHR alone (AUC=0.89). An intrathoracal position of the liver was independently associated with a higher risk of early mortality (p<0.001), chronic lung disease (p=0.007) and need for ECMO therapy (p=0.001). Chronic lung disease and need for ECMO therapy are slightly better predicted by combined measurement of the O/E LHR and the O/E FLV. Early mortality is very well predicted by measurement of the O/E LHR alone. Clinical relevance of additional MRI measurements may be debated.

PP-111. Prediction of chronic lung disease by serum levels of “eosinophil derived neurotoxin—edn”, surface antigen of cells (cd9) and eosinophil count in preterm infants

Results: No significant correlations are observed between radiological aspects, time of surfactant administration and response. Response to surfactant was in good correlation with hemodynamic status. Cardiocirculatory failure in the first hours of life is present in 60% cases of negative response (p value 0.045). Positive response to surfactant is not associated with pulmonary hemorrhage and intraventricular hemorrhage gr.III–IV. Cerebral hemorrhage in non responsive patients associated with pulmonary hemorrhage. An increasing survival rate by 80% in premature infants with positive surfactant response has been observed. The aspect of hyaline membrane was not encountered in histopathological exam. Most frequent aspect encountered was of pulmonary hemorrhage.

The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease.

Matrix metalloproteinases (MMPs) -9 and -2 degrade type-IV collagen, a major constituent of lung basement membrane, and may have a role in the pathogenesis of neonatal chronic lung disease (CLD). We determined factors influencing MMP levels in neonatal bronchoalveolar lavage (BAL) fluid to establish whether an imbalance between MMP and its inhibitor could be implicated in CLD. We measured MMP-9 and -2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in 316 BAL fluid samples from 121 babies of gestational ages 23 to 42 wk over the first 14 d of life to determine effects of gestation and postnatal age. Median MMP-9, -2, TIMP-1 and MMP-9/TIMP-1 ratio in BAL were further studied in a subgroup of 85 babies <33 wk gestation to determine their ability to predict CLD and to establish effects of antenatal corticosteroid therapy (ANCS). MMP-9, -2 and TIMP levels did not vary with postnatal age over the first week. Median MMP-9 levels and MMP-9/TIMP-1 ratio increased with decreasing gestation in preterm babies. The MMP-9/TIMP-1 ratio was higher in babies who developed CLD, implying a proteinase/antiproteinase imbalance, but this association disappeared when controlled for gestational age. ANCS had no effect on BAL fluid MMP or TIMP levels. MMPs may have a role in the development of lung injury and fibrosis, but estimating their levels in the first week of life does not help with prediction of CLD.

Prediction of outcome from the chest radiograph appearance on day 7 of very prematurely born infants

Our aim was to determine whether the chest radiograph appearance at 7 days predicted chronic lung disease development (oxygen dependency at 36 weeks post-menstrual age) or death before discharge and if it was a better predictor than readily available clinical data. Two consecutive studies were performed. In both, chest radiographs taken at 7 days for clinical purposes were assessed using a scoring system for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation and data were collected regarding gestational age, birth weight, use of antenatal steroids and post-natal surfactant and requirement for ventilation at 7 days. Oxygenation indices were calculated in the first study (study A) at 120 h and in the second (study B) at 168 h. In study A, there were 59 infants with a median gestational age of 26 weeks (range 24 to 28 weeks) and in study B, 40 infants with a median gestational age of 27 weeks (range 25-31 weeks). In both studies, infants who developed chronic lung disease had a significantly higher total chest radiograph score, with a higher score for fibrosis/interstitial shadowing than the rest of the cohort. Infants who died before discharge differed significantly from the rest with regard to significantly higher scores for cysts. In both studies, the areas under the receiver operator characteristic curves with regard to prediction of chronic lung disease were higher for the total chest radiograph score compared to those for readily available clinical data. In infants who require a chest radiograph for clinical purposes at 7 days, the chest radiograph appearance can facilitate prediction of outcome of infants born very prematurely.

Early Respiratory System Mechanics and the Prediction of Chronic Lung Disease in Ventilated Preterm Neonates Requiring Surfactant Treatment

The objective of this study was to evaluate the predictive value of the respiratory system compliance (Crs) and resistance (Rrs) measured before surfactant therapy to identify infants at risk for chronic lung disease (CLD). Measurements of Crs and Rrs were obtained on 44 ventilated neonates with respiratory distress syndrome (RDS) before and after surfactant therapy using the passive expiratory flow-volume method. It was found that in addition to a lower gestational age (GA) and a lower birth weight (BW), infants with CLD (n = 10) exhibited a lower Pa/AO₂ [Pa/AO₂ = PaO₂/(PiO₂ – PaCO₂)] and higher Rrs before surfactant compared to the infants without CLD (n = 28). Improvement in gas exchange 18 h after surfactant was reduced in the CLD group. Finally, we concluded that a low GA (< 28 weeks), a low BW (< 942 g), a low Pa/AO₂ before and 18 h after surfactant or a high Rrs before surfactant (>0.21 cm H₂O/ml/s) were associated with an increased risk of CLD.

Early prediction of chronic lung disease by tracheal aspirate cytology in ventilated newborns.

We assessed the specificity of squamous metaplasia in tracheal aspirates of 69 ventilated newborns (gestational age 25-41 weeks) between days 3 and 7 of life for prediction of chronic lung disease (CLD). CLD was diagnosed when the patient was still requiring ventilation or supplementary oxygen at the postconceptional age of 36 weeks (or postnatal age of 28 days for babies born after 32 weeks gestation) and showed X-ray changes compatible with CLD. In the total population the presence of squamous metaplasia had a sensitivity of 59% and a specificity of 74% for the early diagnosis of CLD. The combination of squamous metaplasia and very low birth weight (VLBW) had a much higher specificity (94%), but a lower sensitivity (45%). Our results show that the presence of squamous metaplasia in VLBW babies during the 1st week of life predicts development of CLD with a specificity of 94% and may be helpful for entering patients into early treatment protocols or trials when a high risk population needs to be identified. As sensitivity of this approach is only 45%, further studies are needed to evaluate the predictive value of the combination of cytology with other markers in tracheal aspirate specimens. The presence of squamous metaplasia in tracheal aspirates of VLBW babies between days 3 and 7 of life is significantly associated with the development of chronic lung disease. Simple microscopic evaluation of fresh tracheal aspirates enables us to identify patients at high risk of CLD at a very early stage.

Doppler assessment of pulmonary artery pressure in neonates at risk of chronic lung disease

AIMTo evaluate the pulmonary artery pressure (PAP) change in very low birthweight (VLBW) infants at risk of chronic lung disease (CLD).METHODSThe time to peak velocity:right ventricular ejection time (TPV:RVET) ratio...

Sonographic prediction of chronic lung disease in the premature undergoing mechanical ventilation.

The aims of the study are to investigate the possible role of ultrasound (US) of the chest in predicting the development of chronic lung disease (CLD) in patients with hyaline membrane disease (HMD) and to determine the optimal age for the sonographic examination. One hundred and five consecutive prematures undergoing mechanical ventilation were prospectively studied by US of the chest. The US examinations were performed at birth and at least once a week until discharge from the neonatal unit. The sonographic patterns observed behind the diaphragm and their evolutions were recorded and correlated with the clinical and radiological data at day 28, which corresponds to the currently accepted limit for determining the presence of CLD. CLD is currently defined as oxygen dependency on day 28 with radiographic abnormalities. A diffuse retrodiaphragmatic hyperechogenicity was observed in all the patients with HMD. The hyperechogenicity resolved completely in patients with an uncomplicated clinical evolution. In contrast, in patients with CLD the hyperechogenicity resolved only partially, resulting in less diffuse and less extensive hyperechogenicity. Day 18 was the earliest day where the persistence of the abnormal retrodiaphragmatic hyperechogenicity was observed in 100% of the patients presenting CLD at day 28. At that time, 95.2% of the patients without abnormal hyperechogenicity showed uncomplicated evolution and no CLD. US can be a useful diagnostic tool to determine the occurrence of CLD and to predict as early as day 18 the prematures at risk for the disease.

Prediction of chronic lung disease from the chest radiograph appearance at seven days of age.

The aim of this study was to assess if the chest radiograph appearance at seven days of age could be used to predict chronic lung disease (oxygen dependency at 28 days of age). Sixty preterm infants (median gestational age 28 weeks), who were ventilated and/or had supplementary oxygen at seven days of age and had a chest radiograph performed at that postnatal age, were prospectively recruited. These chest radiographs were scored according to lung volume, presence of opacification, haziness, interstitial changes and cystic elements (maximum score 18). Twenty-eight infants subsequently developed chronic lung disease; their median chest radiograph score was 5.5 (range 2-14) which was significantly higher than that of the non-chronic lung disease infants (median 3; range 0-6). A chest radiograph score of 4 had a 71% sensitivity and 88% specificity in predicting chronic lung disease. We conclude that chest radiograph appearance at seven days of age is a sensitive and specific predictor of chronic lung disease and thus could be used to indicate the need for preventive therapy.

Early prediction of chronic lung disease by pulmonary function testing

Early prediction of chronic lung disease by pulmonary function testing