Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.
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PMID:Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. 882 73

Chronic lung disease (CLD) of prematurity is a common disorder in preterm infants who were ventilated for respiratory distress syndrome (RDS) at birth. Premature birth, mechanical ventilation and supplemental oxygen are the major risk factors for the development of CLD. Although the exact pathophysiology is unclear, recent evidence suggests that pulmonary inflammation may play a pivotal role in the development of CLD. Histologically, the evolution of CLD can be divided into an early inflammatory phase followed by a subacute and chronic fibroproliferative phase. The early, inflammatory phase of CLD is clinically indistinguishable from RDS. In bronchoalveolar lavage fluid an influx of inflammatory cells and increased levels of cytokines can be found. Pathological examination of the lungs reveals persisting hyaline membranes, necrosis of airway and alveolar epithelium and an influx of inflammatory cells in the lung. In the subacute fibroproliferative or reparative phase of CLD, persistent respiratory distress and hypercapnia are seen and patients require oxygen with or without ventilatory support. Histologically, this phase is characterized by hyperplasia of type II pneumocytes, hypertrophy of bronchial and bronchiolar smooth muscle and interstitial and perialveolar fibrosis. In the chronic fibroproliferative phase (up to 1 yr), airway remodelling occurs. Respiratory distress continues and many patients remain oxygen dependent. Cyanotic spells are frequently seen and chronic hypoxia may lead to pulmonary hypertension and right heart failure. Many patients have severe feeding problems and somatic growth is poor. In surviving patients, persisting lung function abnormalities are found. Airway resistance and airway responsiveness are increased and residual volume (RV) and RV/total lung capacity ratios remain elevated, indicating air trapping. Although lung function improves during childhood, residual abnormalities are still found in young adults, raising concerns about the evolution of pulmonary function in old age.
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PMID:Evolution and natural history of chronic lung disease of prematurity. 927 Feb 56

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age--16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose at which reactivity to methacholine (RO2meth) had occurred. In the CLD group, Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR.
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PMID:Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease. 963 36

Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance of Ureaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor kappaB (NF-kappaB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (> or =4 x 10(7) color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P<0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P<0.05) but was attenuated by budesonide and dexamethasone (10(-4) to 10(-6) M) (P<0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids. U. urealyticum antigen triggered NF-kappaB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response against U. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-kappaB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.
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PMID:Activation of nuclear factor kappaB and induction of inducible nitric oxide synthase by Ureaplasma urealyticum in macrophages. 1108 34

Chronic lung disease (CLD) of prematurity remains a substantial problem despite modern perinatal and neonatal care. CLD remains related to gestational age and lung immaturity, although it has become clear that severe initial lung disease is not a prerequisite for CLD to develop. Attempts to prevent CLD to date have not adequately addressed the multifactorial nature of the complex pathophysiology that leads to CLD. Thus, results have been modest at best. Prevention of CLD will require a multifaceted approach with specific interventions and care practices focused on different aspects of the pathway that leads to CLD. This review considers new information related to causation of CLD and the magnitude of the effect of prevention strategies tested to date. This article also advances the hypothesis that CLD is preventable with a global strategy of minimizing inciting events, optimizing management, and specific therapies aimed at intrinsic vulnerabilities.
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PMID:Strategies for prevention of neonatal chronic lung disease. 1115 5

Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in the development of CLD. Steroids have been shown to produce some improvement in neonates with this disease. The purpose of this study was to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the clinical benefit of steroids in babies. Our results showed that dexamethasone, budesonide and rIL-10 significantly inhibited both IL-6 and TNF-alpha production in the THP-1 cell line stimulated by lipopolysaccharide and Ureaplasma urealyticum antigen. Similar effects were found in macrophages from tracheobronchial aspirate fluid from newborn infants. In the rat alveolar macrophage cell line, steroids inhibited IL-6 and TNF-alpha production, while rat rIL-10 did not significantly decrease production. In conclusion, steroids and human rIL-10 were able to downregulate proinflammatory cytokine production, which may explain the beneficial effect of steroids and suggests that rIL-10 could be tried as an anti-inflammatory agent in neonates with a high risk of CLD.
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PMID:Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10. 1150 12

Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (>/=4 x 10(7) color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-alpha production was neutralized with an anti-TNF-alpha antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.
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PMID:Induction of human macrophage vascular endothelial growth factor and intercellular adhesion molecule-1 by Ureaplasma urealyticum and downregulation by steroids. 1211 37

Chronic lung disease (CLD) of prematurity remains a significant cause of morbidity among premature infants. It is a multifactorial disorder and characterized by an early increased number of neutrophils and alveolar macrophages, with later architectural epithelial and endothelial cell damage. Recently, apoptosis of type 2 pneumocytes in the lung of preterm neonates with acute and chronic lung disease has been examined and apoptosis of mesenchymal cells was detected in the chronic stage of bronchopulmonary dysplasia. Infection and inflammatory responses in the lungs play important roles. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated. We found that U. urealyticum induced apoptosis in human type II lung epithelial cells (A549 cell line) and macrophages (derived from human monocytic cell line THP-1) by measuring the outer leaflets translocation of phosphatidylserine (flow cytometry analysis and fluorescence microscopy assessment), DNA fragmentation analysis, cell morphology changes such as diminution in cell volume, increased cytoplasmic staining, and nuclear pyknosis (hematoxylin and eosin staining) and viable counting (trypan blue exclusion). Anti-TNF-alpha monoclonal antibody partially protected the macrophages from undergoing apoptosis after infection with U. urealyticum. Our findings imply that U. urealyticum might be involved in impairing lung structure and host immune response during the development of CLD.
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PMID:Ureaplasma urealyticum induces apoptosis in human lung epithelial cells and macrophages. 1237 67

Advances in obstetrical and neonatal care have increased the survival of very-low-birth-weight (VLBW) infants, defined as infants weighing < or = 1,500 g at birth, in many populations. To understand the morbidity and survival of VLBW infants in Taiwan, the records of all VLBW admitted to the 12 hospitals with a level II+ or level III neonatal intensive care unit (NICU), at < 7 days of age, from January 1 to December 31, 1996, were collected prospectively. A total of 613 VLBW infants (292 males and 301 females) met the enrollment criteria: 305 cases from the northern region, 181 cases from the central region, and 127 cases from the southern region of Taiwan. The mean birth weight was 1,133 g (range, 368-1,500); the mean gestational age (GA) was 28.9 weeks (range, 21-38). Among the VLBW infants, 25.8% were small-for-gestational-age, 90.2% were born to mothers with high-risk factor(s) for preterm delivery, 55% were born by cesarean section, and 68.1% required resuscitation at birth. The percentage of prenatal use of steroids was 52.9%, and < 20% received more than one dose of antenatal steroids. Thirty-three percent were born after antenatal maternal transfer, and the neonatal transfer rate was 23%. The most common neonatal complication was apnea of prematurity (66.1%), followed by respiratory distress syndrome (RDS) (60%). Chronic lung disease occurred in 76 cases (16.5%). The overall survival rate of the 613 VLBW infants was 76.2%; for infants weighing < or = 1000 g at birth, it was 49.2%, and for infants weighing 1,001-1,500 g at birth, it was 88.5%. The survival rate for infants with a GA < or = 26 weeks was 35.3%, and for infants with a GA of 27-36 weeks was 87.5%. No infant with a birth weight < or = 600 g or a GA < 23 weeks survived. The most common cause of death was sepsis, followed by extreme prematurity (GA < or = 23 wks) and RDS. Several perinatal and neonatal factors were related to the mortality. Multiple regression analysis of survival showed that GA < or = 26 weeks, birth weight < or = 800 g, delivery room resuscitation and the occurrence of pneumothorax were related to mortality. Therefore, although the survival rate of VLBW infants admitted to level II(+)-III NICUs showed an improvement over the rate for the previous 20 years in Taiwan, perinatal and neonatal care of extremely preterm infants and neonatal resuscitation programs need to be emphasized to improve the outcome of VLBW infants furthermore.
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PMID:The morbidity and survival of very-low-birth-weight infants in Taiwan. 1498 57

Chronic lung disease is the most common adverse outcome in survivors of prematurity. These infants experience frequent hospitalisation because of respiratory-related illness in their first year, as well as persistent cough, wheeze and oxygen dependence. Although the severity of respiratory illness decreases and supplemental oxygen is needed less as their lungs mature, childhood is still complicated by persistent wheeze, cough and reduced exercise tolerance in comparison with their peers. Although there is little longitudinal follow-up data beyond adolescence, imaging studies suggest that these infants are highly likely to suffer with respiratory problems akin to chronic obstructive pulmonary disease in later adulthood. The nature of their long-term respiratory problems, the impact of cigarette smoking and the effect on life expectancy are all unanswered questions that need addressing as these infants grow up.
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PMID:Some chronic obstructive pulmonary disease will originate in neonatal intensive care units. 1569 12


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