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Background: Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. Methods: Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. Results: The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. Conclusions: This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology. [ABSTRACT FROM AUTHOR]

Club cell 10-kDa protein (CC10) is a documented biomarker for airway obstructive diseases. Primarily produced by nonciliated club cells in the distal airway and in nasal epithelial cells, CC10 suppresses Th2 cell differentiation and Th2 cytokine production. In this study, we aimed to determine whether CC10 can also be used as an alternative biomarker for identifying Type 2 (T2) asthma. 74 patients with asthma, and 24 healthy controls were enrolled in the study. T2-high asthma was defined as elevation in two or more biomarkers, such as sputum eosinophilia ≥ 3%, high blood eosinophils ≥ 300/µL, or high FeNO ≥ 30 ppb. T2-low asthma was defined as no elevation in biomarkers. Enzyme-linked immunosorbent assay (ELISA) was used to assess the CC10 levels in plasma. The plasma CC10 level in patients with T2-high asthma was lower than that of patients with T2-low asthma and healthy controls (P < 0.05). To distinguish between T2-high and T2-low phenotype in patients with asthma, a receiver-operating characteristic (ROC) analysis was performed. It showed a sensitivity of 58.1% and specificity of 78.0% when using 22.74 ng/ml of plasma CC10. Correlation analysis indicated that the plasma CC10 level was inversely correlated with sputum eosinophil, blood eosinophil, and FeNO, and positively correlated with log PD20. However, no correlation with sputum neutrophil percentages, macrophage percentages, IgE, or lung function was found. Plasma CC10 is potentially useful in predicting T2-high and T2-low asthma. Lower plasma CC10 was associated with enhanced airway hyperresponsiveness, and Type 2 inflammation. [ABSTRACT FROM AUTHOR]

The proteins of the secretoglobin (SCGB) family are expressed by secretory tissues of barrier organs. They are embedded in immunoregulatory and anti‐inflammatory processes of airway diseases. This review particularly illustrates the immune regulation of SCGBs by cytokines and their implication in the pathophysiology of airway diseases. The biology of SCGBs is a complex topic of increasing importance, as they are highly abundant in the respiratory tract and can also be detected in malignant tissues and as elements of immune control. In addition, SCGBs react to cytokines, they are embedded in Th1 and Th2 immune responses, and they are expressed in a manner dependent on cell maturation. The big picture of the SCGB family identifies these factors as critical elements of innate immune control at the epithelial barriers and highlights their potential for diagnostic assessment of epithelial activity. Some members of the SCGB family have so far only been superficially examined, but have high potential for translational research. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA), an acute-phase protein whose level tracks infection and inflammation, is the precursor protein of amyloid A (AA) fibrils that is thought to cause AA amyloidosis in human and animals. SAA protein has several isoforms based on the difference of amino acid sequence, such as SAA1 to SAA4 in mice. AA fibrils are associated with chronic inflammation and are mainly originated from SAA1 produced in the liver. SAA3 reportedly contributes to the innate immune response in epithelia; however, little is known about its role at the lung epithelia. Therefore, we investigated SAA3 expression in the lung epithelium activated by bacterial antigens. The expressions of SAA3 and SAA1 mRNA were investigated using quantitative real-time PCR, in vitro using mouse Clara (Club) cells and ex vivo using surgically removed mouse lungs, after their stimulation by using either lipopolysaccharide (LPS), the major outer membranous antigen of gram-negative bacteria, or lipoteichoic acid (LTA), the major outer membranous antigen of gram-positive bacteria. In addition, SAA3 and SAA1/2 proteins in treated lung samples were detected by immunohistochemistry (IHC). SAA3 mRNA expression increased in cells and lungs treated with either LPS or LTA. SAA3 mRNA was more sensitively expressed in LPS than LTA treatment. In contrast, SAA1 mRNA expression did not increase by either LPS or LTA treatment. Furthermore, SAA3 mRNA expression increased in a dose-dependent manner in cells treated with tumor necrosis factor-alpha. By IHC, SAA3 protein was highly expressed in the luminal side of the bronchial epithelium, while SAA1/2 was not expressed. These results obtained from in vitro and ex vivo experiments suggest that SAA3 plays an important role in the innate immune response to bacterial infection in the lung epithelia. [ABSTRACT FROM AUTHOR]

Antioxidants improve semen parameters in terms of concentration and motility, thus we decided to study their efficacy in men with idiopathic infertility. We enrolled 37 men undergoing idiopathic male infertility. The first semen sample was collected at the time of enrollment in the study. From this 0.5 ml of the sample was for standard semen analysis, 1.2 ml of the sample was for the separation of seminal plasma to evaluate oxidative stress (OS) parameters such as malondialdehyde (MDA) and protein carbonyl (PC). A second sample was collected after 6 months of antioxidant treatment. Mean, standard deviation, the Pearson correlation, and paired student t-test were used for statistical analyses. After six months of treatment, the mean sperm concentration before treatment was 13.84, after treatment 20.38, mean ±SD =-6.54 ±5.35. The mean of sperm motility before treatment was 27.16, after treatment 34.05, mean ± SD = -6.89 ± 11.72. Concentration and motility were significantly increased after 6 months of treatment (p<0.001). The mean level of MDA before treatment was 5.172, mean after treatment 3.968, mean ± SD = 1.204 ± 2.26. This shows significantly lower values after six months of therapy with antioxidants (p<0.001). Another oxidative marker denoted as PC was also lower after the treatment, but was not statistically significant (p=0.0554). We suggest that Antioxidants should be used on a routine basis in cases of idiopathic male infertility. [ABSTRACT FROM AUTHOR]

Introduction. Bronchopulmonary dysplasia (BPD) is a respiratory disease that is characterized by long-term respiratory failure and mainly affects premature infants with low birth weight (LBW), undergoing mechanical ventilation (MV) or requiring long-term oxygen therapy. In Europe, among newborns with birth weight <1500g, the incidence of BPD is around 15%. Objective. The purpose of this review was to analyze the pathophysiological mechanisms involved in the development of BPD in premature newborns and to discuss the current possibilities of pharmacological prevention and treatment of BPD. Description of the state of knowledge. The BPD pathogenesis is multifactorial. Lung damage is the result of barotrauma and volutrauma due to high-performance MV, actions of reactive oxygen species (ROS) and infectious agents. Currently used methods of pharmacological treatment of severe forms of BPD are mainly based on systemic steroid therapy and can not be considered completely effective and free of side effects. Conclusion. Despite the widespread use of proper pharmacotherapy and dynamic development of new methods of respiratory therapy, mortality in BPD is estimated at around 10% - 20%. Infants with BPD are much more exposed to respiratory infections caused by respiratory syncytial virus (RSV), which may result in the development of bronchial hyperresponsiveness and bronchial asthma. Among children with BPD there are significantly higher cognitive and behavioral deficits compared to healthy children, and cerebral palsy is also significantly more common. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary dysplasia (BPD) is the second prevalent lung disease and one of the care challenges of premature newborns. Different risk factors play an important role in the development of this disease. Therefore, the aim of the present study was to investigate the relationship between colonization with Ureaplasma urealyticum and BPD. Methods: This prospective cohort study was conducted in 2017 in the neonatal intensive care unit of Alzahra Hospital in Tabriz, Iran. The samples included newborns weighing less than 1500 g with the gestational age of less than 32 weeks who required intubation within 72 h after birth. Following recording the initial information, the secretions within the trachea were aspirated and Ureaplasma urealyticum was detected in reference laboratory by polymerase chain reaction. Afterwards, we completed a follow-up of 28 days after birth for BPD. Results: Our findings demonstrated that out of 82 infants, 21 cases (26.3%) were excluded from the study due to discharge from hospital or death before the age of 28 days. Among the rest (61 newborns), three cases (4.3%) were shown to have secretions infected with Ureaplasma and 33 cases (54.1%) suffered from BPD. All the three newborns infected with Ureaplasma had BPD. However, no significant relationship was observed between Ureaplasma infection and BPD (P=0.24). According to the analysis of data, the most important factors contributing to BPD among the patients were the gestational age and birth weight. In other words, for one week increase in the age of pregnancy and for each 100 g increase in birth weight, the likelihood of BPD is reduced by 55% and 1%, respectively. In the present study, no relationship was found between Ureaplasma infection and BPD, which might be due to the low prevalence of this infection. Nonetheless, prematurity and low birth weight could be regarded as the two considerable risk factors for BPD. Conclusion: In order to perfectly determine the role of bacterial colonization within the trachea in BPD, collecting and analyzing various samples for the existence of other bacteria are recommended. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of antenatal betamethasone and/or postnatal dexamethasone administration on hyperoxic lung and brain injuries in newborn rats. Methods: Newborn Sprague-Dawley rats were divided into five experimental groups: normoxia-vehicle-vehicle group, hyperoxia-vehicle-vehicle group, hyperoxia-betamethasone-vehicle group, hyperoxia-vehicle-dexamethasone group, and hyperoxia-betamethasone-dexamethasone group according to (i) whether rats were exposed to normoxia or hyperoxia after birth to postnatal day (P) 14, (ii) whether antenatal betamethasone (0.2mg/kg) or vehicle was administered to pregnant rats at gestation days 19 and 20, and (iii) whether three tapering doses of dexamethasone (0.5, 0.3, 0.1mg/kg per day) or vehicle were administered on P5, 6 and 7, respectively. The lungs and brains were harvested for histological and biochemical analyses at P8 and P14. Results: Postnatal dexamethasone but not antenatal betamethasone significantly enhanced hyperoxia-induced reduction in body weight gain and alveolarization and increased lung terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells both at P8 and P14, transiently increased hyperoxia-induced reductions in brain weight gain and angiogenesis, and increase in brain TUNEL-positive cells at P8 but not at P14. Co-administration of antenatal betamethasone significantly enhanced dexamethasone-induced impairments in alveolarization both at P8 and P14, transient increases in lung and brain oxidative stresses, and increases in brain TUNEL-positive cells at P8 but not at P14. Conclusion: Although postnatal dexamethasone but not antenatal betamethasone alone significantly increased hyperoxic lung and brain injuries, co-administration of antenatal betamethasone significantly enhanced the detrimental effects of postnatal dexamethasone on hyperoxic lung and brain injuries in newborn rats. [ABSTRACT FROM AUTHOR]

Background: There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants.Methods: Urine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers.Results: Urinary cathepsin B was significantly higher in CF infants compared to healthy infants (p = 0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p = 0.002 & p = 0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p < 0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p = 0.046). BALF CCSP was negatively associated with IL-8 (p = 0.017). There was no correlation between biomarker concentration and FEV0.5.Conclusions: Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed. [ABSTRACT FROM AUTHOR]

Background. Pneumocystis pneumonia is a well-recognized lung disease of premature and malnourished babies. Even though serologic studies have shown that children are exposed to Pneumocystis jirovecii early in life, the epidemiology of human P. jirovecii infection and the host–microorganism relationship in infancy remain poorly understood. The aim of the present study was to investigate the prevalence of P. jirovecii colonization in preterm infants and its possible association with medical complications. Methods. A prospective observational study of preterm infants (birth weight <1500 g and/or gestational age <32 weeks) was carried out. Identification of P. jirovecii colonization was performed by means of molecular techniques in nasal aspirated samples at birth. Results. A total of 128 preterm infants were included during the study period. Pneumocystis DNA was identified in 25.7% (95% confidence interval [CI], 17.8%–33.7%) of newborns studied. A significant increase of respiratory distress syndrome in colonized group, even after adjusting for confounding factors (odds ratio, 2.7 [95% CI, 1.0–7.5]; P = .04), was observed. No differences were observed in other medical conditions between the 2 groups. Conclusions. Pneumocystis jirovecii colonization is frequent in preterm births and could be a risk factor to develop respiratory distress syndrome among preterm infants. [ABSTRACT FROM AUTHOR]

Background: The club cell 10-kDa protein (CC10) is a homeostatic protein that is produced in the lung, diffuses into the blood, and is then excreted into the urine and stool. CC10 is known to have anti-inflammatory properties and to have lower endogenous production in preterm infants. Objectives: As recombinant human CC10 (rhCC10) is being studied in preterm infants to reduce lung injury, understanding CC10 levels in term infants with normal lungs is needed to establish appropriate target dosing ranges. Methods: Serum, urine, and stool samples were collected from 24 healthy full-term infants, and CC10 levels were measured. Levels in term infants were then compared to those in preterm infants who were examined in our previous studies. Results: The mean gestational age and birth weight of the term infants were 38.8 ±1.1 weeks and 3,257 ± 513 g, respectively. The mean gestational age of the preterm infants was 26.8 ± 1.4 weeks. The median serum [CC10] levels with minimum and maximum values in term infants (214.2 ng/mL [34.1, 428.1]) were >7-fold higher than in preterm infants (27.5 ng/mL [8.0, 760.0]; p < 0.05). A significant correlation was found between [CC10] in urine and stool as well as between gestational age and stool [CC10] (p < 0.05). Conclusions: CC10 is detectable in serum, urine, and stool in healthy term infants, with levels significantly higher than in preterm infants. This provides important data for ongoing therapeutic intervention trials with rhCC10 in high-risk preterm infants. [ABSTRACT FROM AUTHOR]

Aim We determined whether the bacteria in the lower respiratory tract (LRT) in extremely premature infants with severe bronchopulmonary dysplasia (BPD) are different from those with nonsevere BPD. Study Design We conducted a retrospective study of extremely premature infants who were admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Japan between April 2005 and March 2014. We screened for the bacterial colonization of the LRT using tracheobronchial aspirate fluid. Results A total of 169 extremely premature infants were included. Overall, 102 did not experience severe BPD, whereas the remaining 67 experienced severe BPD. Corynebacterium species (Cs) were more frequently detected in the severe BPD than nonsevere BPD infants (p = 0.03). There were significant differences between infants with and without severe BPD in the duration of endotracheal ventilation (p = 0.00, odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), the duration of supplemental oxygen (p = 0.00, OR, 1.02; 95% CI, 1.01-1.03) before 36 weeks of postmenstrual age, and the frequency of sepsis after 7 postnatal days (p = 0.01, OR, 1.73; 95% CI, 1.18-2.54). Conclusion Cs are more likely to be present in the severe BPD infants with longer duration of endotracheal ventilation. [ABSTRACT FROM AUTHOR]

Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians. [ABSTRACT FROM AUTHOR]

Peiminine is the main biologically active component derived fromFritillaria ussuriensis. Peiminine was investigated in various pulmonary diseases, but its antiallergic effect and the related mechanism have not been reported yet. The present study aimed to evaluate the effect of peiminine on mast cell-mediated allergic inflammation in HMC-1 cells. The pro-inflammatory cytokine production was measured using ELISA, reverse transcription-polymerase chain reaction and nuclear factor-kappaB (NF-κB), mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Peiminine inhibits the production of the pro-inflammatory cytokine, such as interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and IL-1beta (IL-1β). It was shown to have inhibitory effects on MAPKs phosphorylation and NF-B expression in human mast cells (HMC)-1 using Western blot. HMC-1 cells were observed for confirmation of histamine release. Passive cutaneous anaphylaxis (PCA) reactions were evaluated using an animal model and peiminine demonstrated inhibitory effects on IgE-dependent anaphylaxis. These results suggest that peiminine has regulatory potential for allergic inflammatory reactions mediated by HMC-1 cells. [ABSTRACT FROM PUBLISHER]

New Findings What is the central question of this study? It is not known whether treatment with interleukin-10 (IL-10) attenuates hyperoxia-induced acute lung injury in mice., What is the main finding and its importance? Our results showed that exogenous IL-10 treatment alleviated hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases., Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin-10 (IL-10) in hyperoxia-induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL-10 simultaneously. In the second experiment, wild-type mice and IL-10−/− mice were exposed to room air or 95% O2. Exogenous IL-10 treatment attenuated hyperoxia-induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin-10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin-10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin-6, tumour necrosis factor-α and macrophage inflammatory protein 2, suppressed nuclear factor-κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin-10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL-10 aggravated hyperoxia-induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL-10. In conclusion, our results show that exogenous IL-10 treatment alleviates hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL-10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a life-threating condition with high morbidity and mortality. Inflammation is the main factor in the pathogenesis of ARDS. Therefore systemic corticosteroids are a rational therapeutic approach, but the effect of corticosteroids is still unclear. In this study, we looked at the effects of corticosteroids in ventilated sheep with ARDS, induced by lung lavage. Methods: We performed a prospective, randomised study in 64 ventilated sheep with ARDS, to evaluate the effect of corticosteroids and oxygen concentration on gas exchange and lung injury. Oxygenation index (OI) and ventilation efficacy index (VEI) were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and plasma and histology of the lung. Results: OI, VEI, lung inflammation, surfactant production, or lung histology was not influenced by corticosteroids. In the 100 % oxygen groups, OI was higher and total number of cells and disaturated phospholipids were lower in BALF. Conclusion: Our study showed that corticosteroids did not influence inflammation in early phase ARDS and that hyperoxia aggravated lung injury which could not be modulated by dexamethasone in early phase ARDS. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) pneumonitis may be severe, even lethal, following congenital infection or in premature infants with perinatal infection. Objective: To review the epidemiological, pathogenetic, clinical and therapeutic features of prenatal and perinatal CMV lung diseases. Methods: Evaluation of all published papers listed on PubMed describing CMV pneumonitis in infants. Results: CMV is frequent and severe in immunosuppressed infants but infrequent in full-term neonates and occurs more frequently after perinatal than after congenital infection, particularly in premature infants. In premature infants, CMV infection is often protracted and causes a diffuse interstitial pneumonitis leading to fibrosis and bronchopulmonary dysplasia (BPD). Congenital CMV infection should also be considered in newborns with severe acute respiratory distress syndrome and refractory respiratory failure with progression to early chronic lung disease. The association between breast milk-transmitted CMV and development of cystic lung disease and Wilson-Mikity syndrome has also been reported. Data on the efficacy of antiviral therapy for infants with respiratory CMV diseases are lacking and only anecdotal case reports are available. Conclusions: Persistent CMV infection appears to cause a diffuse necrotizing pneumonitis with fibrosis leading to BPD, in both immunocompromised or preterm infants and, less frequently in immunocompetent infants. The role of antiviral therapy remains to be elucidated. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) results in high morbidity and mortality among preterm neonates and efforts have therefore been devoted to both antenatal and postnatal prevention of the disease. ALI is the result of an inflammatory response which is triggered by a variety of different mechanisms. It mostly affects the fetal lung and, in particular, causes damage to the integrity of the lung's alveolar-capillary unit while weakening its cellular linings. Chemotactic activity and inflammatory products, such as proinflammatory cytokines TNF-α, IL-1, IL-6, IL-11, VEGF,TGF-α and TGF-β, provoke serious damage to the capillary endothelium and the alveolar epithelium, resulting in hyaline membrane formation and leakage of protein-rich edema fluid into the alveoli. Chorioamnionitis plays a major part in triggering fetal lung inflammation, while mechanical ventilation, the application of which is frequently necessary in preterm neonates, also causes ALI by inducing proinflammatory cytokines. Many different ventilation-strategies have been developed in order to reduce potential lung injury. Furthermore, tissue injury may occur as a result of injurious oxygen by-products (Reactive Oxygen Species, ROS), secondary to hyperoxia. Knowledge of the inflammatory pathways that connect intra-amniotic inflammation and ALI can lead to the formulation of novel interventional procedures. Future research should concentrate on the pathophysiology of ALI in preterm neonates and οn possible pharmaceutical interventions targeting prevention and/or resolution of ALI. [ABSTRACT FROM AUTHOR]

The response of the preterm and newborn lung to airborne pathogens, particles, and other insults is initially dependent on innate immune responses since adaptive responses may not fully mature and require weeks for sufficient responses to antigenic stimuli. Foreign material and microbial agents trigger soluble, cell surface, and cytoplasmic receptors that activate signaling cascades that invoke release of surfactant proteins, defensins, interferons, lactoferrin, oxidative products, and other innate immune substances that have antimicrobial activity, which can also influence adaptive responses. For viral infections such as respiratory syncytial virus (RSV), the pulmonary innate immune responses has an essential role in defense as there are no fully effective vaccines or therapies for RSV infections of humans and reinfections are common. Understanding the innate immune response by the preterm and newborn lung may lead to preventive strategies and more effective therapeutic regimens. [ABSTRACT FROM PUBLISHER]

Background: Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)--a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease. Objective: We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response. Methods: We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth. Results: Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD. Conclusions: Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS-induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD. [ABSTRACT FROM AUTHOR]

Background: Bisphenol A (BPA) exposure early in life results in organizational changes in reproductive organs, but the effect of BPA on conducting airway cellular maturation has not been studied. Late gestation is characterized by active differentiation of secretory cells in the lung epithelium. Objective: We evaluated the hypothesis that BPA exposure disrupts epithelial secretory cell development in the fetal conducting airway of the rhesus macaque. Methods: We exposed animals to BPA during either the second (early term) or the third (late term) trimester. There were four treatment groups: a) sham control early term, b) sham control late term, c) BPA early term (BPA-early), and d) BPA late term (BPA-late). Because cellular maturation occurs nonuniformly in the lung, we defined mRNA and protein expression by airway level using microdissection. Results: BPA exposure of the dam during late term significantly accelerated secretory cell maturation in the proximal airways of the fetus; both Clara cell secretory protein (CCSP) and MUC5AC/5B mRNA and protein expression increased. Conclusions: BPA exposure during late gestation accelerates secretory cell maturation in the proximal conducting airways. We identified a critical window of fetal susceptibility for BPA effects on lung epithelial cell maturation in the third trimester. This is of environmental health importance because increases in airway mucins are hallmarks of a number of childhood lung diseases that may be affected by BPA exposure. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS)-mediated endothelial activation contributes to lung inflammation and alveolar remodeling seen in premature infants with bronchopulmonary dysplasia (BPD). The mechanisms underlying LPS-mediated oxidative stress and proinflammatory signaling in human pulmonary microvascular endothelial cells (HPMEC) remain unclear. We hypothesized that NADPH oxidase (Nox) mediates LPS-induced endothelial activation in HPMEC by regulating phosphorylation of Toll-like receptor (TLR) pathway proteins. LPS-induced expression of intercellular adhesion molecule 1 (ICAM-1) was associated with increased 2-OH-E+ (marker for superoxide formation) levels and was attenuated by apocynin and the Nox inhibitor, VAS2870. LPS triggered membrane translocation of p67phox, suggesting activation of Nox2. Silencing Nox2, but not Nox4, suppressed LPS-induced ICAM-1 expression in HPMEC. Immunoprecipitation studies showed that inhibitor of κ-B kinase-β (IKK-β) serine phosphorylation induced by LPS was inhibited by Nox2 silencing. We examined whether Nox2-dependent, LPS-mediated IKK-β phosphorylation was regulated by protein phosphatase 2A (PP2A) or TGF-β associated kinase-1 (TAK1) in HPMEC. LPS increased PP2A activity in HPMEC, and inhibition of PP2A did not alter LPS-mediated ICAM-1 expression but attenuated IKK-β phosphorylation. TAK1 inhibition decreased LPS-induced ICAM-1 expression in HPMEC, and Nox2 silencing attenuated LPS-mediated TAK1 phosphorylation (Thr184/187). We demonstrate that Nox2 regulates LPS-mediated endothelial activation in pulmonary endothelial cells by modulating phosphorylation of key kinases in the TLR signaling cascade. Our data support a novel mechanism by which Nox-dependent signaling regulates proinflammatory signaling in pulmonary endothelial cells. Inhibition of vascular Nox may potentially limit lung injury and alveolar remodeling caused by infections in BPD. [ABSTRACT FROM AUTHOR]

Background: Ventilator–induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar–capillary barrier dysfunction in an established murine model of VILI. Methods: Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O (“lower” tidal volumes of ∼7.5 ml/kg; LVT) or 18 cmH2O (“higher” tidal volumes of ∼15 ml/kg; HVT). Dexamethasone was intravenously administered at the initiation of HVT–ventilation. Non–ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. Results: Particularly HVT–ventilation led to alveolar–capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro–inflammatory response in lungs of HVT–ventilated mice, without improving alveolar–capillary permeability, gas exchange and pulmonary edema formation. Conclusions: Dexamethasone treatment completely abolishes ventilator–induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar–capillary barrier dysfunction in an established murine model of VILI. [ABSTRACT FROM AUTHOR]

Purpose: Epidemic adenoviral keratoconjunctivitis can spread rapidly among preterm infants who frequently undergo ophthalmological examination. Here we present our experience on a nosocomial outbreak that affected 8 nursery staff members and 26 premature infants. We focus on the presentation and progress of the outbreak, the diagnosis of the disease and the measures taken for its control. Methods: Data were collected from patients' files and records of the infection control team. Conjunctival swabs were collected to perform direct fluorescent assay (DFA) and viral culture. Diagnosis was made according to clinical evidence and/or detection of the virus. Statistical analysis was performed using SPSS 15.0 statistical software. Results: Infection was introduced to our unit after a laser photocoagulation procedure of a 28-week gestational infant and circulated rapidly within the unit due to direct transmission through contaminated medical equipment, fomites and hands of nursery staff members. Neither the patients, nor the nursery staff members developed systemic symptoms. While DFA tests were positive in seven infants, culture positivity could be demonstrated in only three infants. Contact and droplet precautions were implemented with the recommendation of the infection control team. No recurrence occurred after definition of the last case on the 32nd day. Conclusion: Ophthalmologic procedures continue to be a potential source of adenovirus outbreaks. However, negligence of contact measures during routine daily nursing care seems to be a more important contributing factor for rapid spread. Strict adherence to appropriate aseptic procedures is required to prevent this potentially hazardous infection in preterm infants. [ABSTRACT FROM AUTHOR]

Aim: To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants. Methods: Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD. Results: Postnatal mean IGF-I levels at postnatal day (PND) 3-21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 μg/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (β)), PNDs 3-21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30-33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 μg/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3-21 were the most predictive risk factors associated with BPD (r2 = 0.634, p < 0.001). Conclusion: Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD. [ABSTRACT FROM AUTHOR]

Background: CCAAT/enhancer-binding protein (C/EBP)α is crucial for lung development and differentiation of the pulmonary epithelium. Conversely, no lung defects have been observed in C/EBPβ-deficient mice, although C/EBPβ trans-activate pulmonary genes by binding to virtually identical DNA-sequences as C/EBPα. Thus, the pulmonary phenotype of mice lacking C/EBPβ could be explained by functional replacement with C/EBPα. We investigated whether C/EBPα and C/EBPβ have overlapping functions in regulating lung epithelial differentiation during organogenesis. Epithelial differentiation was assessed in mice with a lung epithelial-specific ( SFTPC-Cre-mediated) deletion of C/EBPα ( CebpaΔLE), C/EBPβ ( CebpbΔLE), or both genes ( CebpaΔLE; CebpbΔLE). Results: Both CebpaΔLE mice and CebpaΔLE; CebpbΔLE mice demonstrated severe pulmonary immaturity compared to wild-type littermates, while no differences in lung histology or epithelial differentiation were observed in CebpbΔLE mice. In contrast to CebpaΔLE mice, CebpaΔLE; CebpbΔLE mice also displayed undifferentiated Clara cells with markedly impaired protein and mRNA expression of Clara cell secretory protein (SCGB1A1), compared to wild-type littermates. In addition, ectopic mucus-producing cells were observed in the conducting airways of CebpaΔLE; CebpbΔLE mice. Conclusions: Our findings demonstrate that C/EBPα and C/EBPβ play pivotal, and partly overlapping roles in determining airway epithelial differentiation, with possible implications for tissue regeneration in lung homeostasis and disease. Developmental Dynamics 241:911-923, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Clara cell secretory protein (CCSP) is an anti-inflammatory mediator, but its role in neonatal lung adaptation and diseases is uncertain. Objective: To characterize postnatal changes in serum CCSP in relation to gestation, respiratory disease (RDS) and bronchopulmonary dysplasia (BPD) in comparison with other anti-inflammatory cytokines (IL-4, -10 and -13). Methods: Blood was collected from 76 infants (26 of 23-29 weeks' gestation, 33 of 30-36 weeks' gestation and 17 term infants) at birth (preterm cord blood); on admission; at 12, 24 and 48 h; and on days 3-4 and 7 of life. CCSP was assayed by ELISA and cytokines by Bio-Plex. Results: Median serum CCSP in extremely and moderately preterm infants rose from a baseline of 13.6 and 15.9 to 33.4 ng/ml (p = 0.04) and 59.8 ng/ml (p = 0.03) at 12 h of age, respectively. CCSP levels were highest in term infants (80.7 ng/ml at 12 h). CCSP then decreased to 22.5 ng/ml on days 3-4 (p = 0.001). CCSP of 37 RDS infants fell to a lower baseline on days 4 and 7 than that of the 22 non-RDS preterms. The 8 infants who developed BPD had persistently low serum CCSP (12.7 ng/ml at 12 h). In contrast, early postnatal changes were not seen in IL-4, -10 and -13 levels, but low IL-10 and -13 levels were found on day 7 in BPD infants. Conclusions: Serum CCSP levels were characterized by an early postnatal surge. This apparent gestation-influenced surge may represent an initiation of a protective cascade against postnatal lung injury during extrauterine adaptation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Exacerbation of innate immune responses can contribute to development of acute lung injury. Multiple cell populations, including the bronchiolar epithelium, coordinate these inflammatory responses. Clara cells, non-ciliated epithelial cells, are located in the distal airways in humans and conducting airways in mice. These cells actively participate in innate immune responses but their precise contributions remain poorly defined. Methods: To test the hypothesis that E. coli lipopolysaccaride (LPS) treatment stimulates production of proinflammatory mediators in mouse transformed Clara cells (MTCC), MTCC were treated with E. coli lipopolysaccaride (LPS). Results: LPS increased COX-2 expression and stimulated production of prostaglandins, including prostaglandin E2 (PGE2). Enhanced mitogen activated protein kinase (MAPK) activation, nuclear factor-κB (NFκB) activation, and chemokine production were observed in MTCC in response to LPS treatment. Conclusions: While the role for Clara cells in the regulation of host defense and the progression of acute lung injury needs further characterization, our data suggests the importance of this unique cell population in the pathogenesis of LPS-induced acute lung injury. [ABSTRACT FROM AUTHOR]

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by morphological and immunohistochemical examination of intra-alveolar cells and alveolar macrophages in Clara cell-ablated mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg). The mice were then exposed to crystalline silica (Min-U-Sil-5, 97.1 ± 9.5 mg/m3, 6 hours/day, 5 days/week) for up to two weeks. The lungs were assessed by morphometry, as well as by immunohistochemistry of CD36, lectin-like oxygenated low-density lipoprotein receptor (LOX)-1, and matrix metalloproteinases (MMPs) -2, -9 and -12. There was a significantly greater number of intra-alveolar cells in Clara cell-ablated mouse groups than in wild-type mouse groups that were exposed to crystalline silica. A marked number of foamy alveolar macrophages were only detected in the Clara cell-ablated group exposed to crystalline silica, indicating that Clara cells inhibit infiltration and foam cell formation of alveolar macrophages. Immunohistochemical analysis indicated that foamy alveolar macrophages in the Clara cell-ablated group that inhaled crystalline silica overexpress CD36 and LOX-1, indicating upregulation of scavenger receptors of alveolar macrophages. These cells also express MMP-2, -9 and -12, suggesting increased gelatinolytic and elastolytic activities. Our findings suggest that Clara cells not only inhibit infiltration of alveolar macrophages but also their phagocytotic and gelatinolytic functions in silica-induced pulmonary injury. [ABSTRACT FROM AUTHOR]

Aim: To assess whether the levels of inflammatory and anti-inflammatory proteins in gastric fluid of premature infants shortly after birth are associated with the development of bronchopulmonary dysplasia (BPD). Methods: Gastric fluid retrieved within 1 h of birth of premature infants (gestational age <29 weeks) was analysed for interleukin (IL)-8, growth-related oncogene (Gro)-α, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IL-1β and Clara cell secretory protein with ELISA. Results: Of 51 enrolled infants, 86% had BPD. Of these, 54% had mild BPD, 30% had moderate BPD and 16% had severe BPD. Clinical chorioamnionitis was associated with high levels of IL-8, Gro-α, Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) and IL-1β in gastric fluid. Gastric fluid levels of IL-8, Gro-α, ENA-78 and IL-1β were higher in infants with moderate or severe BPD than in those with no or mild BPD. Ligation of the patent ductus arteriosus was associated with the development of moderate or severe BPD. These associations were no longer significant after adjustment for gestational age. Conclusion: The levels of inflammatory mediators in gastric fluid samples retrieved soon after birth from intubated or nonintubated infants can be used to assess the infants' perinatal exposure to inflammatory mediators and its association with neonatal outcome. [ABSTRACT FROM AUTHOR]

Adenoviruses (AdV) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal (GI) tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or encephalitis. Adenovirus infections are more common in young children, owing to lack of humoral immunity. Epidemics of AdV infections may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe, and dissemination is more likely in patients with impaired immunity (eg, organ transplant recipients, human immunodeficiency virus infection, congenital immunodeficiency syndromes). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue trophisms and correlate with clinical manifestations of infection. The predominant serotypes differ among countries or regions and change over time. Transmission of novel strains between countries or across continents and replacement of dominant serotypes by new strains may occur. Treatment of AdV infections is controversial because prospective, randomized therapeutic trials have not been done. Cidofovir is considered the drug of choice for severe AdV infections, but not all patients require treatment. Vaccines have been shown to be highly efficacious in reducing the risk of respiratory AdV infection but are currently not available. [ABSTRACT FROM AUTHOR]

Background: Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. Methods: A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. Results: Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection Conclusions: In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa. [ABSTRACT FROM AUTHOR]

The article offers information on the lung injury induced by lipopolysaccharide (LPS). It states that it remains one of one of the leading causes of morbidity and mortality in children. It mentions that the damage to membrane phospholipids leads to the collapse of the bronchial alveolar epithelial barrier during acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi-square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy-one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4-5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty-seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus-positive placentas compared to preterm adenovirus-negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus-positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth. J. Med. Virol. 82:1379-1383, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ~95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed > 10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for ~4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of ~3% of probed genes by ≥ 1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (≥ 10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells. [ABSTRACT FROM AUTHOR]

To date there are no licensed systemic or topical treatments in Europe or the USA for adenovirus infections. In the present paper, we evaluate the effect of a polyphenol-based grape extract (NE) obtained from Portuguese white-winemaking by-products, and Resveratrol in pure form, on adenovirus type 5 infection. For this purpose, recombinant adenovirus vectors (Ad-5) and a human-derived cell line (293) were used as models. The NE and Resveratrol at the used concentrations do not induce cell cytotoxicity or direct virucidal activity; however, they reduce 4.5 and 6.5 log (TCID50/ml) on total infectious Ad-5 production, respectively. The capacity of Ad-5 replication upon removal of NE and Resveratrol after 24 h post infection was also evaluated. In contrast to Resveratrol, the highest evaluated NE concentration inhibits irreversibly the Ad-5 replication. These results provide useful information for the use of NE and Resveratrol as potential sources of promising natural antiviral agents on Ad-5 infection. [ABSTRACT FROM AUTHOR]

Objective:To investigate the association between leukocytosis, mortality and bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants (VLBW) born to mothers with histological chorioamnionitis.Study Design:A retrospective cohort study from a single level 3 neonatal intensive care unit. The study sample included infants born to mothers with histological chorioamnionitis (n=252). Total white blood cells (WBCs) after birth were measured. Leukocytosis was defined as a total WBC count >30 000 per mm3 in the first 2 days of life. Outcomes investigated included BPD and death. Both unadjusted and multivariable analyses were carried out.Result:After controlling for potential confounding variables, infants who developed a leukocytosis after birth had increased odds of BPD (4.6, 95% confidence interval (95% CI): 2.0 to 10.3), but decreased odds of death (0.3, 95% CI: 0.1 to 0.90).Conclusion:In our population of VLBW infants born to mothers with histological chorioamnionitis, leukocytosis after birth is associated with a decrease in mortality but an increase in BPD. [ABSTRACT FROM AUTHOR]

Background: Clara cell 10-kDa protein (CC10) is a multifunction protein with anti-inflammatory and immunomodulatory effects; hence we compared the CC10 expression between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NPs), analyzed its association with disease severity and response to surgery, and explored its regulation via cytokines. Methods: The plasma and tissue CC10 levels were compared between controls and CRS patients with and without NPs by means of quantitative RT-PCR, ELISA, and immunohistochemistry. Computed tomography (CT) scan and endoscopy findings and symptoms were scored. Nasal explant culture was used to explore the effect of TNF-α, IL-1β, IL-4, INF-γ, and IL-10 on CC10 gene regulation. Results: Compared with controls, the CC10 expression in sinonasal mucosa was significantly inhibited in both CRS patients with and without NPs. There was a significant further decrease of CC10 expression in patients with NPs and asthma. No difference in CC10 plasma levels was found between controls and patients. CC10 levels inversely correlated with preoperative CT scores, and postoperative endoscopy and symptom scores. TNF-α, IL-1β and IL-4 inhibited, whereas INF-γ and IL-10 promoted CC10 production in nasal mucosa. A significantly faster decay of CC10 transcripts was seen after IL-1β treatment. IL-1β and IL-10 induced thyroid transcription factor-1 expression. INF-γ increased, whereas IL-4 inhibited hepatocyte nuclear factor-3α expression. Conclusion: CC10 may take part in the pathogenesis of CRS and correlates with disease severity and response to surgery. Different cytokines can regulate CC10 expression in nasal mucosa differentially through modulating mRNA stability and certain transcriptional factors expression. [ABSTRACT FROM AUTHOR]

Background Associations between Clara cell secretory protein gene variants ( SCGB1A1, also known as CC16, CC10, CCSP and uteroglobin) and the asthma phenotype have been found in five out of eight studies world-wide. No study has investigated the contribution of SCGB1A1 polymorphisms to the development and/or persistence of the asthma phenotype in a birth cohort followed over time. Objective The aim of this study was to determine the role of the SCGB1A1 gene in the development of the asthma phenotype. Methods The Perth Infant Asthma Follow-up (PIAF) cohort ( n=231 unrelated infants, unselected for asthma and recruited at birth) were seen at 1 month, 6 and 11 years of age, and had a questionnaire, lung function, airway responsiveness (AR) and skin prick tests (SPTs) completed. Blood was taken at 6 and 11 years for total and specific immunoglobulin E (sIgE) and DNA extraction. SPT positivity had at least one positive SPT. SIgE>4 kU/L had at least one sIgE above 4 kU/L. SCGB1A1 A38G (rs3741240), that alters gene transcription, was genotyped using Sau96I restriction digestion of exon 1 PCR products. Results At 6 and 11 years of age, 33.0% and 29.7% of those genotyped had doctor-diagnosed asthma, and 35.8% and 52.1% had SPT positivity. In cross-sectional analyses, children with 38G/38A or 38A/38A had increased AR at 1 month (1.72-fold, P=0.013); sIgE>4 kU/L [odds ratio (OR)=6.95, 95% confidence interval (CI)=1.35–35.91, P=0.021]; house dust mite (HDM) SPT positivity (OR=7.21, 95% CI=1.09–47.78, P=0.041) and sIgE (4.57-fold, P=0.045) at 6 years; and doctor-diagnosed asthma (OR=3.93, 95% CI=1.24–12.47, P=0.02) and cat SPT positivity (OR=4.34, 95% CI=1.01–18.77, P=0.049) at 11 years. Longitudinal analyses of 6 and 11 years paired data showed that children with 38A/38A had increased persistent sIgE>4 kU/L (OR=11.87, 95% CI=1.97–71.53, P=0.007) and persistent HDM SPT positivity (OR=7.84, 95% CI=1.04–58.92, P=0.045). Conclusion SCGB1A1 A38G may play a role in the development and persistence of the asthma phenotype in childhood. [ABSTRACT FROM AUTHOR]

Infant respiratory distress syndrome (IRDS) can lead to impaired alveolarization and dysmorphic vascularization of bronchopulmonary dysplasia. Clara cell secretory protein (CC10) has anti-inflammatory properties but is deficient in the premature infant. Because surfactant and vascular endothelial growth factor (VEGF) profiles are impaired by inflammation and CC10 inhibits lung inflammation, we hypothesized that CC10 may up-regulate surfactant protein (SP) and VEGF expression. Preterm lambs ( N?=?24; 126???3 days [standard error] gestation) with IRDS were randomized to receive 100 mg/kg surfactant, 100 mg/kg surfactant followed by intratracheal 0.5, 1.5, or 5 mg/kg rhCC10 and studied for 4 hours. Gas exchange and lung mechanics were monitored; surfactant protein and VEGF mRNA profiles in lung were assessed. There was a significant rhCC10 dose-dependent increase in respiratory compliance and ventilation efficiency index; both parameters were significantly greater in animals treated with 5 mg/kg rhCC10 than those treated with surfactant alone. Similarly, there was a significant rhCC10 dose and protein-dependent increase in surfactant protein (SP-B >?SP-C >?SP-A) and dose- and isoform-dependent increase in VEGF (VEGF189 >?VEGF165 >?VEGF121). These data demonstrate that early intervention with rhCC10 up-regulates surfactant protein and VEGF expression, supporting the role of CC10 to protect against hyperoxia and mechanical ventilation in the immature lung. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is the most common, serious sequela of premature birth. Inflammation is a major contributor to the pathogenesis of BPD. Often initiated by a pulmonary fetal inflammatory response, lung inflammation is exacerbated by mechanical ventilation and exposure to supplemental oxygen. In response to these initiators of injury, a complex interaction occurs between proteins that attract inflammatory cells (ie, chemokines), proteins that facilitate the transendothelial migration of inflammatory cells from blood vessels lie, adhesion molecules), proteins that promote tissue damage lie, pro-inflammatory cytokines and proteases), and proteins that modulate the process leg, anti-inflammatory cytokines, binding proteins and receptor antagonists). In addition, during recovery from inflammatory injury, growth factors and other substances that control normal lung growth and mediate repair influence subsequent lung structure. In this review, we discuss the role of each aspect of the inflammatory process in the development of BPD. This discussion will include data from measurements of biomarkers in samples of fluid aspirated from the airways of human infants relevant to each phase of inflammation. Despite their limitations, these measurements provide some insight into the role of inflammation in the development of BPD and may be useful in identifying infants at risk for the disease. [ABSTRACT FROM AUTHOR]