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Sample records for model maternal asthma

  1. Development of an experimental model of maternal allergic asthma during pregnancy.

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    Clifton, Vicki L; Moss, Timothy J M; Wooldridge, Amy L; Gatford, Kathryn L; Liravi, Bahar; Kim, Dasom; Muhlhausler, Beverly S; Morrison, Janna L; Davies, Andrew; De Matteo, Robert; Wallace, Megan J; Bischof, Robert J

    2016-03-01

    Maternal asthma during pregnancy adversely affects pregnancy outcomes but identification of the cause/s, and the ability to evaluate interventions, is limited by the lack of an appropriate animal model. We therefore aimed to characterise maternal lung and cardiovascular responses and fetal-placental growth and lung surfactant levels in a sheep model of allergic asthma. Immune and airway functions were studied in singleton-bearing ewes, either sensitised before pregnancy to house dust mite (HDM, allergic, n = 7) or non-allergic (control, n = 5), and subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Maternal lung, fetal and placental phenotypes were characterised at 140 ± 1 days gestational age (term, ∼147 days). The eosinophil influx into lungs was greater after HDM challenge in allergic ewes than after saline challenge in control ewes before mating and in late gestation. Airway resistance increased throughout pregnancy in allergic but not control ewes, consistent with increased airway smooth muscle in allergic ewes. Maternal allergic asthma decreased relative fetal weight (-12%) and altered placental phenotype to a more mature form. Expression of surfactant protein B mRNA was 48% lower in fetuses from allergic ewes than controls, with a similar trend for surfactant protein D. Thus, allergic asthma in pregnant sheep modifies placental phenotype, and inhibits fetal growth and lung development consistent with observations from human pregnancies. Preconceptional allergen sensitisation and repeated airway challenges in pregnant sheep therefore provides an animal model to identify mechanisms of altered fetal development and adverse pregnancy outcomes caused by maternal asthma in pregnancy.

  2. Can prenatal maternal stress increase the risk of asthma?

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    Heinrich, Joachim

    2015-08-01

    Maternal stress adversely affects a mother's well-being and health and also negatively impacts her offspring. That this relationship also holds true for maternal stress during the pregnancy period is intuitive. However, whether maternal stress increases the risk of asthma development in her offspring is less clear and will be evaluated in this review. There is evidence from murine models to suggest that maternal stress during pregnancy increases the risk of asthma in the offspring. While recent experimental research adds to the increasing body of evidence supporting a causal relationship between prenatal maternal stress and asthma risk in the offspring, the epidemiological evidence supporting this notion is insufficient. Almost all existing observational studies suffer from severe methodological limitations. Nevertheless, the results from experimental work on maternal stress during pregnancy and asthma risk in the offspring, in concert with other obvious adverse health effects in the offspring are sufficient to justify a recommendation to reduce maternal stressors, particularly during pregnancy.

  3. Maternal infection in pregnancy and risk of asthma in offspring.

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    Collier, Charlene H; Risnes, Kari; Norwitz, Errol R; Bracken, Michael B; Illuzzi, Jessica L

    2013-12-01

    This study estimates the effect of maternal infections during pregnancy on childhood asthma. One-thousand four-hundred and twenty-eight pregnant women were prospectively followed using structured interviews and chart review until their child's 6th year of life. Infections were identified from outpatient and hospital visits. Childhood asthma was defined as physician diagnosis with symptoms at age six. Adjusted odds ratios were calculated from multivariable logistic regression models. Six-hundred and thirty-five women experienced an infection during pregnancy. Among antepartum infections, maternal urinary tract infections were significantly associated with childhood asthma (aOR 1.60, 95 % CI 1.12-2.29). Chorioamnionitis and maternal group beta streptococcus colonization were not significantly associated with an increased risk in childhood asthma. This study found an increased risk of asthma in children of women diagnosed with urinary tract infections during pregnancy, while other maternal infections did not increase the risk.

  4. Maternal allergic contact dermatitis causes increased asthma risk in offspring

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    Kobzik Lester

    2007-07-01

    Full Text Available Abstract Background Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. Methods BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice. Results Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease. Conclusion Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate can result in the maternal transmission of asthma risk in mice.

  5. Maternal complications and the management of asthma in pregnancy.

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    Vanders, Rebecca L; Murphy, Vanessa E

    2015-03-01

    Pregnancy is a unique state requiring alterations in maternal physiology to accommodate the growing fetus. Whilst the maternal immune system is normally well adept at performing this task, the presence of immune disorders, such as asthma, often lead to pregnancy-related complications affecting both mother and baby. Australia has a high prevalence of asthma; with approximately 12% of pregnant women reported to have current asthma. Poor control of asthma is of far greater risk than the use of asthma medications. Being able to identify complications associated with asthma during pregnancy is of great importance in providing appropriate asthma management and medical care to these pregnant women, which may have lifelong consequences for their offspring.

  6. Maternal smoking in pregnancy and asthma in preschool children

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    Neuman, Åsa; Hohmann, Cynthia; Orsini, Nicola;

    2012-01-01

    Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate the effects of prenatal from postnatal exposure....

  7. Maternal fish consumption during pregnancy and risk of early childhood asthma.

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    Salam, Muhammad T; Li, Yu-Fen; Langholz, Bryan; Gilliland, Frank D

    2005-01-01

    Maternal fish consumption during pregnancy may affect children's asthma risk by modulating early-life immune development. Type of fish intake may be important because of differences in fatty acid content. To test this hypothesis, we conducted a nested case-control study, selecting subjects from the Children's Health Study, a population-based study of school-aged children in southern California. Cases had physician-diagnosed asthma and controls were asthma-free by age 5 years. Mothers or guardians provided information on fish consumption during pregnancy in telephone interviews. We computed odds ratio (OR) and 95% confidence interval (CI) by using conditional logistic regression models that accounted for the sampling. In children born to mothers with a history of asthma, the OR of asthma was 0.20 (95% CI = 0.06-0.65) when mothers ate oily fish at least monthly during pregnancy compared with no consumption (p(trend) = 0.006). Maternal oily fish consumption during pregnancy did not benefit children of non-asthmatic mothers. In contrast, fish stick (a source of trans-fats) consumption during pregnancy increased asthma risk in children (OR = 2.04; 95% CI = 1.18-3.51). Our results suggest that maternal oily fish intake during pregnancy may protect offspring from asthma; however, eating fish sticks during pregnancy may increase asthma risk in children.

  8. Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy.

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    Hodyl, Nicolette A; Stark, Michael J; Scheil, Wendy; Grzeskowiak, Luke E; Clifton, Vicki L

    2014-03-01

    Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999-2008; n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios. Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose-response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone. Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.

  9. Maternal propensity for infections and risk of childhood asthma

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    Stokholm, Jakob; Sevelsted, Astrid; Bønnelykke, Klaus;

    2014-01-01

    BACKGROUND: Maternal use of antibiotics during pregnancy has been associated with the development of asthmatic disorders in the offspring. The human microbiome has been suggested to act as an intermediary in this process. To provide clarification on this theory, we studied the temporal relation...... between maternal use of antibiotics and the risk of childhood asthma. METHODS: According to national registries, during the observation period (1997-2010), 910,301 children were born in Denmark and were included in the analysis. From these registries, data for cases of childhood asthma were obtained based...... on hospital admissions, outpatient attendance at a hospital, or use of inhaled corticosteroids. The effect of timing of maternal antibiotic use on the risk of asthma in the offspring was studied by analysis of maternal antibiotic use in the 80 weeks before pregnancy, during pregnancy, and the 80 weeks after...

  10. Maternal bereavement and childhood asthma-analyses in two large samples of Swedish children.

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    Fang Fang

    Full Text Available BACKGROUND: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426,334 and 7-12 (n = 493,813 years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1-4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22 as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24. No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02 and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25. The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant. CONCLUSIONS/SIGNIFICANCE: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.

  11. The Maternal Diet, Gut Bacteria, and Bacterial Metabolites during Pregnancy Influence Offspring Asthma

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    Gray, Lawrence E. K.; O’Hely, Martin; Ranganathan, Sarath; Sly, Peter David; Vuillermin, Peter

    2017-01-01

    This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse models indicates an association between increased maternal dietary MACs, SCFA exposure during pregnancy, and reduced offspring asthma that is, at least in part, mediated by the induction of regulatory T lymphocytes in the fetal lung. Part 4 discusses considerations for future studies investigating maternal diet-by-microbiome determinants of offspring asthma including the challenge of measuring dietary MAC intake; limitations of the existing measures of the gut microbiome composition and metabolic activity; measures of SCFA exposure; and the complexities of childhood respiratory health assessment. PMID:28408909

  12. Maternal smoking in pregnancy and its influence on childhood asthma

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    Angela Zacharasiewicz

    2016-07-01

    Full Text Available Maternal smoking in pregnancy (MSP is a large modifiable risk factor for pregnancy related mortality and morbidity and also the most important known modifiable risk factor for asthma. This review summarises the effects of MSP throughout infancy, childhood and adolescence with regards to asthma (development and severity. Firstly, the direct damage caused by nicotine on fetal lung development, fetal growth and neuronal differentiation is discussed, as well as the indirect effects of nicotine on placental functioning. Secondly, the effects of MSP on later immune functioning resulting in increased infection rate are summarised and details are given on the effects of MSP modulating airway hyperreactivity, reducing lung function and therefore increasing asthma morbidity. Furthermore, epigenetic effects are increasingly being recognised. These can also result in transgenerational detrimental effects induced by cigarette smoke. In summary, the causal relationship between MSP and asthma development is well documented and presents a major health problem for generations to come. The high prevalence of MSP is alarming and epigenetic effects of nicotine on immune functioning potentiate this danger. A considerable part of the increase in asthma prevalence worldwide is due to MSP.

  13. Maternal vitamin D and E intakes during pregnancy are associated with asthma in children.

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    Allan, Keith M; Prabhu, Nanda; Craig, Leone C A; McNeill, Geraldine; Kirby, Bradley; McLay, James; Helms, Peter J; Ayres, Jon G; Seaton, Anthony; Turner, Stephen W; Devereux, Graham

    2015-04-01

    Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74-0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81-1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31-0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81-0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications. Copyright ©ERS 2015.

  14. The observed association between maternal anxiety and adolescent asthma: children of twin design suggest familial effects.

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    Ida Havland

    Full Text Available BACKGROUND: Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear. OBJECTIVE: To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors. METHOD: From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI and Karolinska Scales of Personality (KSP somatic or psychic anxiety and asthma based on subjective (maternal or child report or objective (register-based diagnosis and medication measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association. RESULTS: Maternal BAI anxiety (OR 2.02, CI 1.15-3.55 was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04-2.91 and psychic anxiety (OR 1.74, CI 1.05-2.86 was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding. CONCLUSIONS: We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.

  15. Childhood asthma prediction models: a systematic review.

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    Smit, Henriette A; Pinart, Mariona; Antó, Josep M; Keil, Thomas; Bousquet, Jean; Carlsen, Kai H; Moons, Karel G M; Hooft, Lotty; Carlsen, Karin C Lødrup

    2015-12-01

    Early identification of children at risk of developing asthma at school age is crucial, but the usefulness of childhood asthma prediction models in clinical practice is still unclear. We systematically reviewed all existing prediction models to identify preschool children with asthma-like symptoms at risk of developing asthma at school age. Studies were included if they developed a new prediction model or updated an existing model in children aged 4 years or younger with asthma-like symptoms, with assessment of asthma done between 6 and 12 years of age. 12 prediction models were identified in four types of cohorts of preschool children: those with health-care visits, those with parent-reported symptoms, those at high risk of asthma, or children in the general population. Four basic models included non-invasive, easy-to-obtain predictors only, notably family history, allergic disease comorbidities or precursors of asthma, and severity of early symptoms. Eight extended models included additional clinical tests, mostly specific IgE determination. Some models could better predict asthma development and other models could better rule out asthma development, but the predictive performance of no single model stood out in both aspects simultaneously. This finding suggests that there is a large proportion of preschool children with wheeze for which prediction of asthma development is difficult.

  16. The Relationship between Maternal Atopy and Childhood Asthma in Pretoria, South Africa.

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    Abbott, Salome; Becker, Piet; Green, Robin J

    2013-01-01

    Introduction. Asthma is the commonest chronic condition of children. Diagnosis of this condition remains difficult. Many surrogate markers are used, such as documenting evidence of atopy. Method. A random sample of asthmatic children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital were enrolled. Children were classified as having atopic or nonatopic asthma. Mothers completed a questionnaire to uncover atopic features. Results. Along with their mothers, 64 children with atopic asthma and 36 with nonatopic asthma were studied. The proportion of children with atopic asthma does not differ for mothers with and without a positive SPT (P = 0.836), a history of asthma (P = 0.045), symptoms suggestive of an allergic disease (P = 1.000), or who were considered to be allergic (P = 0.806). The odds ratio of a child having atopic asthma when having a mother with a doctor diagnosed history of asthma is 4.76, but the sensitivity is low (21.9%). Conclusion. The data demonstrates that all maternal allergic or asthmatic associations are poor predictors of childhood atopic asthma. Despite the increased risk of atopic asthma in a child to a mother that has a doctor diagnosis of asthma (OR 4.76 P = 0.045), this is a poor predictor of atopic asthma (sensitivity 21.9%).

  17. Long-term effects of breastfeeding, maternal smoking during pregnancy, and recurrent lower respiratory tract infections on asthma in children.

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    Karmaus, Wilfried; Dobai, Alina L; Ogbuanu, Ikechukwu; Arshard, Syed Hasan; Matthews, Sharon; Ewart, Susan

    2008-10-01

    The effect of breastfeeding on asthma is controversial, which may be explained by related and interacting early childhood risk factors. We assessed the joint effects of a risk-triad consisting of maternal smoking during pregnancy, breastfeeding for less than 3 months, and recurrent lower respiratory tract infections (RLRTI) on physician-diagnosed childhood asthma. The association was assessed in the Isle of Wight birth cohort study (1989-1990) using a repeated measurement approach with data collection at birth, and at ages 1, 2, 4, and 10 years. The population consists of 1,456 children recruited between January 1989 and February 1990. Prenatal smoking, breastfeeding for less than 3 months, and recurrent lower respiratory infections (RLRTI) were combined into eight risk-triads. Relative risks (RR) and 95% confidence intervals were estimated with a log-linear model. The risk-triad involving RLRTI in infancy, maternal smoking during pregnancy, and breastfeeding for less than 3 months showed a stronger association with asthma at ages 4 and 10 compared to other risk-triads (RR of 5.79 for any asthma at ages 1, 2, 4, and 10; and 3.1 for asthma at ages 4 and 10). Of the three individual risk factors, RLRTI appeared to be the major driver of the combined effects in the risk-triads. The effect of RLRTI on asthma was modified by breastfeeding. Breastfeeding for > or = 3 months also attenuated the effect of prenatal smoking on asthma in children without RLRTI. A high proportion of asthma cases in childhood can be prevented by promoting breastfeeding, by preventing smoking during pregnancy, and by avoidance of recurrent lower respiratory tract infections in early childhood.

  18. Maternal overweight before pregnancy and asthma in offspring followed for 8 years.

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    Scholtens, S.; Wijga, A.H.; Brunekreef, B.; Kerkhof, M.; Postma, D.S.; Oldenwening, M.; de Jongste, J.C.; Smit, H.A.

    2010-01-01

    OBJECTIVE: The aim of this study was to investigate the association between maternal overweight before pregnancy and offspring asthma in an ongoing birth cohort study. Maternal overweight may affect the pulmonary and immunological development of the fetus in utero because of the increased levels of

  19. Maternal overweight before pregnancy and asthma in offspring followed for 8 years

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    Scholtens, S.; Wijga, A. H.; Brunekreef, B.; Kerkhof, M.; Postma, D. S.; Oldenwening, M.; de Jongste, J. C.; Smit, H. A.

    2010-01-01

    Objective: The aim of this study was to investigate the association between maternal overweight before pregnancy and offspring asthma in an ongoing birth cohort study. Maternal overweight may affect the pulmonary and immunological development of the fetus in utero because of the increased levels of

  20. Maternal food consumption during pregnancy and the longitudinal development of childhood asthma

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    Willers, Saskia M.; Wijga, Alet H.; Brunekreef, Bert; Kerkhof, Marjan; Gerritsen, Jorrit; Hoekstra, Maarten O.; de Jongste, Johan C.; Smit, Henriette A.

    2008-01-01

    Rationale Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2-cell responses during fetal life. This might increase the risk of developing childhood asthma or allergy. Objectives: We investigated the influence of maternal food consumption during pr

  1. Maternal food consumption during pregnancy and the longitudinal development of childhood asthma

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    Willers, Saskia M.; Wijga, Alet H.; Brunekreef, Bert; Kerkhof, Marjan; Gerritsen, Jorrit; Hoekstra, Maarten O.; de Jongste, Johan C.; Smit, Henriette A.

    2008-01-01

    Rationale Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2-cell responses during fetal life. This might increase the risk of developing childhood asthma or allergy. Objectives: We investigated the influence of maternal food consumption during

  2. A study of neonatal and maternal outcomes of asthma during pregnancy

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    Babu Lal Meena

    2013-02-01

    Full Text Available Background: Asthma is a common problem all around the world with variable prevalence ranging from 1%–18% in different age and geographical distribution. There are proximately 300 million affected individuals. There are growing prevalence and morbidity, due to asthma associated with pregnancy. The course of asthma in pregnancy is unpredictable. Methods: 2400 consecutive pregnant women attending the antenatal clinic of S.P. Medical College and AG of Hospitals, Bikaner, were screened using asthma questionnaire translated in Hindi based on the questionnaire developed for International Union against Tuberculosis and Lung Disease. 52 patients diagnosed as asthma were subjected for PFT and classified according to clinical severity as per GINA guidelines, 2006. All subjects were followed till delivery and postpartum charts reviewed to see neonate and maternal outcome. Results: The prevalence of asthma during pregnancy was 2.1%, among them, 25 (48.1% were categorized as having intermittent asthma, 6 (11.5% with mild persistent asthma, 10 (19.2% with moderate persistent asthma and 11 (21.2% having severe persistent asthma. During the course of pregnancy, 36% had no change in the symptomatology, while (32.5% experienced improvement and (32.5% of worsening of asthma. 22 (42.31% women were newly diagnosed during our study. There was no significant adverse maternal and fetal outcome in asthmatic group compared to control. Conclusions: Asthma is an under diagnosed and under treated disorder, especially during pregnancy and overall morbidity of asthma among women & neonates does not change during pregnancy. [Int J Res Med Sci 2013; 1(1.000: 23-27

  3. Prenatal maternal psychological stress and childhood asthma and wheezing: a meta-analysis.

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    van de Loo, Kim F E; van Gelder, Marleen M H J; Roukema, Jolt; Roeleveld, Nel; Merkus, Peter J F M; Verhaak, Christianne M

    2016-01-01

    The aim of this study was to systematically review and meta-analyse observational studies on prenatal maternal psychological stress and the subsequent development of asthma and wheezing in early childhood.All available published literature from 1960 until November 2013 was systematically searched through electronic databases (PubMed, Embase, PsycInfo and Web of Science). All observational studies assessing associations between any form of prenatal maternal psychological stress and respiratory morbidity in the child were included. Data extraction, quality assessment and meta-analyses were performed.The overall meta-analysis included 10 studies and showed that the prevalence of wheezing, asthma and other respiratory symptoms is higher in children of mothers who were exposed to or experienced some form of psychological stress during pregnancy than in mothers who did not (pooled OR 1.56 (95% CI 1.36-1.80)). Comparable results were observed in subgroup analyses of stress exposure, perceived stress, asthma and wheezing.This study demonstrates that prenatal maternal psychological stress is associated with respiratory morbidity, including asthma and wheezing in the child. Future studies examining the early origins of asthma and wheezing need to account for the impact of prenatal maternal stress.

  4. High dose of maternal folic acid supplementation is associated to infant asthma.

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    Yang, Liu; Jiang, Liwen; Bi, Meirong; Jia, Xiaodong; Wang, Youqing; He, Chuan; Yao, Yao; Wang, Jun; Wang, Zhiping

    2015-01-01

    Maternal folic acid supplementation had a positive effect on preventing neural tube defects (NTDs), but its effects in infant asthma remained unclear. A hospital-based case-control study was conducted with outpatients between March 2010 and March 2011 including 150 onset infant asthma cases and 212 controls, together with a meta-analysis involving 14,438 participants, was performed. The association between maternal folic acid supplementation and the risk of infant asthma was not significant either in the meta-analysis (OR = 1.06, 95% CI =0.99-1.14) or in the case-control study (OR = 0.72, 95% CI =0.37-1.39). However, quantitative analysis of the supplementation dose demonstrated that the risk of infant asthma significantly increased for the infants whose mother were with high-dose supplementation (>72,000 µg•d; OR = 3.16, 95% CI =1.15-8.71) after adjusting for confounding factors in the case-control study. Meanwhile, the risk of infant asthma significantly decreased for the infants whose mother were with low-dose supplementation (folic acid supplementation for mother during pregnancy was associated with an increased risk of infant asthma, whereas supplementation with a relatively low-dose was associated with a decreased risk of infant asthma. These findings should be further investigated in a large population.

  5. Prenatal maternal stress predicts childhood asthma in girls: project ice storm.

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    Turcotte-Tremblay, Anne-Marie; Lim, Robert; Laplante, David P; Kobzik, Lester; Brunet, Alain; King, Suzanne

    2014-01-01

    Little is known about how prenatal maternal stress (PNMS) influences risks of asthma in humans. In this small study, we sought to determine whether disaster-related PNMS would predict asthma risk in children. In June 1998, we assessed severity of objective hardship and subjective distress in women pregnant during the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and corticosteroid utilization were assessed when the children were 12 years old (N = 68). No effects of objective hardship or timing of the exposure were found. However, we found that, in girls only, higher levels of prenatal maternal subjective distress predicted greater lifetime risk of wheezing (OR = 1.11; 90% CI = 1.01-1.23), doctor-diagnosed asthma (OR = 1.09; 90% CI = 1.00-1.19), and lifetime utilization of corticosteroids (OR = 1.12; 90% CI = 1.01-1.25). Other perinatal and current maternal life events were also associated with asthma outcomes. Findings suggest that stress during pregnancy opens a window for fetal programming of immune functioning. A sex-based approach may be useful to examine how prenatal and postnatal environments combine to program the immune system. This small study needs to be replicated with a larger, more representative sample.

  6. Prenatal Maternal Stress Predicts Childhood Asthma in Girls: Project Ice Storm

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    Anne-Marie Turcotte-Tremblay

    2014-01-01

    Full Text Available Little is known about how prenatal maternal stress (PNMS influences risks of asthma in humans. In this small study, we sought to determine whether disaster-related PNMS would predict asthma risk in children. In June 1998, we assessed severity of objective hardship and subjective distress in women pregnant during the January 1998 Quebec Ice Storm. Lifetime asthma symptoms, diagnoses, and corticosteroid utilization were assessed when the children were 12 years old (N=68. No effects of objective hardship or timing of the exposure were found. However, we found that, in girls only, higher levels of prenatal maternal subjective distress predicted greater lifetime risk of wheezing (OR=1.11; 90% CI = 1.01–1.23, doctor-diagnosed asthma (OR=1.09; 90% CI = 1.00–1.19, and lifetime utilization of corticosteroids (OR=1.12; 90% CI = 1.01–1.25. Other perinatal and current maternal life events were also associated with asthma outcomes. Findings suggest that stress during pregnancy opens a window for fetal programming of immune functioning. A sex-based approach may be useful to examine how prenatal and postnatal environments combine to program the immune system. This small study needs to be replicated with a larger, more representative sample.

  7. Maternal smoking in pregnancy and asthma in preschool children: a pooled analysis of eight birth cohorts

    NARCIS (Netherlands)

    Neuman, A.; Hohmann, C.; Pershagen, G.; Eller, E.; Kjaer, H.F.; Gehring, U.; Granell, R.; Henderson, J.; Lau, S.; Nieuwenhuijsen, M.; Sunyer, J.; Tischer, C.; Torrent, M.; Wahn, U.; Wijga, A.H.; Wickman, M.; Keil, T.; Bergström, A.

    2012-01-01

    Rationale: Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate the effects of prenatal from postnatal exposure. Objectives: To assess the effect of

  8. Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

    Directory of Open Access Journals (Sweden)

    Pingsheng Wu

    Full Text Available Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma cohort. The individual and cumulative impact of maternal urinary tract infections (UTI during pregnancy, maternal colonization with group B streptococcus (GBS, mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated.Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C

  9. Maternal antibiotic use and risk of asthma in offspring--Authors' reply

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Stokholm, Jakob; Sevelsted, Astrid

    2014-01-01

    We thank Martin J Blaser and Maria Bello for their interest in our study.1 Our original discovery of an association between use of antibiotics in pregnancy and an offspring's risk of asthma was replicated in the COPSAC2000 birth cohort and another Danish birth cohort, as well as in national...... registries.2,3 We interpreted this association between use of antibiotics in pregnancy and the child's risk of asthma as one that was mediated through changes in the microbiome. In our study we aimed to test this hypothesis by investigating the temporal associations between maternal antibiotics and childhood...

  10. Developmental Perturbation Induced by Maternal Asthma during Pregnancy: The Short- and Long-Term Impacts on Offspring

    Directory of Open Access Journals (Sweden)

    Vicki L. Clifton

    2012-01-01

    Full Text Available Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.

  11. Sport club participation of adolescents with asthma: maternal factors and adolescent cognitions.

    Science.gov (United States)

    Tiggelman, Dana; van de Ven, Monique O M; van Schayck, Onno C P; Kleinjan, Marloes; Engels, Rutger C M E

    2014-09-01

    Sport participation is especially important for patients with asthma in that it decreases psychosocial and physiological problems associated with inactivity. However, adolescents with asthma seem to participate less in sports compared to their non-asthmatic peers. The current study tested the direct associations between maternal sport-specific factors and sport club participation of early adolescents with asthma and the indirect effect through adolescent's sport-specific cognitions. During home visits, 261 adolescents (aged 10-15) completed questionnaires about self-efficacy, beliefs regarding sport participation, and their actual sport club participation. Their mothers reported their sport-specific support, beliefs about offspring's and own sport participation, their own levels of physical activity, and their self-efficacy to stimulate offspring to participate in sports. Path analyses were used to examine the direct and indirect associations of maternal sport-specific factors with adolescents sport club participation via adolescent sport-specific cognitions. Analyses showed that maternal sport-specific support (β = 0.20, P = 0.007) and self-efficacy to stimulate offspring to participate in sports (β = 0.20, P = 0.027) related positively to adolescents' sport club participation. Adolescents' self-efficacy (indirect effect = 0.09, SE = 3.01, P sport and adolescents' participation in sport clubs. Maternal sport-specific factors related to adolescents' sport club participation directly and indirectly through adolescents' sport-specific cognitions. Intervention programs should focus on maternal sport-specific support and self-efficacy and adolescents' self-efficacy to increase sport participation of adolescents with asthma. © 2013 Wiley Periodicals, Inc.

  12. Maternal occupational exposure to asthmogens during pregnancy and risk of asthma in 7-year-old children

    DEFF Research Database (Denmark)

    Christensen, Berit Hvass; Thulstrup, Ane Marie; Hougaard, Karin Sørig;

    2013-01-01

    The objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration.......The objective of this study was to examine whether maternal exposure to asthmogens during pregnancy is associated with the development of asthma in 7-year-old Danish children, taking atopic status and sex into consideration....

  13. Maternal vaginal microflora during pregnancy and the risk of asthma hospitalization and use of antiasthma medication in early childhood

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Thorsen, Poul; Jensen, Jørgen Skov;

    2002-01-01

    BACKGROUND: Infants with wheezing and allergic diseases have a microflora that differs from that of healthy infants. The fetus acquires microorganisms during birth when exposed to the maternal vaginal microflora. It is therefore conceivable that the maternal vaginal microflora might influence...... the establishment of the infant flora and, as a consequence, the development of wheezing and allergic diseases. OBJECTIVE: We sought to study the associations between the composition of the maternal vaginal microflora and the development of wheezing and asthma in childhood. METHODS: We performed a population....... Maternal colonization with staphylococci (OR, 2.2; 95% CI, 1.4-3.4) and use of antibiotics in pregnancy (OR, 1.7; 95% CI, 1.1-2.6) were associated with asthma during the fifth year of life. CONCLUSION: The composition of the maternal vaginal micro-flora might be associated with wheezing and asthma...

  14. Maternal waterpipe smoke exposure and the risk of asthma and allergic diseases in childhood: A post hoc analysis.

    Science.gov (United States)

    Waked, Mirna; Salameh, Pascale

    2015-01-01

    This analysis was conducted with the objective of evaluating association between waterpipe passive smoking exposure and asthma, and allergies among Lebanese children. Data were taken from a crosssectional study on children from public and private schools. A sample of 22 schools participated in the study, where standardized written core questionnaires were distributed. From 5 to 12-year-old students filled in the questionnaires at home, while 13-14-year-old students filled it in in the class. In total, 5522 children were evaluated for the prevalence of asthma, allergic rhinitis and atopic eczema, and their associated factors, including waterpipe exposure due to parents' smoking. The descriptive results of parental smoking were, as follows: among mothers: 1609 (29%) mothers smoked cigarettes, 385 (7%) smoked waterpipe and 98 (1.8%) smoked both; among fathers: 2449 (44.2%) smoked cigarettes, 573 (10.3%) smoked waterpipe and 197 (3.5%) smoked both. Maternal waterpipe smoking was significantly and moderately associated with allergic diseases (p waterpipe smoking was not associated with any of the diseases. Parental cigarette smoking demonstrated some positive effects: father's cigarette smoking did not show association with dermatitis or asthma diagnosed by a physician, while mother's cigarette smoking showed a positive association only with probable asthma. Moreover, no interactions between cigarette and waterpipe smoking were observed. Maternal waterpipe smoking should be regarded as a high risk behavior; however, additional studies are necessary to confirm this finding. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  15. Occupational Medicine Model and Asthma Military Recruitment.

    Science.gov (United States)

    Brooks, Stuart M

    2015-11-01

    Medical evidence hints that asymptomatic recruits with a history of childhood asthma, quiescent since their 13th birthday, are still at risk for adverse changes in their clinical status following unfavorable environmental exposures during military deployment or combat. Asthmatic persons, claiming none or few symptoms, may still manifest airflow obstruction and display biomarkers of airway inflammation even when they are relatively asymptomatic and experience few if any respiratory complaints. The occupational medicine model offers a credible foundation for acknowledging the importance of personal susceptibility in the pathogenesis of military-associated asthma. It is appropriate to re-explore the current military standard for recruits with asymptomatic childhood asthma (≥12 months) not prescribed antiasthma medications. Raising the acceptance age for these recruits may be a consideration. Unfortunately, there is no effectual screening test that recognizes such susceptible soldiers at risk for future asthma attacks. Nevertheless, there is general support for evidence-based, scientifically valid medical screening that judges fitness for military service. Screening tests comprising asthma biomarkers and genetic indices may better verify vulnerable soldiers destined to suffer future asthma reactivation.

  16. Maternal depressive symptoms across early childhood and asthma in school children: findings from a Longitudinal Australian Population Based Study.

    Science.gov (United States)

    Giallo, Rebecca; Bahreinian, Salma; Brown, Stephanie; Cooklin, Amanda; Kingston, Dawn; Kozyrskyj, Anita

    2015-01-01

    There is a growing body of evidence attesting to links between early life exposure to stress and childhood asthma. However, available evidence is largely based on small, genetically high risk samples. The aim of this study was to explore the associations between the course of maternal depressive symptoms across early childhood and childhood asthma in a nationally representative longitudinal cohort study of Australian children. Participants were 4164 children and their biological mothers from the Longitudinal Study of Australian Children. Latent class analysis identified three trajectories of maternal depressive symptoms across four biennial waves from the first postnatal year to when children were 6-7 years: minimal symptoms (74.6%), sub-clinical symptoms (20.8%), and persistent and increasing high symptoms (4.6%). Logistic regression analyses revealed that childhood asthma at age 6-7 years was associated with persistent and increasing high depressive symptoms after accounting for known risk factors including smoking during pregnancy and maternal history of asthma (adjusted OR 2.36, 95% CI 1.61-3.45), p.001). Our findings from a nationally representative sample of Australian children provide empirical support for a relationship between maternal depressive symptoms across the early childhood period and childhood asthma. The burden of disease from childhood asthma may be reduced by strengthening efforts to promote maternal mental health in the early years of parenting.

  17. Maternal depressive symptoms across early childhood and asthma in school children: findings from a Longitudinal Australian Population Based Study.

    Directory of Open Access Journals (Sweden)

    Rebecca Giallo

    Full Text Available There is a growing body of evidence attesting to links between early life exposure to stress and childhood asthma. However, available evidence is largely based on small, genetically high risk samples. The aim of this study was to explore the associations between the course of maternal depressive symptoms across early childhood and childhood asthma in a nationally representative longitudinal cohort study of Australian children. Participants were 4164 children and their biological mothers from the Longitudinal Study of Australian Children. Latent class analysis identified three trajectories of maternal depressive symptoms across four biennial waves from the first postnatal year to when children were 6-7 years: minimal symptoms (74.6%, sub-clinical symptoms (20.8%, and persistent and increasing high symptoms (4.6%. Logistic regression analyses revealed that childhood asthma at age 6-7 years was associated with persistent and increasing high depressive symptoms after accounting for known risk factors including smoking during pregnancy and maternal history of asthma (adjusted OR 2.36, 95% CI 1.61-3.45, p.001. Our findings from a nationally representative sample of Australian children provide empirical support for a relationship between maternal depressive symptoms across the early childhood period and childhood asthma. The burden of disease from childhood asthma may be reduced by strengthening efforts to promote maternal mental health in the early years of parenting.

  18. Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

    Energy Technology Data Exchange (ETDEWEB)

    Shin, In-Sik; Lee, Mee-Young [Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811 (Korea, Republic of); Cho, Eun-Sang [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Choi, Eun-young [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of); Son, Hwa-Young [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Lee, Kyoung-Youl, E-mail: youl10@hanmail.net [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of)

    2014-02-01

    Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

  19. Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring

    DEFF Research Database (Denmark)

    Harpsøe, Maria C; Basit, Saima; Bager, Peter;

    2013-01-01

    BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. OBJECTIVE: We examined the effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children......-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. CONCLUSIONS: Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic....... during the first 7 years of life. METHODS: This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were...

  20. Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring

    DEFF Research Database (Denmark)

    Harpsøe, Maria C; Basit, Saima; Bager, Peter;

    2012-01-01

    BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. OBJECTIVE: We examined the effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children......-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. CONCLUSIONS: Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic....... during the first 7 years of life. METHODS: This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were...

  1. [The degree of asthma severity in children and the level of maternal anxiety and depression].

    Science.gov (United States)

    Witkowska-Płusa, Urszula

    2015-02-01

    Care for sick children most often falls to mothers, which may affect their mental state, causing the states of depression and anxiety. The aim of this study was to determine the relationship between the severity of asthma in children and the level of anxiety and depression in mothers, taking into account the importance of the material status of the family, the educational level of the mothers, the presence of critical events, as well as the coexistence of allergic diseases in other family members. The study included 60 mothers of children with bronchial asthma. Age of mothers in the investigated families was on average 37.28 +/- 6.24 years, and most had a high school education (55.0%) or higher (28.3%). 16.7% of mothers and 8.3% fathers suffered from asthma. 13.3% of mothers of children with asthma were brought child alone. To assess the level of anxiety the inventory for measuring state and trait anxiety (STAI - State Trait Anxiety Inventory) developed by Spielberger, Gorsuch'a and Lushene'a was applied. To determine the changes in depressive the Beck Depression Inventory (BDI - Beck Depression Inventory questionnaire) was used. The Student's t test was included for two independent populations and a comparison of the results obtained in the questionnaire for diagnosing the level of anxiety and depression. For other parameters the correlation coefficient r-Pearson rank and Kendall's tau were performed. Mothers of children with moderate asthma compared to mothers of children with mild asthma had higher levels of anxiety (both state and properties), and also a slightly higher level of depression. Maternal age was connected positively and moderately strongly with the number held by children (r = 0.380; p = 0.003) and age of a child with asthma (r = 0.613, p = 0.0005). The duration of the child's disease was associated positively and moderately strongly with the level of state anxiety mother (X-1) (r = 0.345; p = 0.007) and a bit less and also positively with the

  2. Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford record linkage study

    Directory of Open Access Journals (Sweden)

    Wotton Clare J

    2010-03-01

    Full Text Available Abstract Background There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children. Methods Analysis of data from the Oxford record linkage study (ORLS to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999. Results Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s, low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR 3.1, 95% confidence interval 2.7-3.6, male sex (versus female, 1.8, 1.7-2.0, low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3, maternal smoking (1.1, 1.0-1.3 and delivery by caesarean section (1.2; 1.0-1.3. In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7 and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2. Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7, age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7; high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82. Hospital admission for asthma in people aged over six was more

  3. Breastfeeding and the risk of wheeze and asthma in Japanese infants: the Osaka Maternal and Child Health Study.

    Science.gov (United States)

    Miyake, Y; Tanaka, K; Sasaki, S; Kiyohara, C; Ohya, Y; Fukushima, W; Yokoyama, T; Hirota, Y

    2008-09-01

    Epidemiological evidence for an effect of breastfeeding on asthma continues to be inconclusive. The present prospective study examined the relationship between breastfeeding and the risk of wheeze and asthma in Japanese infants. A birth cohort of 763 infants was followed. The first survey during pregnancy and the second survey between 2 and 9 months postpartum collected information on potential confounding factors. Data on breastfeeding, wheeze, and asthma were obtained from questionnaires in the third survey from 16 to 24 months postpartum. Adjustment was made for maternal age, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, indoor domestic pets (cats, dogs, birds, or hamsters), family income, maternal and paternal education, maternal smoking during pregnancy, baby's sex, baby's older siblings, household smoking in the same room as the infant, and time of delivery before the third survey. By the third survey, the cumulative incidence of wheeze and asthma was 22.1% and 4.3%, respectively. Neither exclusive breastfeeding for 4 months or more nor partial breastfeeding for 6 months or more were materially related to the risk of wheeze. No measurable association was observed between exclusive breastfeeding for 4 months or more and the risk of asthma. Partial breastfeeding for 6 months or more was inversely related to the risk of asthma although the adjusted odds ratio (OR) was not statistically significant. When infants were stratified according to whether there was a negative or positive allergic history in at least 1 parent, a nearly 40% and 60% decrease, respectively, in the ORs were found for exclusive and partial breastfeeding only in infants without a parental allergic history, although the ORs were not statistically significant. The present prospective study showed no statistically significant relationship between breastfeeding duration and the risk of wheeze or asthma in Japanese infants.

  4. Breastfeeding and lung function at school age: does maternal asthma modify the effect?

    Science.gov (United States)

    Dogaru, Cristian M; Strippoli, Marie-Pierre F; Spycher, Ben D; Frey, Urs; Beardsmore, Caroline S; Silverman, Michael; Kuehni, Claudia E

    2012-04-15

    The evidence for an effect of breastfeeding on lung function is conflicting, in particular whether the effect is modified by maternal asthma. To explore the association between breastfeeding and school-age lung function. In the Leicestershire Cohort Studies we assessed duration of breastfeeding (not breastfed, ≤3 months, 4-6 months, and >6 months), other exposures, and respiratory symptoms by repeated questionnaires. Post-bronchodilator FVC, FEV(1), peak expiratory flow (PEF), forced midexpiratory flow (FEF(50)), and skin prick tests were measured at age 12 years. We performed multivariable linear regression and tested potential causal pathways (N = 1,458). In the entire sample, FEF(50) was higher by 130 and 164 ml in children breastfed for 4 to 6 months and longer than 6 months, respectively, compared with those not breastfed (P = 0.048 and 0.041), with larger effects if the mother had asthma. FVC and FEV(1) were associated with breastfeeding only in children of mothers with asthma (P for interaction, 0.018 and 0.008): FVC was increased by 123 and 164 ml for those breastfed 4 to 6 months or longer than 6 months, respectively (P = 0.177 and 0.040) and FEV(1) was increased by 148 and 167 ml, respectively (P = 0.050 and 0.016). Results were unchanged after adjustment for respiratory infections in infancy and asthma and atopy in the child. In this cohort, breastfeeding for more than 4 months was associated with increased FEF(50) and, in children of mothers with asthma, with increased FEV(1) and FVC. It seems that the effect is not mediated via avoidance of early infections or atopy but rather through a direct effect on lung growth.

  5. Effects of socioeconomic status on maternal and child positive behaviors in daily life among youth with asthma.

    Science.gov (United States)

    Imami, Ledina; Tobin, Erin T; Kane, Heidi S; Saleh, Daniel J; Lupro, Toni H; Slatcher, Richard B

    2015-01-01

    Socioeconomic disadvantage is associated with poorer behavioral and emotional outcomes in children with asthma. This study investigated the associations between maternal income and education and naturalistically observed behaviors and affect during everyday parent-child interactions. 53 predominantly low-income youth with asthma, aged 10-17 years, wore a naturalistic event-sampling device, the Electronically Activated Recorder, for 4 days to assess mother and child positive behaviors and affect in daily life. Maternal education, but not income, was positively associated with child positive behaviors, displays of mother and child positive affect, and increased maternal responsiveness. Maternal positive affect and maternal responsiveness mediated the effect of maternal education on child positive affect. Our findings suggest that maternal education has an important influence on the socioemotional adjustment of youth with asthma and point to the importance of investigating the independent influence of socioeconomic status components on everyday parent-child interactions. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Microbiome and Asthma: What Have Experimental Models Already Taught Us?

    Directory of Open Access Journals (Sweden)

    R. Bonamichi-Santos

    2015-01-01

    Full Text Available Asthma is a chronic inflammatory disease that imposes a substantial burden on patients, their families, and the community. Although many aspects of the pathogenesis of classical allergic asthma are well known by the scientific community, other points are not yet understood. Experimental asthma models, particularly murine models, have been used for over 100 years in order to better understand the immunopathology of asthma. It has been shown that human microbiome is an important component in the development of the immune system. Furthermore, the occurrence of many inflammatory diseases is influenced by the presence of microbes. Again, experimental models of asthma have helped researchers to understand the relationship between the microbiome and respiratory inflammation. In this review, we discuss the evolution of murine models of asthma and approach the major studies involving the microbiome and asthma.

  7. Examining the association between childhood asthma and parent and grandparent asthma status: Implications for Practice

    OpenAIRE

    Valerio, Melissa A.; Andreski, Patricia M.; Schoeni, Robert F.; McGonagle, Katherine A.

    2010-01-01

    Examination of intergenerational asthma beyond maternal asthma has been limited. The association between childhood asthma and intergenerational asthma status among a national cohort of children was examined.

  8. Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring.

    Science.gov (United States)

    Morales, Eva; Romieu, Isabelle; Guerra, Stefano; Ballester, Ferrán; Rebagliato, Marisa; Vioque, Jesús; Tardón, Adonina; Rodriguez Delhi, Cristina; Arranz, Leonor; Torrent, Maties; Espada, Mercedes; Basterrechea, Mikel; Sunyer, Jordi

    2012-01-01

    Adequate vitamin D status in mothers during pregnancy may influence the health status of the child later in life. We assessed whether maternal circulating 25-hydroxyvitamin D (25[OH]D) concentrations in pregnancy are associated with risk of lower respiratory tract infections, wheezing, and asthma in the offspring. Data were obtained from 1724 children of the INfancia y Medio Ambiente (INMA) Project, a population-based birth cohort study. Maternal circulating 25(OH)D concentrations were measured in pregnancy (mean gestational age = 12.6 [SD = 2.5] weeks). When the child was age 1 year, parents were asked if their child had a physician-confirmed history of lower respiratory tract infections or a history of wheezing. The questions about wheezing were repeated annually thereafter. Asthma was defined as parental report of doctor diagnosis of asthma or receiving treatment at the age of 4-6 years or wheezing since the age of 4 years. The median maternal circulating 25(OH)D concentration in pregnancy was 29.5 ng/mL (interquartile range, 22.5-37.1 ng/mL). After multivariable adjustment, there was a trend for an independent association between higher levels of maternal circulating 25(OH)D levels in pregnancy and decreased odds of lower respiratory tract infections in offspring (for cohort- and season-specific quartile Q4 vs. Q1, odds ratio = 0.67 [95% confidence interval = 0.50-0.90]; test for trend, P = 0.016). We found no association between 25(OH)D levels in pregnancy and risk of wheezing at age 1 year or 4 years, or asthma at age 4-6 years. Higher maternal circulating 25(OH)D concentrations in pregnancy were independently associated with lower risk of lower respiratory tract infections in offspring in the first year of life but not with wheezing or asthma in childhood.

  9. Asthma

    Directory of Open Access Journals (Sweden)

    Kim Harold

    2011-11-01

    Full Text Available Abstract Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA inhalers are preferred for most adults who fail to achieve control with ICS therapy. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma, but should only be prescribed by physicians with appropriate training in allergy. Regular monitoring of asthma control, adherence to therapy and inhaler technique are also essential components of asthma management. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma.

  10. Asthma

    Science.gov (United States)

    ... 1.25 million of those individuals have severe asthma, a condition that can be difficult to control and treat. Learn more about his research by visiting the NHLBI Laboratory of Asthma and Lung Inflammation website: http://www.nhlbi.nih. ...

  11. Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years

    NARCIS (Netherlands)

    Celedon, JC; Wright, RJ; Litonjua, AA; Sredl, D; Ryan, L; Weiss, ST; Gold, DR

    2003-01-01

    Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheez

  12. Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years

    NARCIS (Netherlands)

    Celedon, JC; Wright, RJ; Litonjua, AA; Sredl, D; Ryan, L; Weiss, ST; Gold, DR

    2003-01-01

    Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and

  13. Asthma

    OpenAIRE

    Kim, Harold; Mazza, Jorge

    2011-01-01

    Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs) represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA) inhalers are pr...

  14. Asthma

    OpenAIRE

    Kim Harold; Mazza Jorge

    2011-01-01

    Abstract Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs) represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA) inhale...

  15. Understanding pediatric inner-city asthma: an explanatory model approach.

    Science.gov (United States)

    Handelman, Lauren; Rich, Michael; Bridgemohan, Carolyn Frazer; Schneider, Lynda

    2004-04-01

    Explanatory models (EMs) for asthma among inner-city school-age children and their families were examined as a means of better understanding health behaviors. Children and parents were interviewed about their concepts of asthma etiology, asthma medications, and alternative therapies. Drawings were elicited from children to understand their beliefs about asthma. Nineteen children with 17 mothers from a variety of cultural backgrounds were interviewed. Among children, contagion was the primary EM for asthma etiology (53%). Twenty-five percent of children reported fear of dying from asthma, while fear of their child dying from asthma was reported by 76% of mothers. Mothers reported a variety of EMs, some culturally specific, but the majority reported biomedical concepts of etiology, pathophysiology, and triggers. Although 76% of mothers knew the names of more than one of their children's medications, 47% thought their child's medications all had similar functions. Thirty-five percent of families used herbal treatments and 35% incorporated religion into asthma treatment. Seventy-one percent of families had discontinued medications and 23% reported currently not giving anti-inflammatory medication. Reasons for discontinuing daily medications included fears of unknown side effects (53%), addiction (18%), tachyphylaxis (18%), and feeling that their child was being given too much medicine (23%). The traditional focus of asthma education is not sufficient to ensure adherence. Asthma education for children should address their views of etiology and fears about dying from asthma. Conversations with parents about their EMs and beliefs about medications and alternative therapies could assist in understanding and responding to parental concerns and choices about medications and help achieve better adherence.

  16. Maternal waterpipe smoke exposure and the risk of asthma and allergic diseases in childhood: A post hoc analysis

    Directory of Open Access Journals (Sweden)

    Mirna Waked

    2015-02-01

    Full Text Available Introduction This analysis was conducted with the objective of evaluating association between waterpipe passive smoking exposure and asthma, and allergies among Lebanese children. Material and methods Data were taken from a crosssectional study on children from public and private schools. A sample of 22 schools participated in the study, where standardized written core questionnaires were distributed. From 5 to 12-year-old students filled in the questionnaires at home, while 13–14-year-old students filled it in in the class. In total, 5522 children were evaluated for the prevalence of asthma, allergic rhinitis and atopic eczema, and their associated factors, including waterpipe exposure due to parents’ smoking. Results The descriptive results of parental smoking were, as follows: among mothers: 1609 (29% mothers smoked cigarettes, 385 (7% smoked waterpipe and 98 (1.8% smoked both; among fathers: 2449 (44.2% smoked cigarettes, 573 (10.3% smoked waterpipe and 197 (3.5% smoked both. Maternal waterpipe smoking was significantly and moderately associated with allergic diseases (p < 0.001; ORa = 1.71, including probable asthma, rhinitis and dermatitis (p < 0.001 for all. Quite on the opposite, father’s waterpipe smoking was not associated with any of the diseases. Parental cigarette smoking demonstrated some positive effects: father’s cigarette smoking did not show association with dermatitis or asthma diagnosed by a physician, while mother’s cigarette smoking showed a positive association only with probable asthma. Moreover, no interactions between cigarette and waterpipe smoking were observed. Conclusions Maternal waterpipe smoking should be regarded as a high risk behavior; however, additional studies are necessary to confirm this finding.

  17. Asthma

    Science.gov (United States)

    ... BS, Burks AW, et al, eds. Middleton's Allergy Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 55. Lugogo N, Que LG, Gilstrap DL, Kraft M. Asthma: clinical diagnosis and management. In: Broaddus VC, Mason RJ, Ernst JD, et ...

  18. A NONLINEAR MATHEMATICAL MODEL FOR ASTHMA: EFFECT OF ENVIRONMENTAL POLLUTION

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    NARESHA RAM

    2009-04-01

    Full Text Available In this paper, we explore a nonlinear mathematical model to study the spread of asthma due to inhaled pollutants from industry as well as tobacco smoke from smokers in a variable size population. The model is analyzed using stability theory of differential equations and computer simulation. It is shown that with an increase in the level of air pollutants concentration, the asthmatic (diseased population increases. It is also shown that along with pollutants present in the environment, smoking (active or passive also helps in the spread of asthma. Moreover, with the increase in the rate of interaction between susceptibles and smokers, the persistence of the spread of asthma is higher. A numerical study of the model is also performed to see the role of certain key parameters on the spread of asthma and to support the analytical results.

  19. Stem cells in animal asthma models: a systematic review.

    Science.gov (United States)

    Srour, Nadim; Thébaud, Bernard

    2014-12-01

    Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. Maternal immune markers in serum during gestation and in breast milk and the risk of asthma-like symptoms at ages 6 and 12 months: a longitudinal study

    OpenAIRE

    Soto-Ramírez Nelís; Karmaus Wilfried; Yousefi Mitra; Zhang Hongmei; Liu Jihong; Gangur Venugopal

    2012-01-01

    Abstract Background The role of breast milk on the risk of childhood asthma is in dispute. The aim of this prospective study is to determine the relationship of immune markers in maternal serum during gestation and breast milk to asthma-like symptoms (AS) in infancy. Methods Pregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median: three weeks before delivery) and breast milk (three weeks after delivery) samples were collected. Concentrations of interferon (IFN)...

  1. Sport club participation of adolescents with asthma: maternal factors and adolescent cognitions

    NARCIS (Netherlands)

    Tiggelman, D.; Ven, M.O.M. van de; Schayck, O.C.P. van; Kleinjan, M.; Engels, R.C.M.E.

    2014-01-01

    Sport participation is especially important for patients with asthma in that it decreases psychosocial and physiological problems associated with inactivity. However, adolescents with asthma seem to participate less in sports compared to their non-asthmatic peers. The current study tested the direct

  2. Sport club participation of adolescents with asthma: maternal factors and adolescent cognitions

    NARCIS (Netherlands)

    Tiggelman, D.; Ven, M.O.M. van de; Schayck, O.C.P. van; Kleinjan, M.; Engels, R.C.M.E.

    2014-01-01

    Sport participation is especially important for patients with asthma in that it decreases psychosocial and physiological problems associated with inactivity. However, adolescents with asthma seem to participate less in sports compared to their non-asthmatic peers. The current study tested the direct

  3. Asthma: a comparison of animal models using stereological methods

    Directory of Open Access Journals (Sweden)

    D. M. Hyde

    2006-12-01

    Full Text Available Asthma is a worldwide health problem that affects 300 million people, as estimated by the World Health Organization. A key question in light of this statistic is: "what is the most appropriate laboratory animal model for human asthma?" The present authors used stereological methods to assess airways in adults and during post-natal development, and their response to inhaled allergens to compare rodents and nonhuman primates to responses in humans. An epithelial–mesenchymal trophic unit was defined in which all of the compartments interact with each other. Asthma manifests itself by altering not only the epithelial compartment but also other compartments (e.g. interstitial, vascular, immunological and nervous. All of these compartments show significant alteration in an airway generation-specific manner in rhesus monkeys but are limited to the proximal airways in mice. The rhesus monkey model shares many of the key features of human allergic asthma including the following: 1 allergen-specific immunoglobulin (IgE and skin-test positivity; 2 eosinophils and IgE+ cells in airways; 3 a T-helper type 2 cytokine profile in airways; 4 mucus cell hyperplasia; 5 subepithelial fibrosis; 6 basement membrane thickening; and 7 persistent baseline hyperreactivity to histamine or methacholine. In conclusion, the unique responses to inhaled allergens shown in rhesus monkeys make it the most appropriate animal model of human asthma.

  4. Sparse modeling of spatial environmental variables associated with asthma.

    Science.gov (United States)

    Chang, Timothy S; Gangnon, Ronald E; David Page, C; Buckingham, William R; Tandias, Aman; Cowan, Kelly J; Tomasallo, Carrie D; Arndt, Brian G; Hanrahan, Lawrence P; Guilbert, Theresa W

    2015-02-01

    Geographically distributed environmental factors influence the burden of diseases such as asthma. Our objective was to identify sparse environmental variables associated with asthma diagnosis gathered from a large electronic health record (EHR) dataset while controlling for spatial variation. An EHR dataset from the University of Wisconsin's Family Medicine, Internal Medicine and Pediatrics Departments was obtained for 199,220 patients aged 5-50years over a three-year period. Each patient's home address was geocoded to one of 3456 geographic census block groups. Over one thousand block group variables were obtained from a commercial database. We developed a Sparse Spatial Environmental Analysis (SASEA). Using this method, the environmental variables were first dimensionally reduced with sparse principal component analysis. Logistic thin plate regression spline modeling was then used to identify block group variables associated with asthma from sparse principal components. The addresses of patients from the EHR dataset were distributed throughout the majority of Wisconsin's geography. Logistic thin plate regression spline modeling captured spatial variation of asthma. Four sparse principal components identified via model selection consisted of food at home, dog ownership, household size, and disposable income variables. In rural areas, dog ownership and renter occupied housing units from significant sparse principal components were associated with asthma. Our main contribution is the incorporation of sparsity in spatial modeling. SASEA sequentially added sparse principal components to Logistic thin plate regression spline modeling. This method allowed association of geographically distributed environmental factors with asthma using EHR and environmental datasets. SASEA can be applied to other diseases with environmental risk factors.

  5. Mouse models of acute exacerbations of allergic asthma.

    Science.gov (United States)

    Kumar, Rakesh K; Herbert, Cristan; Foster, Paul S

    2016-07-01

    Most of the healthcare costs associated with asthma relate to emergency department visits and hospitalizations because of acute exacerbations of underlying chronic disease. Development of appropriate animal models of acute exacerbations of asthma is a necessary prerequisite for understanding pathophysiological mechanisms and assessing potential novel therapeutic approaches. Most such models have been developed using mice. Relatively few mouse models attempt to simulate the acute-on-chronic disease that characterizes human asthma exacerbations. Instead, many reported models involve relatively short-term challenge with an antigen to which animals are sensitized, followed closely by an unrelated triggering agent, so are better described as models of potentiation of acute allergic inflammation. Triggers for experimental models of asthma exacerbations include (i) challenge with high levels of the sensitizing allergen (ii) infection by viruses or fungi, or challenge with components of these microorganisms (iii) exposure to environmental pollutants. In this review, we examine the strengths and weaknesses of published mouse models, their application for investigation of novel treatments and potential future developments.

  6. Niflumic Acid Inhibits Goblet Cell Degranulation in a Guinea Pig Asthma Model

    Directory of Open Access Journals (Sweden)

    Mitsuko Kondo

    2012-01-01

    Conclusions: NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with goblet cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma.

  7. Asthma Self-Management Model: Randomized Controlled Trial

    Science.gov (United States)

    Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

    2016-01-01

    Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

  8. Models of asthma: density-equalizing mapping and output benchmarking

    Directory of Open Access Journals (Sweden)

    Fischer Tanja C

    2008-02-01

    Full Text Available Abstract Despite the large amount of experimental studies already conducted on bronchial asthma, further insights into the molecular basics of the disease are required to establish new therapeutic approaches. As a basis for this research different animal models of asthma have been developed in the past years. However, precise bibliometric data on the use of different models do not exist so far. Therefore the present study was conducted to establish a data base of the existing experimental approaches. Density-equalizing algorithms were used and data was retrieved from a Thomson Institute for Scientific Information database. During the period from 1900 to 2006 a number of 3489 filed items were connected to animal models of asthma, the first being published in the year 1968. The studies were published by 52 countries with the US, Japan and the UK being the most productive suppliers, participating in 55.8% of all published items. Analyzing the average citation per item as an indicator for research quality Switzerland ranked first (30.54/item and New Zealand ranked second for countries with more than 10 published studies. The 10 most productive journals included 4 with a main focus allergy and immunology and 4 with a main focus on the respiratory system. Two journals focussed on pharmacology or pharmacy. In all assigned subject categories examined for a relation to animal models of asthma, immunology ranked first. Assessing numbers of published items in relation to animal species it was found that mice were the preferred species followed by guinea pigs. In summary it can be concluded from density-equalizing calculations that the use of animal models of asthma is restricted to a relatively small number of countries. There are also differences in the use of species. These differences are based on variations in the research focus as assessed by subject category analysis.

  9. Modeling the impact of increased adherence to asthma therapy.

    Directory of Open Access Journals (Sweden)

    Amory Schlender

    Full Text Available BACKGROUND: Nonadherence to medications occurs in up to 70% of patients with asthma. The effect of improving adherence is not well quantified. We developed a mathematical model with which to assess the population-level effects of improving medication prescribing and adherence for asthma. METHODS: A mathematical model, calibrated to clinical trial data from the U.S. NHLBI-funded SOCS trial and validated using data from the NHLBI SLIC trial, was used to model the effects of increased prescribing and adherence to asthma controllers. The simulated population consisted of 4,930 individuals with asthma, derived from a sample the National Asthma Survey. Main outcomes were controller use, reliever use, unscheduled doctor visits, emergency department (ED visits, and hospitalizations. RESULTS: For the calibration, simulated outcomes agreed closely with SOCS trial outcomes, with treatment failure hazard ratios [95% confidence interval] of 0.92 [0.58-1.26], 0.97 [0.49-1.45], and 1.01 [0-1.87] for simulation vs. trial in the in placebo, salmeterol, and triamcinolone arms, respectively. For validation, simulated outcomes predicted mid- and end-point treatment failure rates, hazard ratios 1.21 [0.08-2.34] and 0.83 [0.60-1.07], respectively, for patients treated with salmeterol/triamcinolone during the first half of the SLIC study and salmeterol monotherapy during the second half. The model performed less well for patients treated with salmeterol/triamcinolone during the entire study duration, with mid- and end-point hazard ratios 0.83 [0.00-2.12] and 0.37 [0.10-0.65], respectively. Simulation of optimal adherence and prescribing indicated that closing adherence and prescription gaps could prevent as many as nine million unscheduled doctor visits, four million emergency department visits, and one million asthma-related hospitalizations each year in the U.S. CONCLUSIONS: Improvements in medication adherence and prescribing could have a substantial impact on

  10. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    NARCIS (Netherlands)

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome

    2014-01-01

    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to inve

  11. Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana

    Science.gov (United States)

    Nuss, Henry J.; Hester, Laura L.; Perry, Mark A.; Stewart-Briley, Collette; Reagon, Valamar M.; Collins, Pamela

    2016-01-01

    Background: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years. Methods: Activities included a needs…

  12. Rat models of asthma and chronic obstructive lung disease.

    Science.gov (United States)

    Martin, James G; Tamaoka, Meiyo

    2006-01-01

    The rat has been extensively used to model asthma and somewhat less extensively to model chronic obstructive pulmonary disease (COPD). The features of asthma that have been successfully modeled include allergen-induced airway constriction, eosinophilic inflammation and allergen-induced airway hyperresponsiveness. T-cell involvement has been directly demonstrated using adoptive transfer techniques. Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13). Repeated allergen exposure causes airway remodeling. Dry gas hyperpnea challenge also evokes increases in lung resistance, allowing exercise-induced asthma to be modeled. COPD is modeled using elastase-induced parenchymal injury to mimic emphysema. Cigarette smoke-induced airspace enlargement occurs but requires months of cigarette exposure. Inflammation and fibrosis of peripheral airways is an important aspect of COPD that is less well modeled. Novel approaches to the treatment of COPD have been reported including treatments aimed at parenchymal regeneration.

  13. Nonspecific airway reactivity in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Collie, D.D.; Wilder, J.A.; Bice, D.E.

    1995-12-01

    Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

  14. A systematic review of predictive models for asthma development in children.

    Science.gov (United States)

    Luo, Gang; Nkoy, Flory L; Stone, Bryan L; Schmick, Darell; Johnson, Michael D

    2015-11-28

    Asthma is the most common pediatric chronic disease affecting 9.6 % of American children. Delay in asthma diagnosis is prevalent, resulting in suboptimal asthma management. To help avoid delay in asthma diagnosis and advance asthma prevention research, researchers have proposed various models to predict asthma development in children. This paper reviews these models. A systematic review was conducted through searching in PubMed, EMBASE, CINAHL, Scopus, the Cochrane Library, the ACM Digital Library, IEEE Xplore, and OpenGrey up to June 3, 2015. The literature on predictive models for asthma development in children was retrieved, with search results limited to human subjects and children (birth to 18 years). Two independent reviewers screened the literature, performed data extraction, and assessed article quality. The literature search returned 13,101 references in total. After manual review, 32 of these references were determined to be relevant and are discussed in the paper. We identify several limitations of existing predictive models for asthma development in children, and provide preliminary thoughts on how to address these limitations. Existing predictive models for asthma development in children have inadequate accuracy. Efforts to improve these models' performance are needed, but are limited by a lack of a gold standard for asthma development in children.

  15. Maternal and paternal indoor or outdoor smoking and the risk of asthma in their children: a nationwide prospective birth cohort study.

    Science.gov (United States)

    Tabuchi, Takahiro; Fujiwara, Takeo; Nakayama, Tomio; Miyashiro, Isao; Tsukuma, Hideaki; Ozaki, Koken; Kondo, Naoki

    2015-02-01

    Little is known about the differential impact of combinations of parental smoking behavior (indoor or outdoor smoking, or not smoking) on preventing childhood asthma. Our objective was to examine the association between parental smoking behavior and children's asthma. A nationally representative population-based birth cohort of 40,580 babies, aged 0.5 years in 2001 (response rate, 87.8%), was studied to estimate adjusted odds ratios of combinations of maternal and paternal indoor or outdoor smoking at home for physician visits and hospitalization for childhood asthma up to 8-years-old, and population attributable fractions. Odds of hospitalization for asthma among children whose father alone smokes indoors at home did not largely increase (up to 20%). However, if the mother also smokes indoors at home, the odds strongly increased. After adjusting for demographic, perinatal and socioeconomic factors, the increase in odds for children whose father and mother both smoke indoors compared to children with non-smoking parents was 54% (95% confidence interval: 21-96%), 43% (8-90%) and 72% (22-143%) for children aged 0.5children for asthma could be reduced by 8.3% (2.2-14.3%), 9.3% (0.9-17.6%) and 18.2% (7.7-28.8%), respectively. Parental indoor smoking at home increased and exacerbated children's asthma. Smoking at home, whether it is indoors or outdoors, may increase the risks for asthma attacks of their children. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Role of community pharmacists in asthma – Australian research highlighting pathways for future primary care models

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    Saini B

    2011-04-01

    Full Text Available Asthma is one of the most common chronic conditions affecting the Australian population. Amongst primary healthcare professionals, pharmacists are the most accessible and this places pharmacists in an excellent position to play a role in the management of asthma. Globally, trials of many community pharmacy-based asthma care models have provided evidence that pharmacist delivered interventions can improve clinical, humanistic and economic outcomes for asthma patients. In Australia, a decade of coordinated research efforts, in various aspects of asthma care, has culminated in the implementation trial of the Pharmacy Asthma Management Service (PAMS, a comprehensive disease management model. There has been research investigating asthma medication adherence through data mining, ways in which usual asthma care can be improved. Our research has focused on self-management education, inhaler technique interventions, spirometry trials, interprofessional models of care, and regional trials addressing the particular needs of rural communities. We have determined that inhaler technique education is a necessity and should be repeated if correct technique is to be maintained. We have identified this effectiveness of health promotion and health education, conducted within and outside the confines of the pharmacy, in public for a and settings such as schools, and established that this outreach role is particularly well received and increases the opportunity for people with asthma to engage in their asthma management. Our research has identified that asthma patients have needs which pharmacists delivering specialized models of care, can address. There is a lot of evidence for the effectiveness of asthma care by pharmacists, the future must involve integration of this role into primary care.

  17. The WHO maternal near-miss approach and the maternal severity index model (MSI: tools for assessing the management of severe maternal morbidity.

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    Joao Paulo Souza

    Full Text Available OBJECTIVES: To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments. METHODS: In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity. RESULTS: Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56-114.6. The maternal severity index (MSI model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909-0.993. CONCLUSION: The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.

  18. Computational modeling of the obstructive lung diseases asthma and COPD.

    Science.gov (United States)

    Burrowes, Kelly Suzanne; Doel, Tom; Brightling, Chris

    2014-11-28

    Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow imitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the currentstate

  19. Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review.

    Science.gov (United States)

    Kianmeher, Majid; Ghorani, Vahideh; Boskabady, Mohammad Hosein

    2016-12-01

    Asthma is a chronic inflammatory disease of the airway with extensive airway remodeling. The ethical issues associated with the studies in asthmatic patients, required development of animal model of asthma. Animal models of asthma can provide valuable information on several features of asthma pathogenesis and treatment. Although these models cannot carry out all clinical features, they are valuable to understand mechanisms of the disease and curative access. Related articles were searched in different databases from September 1994 to April 2016 using; animal model of asthma, animal sensitization, allergen-induced asthma in animals terms. Although there are several reviews on this topic, in the present article, induction of animal model of asthma in different animals, various methods used for this purpose, measured parameters and research purposes were reviewed, which will help investigators to use the appropriate animal, methods, and evaluating parameters depending on their study design. In this study various method used for induction of animal model of asthma in different animals and measured parameters were described, which will help investigators to use the appropriate animal, method and evaluating parameters depending on their study design.

  20. Using the ecology model to describe the impact of asthma on patterns of health care

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    Yawn Barbara P

    2005-05-01

    Full Text Available Abstract Background Asthma changes both the volume and patterns of healthcare of affected people. Most studies of asthma health care utilization have been done in selected insured populations or in a single site such as the emergency department. Asthma is an ambulatory sensitive care condition making it important to understand the relationship between care in all sites across the health service spectrum. Asthma is also more common in people with fewer economic resources making it important to include people across all types of insurance and no insurance categories. The ecology of medical care model may provide a useful framework to describe the use of health services in people with asthma compared to those without asthma and identify subgroups with apparent gaps in care. Methods This is a case-control study using the 1999 U.S. Medical Expenditure Panel Survey. Cases are school-aged children (6 to 17 years and young adults (18 to 44 years with self-reported asthma. Controls are from the same age groups who have no self-reported asthma. Descriptive analyses and risk ratios are placed within the ecology of medical care model and used to describe and compare the healthcare contact of cases and controls across multiple settings. Results In 1999, the presence of asthma significantly increased the likelihood of an ambulatory care visit by 20 to 30% and more than doubled the likelihood of making one or more visits to the emergency department (ED. Yet, 18.8% of children and 14.5% of adults with asthma (over a million Americans had no ambulatory care visits for asthma. About one in 20 to 35 people with asthma (5.2% of children and 3.6% of adults were seen in the ED or hospital but had no prior or follow-up ambulatory care visits. These Americans were more likely to be uninsured, have no usual source of care and live in metropolitan areas. Conclusion The ecology model confirmed that having asthma changes the likelihood and pattern of care for Americans

  1. Community violence and urban childhood asthma: a multilevel analysis.

    Science.gov (United States)

    Sternthal, M J; Jun, H-J; Earls, F; Wright, R J

    2010-12-01

    We examined the association between community violence exposure and childhood asthma risk in a multilevel, multimethod, longitudinal study controlling for individual- and neighbourhood-level confounders and pathway variables. Analyses included 2,071 children aged 0-9 yrs at enrolment from the Project on Human Development in Chicago Neighborhoods. Multilevel logistic regression models estimated the likelihood of asthma, controlling for individual-level (child's age, sex, race/ethnicity, maternal asthma, socioeconomic status and family violence in the home) and neighbourhood-level confounders (concentrated disadvantage, collective efficacy and social disorder), and pathway variables (maternal smoking, breastfeeding). In adjusted analyses, medium (OR 1.60, 95% CI 1.17-2.19) and high levels (OR 1.56, 95% CI 1.12-2.18) of community violence were associated with increased asthma risk, relative to low levels. The increased asthma risk remained for African Americans when models included community violence and all other individual-level covariates, but attenuated to borderline nonsignificance when further adjusting for collective efficacy. Community violence is associated with asthma risk when controlling for individual- and neighborhood-level confounders. Neither community violence, nor the other individual-level factors, fully accounted for the excess asthma burden among African Americans. These data suggest that public health interventions outside the biomedical model may be needed to reduce asthma in disadvantaged populations.

  2. Geospatial Modeling of Asthma Population in Relation to Air Pollution

    Science.gov (United States)

    Kethireddy, Swatantra R.; Tchounwou, Paul B.; Young, John H.; Luvall, Jeffrey C.; Alhamdan, Mohammad

    2013-01-01

    Current observations indicate that asthma is growing every year in the United States, specific reasons for this are not well understood. This study stems from an ongoing research effort to investigate the spatio-temporal behavior of asthma and its relatedness to air pollution. The association between environmental variables such as air quality and asthma related health issues over Mississippi State are investigated using Geographic Information Systems (GIS) tools and applications. Health data concerning asthma obtained from Mississippi State Department of Health (MSDH) for 9-year period of 2003-2011, and data of air pollutant concentrations (PM2.5) collected from USEPA web resources, and are analyzed geospatially to establish the impacts of air quality on human health specifically related to asthma. Disease mapping using geospatial techniques provides valuable insights into the spatial nature, variability, and association of asthma to air pollution. Asthma patient hospitalization data of Mississippi has been analyzed and mapped using quantitative Choropleth techniques in ArcGIS. Patients have been geocoded to their respective zip codes. Potential air pollutant sources of Interstate highways, Industries, and other land use data have been integrated in common geospatial platform to understand their adverse contribution on human health. Existing hospitals and emergency clinics are being injected into analysis to further understand their proximity and easy access to patient locations. At the current level of analysis and understanding, spatial distribution of Asthma is observed in the populations of Zip code regions in gulf coast, along the interstates of south, and in counties of Northeast Mississippi. It is also found that asthma is prevalent in most of the urban population. This GIS based project would be useful to make health risk assessment and provide information support to the administrators and decision makers for establishing satellite clinics in future.

  3. Review of family relational stress and pediatric asthma: the value of biopsychosocial systemic models.

    Science.gov (United States)

    Wood, Beatrice L; Miller, Bruce D; Lehman, Heather K

    2015-06-01

    Asthma is the most common chronic disease in children. Despite dramatic advances in pharmacological treatments, asthma remains a leading public health problem, especially in socially disadvantaged minority populations. Some experts believe that this health gap is due to the failure to address the impact of stress on the disease. Asthma is a complex disease that is influenced by multilevel factors, but the nature of these factors and their interrelations are not well understood. This paper aims to integrate social, psychological, and biological literatures on relations between family/parental stress and pediatric asthma, and to illustrate the utility of multilevel systemic models for guiding treatment and stimulating future research. We used electronic database searches and conducted an integrated analysis of selected epidemiological, longitudinal, and empirical studies. Evidence is substantial for the effects of family/parental stress on asthma mediated by both disease management and psychobiological stress pathways. However, integrative models containing specific pathways are scarce. We present two multilevel models, with supporting data, as potential prototypes for other such models. We conclude that these multilevel systems models may be of substantial heuristic value in organizing investigations of, and clinical approaches to, the complex social-biological aspects of family stress in pediatric asthma. However, additional systemic models are needed, and the models presented herein could serve as prototypes for model development.

  4. Towards excellence in asthma management (TEAM): a populational disease-management model.

    Science.gov (United States)

    Boulet, Louis-Philippe; Thivierge, Robert L; Amesse, André; Nunes, Fatima; Francoeur, Suzanne; Collet, Jean-Paul

    2002-06-01

    Asthma management is not always optimal, and deficiencies such as inadequate treatment and insufficient patient education are often reported. Towards Excellence in Asthma Management (TEAM) is a four-phase disease management program of the Quebec Asthma Education Network (QAEN), to be carried out over a 5-year period. The program aims to achieve a continuous improvement of asthma management by caregivers and patients. The first phase, completed in January 2000, consisted of determining the actual level of asthma-associated morbidity and mortality in various Quebec regions. The second phase, which began in September 1999, included three parts: 1. Definition of the burden of asthma, taking into account the socioeconomic consequences of the disease and the quality of life of the patients, 2. Comparison of current medical practices with the Canadian Asthma Consensus Guidelines for adult and pediatric populations, 3. Evaluation of the level of compliance with medical treatment and with the environmental changes recommended to asthmatic patients. This phase is carried out via a cohort study of physicians, mainly general practitioners and pediatricians, generating a patient cohort study, in addition to substudies evaluating specific aspects of asthma care. Once the care gap is identified, it will be possible to define, apply, and evaluate a series of interventions for physicians, other health professionals, and patients. The interventions will be particularly targeted at regions where asthma incidence and morbidity are higher. We hope that this model of disease management will progressively reduce the burden associated with asthma, and potentially other chronic diseases, and will result in the more effective use of health services.

  5. Perinatal Factors and the Risk of Asthma in Childhood-A Population-based Register Study in Finland

    National Research Council Canada - National Science Library

    Metsälä, Johanna; Kilkkinen, Annamari; Kaila, Minna; Tapanainen, Heli; Klaukka, Timo; Gissler, Mika; Virtanen, Suvi M

    2008-01-01

    .... In the final multivariate model, maternal asthma, young age, smoking, previous miscarriages, and a high number of previous deliveries, as well as cesarean section, low gestational age, and low...

  6. Maternal asthma, diabetes, and high blood pressure are associated with low birth weight and increased hospital birth and delivery charges; Hawai'i hospital discharge data 2003-2008.

    Science.gov (United States)

    Hayes, Donald K; Feigal, David W; Smith, Ruben A; Fuddy, Loretta J

    2014-02-01

    Asthma, diabetes, and high blood pressure are common maternal conditions that can impact birth outcomes. Data from hospital discharges in Hawai'i were analyzed for 107,034 singleton births from 2003-2008. Categories were determined using the International Statistical Classification of Diseases, ninth revision (ICD-9) from linked delivery records of mother and infant. Prevalence estimates of asthma (ICD-9: 493), diabetes (ICD-9: 250,648.0, 648.8), high blood pressure (ICD-9: 401-405,642) as coded on the delivery record, low birth weight (high birth weight (>4500 grams), Cesarean delivery, and median hospital charges were calculated. Median regression analysis assessed total hospital charges adjusting for maternal age, maternal race, insurance, and Cesarean delivery. Maternal asthma was present in 4.3% (95% confidence interval=4.1-4.4%), maternal diabetes was present in 7.7% (95% CI=7.6-7.9%), and maternal high blood pressure was present in 9.2% (95% CI=9.0-9.3%) of births. In the adjusted median regression analysis, mothers with asthma had $999 (95% CI: $886 to $1,112) higher hospital charges compared to those without; mothers with diabetes had $743 (95% CI: $636 to $850) higher charges compared to those without; and mothers with high blood pressure had $2,314 (95% CI: $2,194 to $2,434) higher charges compared to those without. Asthma, diabetes, and high blood pressure are associated with higher hospital delivery charges and low birth weight. Diabetes and high blood pressure were also associated with Cesarean delivery. An increased awareness of the impact of these conditions on both adverse birth outcomes and the development of chronic disease is needed.

  7. Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

    Science.gov (United States)

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-06-01

    We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p lung homogenate, the expression of IL-1β was significantly upregulated (p lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

  8. Forecasting asthma-related hospital admissions in London using negative binomial models.

    Science.gov (United States)

    Soyiri, Ireneous N; Reidpath, Daniel D; Sarran, Christophe

    2013-05-01

    Health forecasting can improve health service provision and individual patient outcomes. Environmental factors are known to impact chronic respiratory conditions such as asthma, but little is known about the extent to which these factors can be used for forecasting. Using weather, air quality and hospital asthma admissions, in London (2005-2006), two related negative binomial models were developed and compared with a naive seasonal model. In the first approach, predictive forecasting models were fitted with 7-day averages of each potential predictor, and then a subsequent multivariable model is constructed. In the second strategy, an exhaustive search of the best fitting models between possible combinations of lags (0-14 days) of all the environmental effects on asthma admission was conducted. Three models were considered: a base model (seasonal effects), contrasted with a 7-day average model and a selected lags model (weather and air quality effects). Season is the best predictor of asthma admissions. The 7-day average and seasonal models were trivial to implement. The selected lags model was computationally intensive, but of no real value over much more easily implemented models. Seasonal factors can predict daily hospital asthma admissions in London, and there is a little evidence that additional weather and air quality information would add to forecast accuracy.

  9. Maternal immune markers in serum during gestation and in breast milk and the risk of asthma-like symptoms at ages 6 and 12 months: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Soto-Ramírez Nelís

    2012-07-01

    Full Text Available Abstract Background The role of breast milk on the risk of childhood asthma is in dispute. The aim of this prospective study is to determine the relationship of immune markers in maternal serum during gestation and breast milk to asthma-like symptoms (AS in infancy. Methods Pregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median: three weeks before delivery and breast milk (three weeks after delivery samples were collected. Concentrations of interferon (IFN-γ, IFN gamma-induced protein 10 (IP-10 or CXCL10, CCL11, interleukin (IL 1β, IL-4, IL-5, IL-6, CXCL8, IL-10, IL-12(p70, IL-13, transforming growth factor (TGF-β1, and immunoglobulin (Ig A in both maternal serum and milk whey were determined via immunoassays. Asthma-like symptoms (AS of the infant were ascertained at 6 and 12 months, respectively. Generalized estimating equations assessed relative risks (RRs of immune markers for repeated measurements of AS, considering intra-individual correlations and adjusting for confounders. To provide comparable risk estimates, quartiles of the immune markers were used, except for IL-5 in whey and IgA in serum, which were dichotomized. Results Of 178 women, 161 provided blood and 115 breast milk samples. IL-12(p70, IL-4, IL-10, IL-1β, and CCL11 in serum and in whey were not further considered for the statistical analyses since the proportion of non-detectable values was high. Most immune markers in serum and milk whey were moderately or highly correlated; however, IgA was negatively correlated. Infants in the highest quartile of IL-13 in both serum and whey were at a higher risk of AS (RR = 3.02 and 4.18; respectively compared to infants in the first quartile. High levels of IL-5 in serum and whey was also identified as a risk. In addition, increased secretory IgA and TGF-β1 in breast milk reduced the risks of AS. Conclusions Maternal serum and whey levels of IL-5 and IL-13 are risk markers for AS; whey IgA and TGF

  10. Maternal immune markers in serum during gestation and in breast milk and the risk of asthma-like symptoms at ages 6 and 12 months: a longitudinal study.

    Science.gov (United States)

    Soto-Ramírez, Nelís; Karmaus, Wilfried; Yousefi, Mitra; Zhang, Hongmei; Liu, Jihong; Gangur, Venugopal

    2012-07-17

    The role of breast milk on the risk of childhood asthma is in dispute. The aim of this prospective study is to determine the relationship of immune markers in maternal serum during gestation and breast milk to asthma-like symptoms (AS) in infancy. Pregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median: three weeks before delivery) and breast milk (three weeks after delivery) samples were collected. Concentrations of interferon (IFN)-γ, IFN gamma-induced protein 10 (IP-10 or CXCL10), CCL11, interleukin (IL) 1β, IL-4, IL-5, IL-6, CXCL8, IL-10, IL-12(p70), IL-13, transforming growth factor (TGF)-β1, and immunoglobulin (Ig) A in both maternal serum and milk whey were determined via immunoassays. Asthma-like symptoms (AS) of the infant were ascertained at 6 and 12 months, respectively. Generalized estimating equations assessed relative risks (RRs) of immune markers for repeated measurements of AS, considering intra-individual correlations and adjusting for confounders. To provide comparable risk estimates, quartiles of the immune markers were used, except for IL-5 in whey and IgA in serum, which were dichotomized. Of 178 women, 161 provided blood and 115 breast milk samples. IL-12(p70), IL-4, IL-10, IL-1β, and CCL11 in serum and in whey were not further considered for the statistical analyses since the proportion of non-detectable values was high. Most immune markers in serum and milk whey were moderately or highly correlated; however, IgA was negatively correlated. Infants in the highest quartile of IL-13 in both serum and whey were at a higher risk of AS (RR = 3.02 and 4.18; respectively) compared to infants in the first quartile. High levels of IL-5 in serum and whey was also identified as a risk. In addition, increased secretory IgA and TGF-β1 in breast milk reduced the risks of AS. Maternal serum and whey levels of IL-5 and IL-13 are risk markers for AS; whey IgA and TGF-β1 seem to be protective. Only focusing on breast milk

  11. Revisiting the Hispanic health paradox: the relative contributions of nativity, country of origin, and race/ethnicity to childhood asthma.

    Science.gov (United States)

    Camacho-Rivera, Marlene; Kawachi, Ichiro; Bennett, Gary G; Subramanian, S V

    2015-06-01

    This study examined the relationship between race and Hispanic ethnicity, maternal and child nativity, country of origin and asthma among 2,558 non-Hispanic white and Hispanic children across 65 Los Angeles neighborhoods. A series of two-level multilevel models were estimated to examine the independent effects of race, ethnicity, and country of origin on childhood asthma. Lifetime asthma prevalence was reported among 9% of children, with no significant differences between Hispanics and non-Hispanic whites overall. However, in fully adjusted models, Hispanic children of non-Mexican origin reported higher odds of asthma compared to non-Hispanic white children. A protective nativity effect was also observed among children of foreign born mothers compared to US born mothers. Our study provides evidence in support of the heterogeneity of childhood asthma by Hispanic ethnicity and maternal nativity. These findings suggest moving beyond solely considering racial/ethnic classifications which could mask subgroups at increased risk of childhood asthma.

  12. The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model

    Directory of Open Access Journals (Sweden)

    Fabian M Patricia

    2012-09-01

    Full Text Available Abstract Background In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date. Methods We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%, which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold. Results Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates. Conclusions We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens

  13. Ligustrazine attenuates inflammation and the associated chemokines and receptors in ovalbumine-induced mouse asthma model.

    Science.gov (United States)

    Wei, Ying; Liu, Jiaqi; Zhang, Hongying; Du, Xin; Luo, Qingli; Sun, Jing; Liu, Feng; Li, Mihui; Xu, Fei; Wei, Kai; Dong, Jingcheng

    2016-09-01

    Ligustrazine which is isolated from Chinese herb ligusticum chuanxiong hort, has been widely used in traditional Chinese medicine (TCM) for asthma treatment. In this study, we aim to observe the effect of ligustrazine on inflammation and the associated chemokines and receptors in ovalbumin (OVA)-induced mouse asthma model. Our data demonstrates that ligustrazine suppresses airway hyperresponsiveness to methacholine and lung inflammation in OVA-induced mouse asthma model. Ligustrazine also induces inhibition of inflammatory cells including neutrophils, lymphocytes and eosinophils. In addition, ligustrazine significantly reduces IL-4, IL-5, IL-17A, CCL3, CCL19 and CCL21 level in BALF of asthma mice. Furthermore, ligustrazine induces down-regulation of CCL19 receptor CCR7, STAT3 and p38 MAPK protein expression. Collectively, these results suggest that ligustrazine is effective in attenuation of allergic airway inflammatory changes and related chemokines and receptors in OVA-induced asthma model, and this action might be associated with inhibition of STAT3 and p38 MAPK pathway, which indicates that ligustrazine may be used as a potential therapeutic method to treat asthma.

  14. Maternal vaginal microflora during pregnancy and the risk of asthma hospitalization and use of antiasthma medication in early childhood

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Thorsen, Poul; Jensen, Jørgen Skov;

    2002-01-01

    BACKGROUND: Infants with wheezing and allergic diseases have a microflora that differs from that of healthy infants. The fetus acquires microorganisms during birth when exposed to the maternal vaginal microflora. It is therefore conceivable that the maternal vaginal microflora might influence the...

  15. Periconception endogenous and exogenous maternal sex steroid hormones and risk of asthma and allergy in offspring: protocol for a systematic review and meta-analysis.

    Science.gov (United States)

    Talovic, Merhunisa; Sheikh, Aziz; McCleary, Nicola; Erkkola, Maijaliisa; Kaila, Minna; Virtanen, Suvi M; Nwaru, Bright I

    2017-07-12

    Pregnancy is associated with several hormonal changes which influence the developing fetus. Variations in maternal endogenous hormones and prepregnancy use of hormonal preparations have been linked to asthma and allergy in the offspring, but findings are inconsistent. We plan to undertake a systematic review to synthesise the evidence on the association between endogenous and exogenous maternal sex hormones and the risk of asthma and allergy in the offspring. We will search Medline, Embase, Cochrane Library, Institute of Scientific Information Web of Science, Cumulative Index of Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary Medicine Database, Global Health, Psychological Information (PsycINFO), Centre for Agriculture and Bioscience (CAB) International and WHO Global Health Library from inception until 2016 to identify relevant studies on the topic. Additional studies will be identified by searching databases of proceedings of international conferences, contacting international experts in the field and searching the references cited in identified studies. We will include analytical epidemiological studies. Two researchers will independently screen identified studies, undertake data extraction and assess risk of bias in eligible studies, while a third reviewer will arbitrate any disagreement. We will use the Effective Public Health Practice Project tool to assess the risk of bias in the studies. We will perform a random-effects meta-analysis to synthesise the evidence. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the strength and quality of the overall evidence with respect to each outcome. Ethical approval is not required since the study is a systematic review of published literature. Our findings will be reported in a peer-reviewed scientific journal. CRD42016048324. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  16. Safranal of Crocus sativus L. inhibits inducible nitric oxide synthase and attenuates asthma in a mouse model of asthma.

    Science.gov (United States)

    Bukhari, Syed Imran; Pattnaik, Bijay; Rayees, Sheikh; Kaul, Sanjana; Dhar, Manoj K

    2015-04-01

    The present study involves evaluation of antioxidant potential of Crocus sativus and its main constituents, safranal (SFN) and crocin (CRO), in bronchial epithelial cells, followed antiinflammatory potential of the active constituent safranal, in a murine model of asthma. To investigate the antioxidizing potential of Crocus sativus and its main constituents in bronchial epithelial cells, the stress was induced in these cells by a combination of different cytokines that resulted in an increase in nitric oxide production (NO), induced nitric oxide synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release. Treatment with saffron and its constituents safranal and crocin resulted in a decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented cytochrome c release. However, safranal significantly reduced oxidative stress in bronchial epithelial cells via iNOS reduction besides preventing apoptosis in these cells. In the murine model of asthma study, antiinflammatory role of safranal was characterized by increased airway hyper-responsiveness, airway cellular infiltration, and epithelial cell injury. Safranal pretreatment to these allergically inflamed mice lead to a significant decrease in airway hyper-responsiveness and airway cellular infiltration to the lungs. It also reduced iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine production in the lungs.

  17. Lifetime-dependent effects of bisphenol A on asthma development in an experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Susanne Petzold

    Full Text Available BACKGROUND: Environmental factors are thought to contribute significantly to the increase of asthma prevalence in the last two decades. Bisphenol A (BPA is a xenoestrogen commonly used in consumer products and the plastic industry. There is evidence and an ongoing discussion that endocrine disruptors like BPA may affect human health and also exert alterations on in the immune system. The aim of this study was to investigate age-dependent effects of BPA on the asthma risk using a murine model to explain the controversial results reported till date. METHODS: BALB/c mice were exposed to BPA via the drinking water for different time periods including pregnancy and breastfeeding. To induce an asthma phenotype, mice were sensitized to ovalbumin (OVA, followed by an intrapulmonary allergen challenge. RESULTS: BPA exposure during pregnancy and breastfeeding had no significant effect on asthma development in the offspring. In contrast, lifelong exposure from birth until the last antigen challenge clearly increased eosinophilic inflammation in the lung, airway hyperreactivity and antigen-specific serum IgE levels in OVA-sensitized adult mice compared to mice without BPA exposure. Surprisingly, BPA intake during the sensitization period significantly reduced the development of allergic asthma. This effect was reversed in the presence of a glucocorticoid receptor antagonist. CONCLUSIONS: Our results demonstrate that the impact of BPA on asthma risk is strongly age-dependent and ranges from asthma-promoting to asthma-reducing effects. This could explain the diversity of results from previous studies regarding the observed health impact of BPA.

  18. Lifetime-Dependent Effects of Bisphenol A on Asthma Development in an Experimental Mouse Model

    Science.gov (United States)

    Petzold, Susanne; Averbeck, Marco; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

    2014-01-01

    Background Environmental factors are thought to contribute significantly to the increase of asthma prevalence in the last two decades. Bisphenol A (BPA) is a xenoestrogen commonly used in consumer products and the plastic industry. There is evidence and an ongoing discussion that endocrine disruptors like BPA may affect human health and also exert alterations on in the immune system. The aim of this study was to investigate age-dependent effects of BPA on the asthma risk using a murine model to explain the controversial results reported till date. Methods BALB/c mice were exposed to BPA via the drinking water for different time periods including pregnancy and breastfeeding. To induce an asthma phenotype, mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge. Results BPA exposure during pregnancy and breastfeeding had no significant effect on asthma development in the offspring. In contrast, lifelong exposure from birth until the last antigen challenge clearly increased eosinophilic inflammation in the lung, airway hyperreactivity and antigen-specific serum IgE levels in OVA-sensitized adult mice compared to mice without BPA exposure. Surprisingly, BPA intake during the sensitization period significantly reduced the development of allergic asthma. This effect was reversed in the presence of a glucocorticoid receptor antagonist. Conclusions Our results demonstrate that the impact of BPA on asthma risk is strongly age-dependent and ranges from asthma-promoting to asthma-reducing effects. This could explain the diversity of results from previous studies regarding the observed health impact of BPA. PMID:24950052

  19. Interleukin-16 in a mouse model of allergic asthma

    NARCIS (Netherlands)

    Bie, J.J. (Joris Johannes) de

    2001-01-01

    Allergic asthma is a disease which affects an increasing number of people. Patients with this illness suffer from variable airflow obstruction and increased airway responsiveness to a variety of stimuli. Furthermore, an inflammatory response in the lungs occurs, accompanied by enhanced mucus product

  20. Asthma Basics

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Asthma Basics KidsHealth > For Parents > Asthma Basics A A ... Asthma Categories en español Asma: aspectos fundamentales About Asthma Asthma is a common lung condition in kids ...

  1. Unintentional role models : links between maternal eating psychopathology and the modelling of eating behaviours\\ud

    OpenAIRE

    2013-01-01

    This study explored the relationships between maternal modelling of eating behaviours with reported symptoms of maternal eating psychopathology, anxiety and depression. Mothers (N = 264) with a child aged 1.5 to 8 years completed three self-report measures designed to assess modelling of eating behaviours, eating psychopathology and levels of anxiety and depression. The study found that higher levels of maternal eating psychopathology were positively associated with eating behaviours that wer...

  2. Road-traffic pollution and asthma – using modelled exposure assessment for routine public health surveillance

    Directory of Open Access Journals (Sweden)

    Daly Mark

    2004-10-01

    Full Text Available Abstract Asthma is a common disease and appears to be increasing in prevalence. There is evidence linking air pollution, including that from road-traffic, with asthma. Road traffic is also on the increase. Routine surveillance of the impact of road-traffic pollution on asthma, and other diseases, would be useful in informing local and national government policy in terms of managing the environmental health risk. Several methods for exposure assessment have been used in studies examining the association between asthma and road traffic pollution. These include comparing asthma prevalence in areas designated as high and low pollution areas, using distance from main roads as a proxy for exposure to road traffic pollution, using traffic counts to estimate exposure, using vehicular miles travelled and using modelling techniques. Although there are limitations to all these methods, the modelling approach has the advantage of incorporating several variables and may be used for prospective health impact assessment. The modelling approach is already in routine use in the United Kingdom in support of the government's strategy for air quality management. Combining information from such models with routinely collected health data would form the basis of a routine public health surveillance system. Such a system would facilitate prospective health impact assessment, enabling policy decisions concerned with road-traffic to be made with knowledge of the potential implications. It would also allow systematic monitoring of the health impacts when the policy decisions and plans have been implemented.

  3. Tobaksrygning og asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2002-01-01

    with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke, especially maternal smoking in children, may be a significant risk factor for asthma. Such exposure in patients with established asthma is not only associated with more severe symptoms......Cigarette smoking is a well-known health hazard, probably not least for patients suffering from asthma. This review gives a short overview of the effects of passive and active smoking on the inception and outcome with of longitudinal changes in the lung function and mortality of patients......, but also with a poorer quality of life, reduced lung function, and increased utilisation of health care including hospital admissions. Active smoking does not appear to be a significant risk factor for asthma, but is associated with a worse outcome with regard to both longitudinal changes in lung function...

  4. Tobaksrygning og asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2002-01-01

    with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke, especially maternal smoking in children, may be a significant risk factor for asthma. Such exposure in patients with established asthma is not only associated with more severe symptoms......Cigarette smoking is a well-known health hazard, probably not least for patients suffering from asthma. This review gives a short overview of the effects of passive and active smoking on the inception and outcome with of longitudinal changes in the lung function and mortality of patients......, but also with a poorer quality of life, reduced lung function, and increased utilisation of health care including hospital admissions. Active smoking does not appear to be a significant risk factor for asthma, but is associated with a worse outcome with regard to both longitudinal changes in lung function...

  5. The “time-window” effect of early allergen exposure on a rat asthma model

    Institute of Scientific and Technical Information of China (English)

    HU Yan; LIU Ping; LI Hai-chao; WANG Yue-dan

    2013-01-01

    Background The hygiene hypothesis has been proposed to explain the pathogenesis of asthma.Allergen exposure was shown to inhibit asthma in an animal model.But the optimal timing of allergen exposure remains unclear.This study aims to explore the time effcct of allergen exposure and the possible mechanisms.Methods Neonate Wistar rats were randomly divided into asthma group,control group and day 1,day 3,day 7,and day 14 groups.The day 1,day 3,day 7 and day 14 groups were injected with ovalbumin (OVA) subcutaneously on days 1,3,7 and 14 after birth,respectively.Six weeks later,all groups,except the control group,were sensitized and stimulated with OVA to make the asthma model.We observed the pulmonary pathologic changes,detected the regulatory T cells,and CD28 expression level in thymus and spleen by flow cytometry.Results The asthmatic inflammation in the day 1,day 3 and day 7 groups,but not the day 14 group,was alleviated.The asthma group and day 14 group had lower proportions of regulatory T cells in the thymus compared with the control group,day 1,day 3,and day 7 groups.There was no significant difference in the CD28 expression levels on the regulatory and conventional T cells among groups.But the control group and the day 1,day 3,and day 7 groups had relatively higher proportions of CD28 positive regulatory T cells in the thymus than the day 14 group and the asthma group.Conclusions There is a “time-window” for early allergen exposure.The impairment of regulatory T cells may promote the development of asthma.Allergen exposure in the “time-window” can make the thymus produce normal quantity of regulatory cells.The CD28 signal on regulatory T cells may participate in the production of regulatory T cells.

  6. Rush immunotherapy in an experimental model of feline allergic asthma.

    Science.gov (United States)

    Reinero, Carol R; Byerly, Jenni R; Berghaus, Roy D; Berghaus, Londa J; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

    2006-03-15

    Specific allergen immunotherapy represents the only curative treatment of allergy. No studies have evaluated its efficacy in feline allergic asthma. We hypothesized that an abbreviated course of immunotherapy (rush immunotherapy, RIT) would blunt eosinophilic airways inflammation in experimental feline asthma induced with Bermuda grass allergen (BGA). The 6-month study included asthmatic-RIT treated cats; asthmatic-no RIT treated cats; and non-asthmatic cats. RIT involved increasing parenteral doses (20-200 microg) of BGA over 2 days. Numbers of eosinophils in bronchoalveolar lavage fluid (BALF), serum and BALF immunoglobulins, lymphocyte blastogenesis assays, and cytokines in blood and BALF were evaluated. BALF eosinophils decreased (P=0.048) only in asthmatic-RIT treated cats (baseline 1.1 x 10(6); Month 6, 2.4 x 10(5)). Serum BGA-specific IgG was higher (Peosinophilic airways inflammation in cats with experimental asthma. The mechanism of RIT may involve changes in allergen-specific immunoglobulins, induction of hyporesponsive lymphocytes, or alteration of cytokine profiles.

  7. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Chia-Rui Shen

    2015-11-01

    Full Text Available Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.

  8. Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

    Science.gov (United States)

    Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

    2017-03-04

    Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Periconceptional and Gestational Exposure to Antibiotics and Childhood Asthma.

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    Shuyuan Chu

    Full Text Available Previous studies suggest that maternal antibiotics exposure during pregnancy may increase the risk of childhood asthma, but the results were inconsistent. Furthermore, most studies did not examine periconception period as an exposure window. We aim to assess the associations between maternal exposure to specific antibiotics before and during pregnancy and the risk of asthma in early childhood.Data from the Collaborative Perinatal Project were used. Maternal exposure to antibiotics before and during pregnancy was recorded at each prenatal visit. A total of 39,907 singleton children were followed up to 7 years of age. Multilevel multiple logistic regression models were used to control for potential confounders and account for multiple pregnancies per woman.Maternal use of penicillin or chloramphenicol was associated with an increased risk of asthma in the offspring (adjusted odds ratio = 1.21, 95% confidence interval 1.08-1.36 for penicillin; 1.72 [1.14-2.59] for chloramphenicol. The risk was significantly increased if penicillin or chloramphenicol was used in the 1st trimester (1.09 [1.04-1.13] for penicillin and 1.23 [1.01-1.51] for chloramphenicol.Maternal exposure to certain antibiotics is associated with childhood asthma by 7 years of age. Early pregnancy may be a sensitive window.

  10. Mild Diabetes Models and Their Maternal-Fetal Repercussions

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2013-01-01

    Full Text Available The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.

  11. The Chronic Care Model: A Collaborative Approach to Preventing and Treating Asthma in Infants and Young Children

    Science.gov (United States)

    Wessel, Lois; Spain, Jacqueline

    2005-01-01

    The authors that a collaborative approach between parents and professionals is the best way to care for a young child with asthma. They use Ed Wagner's transdisciplinary 1998 Chronic Care Model as their preferred method for collaboration. More than 5 million children in the U.S. are currently affected by asthma, and a growing body of evidence…

  12. Effects of inhaled L-arginine administration in a murine model of acute asthma.

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    Zeynep Arikan-Ayyildiz

    2014-10-01

    Full Text Available Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂ and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control. All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I, saline (Group II and budesonide (Group III, respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043. Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05. Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

  13. Regulation of Th1/Th2 cells in asthma development: a mathematical model.

    Science.gov (United States)

    Kim, Yangjin; Lee, Seongwon; Kim, You-Sun; Lawler, Sean; Gho, Yong Song; Kim, Yoon-Keun; Hwang, Hyung Ju

    2013-08-01

    Airway exposure levels of lipopolysaccharide (LPS) determine type I versus type II helper T cell induced experimental asthma. While high LPS levels induce Th1-dominant responses, low LPS levels derive Th2 cell induced asthma. The present paper develops a mathematical model of asthma development which focuses on the relative balance of Th1 and Th2 cell induced asthma. In the present work we represent the complex network of interactions between cells and molecules by a mathematical model. The model describes the behaviors of cells (Th0, Th1, Th2 and macrophages) and regulatory molecules (IFN- γ, IL-4, IL-12, TNF-α) in response to high, intermediate, and low levels of LPS. The simulations show how variations in the levels of injected LPS affect the development of Th1 or Th2 cell responses through differential cytokine induction. The model also predicts the coexistence of these two types of response under certain biochemical and biomechanical conditions in the microenvironment.

  14. TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA

    Science.gov (United States)

    TRIMELLITIC ANHYDRIDE-INDUCED EOSINOPHILIA IN A MURINE MODEL OF OCCUPATIONAL ASTHMA. J F Regal, ME Mohrman, E Boykin and D Sailstad. Dept. of Pharmacology, University of Minnesota, Duluth, MN, USA and NHEERL, ORD, US EPA, RTP, NC, USA.Trimellitic anhydride (TMA) is a small m...

  15. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  16. Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma.

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    -remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies.

  17. The management of asthma in the phenotype and biomarker era: The proposal of a new diagnostic-therapeutic model.

    Science.gov (United States)

    Blasi, Francesco; Bettoncelli, Germano; Canonica, Giorgio Walter; Centanni, Stefano; Crimi, Nunzio; DiMaria, Giuseppe; Gasparini, Stefano; Gentili, Gilberto; Girbino, Giuseppe; Mereu, Carlo; Minghetti, Paola; Nardini, Stefano; Paggiaro, Pierluigi; Papi, Alberto; Pistolesi, Massimo; Rossi, Andrea

    2016-09-01

    Treatment goals in asthma patients are the achievement of a good control of symptoms and the reduction of the risk of exacerbation. However, a "one-size-fits-all" therapeutic strategy is no longer appropriate to effectively pursue these goals, due to the heterogeneity of asthma. To make the treatment scenario even more complex, asthma patients often present comorbidities that may alter response to therapy. In addition, adherence to asthma treatment is poor. Given this complex and heterogeneous picture, the management of asthma is highly challenging. A clear diagnostic-therapeutic model of patients' care and the definition of the specific responsibilities of different healthcare providers appear necessary to improve clinical outcomes and better allocate healthcare resources. We present here a proposal for this model.

  18. Pediatric Asthma

    Science.gov (United States)

    ... Science Education & Training Home Conditions Asthma (Pediatric) Asthma (Pediatric) Make an Appointment Refer a Patient Ask a ... meet the rising demand for asthma care. Our pediatric asthma team brings together physicians, nurses, dietitians, physical ...

  19. Pediatric Asthma

    Science.gov (United States)

    ... Plan Asthma Epidemic Eating with Asthma Helping Your Child Cope With a Medical Condition Nasal Wash Guide Cleaning Dirty Items Impact on Families Asthma & Pets Peak Flow Meter Athletes & Asthma Helpful Tools for ...

  20. The maternal deprivation animal model revisited.

    Science.gov (United States)

    Marco, Eva M; Llorente, Ricardo; López-Gallardo, Meritxell; Mela, Virginia; Llorente-Berzal, Álvaro; Prada, Carmen; Viveros, María-Paz

    2015-04-01

    Early life stress, in the form of MD (24h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry.

  1. Modeling of Regional Climate Change Effects on Ground-Level Ozone and Childhood Asthma

    Science.gov (United States)

    Sheffield, Perry E.; Knowlton, Kim; Carr, Jessie L.; Kinney, Patrick L.

    2011-01-01

    Background The adverse respiratory effects of ground-level ozone are well-established. Ozone is the air pollutant most consistently projected to increase under future climate change. Purpose To project future pediatric asthma emergency department visits associated with ground-level ozone changes, comparing 1990s to 2020s. Methods This study assessed future numbers of asthma emergency department visits for children aged 0–17 years using (1) baseline New York City metropolitan area emergency department rates, (2) a dose–response relationship between ozone levels and pediatric asthma emergency department visits, and (3) projected daily 8-hour maximum ozone concentrations for the 2020s as simulated by a global-to-regional climate change and atmospheric chemistry model. Sensitivity analyses included population projections and ozone precursor changes. This analysis occurred in 2010. Results In this model, climate change could cause an increase in regional summer ozone-related asthma emergency department visits for children aged 0–17 years of 7.3% across the New York City metropolitan region by the 2020s. This effect diminished with inclusion of ozone precursor changes. When population growth is included, the projections of morbidity related to ozone are even larger. Conclusions The results of this analysis demonstrate that the use of regional climate and atmospheric chemistry models make possible the projection of local climate change health effects for specific age groups and specific disease outcomes – such as emergency department visits for asthma. Efforts should be made to improve on this type of modeling to inform local and wider-scale climate change mitigation and adaptation policy. PMID:21855738

  2. Using the Health Belief Model to Understand School Nurse Asthma Management

    Science.gov (United States)

    Quaranta, Judith E.; Spencer, Gale A.

    2015-01-01

    Ten million children in the United States have asthma. Since children are in school about 6 hr a day, school nurses are positioned to intervene and influence asthma outcomes. A descriptive correlational study was designed to investigate performance of school nurses' asthma management behaviors in relationship to asthma knowledge, asthma attitude,…

  3. Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model.

    Science.gov (United States)

    Zhou, De-Gang; Diao, Bao-Zhong; Zhou, Wen; Feng, Jia-Long

    2016-04-01

    Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory property. In this study, we aimed to investigate the protective effects and mechanism of oroxylin A on allergic inflammation in OVA-induced asthma murine model. BABL/c mice were sensitized and airway-challenged with OVA to induce asthma. Oroxylin A (15, 30, and 60 mg/kg) was administered by oral gavage 1 h before the OVA treatment on day 21 to 23. The results showed that oroxylin A attenuated OVA-induced lung histopathologic changes, airway hyperresponsiveness, and the number of inflammatory cells. Oroxylin A also inhibited the levels of IL-4, IL-5, IL-13, and OVA-specific IgE in BALF. Furthermore, oroxylin A significantly inhibited OVA-induced NF-κB activation. In conclusion, these results suggested that oroxylin A inhibited airway inflammation in OVA-induced asthma murine model by inhibiting NF-κB activation. These results suggested that oroxylin A was a potential therapeutic drug for treating allergic asthma.

  4. Difficult Asthma

    Directory of Open Access Journals (Sweden)

    Ahmet Uslu

    2003-03-01

    Full Text Available Difficult asthma is a distinct entity of asthma, comprising approximately %5 of asthmatic patients. There is no agreed definition of difficult asthma. It will include asthma uncontrolled by new standard therapy, steroid dependent, steroid resistant and severe asthma. In this study difficult asthma; clinical features, risk factors, pathophysiology and novel therapies are summarized by literatures.

  5. Difficult asthma

    OpenAIRE

    Ahmet Uslu; Tülay Özdemir

    1989-01-01

    Difficult asthma is a distinct entity of asthma, comprising approximately %5 of asthmatic patients. There is no agreed definition of difficult asthma. It will include asthma uncontrolled by new standard therapy, steroid dependent, steroid resistant and severe asthma. In this study difficult asthma; clinical features, risk factors, pathophysiology and novel therapies are summarized by literatures.

  6. Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma.

    Science.gov (United States)

    Ather, Jennifer L; Chung, Michael; Hoyt, Laura R; Randall, Matthew J; Georgsdottir, Anna; Daphtary, Nirav A; Aliyeva, Minara I; Suratt, Benjamin T; Bates, Jason H T; Irvin, Charles G; Russell, Sheila R; Forgione, Patrick M; Dixon, Anne E; Poynter, Matthew E

    2016-08-01

    Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery-induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma.

  7. An emerging model of maternity care: smartphone, midwife, doctor?

    Science.gov (United States)

    Tripp, Nadia; Hainey, Kirsten; Liu, Anthony; Poulton, Alison; Peek, Michael; Kim, Jinman; Nanan, Ralph

    2014-03-01

    Mobile technology in the form of the smartphone is widely used, particularly in pregnancy and they are an increasing and influential source of information. To describe the diverse nature of pregnancy related applications (apps) for the smartphone and to flag that these apps can potentially affect maternity care and should be considered in future planning of care provision. The 2 smartphone platforms, Apple and Android, were searched for pregnancy related apps and reviewed for their purpose and popularity. iTunes and Google Play returned 1059 and 497 pregnancy related apps respectively. Forty percent of the apps were informative, 13% interactive, 19% had features of a medical tool and 11% were social media apps. By far the most popular apps, calculated as the number of reviews multiplied by average reviewer rating, were those with interactive features. The popularity of pregnancy-related apps could indicate a shift towards patient empowerment within maternity care provision. The traditional model of 'shared maternity care' needs to accommodate electronic devices into its functioning. Reliance on healthcare professionals may be reduced by the availability of interactive and personalised information delivered via a smartphone. This combined with the fact that smartphones are widely used by many women of childbearing age, has the potential to modify maternity care and experiences of pregnancy. Therefore it is important that healthcare professionals and policy-makers are more aware of these new developments, which are likely to influence healthcare and alter health-seeking behaviour. In addition healthcare professionals need to consider whether to discuss the use of apps in pregnancy with the women in their care. Copyright © 2013 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  8. Active immunotherapy of allergic asthma with a recombinant human interleukin-5 protein as vaccine in a murine model

    Institute of Scientific and Technical Information of China (English)

    TAN Guang-hong; WANG Cai-chun; HUANG Feng-ying; WANG Hua; HUANG Yong-hao; LIN Ying-ying

    2007-01-01

    Background Eosinophils are highly related to allergic asthma inflammation. Interleukin (IL)-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities.Methods Recombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted. Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay (ELISA) and Western blot assay.Results Vaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 (IL-4) to Th1 (INF-γ) in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5.Conclusions Active immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.

  9. Prenatal Stress, Prematurity, and Asthma.

    Science.gov (United States)

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C

    2015-12-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the United States and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced "premature asthma." Prenatal stress may cause not only abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring TH2 (allergic) immune responses characteristic of atopic asthma: interleukin 6 (IL-6), which has been associated with premature labor, can promote TH2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing "premature asthma." If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common comorbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (eg, from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health.

  10. Asthma and Pregnancy

    Science.gov (United States)

    ... increase the risk for birth defects over that background risk. This information should not take the place of medical care ... RL, Murphy VE. 2015. Maternal complications and the management of asthma in pregnancy. Womens Health (Lond Engl);11(2):183-91. ... "When I called MotherToBaby looking for information on medication to use during pregnancy, I was ...

  11. An integrated model of environmental factors in adult asthma lung function and disease severity: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Katz Patricia P

    2010-05-01

    Full Text Available Abstract Background Diverse environmental exposures, studied separately, have been linked to health outcomes in adult asthma, but integrated multi-factorial effects have not been modeled. We sought to evaluate the contribution of combined social and physical environmental exposures to adult asthma lung function and disease severity. Methods Data on 176 subjects with asthma and/or rhinitis were collected via telephone interviews for sociodemographic factors and asthma severity (scored on a 0-28 point range. Dust, indoor air quality, antigen-specific IgE antibodies, and lung function (percent predicted FEV1 were assessed through home visits. Neighborhood socioeconomic status, proximity to traffic, land use, and ambient air quality data were linked to the individual-level data via residential geocoding. Multiple linear regression separately tested the explanatory power of five groups of environmental factors for the outcomes, percent predicted FEV1 and asthma severity. Final models retained all variables statistically associated (p Results Mean FEV1 was 85.0 ± 18.6%; mean asthma severity score was 6.9 ± 5.6. Of 29 variables screened, 13 were retained in the final model of FEV1 (R2 = 0.30; p 2 = 0.16; p 1 as an independent variable to the severity model further increased its explanatory power (R2 = 0.25. Conclusions Multivariate models covering a range of individual and environmental factors explained nearly a third of FEV1 variability and, taking into account lung function, one quarter of variability in asthma severity. These data support an integrated approach to modeling adult asthma outcomes, including both the physical and the social environment.

  12. Effect of Orem’s Self-Care Model on Self-Esteem of Adolescents with Asthma Referred to an Asthma and Allergy Clinic in Isfahan

    Science.gov (United States)

    Hemati, Zeinab; Mosaviasl, Fatemeh Sadat; Abasi, Samira; Ghazavi, Zohre

    2015-01-01

    Introduction: Acquisition of chronic diseases such as asthma leads to psychological, mental and physical complications in adolescents, and hence their self-esteem may be compromised. Therefore, the present study was conducted to assess the effect of Orem’s self-care model on self-esteem of adolescents with asthma. Materials and Methods: This semi-experimental study enrolled 64 asthmatic adolescents referred to Shariati Hospital, Isfahan. Subjects were assigned to two groups of control and intervention consecutively. Then, the self-care training program was conducted according to Orem’s self-care model in eight two-hour sessions based on self-care needs, and self-esteem was measured in the two groups prior to and two months after the last training session. The data were collected by a questionnaire of demographic characteristics and the Coopersmith Self-Esteem Inventories (CSEI) and analyzed by SPSS version 20. Results: Independent t-test showed a significant difference in the mean score of self-esteem between the intervention and control groups after the training (P0.05). Conclusion: Regarding the effect of Orem’s self-care model on self-esteem of adolescents with asthma, we recommend the use of this model as a care intervention in healthcare centers to promote adolescents’ health. PMID:27114724

  13. Effect of Orem's Self-Care Model on Self-Esteem of Adolescents with Asthma Referred to an Asthma and Allergy Clinic in Isfahan.

    Science.gov (United States)

    Hemati, Zeinab; Mosaviasl, Fatemeh Sadat; Abasi, Samira; Ghazavi, Zohre; Kiani, Davood

    2015-01-01

    Acquisition of chronic diseases such as asthma leads to psychological, mental and physical complications in adolescents, and hence their self-esteem may be compromised. Therefore, the present study was conducted to assess the effect of Orem's self-care model on self-esteem of adolescents with asthma. This semi-experimental study enrolled 64 asthmatic adolescents referred to Shariati Hospital, Isfahan. Subjects were assigned to two groups of control and intervention consecutively. Then, the self-care training program was conducted according to Orem's self-care model in eight two-hour sessions based on self-care needs, and self-esteem was measured in the two groups prior to and two months after the last training session. The data were collected by a questionnaire of demographic characteristics and the Coopersmith Self-Esteem Inventories (CSEI) and analyzed by SPSS version 20. Independent t-test showed a significant difference in the mean score of self-esteem between the intervention and control groups after the training (Pself-esteem before and after the training in the intervention group (P0.05). Regarding the effect of Orem's self-care model on self-esteem of adolescents with asthma, we recommend the use of this model as a care intervention in healthcare centers to promote adolescents' health.

  14. The role of CTLA4-Ig in a mouse model against allergic asthma

    Institute of Scientific and Technical Information of China (English)

    万欢英; 周敏; 徐青; 黄绍光; 邓伟吾

    2003-01-01

    Objective To investigate CTLA4-Ig's potential role in therapy for allergic asthma by blocking B7/CD28 interactions with cytotoxic T lymphocyte antigen 4-Ig (CTLA4-Ig).Methods We divided BALB/C mice into the three groups: Sham/Sham (control), ovalbumin (OVA)/OVA and mCTLA4-Ig. Blood, bronchoalveolar lavage, histology and determination of cytokines were performed 24 hours after airway challenge. Results In the OVA/OVA group, the number of cells, the percentage of inflamed cells and the level of IL-4 in BALF were increased. Airways in our murine model for allergic asthma underwent pathological changes, which were significantly reduced after treatment with mCTLA4-Ig. Conclusion Blockage of co-stimulation with mCTLA4-Ig can inhibit allergy-specific response of T cells, and asthmatic response as well.

  15. Anti-asthmatic effects of matrine in a mouse model of allergic asthma.

    Science.gov (United States)

    Fu, Qiang; Wang, Jing; Ma, Zhanqing; Ma, Shiping

    2014-04-01

    The aim of the study was to investigate the anti-asthmatic effects of matrine and the possible mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg) and matrine (50 mg/kg, 100 mg/kg). Airway resistance (Raw) was measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and interleukin-13 were evaluated by enzyme-linked immunosorbent assay (ELISA), IL-4 and IL-13 signal protein STAT6 was measured by western blotting. Our study demonstrated that matrine inhibited OVA-induced increases in Raw and eosinophil count; IL-4 and IL-13 were recovered. Histological studies demonstrated that matrine substantially inhibited OVA-induced eosinophilia in lung tissue. Western blotting studies demonstrated that matrine substantially inhibited STAT6 protein level. These findings suggest that matrine may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

  16. Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

    Directory of Open Access Journals (Sweden)

    Kang JY

    2013-10-01

    Full Text Available Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA for 1 month (n = 8–12 per group. We analyzed inflammatory cells and T-helper (Th2 cytokines in bronchoalveolar lavage (BAL fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old mice than in the young (6-week-old mice. Interleukin (IL 4 (IL-4 concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma

  17. Fine particulate matter estimated by mathematical model and hospitalizations for pneumonia and asthma in children

    Directory of Open Access Journals (Sweden)

    Ana Cristina Gobbo César

    2016-03-01

    Full Text Available Abstract Objective: To estimate the association between exposure to fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5 and hospitalizations for pneumonia and asthma in children. Methods: An ecological study of time series was performed, with daily indicators of hospitalization for pneumonia and asthma in children up to 10 years of age, living in Taubaté (SP and estimated concentrations of PM2.5, between August 2011 and July 2012. A generalized additive model of Poisson regression was used to estimate the relative risk, with lag zero up to five days after exposure; the single pollutant model was adjusted by the apparent temperature, as defined from the temperature and relative air humidity, seasonality and weekday. Results: The values of the relative risks for hospitalization for pneumonia and asthma were significant for lag 0 (RR=1.051, 95%CI; 1.016 to 1.088; lag 2 (RR=1.066, 95%CI: 1.023 to 1.113; lag 3 (RR=1.053, 95%CI: 1.015 to 1.092; lag 4 (RR=1.043, 95%CI: 1.004 to 1.088 and lag 5 (RR=1.061, 95%CI: 1.018 to 1.106. The increase of 5mcg/m3 in PM2.5 contributes to increase the relative risk for hospitalization from 20.3 to 38.4 percentage points; however, the reduction of 5µg/m3 in PM2.5 concentration results in 38 fewer hospital admissions. Conclusions: Exposure to PM2.5 was associated with hospitalizations for pneumonia and asthma in children younger than 10 years of age, showing the role of fine particulate matter in child health and providing subsidies for the implementation of preventive measures to decrease these outcomes.

  18. Ag85B DNA vaccine suppresses airway inflammation in a murine model of asthma

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    Gao Xinglin

    2009-06-01

    Full Text Available Abstract Background In allergic asthma, Th2 lymphocytes are believed to play important roles in orchestrating airway eosinophilia and inflammation. Resetting the Th1/Th2 imbalance may have a therapeutic role in asthma. The mycobacterium tuberculosis 30-kilodalton major secretory protein (antigen 85B, Ag85B can protect animals from M. tuberculosis infection by inducing a Th1-dominant response. Methods In this study, the Ag85B gene was cloned into pMG plasmids to yield the pMG-Ag85B plasmid. The expression of Ag85B gene in murine bronchial epithelia cells was detected by Western blotting and immunohistochemical staining after intranasal immunization with reconstructed pMG-Ag85B plasmids. The protective effect of pMG-Ag85B plasmids immunization in airway inflammation was evaluated by histological examination and bronchoalveolar lavage (BAL. IL-4 and IFN-γ levels in the BAL and supernatant from splenocyte culture were determined using ELISA kits. Results The Ag85B gene was successfully expressed in murine bronchial epithelia cells by intranasal immunization with reconstructed pMG-Ag85B plasmids. Using a murine model of asthma induced by ovalbumin (OVA, pMG-Ag85B immunization significantly inhibited cellular infiltration across the airway epithelium with a 37% decrease in the total number of cells (9.6 ± 2.6 × 105/ml vs. 15.2 ± 3.0 × 105/ml, p 5/ml vs. 5.4 ± 1.1 × 105/ml, p Conclusion In a murine model of asthma induced by OVA, intranasal immunization with pMG-Ag85B significantly reduced allergic airway inflammation with less eosinophil infiltration. This protective effect was associated with decreased IL-4 and increased IFN-γ production in the BAL fluid and in the supernatant of cultured splenocytes.

  19. Tobaksrygning og asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Lange, Peter

    2002-01-01

    Cigarette smoking is a well-known health hazard, probably not least for patients suffering from asthma. This review gives a short overview of the effects of passive and active smoking on the inception and outcome with of longitudinal changes in the lung function and mortality of patients with ast......Cigarette smoking is a well-known health hazard, probably not least for patients suffering from asthma. This review gives a short overview of the effects of passive and active smoking on the inception and outcome with of longitudinal changes in the lung function and mortality of patients...... with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke, especially maternal smoking in children, may be a significant risk factor for asthma. Such exposure in patients with established asthma is not only associated with more severe symptoms......, but also with a poorer quality of life, reduced lung function, and increased utilisation of health care including hospital admissions. Active smoking does not appear to be a significant risk factor for asthma, but is associated with a worse outcome with regard to both longitudinal changes in lung function...

  20. Dietary pattern and asthma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Lv N

    2014-08-01

    Full Text Available Nan Lv,1 Lan Xiao,1 Jun Ma1,2 1Palo Alto Medical Foundation Research Institute, 2Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA Background: The literature on the relationship between diet and asthma has largely focused on individual nutrients, with conflicting results. People consume a combination of foods from various groups that form a dietary pattern. Studying the role of dietary patterns in asthma is an emerging area of research. The purpose of this study was to systematically review dietary patterns and asthma outcomes in adults and children, to review maternal diet and child asthma, and to conduct a meta-analysis on the association between asthma prevalence and dietary patterns in adults. Methods: We searched Medline, Scopus, and ISI Web of Knowledge up to January 2014. Two researchers independently reviewed studies meeting the inclusion criteria using the American Dietetic Association quality criteria. A linear mixed model was used to derive the pooled effect size (95% confidence interval for each of three dietary pattern categories (healthy, unhealthy, and neutral. Results: Thirty-one studies were identified (16 cross-sectional, one case-control, 13 cohort, and one randomized controlled trial, including 12 in adults, 13 in children, five in pregnant woman–child pairs, and one in both children and pregnant woman–child pairs. Six of the 12 adult studies reported significant associations between dietary patterns and asthma outcomes (eg, ever asthma and forced expiratory volume in one second. Seven of ten studies examining the Mediterranean diet showed protective effects on child asthma and/or wheeze. Four of the six studies in mother-child pairs showed that maternal dietary patterns during pregnancy were not associated with child asthma or wheeze. The meta-analysis including six adult studies, the primary outcome of which was the prevalence of current or ever asthma, showed no association with healthy

  1. Occupational asthma

    Science.gov (United States)

    ... Names Asthma - occupational exposure; Irritant-induced reactive airways disease Images Spirometry Respiratory system References Lemiere C, Vandenplas O. Occupational allergy and asthma. In: Adkinson NF Jr., Bochner ...

  2. INTERCONNECTION BETWEEN NITRIC OXIDE FORMATION AND HYPERSENSITIVITY PARAMETERS UNDER GUINEA PIG MODEL OF ACUTE ASTHMA WITH MULTIPLE CHALLENGES.

    Science.gov (United States)

    Parilova, O O; Shandrenko, S G

    2015-01-01

    An immunoregulatory role of nitric oxide (NO) in the development of adaptive immune responses associated with allergic diseases is very important. The present study extended these observations by the examination of the reciprocal changes in characteristic immunologic parameters of the disease and NO level of bronchoalveolar lavage (BAL) cells under guinea pig model of acute asthma with multiple challenges. Development of guinea pig Th2 mediated asthma was accompanied by increasing the level of allergic markers: ovalbumin (OVA) specific IgG and IL-4. We demonstrated that the infiltrate of airway cells contributes to NO synthesis in the respiratory tract during allergic inflammation. The level of intracellular NO formation significantly correlated with plasma allergen specific IgG value in OVA-induced asthma. The presented data evidence that the elevated intracellular NO level in BAL fluid may reflect a nitrosative stress in respiratory tract in general, when allergic asthma exacerbation is present.

  3. Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

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    Jing Wang

    2016-01-01

    Full Text Available Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

  4. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    Science.gov (United States)

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.

  5. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study.

    Science.gov (United States)

    Whitrow, Melissa J; Moore, Vivienne M; Rumbold, Alice R; Davies, Michael J

    2009-12-15

    This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participated in the study, respectively. Maternal folate intake from diet and supplements was assessed by food frequency questionnaire in early (late (30-34 weeks) pregnancy. The primary outcome was physician-diagnosed asthma, obtained by maternal-completed questionnaire. Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69). The effect sizes did not change with adjustment for potential confounders. The association was similar at 5.5 years but did not reach statistical significance (RR = 1.17, 95% CI: 0.96, 1.42) in univariable models. These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children.

  6. A model to predict short-time asthma morbidity: what could be the explanatory factors?

    Directory of Open Access Journals (Sweden)

    Minoo Habibi

    2015-10-01

    Full Text Available Background: There is an increase in the worldwide prevalence, morbidity and mortality of asthma. Therefore, study of the possible factors related to the burden of this disorder could help the health providers to introduce effective initiatives and reduce adverse consequences due to this condition. This study was designed to investigate any relationship between asthma morbidity with inhaler technique and other probable explanatory factors in asthmatic patients.Methods: An observational, cross-sectional study was designed in which asthmatic patients referring to the outpatient respiratory clinic of the Shaheed Labbafinezhad hospital were entered the study using a non-probability sampling method. Their demographic, socio-economic, medical and medication history, inhaler technique (using a 10-step check list, as well as short-term morbidity index (in the past 4 weeks using the Jone’s morbidity questionnaire were determined and recorded in organized data collection forms. These data were entered the Excel and SPSS (version 17.0 worksheets and analyzed using appropriate statistical tests. A step-by-step analysis method was used in order to find out any relationship between possible explanatory factors and the morbidity index of the patients. Results: 199 adult asthmatic patients (94 male and 105 female with mean ± SD age of 54.29 ±15.52 years enrolled the study. In the first step of data analysis only 5 factors out of 20 explanatory factors were eligible to be included in the multivariate analysis leading to the final predictive model. In the multivariate regression analysis, 2 out of 5 factors could remain in the final model, which were “history of systemic steroid usage” and “age” (p=0.007, r=0.32. So that, patients with a positive history of systemic steroid use and those with a younger age had higher asthma morbidity rate. Conclusion: The observed positive relationship between history of systemic steroid usage and asthma morbidity

  7. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy

    OpenAIRE

    Kappen, Claudia; Kruger, Claudia; Macgowan, Jacalyn; Salbaum, J. Michael

    2010-01-01

    Pregnancies complicated by maternal diabetes have long been known to carry a higher risk for congenital malformations, such as neural tube defects. Using the FVB inbred mouse strain and the Streptozotocin-induced diabetes model, we tested whether the incidence of neural tube defects in diabetic pregnancies can be modulated by maternal diet. In a comparison of two commercial mouse diets, which are considered nutritionally replete, we found that maternal consumption of the unfavorable diet was ...

  8. Breastfeeding duration and asthma in Puerto Rican children.

    Science.gov (United States)

    Rosas-Salazar, Christian; Forno, Erick; Brehm, John M; Han, Yueh-Ying; Acosta-Pérez, Edna; Cloutier, Michelle M; Wakefield, Dorothy B; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

    2015-06-01

    Little is known about breastfeeding and asthma in Puerto Ricans, the ethnic group most affected by this disease in the US. We examined the relation between the currently recommended duration of breastfeeding and asthma in school-aged Puerto Rican children. Case-control study of 1,127 Puerto Rican children aged 6-14 years living in Hartford, Connecticut (n = 449) and San Juan, Puerto Rico (n = 678). Parental recall of breastfeeding was categorized based on duration and according to current guidelines (i.e., none, 0-6 months, and >6 months). Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. We used logistic regression for the multivariate analysis, which was conducted separately for each study site and for the combined cohort. All multivariate models were adjusted for age, gender, household income, atopy, maternal asthma, body mass index, early-life exposure to environmental tobacco smoke, and (for the combined cohort) study site. After adjustment for covariates, children who were breastfed for up to 6 months had 30% lower odds of asthma (95% CI = 0.5-1.0, P = 0.04) than those who were not breastfed. In this analysis, breastfeeding for longer than 6 months was not significantly associated with asthma (OR = 1.5, 95% CI = 1.0-2.4, P = 0.06). Our results suggest that breastfeeding for up to 6 months (as assessed by parental recall) is associated with decreased odds of asthma in Puerto Rican children, and that there is no additional beneficial effect of breastfeeding for over 6 months. These results support current recommendations on the duration of breastfeeding in an ethnic group at risk for asthma. © 2014 Wiley Periodicals, Inc.

  9. Cyclic nitroxide radicals attenuate inflammation and Hyper-responsiveness in a mouse model of allergic asthma.

    Science.gov (United States)

    Assayag, Miri; Goldstein, Sara; Samuni, Amram; Berkman, Neville

    2015-10-01

    The effects of stable cyclic nitroxide radicals have been extensively investigated both in vivo and in vitro demonstrating anti-inflammatory, radioprotective, anti-mutagenic, age-retardant, hypotensive, anti-cancer and anti-teratogenic activities. Yet, these stable radicals have not been evaluated in asthma and other airway inflammatory disorders. The present study investigated the effect of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (TPL) and 3-carbamoyl-proxyl (3-CP) in a mouse model of ovalbumin (OVA)-induced allergic asthma. Both 3-CP and TPL were non-toxic when administered either orally (1% w/w nitroxide-containing chow) or via intraperitoneal (IP) injection (∼300 mg/kg). Feeding the mice orally demonstrated that 3-CP was more effective than TPL in reducing inflammatory cell recruitment into the airway and in suppressing airway hyper-responsiveness (AHR) in OVA-challenged mice. To characterize the optimal time-window of intervention and mode of drug administration, 3-CP was given orally during allergen sensitization, during allergen challenge or during both sensitization and challenge stages, and via IP injection or intranasal instillation for 3 days during the challenge period. 3-CP given via all modes of delivery markedly inhibited OVA-induced airway inflammation, expression of cytokines, AHR and protein nitration of the lung tissue. Oral administration during the entire experiment was the most efficient delivery of 3-CP and was more effective than dexamethasone a potent corticosteroid used for asthma treatment. Under a similar administration regimen (IP injection before the OVA challenge), the effect of 3-CP was similar to that of dexamethasone and even greater on AHR and protein nitration. The protective effect of the nitroxides, which preferentially react with free radicals, in suppressing the increase of main asthmatic inflammatory markers substantiate the key role played by reactive oxygen and nitrogen species in the molecular mechanism of

  10. Modelling Drug Administration Regimes for Asthma: A Romanian Experience

    Science.gov (United States)

    Andras, Szilard; Szilagyi, Judit

    2010-01-01

    In this article, we present a modelling activity, which was a part of the project DQME II (Developing Quality in Mathematics Education, for more details see http://www.dqime.uni-dortmund.de) and some general observations regarding the maladjustments and rational errors arising in such type of activities.

  11. PARP inhibition treatment in a nonconventional experimental mouse model of chronic asthma.

    Science.gov (United States)

    Zaffini, Raffaela; Di Paola, Rosanna; Cuzzocrea, Salvatore; Menegazzi, Marta

    2016-12-01

    Allergic asthma is an immunological disease that occurs as a consequence of aeroallergen exposure. Inhibition of poly(ADP-ribose) polymerases (PARPs) in conventional models of asthma-like reaction has emerged as an effective anti-inflammatory and airway remodeling intervention. In a house dust mite (HDM) exposure mouse model, we investigated the impact of PARP inhibition on allergic airway inflammation, sensitization, and remodeling. Mice were intranasally exposed to a HDM extract for 5 days per week for up to 5 weeks. Mice were administered, or not, by PARP inhibitors 3-aminobenzamide (3-ABA) or 5-aminoisoquinolinone (5-AIQ) during the last 2 weeks of HDM treatment. Mice treated with PARP inhibitors after HDM stimulation showed a significant decrease in the number of total cells and eosinophils detectable in the bronchoalveolar lavage fluid as compared with the HDM-stimulated ones. In vitro HDM-stimulated splenocyte culture produced considerable amounts of the Th2 cytokines that were not affected by treatment with PARP inhibitors. Immunoglobulin levels in the serum were also unchanged. In the lung tissue, collagen deposition was decreased, whereas α-smooth muscle actin thickening was not significantly affected. Moreover, in HDM-stimulated PARP inhibitor-treated groups, we found a downregulation in the activation of signal transducer and activator of trascription-6 (STAT-6) and a significant decrease in the mRNA levels of C-C motif chemokine 11 (CCL11). In this mouse model of chronic asthma PARP inhibition treatment, although it does not affect sensitization, it effectively reduces the allergic airway inflammation and affects the remodeling through a mechanism involving STAT6 and CCL11.

  12. Persistent influence of maternal obesity on offspring health: Mechanisms from animal models and clinical studies

    Science.gov (United States)

    The consequences of excessive maternal weight and adiposity at conception for the offspring are now well recognized. Maternal obesity increases the risk of overweight and obesity even in children born with appropriate-for-gestational age (AGA) birth weights. Studies in animal models have employed bo...

  13. GP obstetricians' views of the model of maternity care in New Zealand.

    Science.gov (United States)

    Miller, Dawn L; Mason, Zara; Jaye, Chrystal

    2013-02-01

    The Lead Maternity Carer (LMC) model of maternity care, and independent midwifery practice, was introduced to New Zealand in the 1990s. The LMC midwife or general practitioner obstetrician (GPO) has clinical and budgetary responsibility for women's primary maternity care. To determine views of practising GPOs and former GPOs about the LMC model of care, its impact on maternity care in general practice, and future of maternity care in general practice. 10 GPOs and 13 former GPOs were interviewed: one focus group (n = 3), 20 semi-structured interviews. The qualitative data analysis program ATLAS.ti assisted thematic analysis. Participants thought the LMC model isolates the LMC - particularly concerning during intrapartum care, in rural practice, and covering 24-hour call; Is not compatible with or adequately funded for GP participation; Excludes the GP from caring for their pregnant patients. Participants would like a flexible, locally adaptable, adequately funded maternity model, supporting shared care. Some thought work-life balance and low GPO numbers could deter future GPs from maternity practice. Others felt with political will, support of universities, and Royal New Zealand College of General Practice and Royal Australian and New Zealand College of Obstetrics and Gynaecology, GPs could become more involved in maternity care again. Participants thought the LMC model isolates maternity practitioners, is incompatible with general practice and causes loss of continuity of general practice care. They support provision of maternity care in general practice; however, for more GPs to become involved, the LMC model needs review. © 2013 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Different Nebulized Budesonide Dosing Regimens in a Mouse Model of Chronic Asthma

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    Pınar Uysal

    2016-12-01

    Full Text Available Objective: The aim of this study was to compare the effectiveness of different inhaled steroid regimens on the lungs and their potential side effects on the bone tissues in chronic asthma model. Materials and Methods: Thirty-five specific pathogen-free BALB/c mice were divided into five groups. The mice in all of the study groups except the control group were sensitized with chicken egg albumin. After sensitization, the mice in group 2 were treated with saline modeling twice daily, the mice in group 3 were treated with 250 mcg of nebulized budesonide twice daily, the mice in group 4 were treated with 500 mcg of budesonide once daily, and the mice in group 5 were treated with 1000 mcg of budesonide every other day for the last 14 days of the challenge period. After challenge, the mice were sacrificed and lung and tibia samples were histologically examined. Results: Pulmonary parameters, including subepithelial smooth muscle thickness, goblet cell count, mast cell count and epithelial thickness, were the lowest in group 5 compared to other groups (p0.01. Conclusion: The beneficial effect on lung tissue was highest in the treatment group receiving budesonide every other day (group 5 and no further measureable side effects on bone mineralization were observed in this group compared with the other treatment groups. Every-other-day treatment application seems to be the most effective regimen in chronic asthma model.

  15. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  16. The Common Sense Model in early adolescents with asthma: Longitudinal relations between illness perceptions, asthma control and emotional problems mediated by coping

    NARCIS (Netherlands)

    Tiggelman, D.; Ven, M.O.M. van de; Schayck, O.C.P. van; Kleinjan, M.; Engels, R.C.M.E.

    2014-01-01

    Objective: The present study examined the longitudinal relations between illness perceptions and asthma control and emotional problems (i.e., anxiety, depression, stress), respectively, in adolescents with asthma. Furthermore, the mediating effects of asthma-specific coping strategies on these relat

  17. Acinetobacter baumannii Infection Inhibits Airway Eosinophilia and Lung Pathology in a Mouse Model of Allergic Asthma

    Science.gov (United States)

    Qiu, Hongyu; KuoLee, Rhonda; Harris, Greg; Zhou, Hongyan; Miller, Harvey; Patel, Girishchandra B.; Chen, Wangxue

    2011-01-01

    Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen. PMID:21789200

  18. Antioxidant Effect of MnTE-2-PyP on Lung in Asthma Mice Model

    Directory of Open Access Journals (Sweden)

    Lyudmil Terziev

    2012-01-01

    Full Text Available Aim. To investigate the effects of MnTE-2-PyP on some markers of antioxidant defence system in asthma mice model. Material and Methods. The animals were divided into four groups: group 1, controls; group 2, injected with ovalbumin, group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2-PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and nonprotein sulfhydryl groups content (NPSH were determined in lung homogenate. Results. The activities of superoxide dismutase and catalase in group 2 decreased significantly as compared to control group. The decrease of the same enzymes in group 4 was lower and significant as compared to group 2. Changes in the glutathione peroxidase activity showed a similar dynamics. The NPSH groups content decreased in group 2. In group 4 this decrease was relatively lower as compared to group 2. Conclusions. The application of MnTE-2-PyP mitigated the effects of oxidative stress in asthma mice model.

  19. Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma.

    Science.gov (United States)

    De Alba, Jorge; Otal, Raquel; Calama, Elena; Domenech, Anna; Prats, Neus; Gozzard, Neil; Miralpeix, Montserrat

    2015-12-01

    RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition.

  20. Inbred and outbred mice have equivalent variability in a cockroach allergen-induced model of asthma.

    Science.gov (United States)

    Vaickus, Louis J; Bouchard, Jacqueline; Kim, Jiyoun; Natarajan, Sudha; Remick, Daniel G

    2010-12-01

    Outbred mice traditionally are considered to display high variability, thereby limiting their use in some studies. Researchers frequently are encouraged to use inbred strains of mice because of the greater homogeneity of these experimental animals. We compared the pulmonary inflammatory response of inbred BALB/cJ mice to that of outbred HSD-ICR mice by measuring multiple variables, including cytokines, chemokines, number of pulmonary inflammatory cells, and respiratory parameters. Cockroach allergens induced significant pulmonary inflammation in both BALB and ICR mice. Our comparisons of the coefficients of variance for 148 discrete data sets for each strain or stock indicated that BALB and ICR mice have roughly equivalent intrastrain or -stock variability in our model of asthma-like pulmonary inflammation. The average coefficient of variance, calculated as the ratio of the SD to the mean of a data set, was 0.35 ± 0.34 for BALB mice compared with 0.31 ± 0.32 for ICR mice. In conclusion, inbred BALB and outbred ICR mice have roughly equivalent intrastrain or -stock variability in a murine model of asthma-like pulmonary inflammation.

  1. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-01-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal...... that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care...... unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard...

  2. Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models.

    Science.gov (United States)

    Sheller-Miller, Samantha; Lei, Jun; Saade, George; Salomon, Carlos; Burd, Irina; Menon, Ramkumar

    2016-01-01

    Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO In vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes.

  3. Feto-maternal Trafficking of Exosomes in Murine Pregnancy Models

    Directory of Open Access Journals (Sweden)

    Samantha Sheller

    2016-11-01

    Full Text Available Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR. All our analyses were performed on samples collected on Day 18. After 24 hours, mice were imaged using Bruker MS FX PRO In Vivo Imager and tissues were collected. In vivo imaging of mouse showed fluorescence in the uterus, on the exosome-injected side whereas the uterine tissues from the uninjected side and saline and dye alone injected animals remained negative. Histological analysis of placenta showed exosome migration from the fetal to the maternal side of the placenta. Fluorescence released from exosomes was seen in maternal blood samples as well as in maternal uterus and kidneys. This study demonstrates that exosomal cargo can be carried through systemic route from the fetal to the maternal side of the uterine tissues during pregnancy, supporting the idea that fetal signals can be delivered via exosomes.

  4. Psychosocial stress and asthma morbidity.

    Science.gov (United States)

    Yonas, Michael A; Lange, Nancy E; Celedón, Juan C

    2012-04-01

    The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity. Recent findings suggest that stress, whether at the individual (i.e. epigenetics, perceived stress), family (i.e. prenatal maternal stress, early-life exposure, or intimate partner violence) or community (i.e. neighborhood violence; neighborhood disadvantage) level, influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Posttraumatic Stress Disorder, prenatal and postnatal maternal/caregiver stress, and community violence and deprivation are highlighted. New research illustrates the need to further examine, characterize, and address the influence of social and environmental factors (i.e. psychological stress) on asthma. Further, research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.

  5. Risk for asthma in offspring of asthmatic mothers versus fathers

    DEFF Research Database (Denmark)

    Lim, Robert H; Kobzik, Lester; Dahl, Morten

    2010-01-01

    Many human epidemiologic studies demonstrate that maternal asthma confers greater risk of asthma to offspring than does paternal disease. However, a handful have shown the opposite. Given this disparity, a meta-analysis is necessary to determine the veracity and magnitude of the "maternal effect."...

  6. What accounts for the association between late preterm births and risk of asthma?

    Science.gov (United States)

    Voge, Gretchen A.; Carey, William A.; Ryu, Euijung; King, Katherine S.; Wi, Chung-Il

    2017-01-01

    Background: Although results of many studies have indicated an increased risk of asthma in former late preterm (LPT) infants, most of these studies did not fully address covariate imbalance. Objective: To compare the cumulative frequency of asthma in a population-based cohort of former LPT infants to that of matched term infants in their early childhood, when accounting for covariate imbalance. Methods: From a population-based birth cohort of children born 2002–2006 in Olmsted County, Minnesota, we assessed a random sample of LPT (34 to 36 6/7 weeks) and frequency-matched term (37 to 40 6/7 weeks) infants. The subjects were followed-up through 2010 or censored based on the last date of contact, with the asthma status based on predetermined criteria. The Kaplan-Meier method was used to estimate the cumulative incidence of asthma during the study period. Cox models were used to estimate the hazard ratio and 95% confidence interval for the risk of asthma, when adjusting for potential confounders. Results: LPT infants (n = 282) had a higher cumulative frequency of asthma than did term infants (n = 297), 29.9 versus 19.5%, respectively; p = 0.01. After adjusting for covariates associated with the risk of asthma, an LPT birth was not associated with a risk of asthma, whereas maternal smoking during pregnancy was associated with a risk of asthma. Conclusion: LPT birth was not independently associated with a risk of asthma and other atopic conditions. Clinicians should make an effort to reduce exposure to smoking during pregnancy as a modifiable risk factor for asthma. PMID:28234052

  7. Suppression of ovalbumin-induced airway inflammatory responses in a mouse model of asthma by Mimosa pudica extract.

    Science.gov (United States)

    Yang, Eun Ju; Lee, Ji-Sook; Yun, Chi-Young; Ryang, Yong Suk; Kim, Jong-Bae; Kim, In Sik

    2011-01-01

    Asthma is an inflammatory airway disease. The pathogenic mechanisms of asthma include the infiltration of leukocytes and release of cytokines. Mimosa pudica (Mp) has been used traditionally for the treatment of insomnia, diarrhea and inflammatory diseases. Although Mp extract has various therapeutic properties, the effect of this extract on asthma has not yet been reported. This study investigated the suppressive effects of Mp extract on asthmatic responses both in vitro and in vivo. Mp extract was acquired from dried and powdered whole plants of M. pudica using 80% ethanol. BALB/c mice were used for the mouse model of asthma induced by ovalbumin. Mp extract significantly inhibited the HMC-1 cell migration induced by stem cell factor and blocked the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in EoL-1 cells. Leukocytosis, eosinophilia and mucus hypersecretion in asthmatic lung were significantly suppressed by Mp extract. The release of ovalbumin-specific IgE in bronchoalveolar lavage fluid and serum was also decreased. Mp extract treatment resulted in no liver cytotoxicity. The Mp extract has inhibitory properties on asthma and may be used as a potent therapeutic agent for allergic lung inflammation. Copyright © 2010 John Wiley & Sons, Ltd.

  8. Accessible Modelling of Complexity in Health (AMoCH and associated data flows: asthma as an exemplar

    Directory of Open Access Journals (Sweden)

    Harshana Liyanage

    2016-04-01

    Full Text Available Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1 to describe the data and information flows in clinical practice to information scientists, (2 to compare health systems and care pathways, (3 to understand how clinical cases are recorded in record systems and (4 to model health care business models. Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain. Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar. Method The four steps in our process are: 1. Drawing a rich picture, following Checkland’s soft systems methodology; 2. Constructing data flow diagrams (DFDs; 3. Creating Unified Modelling Language (UML use case diagrams to describe the interaction of the key actors with the system; 4. Activity diagrams, either UML activity diagram or business process modelling notation diagram. Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding. Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of

  9. Accessible Modelling of Complexity in Health (AMoCH) and associated data flows: asthma as an exemplar.

    Science.gov (United States)

    Liyanage, Harshana; Luzi, Daniela; De Lusignan, Simon; Pecoraro, Fabrizio; McNulty, Richard; Tamburis, Oscar; Krause, Paul; Rigby, Michael; Blair, Mitch

    2016-04-18

    Background Modelling is an important part of information science. Models are abstractions of reality. We use models in the following contexts: (1) to describe the data and information flows in clinical practice to information scientists, (2) to compare health systems and care pathways, (3) to understand how clinical cases are recorded in record systems and (4) to model health care business models.Asthma is an important condition associated with a substantial mortality and morbidity. However, there are difficulties in determining who has the condition, making both its incidence and prevalence uncertain.Objective To demonstrate an approach for modelling complexity in health using asthma prevalence and incidence as an exemplar.Method The four steps in our process are:1. Drawing a rich picture, following Checkland's soft systems methodology;2. Constructing data flow diagrams (DFDs);3. Creating Unified Modelling Language (UML) use case diagrams to describe the interaction of the key actors with the system;4. Activity diagrams, either UML activity diagram or business process modelling notation diagram.Results Our rich picture flagged the complexity of factors that might impact on asthma diagnosis. There was consensus that the principle issue was that there were undiagnosed and misdiagnosed cases as well as correctly diagnosed. Genetic predisposition to atopy; exposure to environmental triggers; impact of respiratory health on earnings or ability to attend education or participate in sport, charities, pressure groups and the pharmaceutical industry all increased the likelihood of a diagnosis of asthma. Stigma and some factors within the health system diminished the likelihood of a diagnosis. The DFDs and other elements focused on better case finding.Conclusions This approach flagged the factors that might impact on the reported prevalence or incidence of asthma. The models suggested that applying selection criteria may improve the specificity of new or confirmed diagnosis.

  10. Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma.

    Science.gov (United States)

    Anderson, Stacey E; Franko, Jennifer; Kashon, Michael L; Anderson, Katie L; Hubbs, Ann F; Lukomska, Ewa; Meade, B Jean

    2013-03-01

    During the last decade, there has been a remarkable and unexplained increase in the prevalence of asthma. These studies were conducted to investigate the role of dermal exposure to triclosan, an endocrine-disrupting compound, on the hypersensitivity response to ovalbumin (OVA) in a murine model of asthma. Triclosan has had widespread use in the general population as an antibacterial and antifungal agent and is commonly found in consumer products such as soaps, deodorants, toothpastes, shaving creams, mouthwashes, and cleaning supplies. For these studies, BALB/c mice were exposed dermally to concentrations of triclosan ranging from 0.75 to 3% (0.375-1.5mg/mouse/day) for 28 consecutive days. Concordantly, mice were ip injected with OVA (0.9 µg) and aluminum hydroxide (0.5mg) on days 1 and 10 and challenged with OVA (125 µg) by pharyngeal aspiration on days 19 and 27. Compared with the animals exposed to OVA alone, increased spleen weights, OVA-specific IgE, interleukin-13 cytokine levels, and numbers of lung eosinophils were demonstrated when mice were coexposed to OVA and triclosan. Statistically significant increases in OVA-specific and nonspecific airway hyperreactivity were observed for all triclosan coexposed groups compared with the vehicle and OVA controls. In these studies, exposure to triclosan alone was not demonstrated to be allergenic; however, coexposure with a known allergen resulted in enhancement of the hypersensitivity response to that allergen, suggesting that triclosan exposure may augment the allergic responses to other environmental allergens.

  11. Polyopes affinis alleviates airway inflammation in a murine model of allergic asthma

    Indian Academy of Sciences (India)

    Dae-Sung Lee; Won Sun Park; Soo-Jin Heo; Seon-Heui Cha; Daekyung Kim; You-Jin Jeon; Sae-Gwang Park; Su-Kil Seo; Jung Sik Choi; Sung-Jae Park; Eun Bo Shim; Il-Whan Choi; Won-Kyo Jung

    2011-12-01

    Marine algae have been utilized in food as well as medicine products for a variety of purposes. The purpose of this study was to determine whether an ethanol extract of Polyopes affinis (P.affinis) can inhibit the pathogenesis of T helper 2 (Th2)-mediated allergen-induced airway inflammation in a murine model of asthma. Mice that were sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions such as the following: an increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways as well as the narrowing of the airway luminal; the development of airway hyperresponsiveness (AHR); the presence of pulmonary Th2 cytokines; and the presence of allergen-specific immunoglobulin E (IgE) in the serum. The successive intraperitoneal administration of P. affinis ethanolic extracts before the last airway OVA-challenge resulted in a significant inhibition of all asthmatic reactions. These data suggest that P. affinis ethanolic extracts possess therapeutic potential for the treatment of pulmonary allergic disorders such as allergic asthma.

  12. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Directory of Open Access Journals (Sweden)

    Jun Kurai

    Full Text Available An Asian dust storm (ADS contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil in asthma model mice.Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df, and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF were measured, and airway inflammation was examined histopathologically.Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles.These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  13. Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic Asthma.

    Science.gov (United States)

    Brüggemann, T R; Ávila, L C M; Fortkamp, B; Greiffo, F R; Bobinski, F; Mazzardo-Martins, L; Martins, D F; Duarte, M M M F; Dafre, A; Santos, A R S; Silva, M D; Souza, L F; Vieira, R P; Hizume-Kunzler, D C

    2015-06-01

    In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming (non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48 h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (pswimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (pSwimming group when compared to all groups (pswimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (pswimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Lung inflammation and epithelial changes in a murine model of atopic asthma.

    Science.gov (United States)

    Blyth, D I; Pedrick, M S; Savage, T J; Hessel, E M; Fattah, D

    1996-05-01

    A murine model of allergen-induced airway inflammation and epithelial phenotypic change, and the time-courses of these events, are described. Mice were sensitized to ovalbumin using an adjuvant-free protocol, and challenged by multiple intratracheal instillations of ovalbumin by a non-surgical technique. Many of the characteristic features of human atopic asthma were seen in the mice. A marked eosinophilic infiltration of lung tissue and airways followed allergen challenge, and its severity increased with each challenge, as did the number of eosinophils in the blood. Lymphocytes, neutrophils, and monocytes also invaded the lungs. Airway macrophages showed signs of activation, their appearance resembling those recovered from antigen-challenged human asthmatic airways. The airway epithelium was thickened and displayed a marked goblet cell hyperplasia in terminal bronchioles and larger airways. After repeated challenges, the reticular layer beneath the basement membrane of the airway epithelium showed fibrosis, reproducing a commonly observed histologic feature of human asthma. Goblet cell hyperplasia began to appear before eosinophils or lymphocytes had migrated across the airway epithelium, and persisted for at least 11 days after the third intratracheal challenge with ovalbumin, despite the number of inflammatory cells in the lungs and airways having decreased to near-normal levels by 4 days. Plugs of mucus occluded some of the airways. These results indicate that some of the phenotypic changes in airway epithelium that follow an allergic response in the lung can be initiated before the migration of eosinophils or lymphocytes across the epithelial layer.

  15. Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models

    Directory of Open Access Journals (Sweden)

    D. Betty Lew

    2017-01-01

    Full Text Available One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM remodeling effects. The mannose receptor (MR family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR and that mannan derived from Saccharomyces cerevisiae (SC-MN inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2 expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

  16. Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma.

    Science.gov (United States)

    Hesse, Laura; Nawijn, Martijn C

    2017-01-01

    Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath. Allergen specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma and both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have proven clinical efficacy in long term suppression of the allergic response. Although these treatments are very successful for rhinitis, application of AIT in asthma is hampered by variable efficacy, long duration of treatment, and the risk of severe side-effects. A more profound understanding of the mechanisms by which AIT achieves tolerance to allergens in sensitized individuals is needed to improve its efficacy. Mouse models have been very valuable as a preclinical model to characterize the mechanisms of desensitization in AIT and to evaluate novel approaches for improved efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen absorbed to aluminum hydroxide to induce allergic sensitization, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of the allergen as immunotherapy treatment. Finally, mice are challenged by three intranasal allergen administrations. We will describe the protocols as well as the most important read-out parameters including measurement of invasive lung

  17. Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

    Directory of Open Access Journals (Sweden)

    Campos H.S.

    2006-01-01

    Full Text Available The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance, histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9, mice were immunized with 10 µg ovalbumin (OVA, ip on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 µg OVA at 3-day intervals. Control mice (N = 8 received saline under the same protocol. In the dexamethasone (N = 8 and LASSBio596 (N = 8 groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76%, respectively compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

  18. Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Haim Bibi

    2014-01-01

    Conclusion: In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO.

  19. Asma na gestação: efeitos na vitalidade fetal, complicações maternas e perinatais Asthma during pregnancy: effects on fetal well-being, and maternal and perinatal complications

    Directory of Open Access Journals (Sweden)

    Renata Franco Pimentel Mendes

    2013-04-01

    Full Text Available OBJETIVO: Avaliar os efeitos da asma materna sobre a gravidez, analisando as repercussões da gravidade da doença no comprometimento do bem-estar fetal, bem como as complicações maternas e perinatais associadas. MÉTODOS: Foi realizado estudo retrospectivo de 117 gestações complicadas pela asma materna e sem outras comorbidades, no período de janeiro de 2005 a dezembro de 2010. Os critérios de inclusão foram: gestação única; diagnóstico de asma prévio à gestação; início do pré-natal antes da 28ª semana de gravidez; parto realizado na instituição; peso do recém-nascido acima de 500g e idade gestacional no parto acima de 22 semanas; ausência de malformações fetais ou anomalias cromossômicas; ausência de comorbidades maternas. A gravidade da asma foi classificada em intermitente, persistente leve, persistente moderada, persistente grave. Foram analisados os resultados do perfil biofísico fetal e da dopplervelocimetria de artéria umbilical realizados até 14 dias antes do parto. RESULTADOS: Do total de 117 gestantes asmáticas analisadas: 41 (35,0% eram intermitentes, 33 (28,2% persistentes leves, 21 (17,9% persistentes moderadas e 22 (18,8% persistentes graves. Não houve diferença significativa entre os grupos quanto ao tipo de parto: a cesárea foi realizada em 65,8% dos casos, a corticoterapia materna no momento do parto em 20,5%, a idade gestacional no parto apresentou média de 38,6 semanas (DP 1,9 semanas e o peso ao nascimento apresentou média de 3056 g (DP 581 g. O perfil biofísico fetal realizado no período anteparto (n = 90, 76,9% apresentou resultado normal (8 ou 10 em 99% dos casos. A dopplervelocimetria de artéria umbilical foi avaliada em 23,9% (n = 28 das gestantes, e apresentou-se normal em 100% dos casos. O uso de corticoterapia sistêmica foi significativamente (pOBJECTIVE: To assess the effects of maternal asthma on pregnancy, analyzing the consequences of the severity of the disease in the

  20. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Xiao X

    2013-11-01

    Full Text Available Xiaojun Xiao,1,* Xiaowei Zeng,2,* Xinxin Zhang,3,* Li Ma,3 Xiaoyu Liu,1 Haiqiong Yu,1 Lin Mei,2 Zhigang Liu1 1Institute of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, 2Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 3Faculty of Basic Medical Science, Nanchang University, Nanchang, People's Republic of China *These authors contributed equally to this work Background: Pollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid (PLGA has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP-loaded PLGA nanoparticles and the underlying mechanisms involved. Methods: A mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a and cytokines, and observing histologic sections of lung tissue. Results: The rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms. Conclusion: PLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed

  1. Impact of psychosocial stress on airway inflammation and its mechanism in a murine model of allergic asthma

    Institute of Scientific and Technical Information of China (English)

    LI Bei; DUAN Xiao-hong; WU Jin-feng; LIU Bao-jun; LUO Qing-li; JIN Hua-liang; DU Yi-jie

    2013-01-01

    .05).Moreover,the lung histology showed that infiltrated inflammatory cells were significantly increased in the asthma-SDR group compared with the asthma group (P <0.05).Interestingly,serum corticosterone was remarkably raised by psychosocial stress (P <0.05).In addition,the inhibitory effect of corticosterone on IL-6 and TNF-α in LPS-stimulated splenocyte cultures in vitro was diminished in the asthma-SDR group compared to the asthma group.The CCK-8 test revealed that the inhibition effect of corticosterone on splenocyte proliferation induced by LPS was significantly impaired in the SDR and asthma-SDR groups,while no significant effect was observed in the control and asthma groups.Furthermore,expression of GR mRNA and GR protein were significantly reduced in the lung tissues of the asthma-SDR group (P <0.05).Conclusions Social disruption stress can promote anxiety behavior,activate the hypothalamic-pituitary-adrenal (HPA) axis,increase AHR and inflammation,and also impair glucocorticoid sensitivity and its function in a murine model of asthma.The down-regulation of GR expression induced by social disruption stress is in part associated with glucocorticoid insensitivity,which leads to asthma exacerbation.

  2. GITR signaling potentiates airway hyperresponsiveness by enhancing Th2 cell activity in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Van Oosterhout Antoon JM

    2009-10-01

    Full Text Available Abstract Background Allergic asthma is characterized by airway hyperresponsiveness (AHR and allergic inflammation of the airways, driven by allergen-specific Th2 cells. The asthma phenotypes and especially AHR are sensitive to the presence and activity of regulatory T (Treg cells in the lung. Glucocorticoid-induced tumor necrosis factor receptor (GITR is known to have a co-stimulatory function on effector CD4+ T cells, rendering these cells insensitive to Treg suppression. However, the effects of GITR signaling on polarized Th1 and Th2 cell effector functions are not well-established. We sought to evaluate the effect of GITR signaling on fully differentiated Th1 and Th2 cells and to determine the effects of GITR activation at the time of allergen provocation on AHR and airway inflammation in a Th2-driven mouse model of asthma. Methods CD4+CD25- cells were polarized in vitro into Th1 and Th2 effector cells, and re-stimulated in the presence of GITR agonistic antibodies to assess the effect on IFNγ and IL-4 production. To evaluate the effects of GITR stimulation on AHR and allergic inflammation in a mouse asthma model, BALB/c mice were sensitized to OVA followed by airway challenges in the presence or absence of GITR agonist antibodies. Results GITR engagement potentiated cytokine release from CD3/CD28-stimulated Th2 but not Th1 cells in vitro. In the mouse asthma model, GITR triggering at the time of challenge induced enhanced airway hyperresponsiveness, serum IgE and ex vivo Th2 cytokine release, but did not increase BAL eosinophilia. Conclusion GITR exerts a differential effect on cytokine release of fully differentiated Th1 and Th2 cells in vitro, potentiating Th2 but not Th1 cytokine production. This effect on Th2 effector functions was also observed in vivo in our mouse model of asthma, resulting in enhanced AHR, serum IgE responses and Th2 cytokine production. This is the first report showing the effects of GITR activation on cytokine

  3. A Group of Asthma Patients\\\\\\' Treatment Related Thoughts Based on Health Belief Model and Perception of Medication Success

    Directory of Open Access Journals (Sweden)

    Mesut Cimen

    2012-02-01

    Full Text Available Purpose: This study is a descriptive study which aims to determine the attitude and perceptions of asthma patients about their health and their opinion regarding the success of treatment. Method: The study is carried out without any sampling. The participants are 74 patients who were admitted in a public pulmonary disease clinic between April and June 2010. A revised version of Health Belief Model scale for asthma treatment and another scale, which was developed to determine the opinion and observations of patients regarding the success of treatment, are used for data collection. In addition to descriptive statistics, regression analysis, Mann-Whitney U and Kruskal Wallis tests are used in the data analysis. Findings: The mean score of attitudes and perceptions of asthma patients, which is defined with the Health Belief Model and which can affect their responsiveness to treatment, is found out 3,37(±0,38 and the attitude and perceptions of patients are positive. The mean value for success treatment is 2,35(±0,49. Since the treatment is deemed to be more successful as it gets closer to 1 hence it can be said that the opinion of asthma patients regarding the success of treatment is positive. In the study, it is found out that the participants have a high admission rate to hospitals and that there is no significant difference for socio-demographic characteristics in the positive attitude development and in their belief in the efficiency of the treatment that they are receiving, of which both are components of health belief model concept. The findings from regression analysis indicate that the duration of the asthma sickness and the number of people living in the household not only affect the perceptions and attitudes of patients that are investigated by health belief model, but also the effectiveness of the treatment and the number of admissions to the Emergency Room in the last 6 months. Conclusion: In order to prevent long-term complications

  4. Maternal sensitivity and language in early childhood: a test of the transactional model.

    Science.gov (United States)

    Leigh, Patricia; Nievar, M Angela; Nathans, Laura

    2011-08-01

    This study examined the relation between mothers' sensitive responsiveness to their children and the children's expressive language skills during early childhood. Reciprocal effects were tested with dyads of mothers and their children participating in the National Institute of Health and Human Development Study of Early Child Care and Youth Development. Sensitive maternal interactions positively affected children's later expressive language in the second and third years of life. Although maternal sensitivity predicted later language skills in children, children's language did not affect later maternal sensitivity as indicated in a structural equation model. These results do not support the 1975 transactional model of child development of Sameroff and Chandler. A consistent pattern of sensitivity throughout infancy and early childhood indicates the importance of fostering maternal sensitivity in infancy for prevention or remediation of expressive language problems in young children.

  5. Generalized Whittle-Matern random field as a model of correlated fluctuations

    Energy Technology Data Exchange (ETDEWEB)

    Lim, S C [Faculty of Engineering, Multimedia University, Jalan Multimedia, Cyberjaya, 63100, Selangor Darul Ehsan (Malaysia); Teo, L P [Faculty of Information Technology, Multimedia University, Jalan Multimedia, Cyberjaya, 63100, Selangor Darul Ehsan (Malaysia)], E-mail: sclim@mmu.edu.my, E-mail: lpteo@mmu.edu.my

    2009-03-13

    This paper considers a generalization of the Gaussian random field with covariance function of the Whittle-Matern family. Such a random field can be obtained as the solution to the fractional stochastic differential equation with two fractional orders. Asymptotic properties of the covariance functions belonging to this generalized Whittle-Matern family are studied, which are used to deduce the sample path properties of the random field. The Whittle-Matern field has been widely used in modeling geostatistical data such as sea beam data, wind speed, field temperature and soil data. In this paper we show that the generalized Whittle-Matern field provides a more flexible model for wind speed data.

  6. Ffects Of Mntnhex-2-Pyp On Markers Of Inflammation And Lipid Peroxidation In Asthma Mice Model

    Directory of Open Access Journals (Sweden)

    Veneta Lyubenova Shopova

    2011-10-01

    Full Text Available Background and objective: Iinvestigation of the effects of MnTnHex-2-PyP on some markers of inflammation and lipid peroxidation in an asthma mice model.Methods: The experiment was carried out on 24 female mice C57Bl/6, divided into four groups: group 1, controls; group 2, injected with ovalbumin (OVA; group 3, treated with MnTnHex-2-PyP and group 4, treated with OVA and MnTnHex-2-PyP. The animals from groups 1 and 3 were injected i.p. on days 0 and 14 with a 100 μl phosphate-buffered saline (PBS, and those from groups 2 and 4 were injected with a 100 μl ovalbumin solution, containing 20 μg OVA. On days 24, 25 and 26 the mice from groups 1 and 2 were inhaled with PBS for 30 min, and those from groups 2 and 4 were given a 1% ovalbumin solution. One hour before inhalation, and 12 hours later the animals from groups 1 and 2 were injected i.p. with 100 μl PBS, and those from groups 3 and 4 received a 100 μl MnTnHex-2-Pyp solution in PBS сontaining 0.05mg/kg.Results: Ovalbumin alone (group 2 increased the total cell number, total protein content, the levels of IL-4, IL-5 and 8-isoprostane in bronchoalveolar lavage. Elevations were observed in IgE level in serum, and the malone dialdehyde (MDA content in the lung homogenate. These markers were decreased significantly in group 4 as compared to the OVA group.Conclusions: MnTnHex-2-Pyp reduces the inflammation and lipid peroxidation in Ovalbumin-induced mice asthma model.

  7. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

    Science.gov (United States)

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

    2015-01-01

    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

  8. Behavioural deficits associated with maternal immune activation in the rat model of schizophrenia.

    Science.gov (United States)

    Wolff, Amy R; Cheyne, Kirsten R; Bilkey, David K

    2011-11-20

    Schizophrenia is associated with changes in memory and contextual processing. As maternal infection is a risk factor in schizophrenia we tested for these impairments in a maternal immune activation (MIA) animal model. MIA rats displayed impaired object recognition memory, despite intact object discrimination, and a reduced reinstatement of rearing in response to a contextual manipulation. These results link MIA to contextual impairments in schizophrenia, possibly through changes in hippocampal function.

  9. Role of Late Maternal Thyroid Hormones in Cerebral Cortex Development: An Experimental Model for Human Prematurity

    OpenAIRE

    Berbel, P.; Navarro, D.; Ausó, E.; Varea, E; Rodríguez, A E; Ballesta, J. J.; Salinas, M; Flores, E; Faura, C. C.; Morreale de Escobar, G

    2009-01-01

    Hypothyroxinemia affects 35–50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats...

  10. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

    Directory of Open Access Journals (Sweden)

    Kayla G Kinker

    Full Text Available Levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1 and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR. ADMA levels in bronchoalveolar lavage fluid (BALF and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM. Airway inflammation was assessed by bronchoalveolar lavage (BAL total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses.

  11. Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro-Filho, Jaime [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); Calheiros, Andrea Surrage; Vieira-de-Abreu, Adriana [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Moraes de Carvalho, Katharinne Ingrid [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Mendes, Diego da [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Melo, Christianne Bandeira [Laboratório de Inflamação, Instituto Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro (Brazil); Martins, Marco Aurélio [Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro (Brazil); Silva Dias, Celidarque da [Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba (Brazil); Piuvezam, Márcia Regina, E-mail: mrpiuvezam@ltf.ufpb.br [Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba (Brazil); and others

    2013-11-15

    Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca{sup ++} influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs. - Highlights: • Curine is a bisbenzylisoquinoline alkaloid from Chondrodendron platyphyllum. • Curine inhibits eosinophil influx and activation and airway hyper-responsiveness. • Curine

  12. Examining the Consulting Physician Model to Enhance the School Nurse Role for Children with Asthma

    Science.gov (United States)

    Wilson, Kristin D.; Moonie, Sheniz; Sterling, David A.; Gillespie, Kathleen N.; Kurz, Richard S.

    2009-01-01

    Background: The Centers for Disease Control and Prevention's "Strategies for Addressing Asthma Within a Coordinated School Health Program" recommends a consulting physician for schools to help manage asthma. The literature examines the effects when a school nurse is present, but the addition of a consulting physician is not well understood. The…

  13. Examining the Consulting Physician Model to Enhance the School Nurse Role for Children with Asthma

    Science.gov (United States)

    Wilson, Kristin D.; Moonie, Sheniz; Sterling, David A.; Gillespie, Kathleen N.; Kurz, Richard S.

    2009-01-01

    Background: The Centers for Disease Control and Prevention's "Strategies for Addressing Asthma Within a Coordinated School Health Program" recommends a consulting physician for schools to help manage asthma. The literature examines the effects when a school nurse is present, but the addition of a consulting physician is not well understood. The…

  14. Modeling variation in early life mortality in the western lowland gorilla: Genetic, maternal and other effects.

    Science.gov (United States)

    Ahsan, Monica H; Blomquist, Gregory E

    2015-06-01

    Uncovering sources of variation in gorilla infant mortality informs conservation and life history research efforts. The international studbook for the western lowland gorilla provides information on a sample of captive gorillas large enough for which to analyze genetic, maternal, and various other effects on early life mortality in this critically endangered species. We assess the importance of variables such as sex, maternal parity, paternal age, and hand rearing with regard to infant survival. We also quantify the proportions of variation in mortality influenced by heritable variation and maternal effects from these pedigree and survival data using variance component estimation. Markov chain Monte Carlo simulations of generalized linear mixed models produce variance component distributions in an animal model framework that employs all pedigree information. Two models, one with a maternal identity component and one with both additive genetic and maternal identity components, estimate variance components for different age classes during the first 2 years of life. This is informative of the extent to which mortality risk factors change over time during gorilla infancy. Our results indicate that gorilla mortality is moderately heritable with the strongest genetic influence just after birth. Maternal effects are most important during the first 6 months of life. Interestingly, hand-reared infants have lower mortality for the first 6 months of life. Aside from hand rearing, we found other predictors commonly used in studies of primate infant mortality to have little influence in these gorilla data.

  15. Protective Effects of Scrophularia Striata in Ovalbumin-induced Mice Asthma Model

    Directory of Open Access Journals (Sweden)

    Abbas Azadmehr

    2013-07-01

    Full Text Available Background:Scrophularia striata Boiss. (Scrophulariaceae is a plant growing in the northeastern part of Iran and being used as a traditional herb for various inflammatory disorders.This study was designed to investigate the protective effects of the Scrophularia striata extract in Ovalbumin (OVA induced-asthma mice model.Methods:OVA-sensitized mice were intrapritonealy treated with two doses (100 and 200 mg/kg of the extract on days 8 to 14 separately. Broncoalveolar lavage fluids (BALF was collected 48 h after the final OVA challenge and then the number of eosinophils and other inflammatory cells were assessed by direct microscopic counting. In addition, total immunoglubolin (Ig E and OVA-specific IgE levels in serum, IL-4 and IL-5 cytokines in BALF were determined by Enzyme-Linked Immunosorbent Assay. Moreover, phytochemical assay by thin layer chromatography (TLC and the 2, 2 diphenyl-1-picrylhydrazyl (DPPH were used to evaluate the main compounds and the antioxidant capacity of the plant extract, respectively.Results:The results showed that the main components; including flavonoids, phenolic compounds and phenyl propanoids were presented in the S. striata extract. In addition, the treatment with extract significantly reduced the number of inflammatory cells and suppressed T-helper 2 (Th2 cytokines including IL-4 and IL-5 in BALF. Also, total IgE and OVA-specific IgE levels in the serum decreased.Conclusion:Collectively, it is concluded that the extract has the potential to modulate the Th2 cytokines and could be used as immunomodulatory agent in the treatment of allergic asthma.

  16. Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations.

    Science.gov (United States)

    Cooney, Lewis; McBride, Antonia; Lilley, Andrew; Sinha, Ian; Johnson, Trevor N; Hawcutt, Daniel B

    2017-04-01

    To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those model. PBPK modelling of a 5 mg/kg iv loading dose (≤18yr) shows a mean Cmax of 8.99 mg/L (5th-95th centiles 5.5-13.7 mg/L), with 70.3% of subjects  20 mg/L. For an aminophylline infusion (0-12 y) of 1.0  mg/kg/h, the mean steady state infusion concentration was 16.4 mg/L, (5th-95th centiles 5.3-32 mg/L), with 26.8% having a serum concentration >20 mg/L. For 12-18yr receiving 0.5  mg/kg/h infusion, the mean steady state infusion concentration was 9.37 mg/L (5th-95th centiles 3.4-18 mg/L), with 59.8% having a serum concentration modelling correlates well with clinical data. Current aminophylline iv loading dosage recommendations achieve levels 20 mg/l). Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effects of S100A9 in a rat model of asthma and in isolated tracheal spirals.

    Science.gov (United States)

    Yin, Lei-Miao; Li, Hai-Yan; Zhang, Qing-Hua; Xu, Yu-Dong; Wang, Yu; Jiang, Yong-Liang; Wei, Ying; Liu, Yan-Yan; Yang, Yong-Qing

    2010-07-30

    S100A9 is a member of the S100 family of proteins that contain two EF-hand calcium-binding motifs. We previously reported that S100A9 was differentially expressed during the early airway response phase of asthma and can be regulated by acupuncture. To understand the possible role of S100A9 in asthma, the effects of the S100A9 were investigated in a rat model of asthma and in isolated tracheal spirals. The pulmonary function and isometric tension were measured after the administration of purified recombinant S100A9. The results of in vivo experiments showed that S100A9 (0.1microg/kg) significantly decreased the pulmonary resistance and increased the dynamic compliance. The in vitro experimental results showed that S100A9 (100, 200, 400, or 800ng/ml, final concentrations) significantly reduced the isometric tension of isolated tracheal spirals. These results suggest that S100A9 elicits dose-dependent anti-asthmatic effects and may provide further insight into the treatment of asthma.

  18. Clinical Models to Compare the Safety and Efficacy of Inhaled Corticosteroids in Patients with Asthma

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2003-01-01

    Full Text Available There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic drug is being evaluated in comparison with the innovator drug (same compound and same device, it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.

  19. Improving Asthma during Pregnancy with Dietary Antioxidants: The Current Evidence

    Directory of Open Access Journals (Sweden)

    Vicki L. Clifton

    2013-08-01

    Full Text Available The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS. Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health.

  20. Improving asthma during pregnancy with dietary antioxidants: the current evidence.

    Science.gov (United States)

    Grieger, Jessica A; Wood, Lisa G; Clifton, Vicki L

    2013-08-14

    The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health.

  1. Improving Asthma during Pregnancy with Dietary Antioxidants: The Current Evidence

    Science.gov (United States)

    Grieger, Jessica A.; Wood, Lisa G.; Clifton, Vicki L.

    2013-01-01

    The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health. PMID:23948757

  2. Investigation into the Role of PI3K and JAK3 Kinase Inhibitors in Murine Models of Asthma

    Science.gov (United States)

    Wagh, Akshaya D.; Sharma, Manoranjan; Mahapatra, Jogeshwar; Chatterjee, Abhijeet; Jain, Mukul; Addepalli, Veeranjaneyulu

    2017-01-01

    Asthma is a clinical disorder commonly characterized by chronic eosinophilic inflammation, remodeling and hyper responsiveness of the airways. However, the kinases like Phosphoinositide 3 kinase (PI3K) and Janus kinase 3 (JAK3) are involved in mast cell proliferation, activation, recruitment, migration, and prolonged survival of inflammatory cells. The present study was designed to evaluate the in-vivo comparative effects of two kinase inhibitors on airway inflammation and airway remodeling in acute and chronic models of asthma. Mice were sensitized twice intra-peritoneally and then challenged by inhalation with ovalbumin (OVA). They developed an extensive inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening similar to pathologies observed in human asthma. The effects of PI3K inhibitor (30 mg/kg, p.o), JAK3 inhibitor (30 mg/kg, p.o) and Dexamethasone (0.3 mg/kg) on airway inflammation and remodeling in OVA sensitized/challenged BALB/c mice were evaluated. Twenty-four hours after the final antigen challenge, bronchoalveolar lavage (BAL) and histological examinations were carried out. It was observed that kinase inhibitors significantly reduced airway inflammation as evidenced by the decrease in pro inflammatory cytokines in BALF and lung homogenate and inflammatory cell count in sensitized mice after allergen challenge. Lung histological analysis showed increased infiltration of inflammatory cells, hyperplasia of goblet cells and the collagen deposition, which were significantly reduced with kinase inhibitor. In conclusion, our data suggest that PI3K and JAK3 inhibitors showed promising alternative therapeutic activity in asthma, which might significantly counteract the airway inflammation in patients with allergic asthma. PMID:28293189

  3. Effects of the Immunomodulatory Agent Cordyceps militaris on Airway Inflammation in a Mouse Asthma Model

    Directory of Open Access Journals (Sweden)

    Chia-Hsiu Hsu

    2008-10-01

    Conclusion: C. militaris can modulate airway inflammation in asthma, but it is less effective than prednisolone or montelukast. These results demonstrate that C. militaris is unable to adequately block the potent mediators of asthmatic airway inflammation.

  4. Novel drug targets for asthma and COPD : Lessons learned from in vitro and in vivo models

    NARCIS (Netherlands)

    Baker, Katie E.; Bonvini, Sara J.; Donovan, Chantal; Foong, Rachel E.; Han, Bing; Jha, Aruni; Shaifta, Yasin; Smit, Marieke; Johnson, Jill R.; Moir, Lyn M.

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as beta-agonists and glucocorticoids, may be effective at reducing symptoms, they

  5. The role of trait mindfulness in quality of life and asthma control among adolescents with asthma.

    Science.gov (United States)

    Cillessen, Linda; van de Ven, Monique O; Karremans, Johan C

    2017-08-01

    The current study focused on the role of trait mindfulness in asthma-related quality of life (QoL) and asthma control in adolescent asthma patients. Furthermore, potential underlying mechanisms (general and asthma-specific stress) of this relationship were investigated. In this cross-sectional study, questionnaire data of 94 adolescents with asthma that were prescribed daily asthma medication were included. Two Structural Equation Models (SEMs), a direct model and an indirect model, were tested. We found that trait mindfulness was directly related to asthma-related QoL, but not to asthma control. The relationship between trait mindfulness and asthma-related QoL was explained by asthma-specific, but not by general stress. Furthermore, an indirect relation from mindfulness to asthma control via asthma-specific stress was found. Cross-sectional evidence for a relation between mindfulness and asthma-related QoL is found. These findings may point to the possibility that an intervention aimed at increasing mindfulness could be a promising tool to improve asthma-related QoL in adolescents via a decrease in asthma-specific stress. Copyright © 2017. Published by Elsevier Inc.

  6. Korean Asthma Guideline 2014: Summary of Major Updates to the Korean Asthma Guideline 2014.

    Science.gov (United States)

    Kim, Deog Kyeom; Park, Yong Bum; Oh, Yeon-Mok; Jung, Ki-Suck; Yoo, Ji Hong; Yoo, Kwang-Ha; Kim, Kwan Hyung

    2016-07-01

    Asthma is a prevalent and serious health problem in Korea. Recently, the Korean Asthma Guideline has been updated by The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) in an effort to improve the clinical management of asthma. This guideline focuses on adult patients with asthma and aims to deliver up to date scientific evidence and recommendations to general physicians for the management of asthma. For this purpose, this guideline was updated following systematic review and meta-analysis of recent studies and adapting some points of international guidelines (Global Initiative for Asthma [GINA] report 2014, National Asthma Education and Prevention Program [NAEPP] 2007, British Thoracic Society [BTS/SIGN] asthma guideline 2012, and Canadian asthma guideline 2012). Updated issues include recommendations derived using the population, intervention, comparison, and outcomes (PICO) model, which produced 20 clinical questions on the management of asthma. It also covers a new definition of asthma, the importance of confirming various airflow limitations with spirometry, the epidemiology and the diagnostic flow of asthma in Korea, the importance and evidence for inhaled corticosteroids (ICS) and ICS/formoterol as a single maintenance and acute therapy in the stepwise management of asthma, assessment of severity of asthma and management of exacerbation, and an action plan to cope with exacerbation. This guideline includes clinical assessments, and treatment of asthma-chronic obstructive pulmonary disease overlap syndrome, management of asthma in specific conditions including severe asthma, elderly asthma, cough variant asthma, exercise-induced bronchial contraction, etc. The revised Korean Asthma Guideline is expected to be a useful resource in the management of asthma.

  7. Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice.

    Science.gov (United States)

    Hubeau, Cedric; Apostolou, Irina; Kobzik, Lester

    2007-02-01

    Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2Ralpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.

  8. Population Intervention Models to Estimate Ambient NO2 Health Effects in Children with Asthma

    Science.gov (United States)

    Snowden, Jonathan M.; Mortimer, Kathleen M.; Dufour, Mi-Suk Kang; Tager, Ira B.

    2015-01-01

    Health effects of ambient air pollution are most frequently expressed in individual studies as responses to a standardized unit of air pollution changes (e.g., an interquartile interval), which is thought to enable comparison of findings across studies. However, this approach does not necessarily convey health effects in terms of a real-world air pollution scenario. In the present study, we employ population intervention modeling to estimate the effect of an air pollution intervention that makes explicit reference to the observed exposure data and is identifiable in those data. We calculate the association between ambient summertime NO2 and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25–75) in a cohort of children with asthma in Fresno, California. We scale the effect size to reflect NO2 abatement on a majority of summer days. The effect estimates were small, imprecise, and consistently indicated improved pulmonary function with decreased NO2. The effects ranged from −0.8% of mean FEF25–75 (95% Confidence Interval: −3.4 , 1.7) to −3.3% (95% CI: −7.5, 0.9). We conclude by discussing the nature and feasibility of the exposure change analyzed here given the observed air pollution profile, and we propose additional applications of the population intervention model in environmental epidemiology. PMID:25182844

  9. Tracheal compliance and limit flow rate changes in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Trachea is the unique passage for air to flow in and out. Its tone is of importance for the respiration system. However, investigation on how tracheal tone changes due to asthma is limited. Aiming at studying how the mechanical property changes due to asthma as well as the compliance and flow limitation, the following methods are adopted. Static and passive pressure-volume tests of rats’ trachea of the asthmatic and control groups are carried out and a new type of tube law is formulated to fit the experimental data, based on which changes of compliance and limit flow rate are investigated. In order to give explanation to such changes, histological examinations with tracheal soft tissues are made. The results show that compliance, limit flow rate and material constants included in the tube law largely depend on the longitudinal stretching ratio. Compared with the control group, the tracheal compliance of asthmatic animals decreases significantly, which results in an increased limit flow rate. Histological studies indicate that asthma can lead to hyperplasia/hypertrophy of smooth muscle cells, and increase elastin and collagen fibres in the muscular membrane. Though decreasing compliance increases sta- bility, during the onset of asthma, limit flow rate is much smaller due to the lower transmural pressure. Asthma leads to a stiffer trachea and the obtained results reveal some aspects relevant to asthma-induced tracheal remodelling.

  10. Tracheal compliance and limit flow rate changes in a urine model of asthma

    Institute of Scientific and Technical Information of China (English)

    TENG ZhongZhao; WANG YiQin; LI FuFeng; YAN HaiXia; LIU ZhaoRong

    2008-01-01

    Trachea is the unique passage for air to flow in and out. Its tone is of importance for the respiration system. However, investigation on how tracheal tone changes due to asthma is limited. Aiming at studying how the mechanical property changes due to asthma as well as the compliance and flow limitation, the following methods are adopted. Static and passive pressure-volume tests of rats' trachea of the asthmatic and control groups are carried out and a new type of tube law is formulated to fit the experimental data, based on which changes of compliance and limit flow rate are investigated. In order to give explanation to such changes, histological examinations with tracheal soft tissues are made. The results show that compliance, limit flow rate and material constants included in the tube law largely depend on the longitudinal stretching ratio. Compared with the control group, the tracheal compliance of asthmatic animals decreases significantly, which results in an increased limit flow rate. Histological studies indicate that asthma can lead to hyperplasia/hypertrophy of smooth muscle cells, and increase elastin and collagen fibres in the muscular membrane. Though decreasing compliance increases sta-bility, during the onset of asthma, limit flow rate is much smaller due to the lower transmural pressure. Asthma leads to a stiffer trachea and the obtained results reveal some aspects relevant to asthma-induced tracheal remodelling.

  11. Effect of Orem’s Self-Care Model on Perceived Stress in Adolescents with Asthma Referring the Asthma and Allergy Clinic, Isfahan, 2014

    Directory of Open Access Journals (Sweden)

    Zeinab Hemati

    2016-07-01

    Full Text Available Background: Incidence of asthma in adolescents leads to variations in family status, roles and interaction with peers for them, which could be a source of stress and psychological tensions in them. Therefore, the present study was conducted to investigate the effect of Orem’s self-care model on perceived stress in adolescents with asthma. Methods: In this semi-experimental study conducted from April 2013 to February 2014, 64 asthmatic adolescents referring Shariati Hospital, Isfahan were enrolled by simple random sampling and the patients were assigned to two groups of control and intervention. Then, Orem’s self-care model-based training was implemented throughout eight sessions of two hours each and the Cohen Perceived Stress Scale was administered to both groups prior to and two months after the completion of the training. The data were analyzed by descriptive and analytical statistics consisting of paired t-test, independent t-test, Chi-square and Mann-Whitney using SPSS Version 20. Results: Mean age of the participants was 14.15±3.12 years in the intervention group and 15.21±3.09 years in the control groups. 68.8% and 59.4% of the participants were male in the intervention and control groups, respectively. Independent t-test indicated a significant difference in the mean scores of perceived stress in the intervention (25.46±5.31 and control groups (28.90±5.27 after the training. Also, the result of paired t-test indicated a significant difference in the mean score of perceived stress between before (29.18±5.27 and after (25.46±5.31 training. Conclusion: As the training based on Orem’s model had a positive effect on declining perceived stress in asthmatic adolescents, continuation of using these training interventions could contribute to ultimately achieving positive outcomes in health functions of these patients.

  12. Student midwives' perceptions on the organisation of maternity care and alternative maternity care models in the Netherlands - a qualitative study.

    NARCIS (Netherlands)

    Warmelink, J.C.; Cock, T.P. de; Combee, Y.; Rongen, M.; Wiegers, T.A.; Hutton, E.K.

    2017-01-01

    BACKGROUND: A major change in the organisation of maternity care in the Netherlands is under consideration, going from an echelon system where midwives provide primary care in the community and refer to obstetricians for secondary and tertiary care, to a more integrated maternity care system

  13. FcgammaRIIb inhibits allergic lung inflammation in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nilesh Dharajiya

    Full Text Available Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcgammaRIIb, an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcgammaRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcgammaRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcgammaRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE challenge. RWE challenge in sensitized mice upregulated FcgammaRIIb in the lungs. Disruption of IFN-gamma gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcgammaRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcgammaRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcgammaRIIb in the lungs by IFN-gamma- and Th1-dependent mechanisms. RWE challenge upregulated FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcgammaRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcgammaRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1 allergen challenge mediates upregulation of FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-gamma dependent mechanism; and 2 by attenuating the allergen specific Ig

  14. Household environmental tobacco smoke and risks of asthma, wheeze and bronchitic symptoms among children in Taiwan

    Directory of Open Access Journals (Sweden)

    Hwang Bing-Fang

    2010-01-01

    Full Text Available Abstract Background Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS exposure remains inconsistent. Methods We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children's exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms. Results The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02, but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87. Conclusion We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.

  15. Comparative study analysing women's childbirth satisfaction and obstetric outcomes across two different models of maternity care

    OpenAIRE

    Conesa Ferrer, Ma Belén; Canteras Jordana, Manuel; Ballesteros Meseguer, Carmen; Carrillo García, César; Martínez Roche, M Emilia

    2016-01-01

    Objectives To describe the differences in obstetrical results and women's childbirth satisfaction across 2 different models of maternity care (biomedical model and humanised birth). Setting 2 university hospitals in south-eastern Spain from April to October 2013. Design A correlational descriptive study. Participants A convenience sample of 406 women participated in the study, 204 of the biomedical model and 202 of the humanised model. Results The differences in obstetrical results were (biom...

  16. Maternal, Infant Characteristics, Breastfeeding Techniques, and Initiation: Structural Equation Modeling Approaches

    OpenAIRE

    2015-01-01

    Objectives The aim of this study was to examine the relationships among maternal and infant characteristics, breastfeeding techniques, and exclusive breastfeeding initiation in different modes of birth using structural equation modeling approaches. Methods We examined a hypothetical model based on integrating concepts of a breastfeeding decision-making model, a breastfeeding initiation model, and a social cognitive theory among 952 mother-infant dyads. The LATCH breastfeeding assessment tool ...

  17. Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin-induced murine model of asthma.

    Science.gov (United States)

    Li, Bei; Duan, Xiaohong; Xu, Changqing; Wu, Jinfeng; Liu, Baojun; Du, Yiji; Luo, Qingli; Jin, Hualiang; Gong, Weiyi; Dong, Jingcheng

    2014-04-01

    Evidence shows that psychosocial stress exacerbates asthma, but there is little intervention to alleviate negative effects of psychosocial stress on asthma. We investigated the role of icariin in anti-inflammation and anti-anxiety potential in a murine model combined psychosocial stress with allergic exposure. The results indicated that icariin administered remarkable increased activity in the center of the open field, reversed airway hyperresponsivenesss, reduced inflammatory cytokine infiltration to the lung and whole body and also in part recovered glucocorticoid responsiveness. Furthermore, our data also showed that icariin significantly inhibited increases of corticosterone and markedly increased glucocorticoid receptor mRNA and protein expression in the lungs of mice exposed to both stress and allergen. Collectively, we speculate that inducing glucocorticoid receptor modulation might be the potential mechanisms of icariin to facilitate corticosteroid responsiveness of cytokine production.

  18. Comparison of two rodent models of maternal separation on juvenile social behavior

    Directory of Open Access Journals (Sweden)

    Betty eZimmerberg

    2011-06-01

    Full Text Available Early childhood deprivation is associated with an increased risk of attachment disorders and psychopathology. The neural consequences of exposure to stress early in life have used two major rodent models to provide important tools for translational research. Although both models have been termed Maternal Separation, the paradigms differ in ways that clearly shift the focus of stress between maternal and offspring units. The first model, here called Early Deprivation (ED, isolates pups individually while the dam is left not alone, but with a subset of littermates in the home nest (Stay-at-homes. The other model, here called Maternal Separation (MS, isolates the dam in a novel cage while the pups are separated together. In this study, these two early stress models were directly compared for their effects on social behaviors in male and female juvenile offspring. Although both models altered play behavior compared to controls, patterns of prosocial behaviors versus submissive behaviors differed by model and sex. Additionally, there were main effects of sex, with female ED subjects exhibited masculinizing effects of early stress during play sessions. Maternal behavior upon reunion with the isolated subjects was significantly increased in the MS condition compared to both ED and control conditions, which also differed but by a lesser magnitude. Stay-at-homes were tested since some laboratories use them for controls rather than undisturbed litters; they displayed significantly different sex-dependent play compared to undisturbed subjects. These results indicate that early stress effects vary by paradigm of separation. We suggest that MS produces greater stress on the dam and thus greater maternal mediation, while ED causes greater stress on the neonates, resulting in different behavioral sequela that warrant attention when using these models for translational research.

  19. Resveratrol inhibits mucus overproduction and MUC5AC expression in a murine model of asthma.

    Science.gov (United States)

    Ni, Zhen-Hua; Tang, Ji-Hong; Chen, Guo; Lai, Yi-Min; Chen, Qing-Ge; Li, Zao; Yang, Wei; Luo, Xu-Min; Wang, Xiong-Biao

    2016-01-01

    Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol‑mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)‑challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA‑induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA‑challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium‑activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose‑dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway.

  20. EFFICACY OF ANTIHISTAMINE AGENTS ON MODEL FOR EXERCISE-INDUCED ASTHMA IN GUINEA PIGS

    Institute of Scientific and Technical Information of China (English)

    TAO Meng-Fei; REN Tao; LIANG Yong-Jie

    2006-01-01

    Objective To investigate the effects of antihistamine agents, loratadine and ketotifen, on the model of exercise-induced asthma in guinea pigs with lipopolysaccharide ( LPS) and metyapone. Methods Nineteen guinea pigs were injected peritoneolly with LPS (1mg/kg, i. p. ) and metyapone ( 50mg/kg, i. p. ). Then they were randomized into 3 groups. The control group ( n =7) did not take any drug, ketotifen group ( n =6) adminisd-1 ) for 4 days. On the fifth day, lung resistance (RL) and dynamic compliance of respiratory system (Cdyn) of 3 groups were measured before and after exercise challenge. The total number of leukocytes in bronchoalveolar lavage fluid (BALF) from 3 groups was counted and differentiated cell type count was measured. Morphometric examination of the animal lungs was performed. Results In control group, RLincreased and Cdyn decreased significantly after exercise challenge. In ketotifen group and loratadine group with no change. There was a significant increase in the number of neutrophils, macrophages and eosinophils in BALF from control group. The infiltration of neutrophils in the bronchial mucosa was shown in control group in the morphometric study. Conclusion Loratadine and ketotifen can inhibit the exercise-indaced bronchoconstriction in guinea pigs pretreated with LPS and metyrapone. Inhibiting the formation of inflammation in airway may be the therapeutic mechanism of these H-1 receptor antagonists.

  1. Early-life gut microbial colonization shapes Th1/Th2 balance in asthma model in BALB/c mice.

    Science.gov (United States)

    Qian, Li-Juan; Kang, Shu-Min; Xie, Jia-Li; Huang, Li; Wen, Quan; Fan, Yuan-Yuan; Lu, Li-Jun; Jiang, Li

    2017-06-17

    We aimed to investigate the effect of early-life diverse microbial exposures on gut microbial colonization in an OVA-induced asthma model in BALB/c mice. BALB/c mice were divided into 4 groups: A, offsprings were kept in a SPF environment during fetal, lactation, and childhood periods; B, offsprings were kept in the SPF environment during fetal and lactation periods, and kept in the general environment during childhood; C, offsprings were kept in the SPF environment only during fetal period, and then kept in the general environment; and D, offsprings were kept in the general environment during whole periods. The diversity of intestinal flora was analyzed using denaturing gradient gel electrophoresis. Mice were sensitized with OVA to establish an animal model of asthma. Then asthma-related inflammatory cytokines and histological analysis were performed. The diversity of intestinal microflora in group D was significantly higher than groups A, B and C at three days and three weeks after birth, and the diversity of intestinal microflora in groups C and D were significantly higher than groups A and B at five weeks after birth. The pathologic scores of OVA-induced asthmatic mice in group D were significantly lower than group A, and serum IFN-γ levels and the IFN-γ/IL-4 ratio in group D were significantly higher than group A. Exposure to diverse microbial environments in early life affects gut microbial colonization in BALB/c mice. The diversity of the intestinal flora in early life may prevent airway inflammation in asthma via regulating the Th1/Th2 balance.

  2. Duration and exclusiveness of breastfeeding and school-age lung function and asthma.

    Science.gov (United States)

    van Meel, Evelien R; de Jong, Mandy; Elbert, Niels J; den Dekker, Herman T; Reiss, Irwin K; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

    2017-07-01

    Breastfeeding reduces the risk of asthma in early childhood, but it is not clear whether its effect on respiratory morbidity is still present in later childhood. To examine the associations of any breastfeeding, breastfeeding duration, and breastfeeding exclusiveness with lung function and asthma in school-aged children and whether associations were influenced by respiratory tract infections and maternal or child's atopic status. This study of 4,464 children was embedded in a population-based prospective cohort study. Information on breastfeeding was obtained by multiple questionnaires from birth until 1 year of age. At 10 years of age, lung function was measured by spirometry, and information on asthma was obtained by questionnaire. Adjusted linear and logistic regression models were used to examine the associations. Shorter duration of breastfeeding was associated with a lower forced expiratory volume in 1 second (FEV1) only (z score change, -0.01; 95% confidence interval [CI], -0.02 to -0.00) per month shorter breastfeeding, but not asthma. When categorized, breastfeeding for 2 to 4 months was associated with a lower forced vital capacity (FVC) (z score change, -0.11; 95% CI, -0.20 to -0.03) compared with breastfeeding for 6 months or longer. Nonexclusive breastfeeding for 4 months was associated with a lower FVC (z score change, -0.08; 95% CI, -0.16 to -0.01) compared with exclusive breastfeeding for 4 months. Results did not materially change after additional adjustment for lower respiratory tract infections and were not modified by maternal history of asthma or atopy, child's eczema, or inhalant allergic sensitization. Shorter duration and nonexclusivity of breastfeeding were associated with a lower FEV1 and FVC but not asthma at school-age. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. Individual-level socioeconomic status is associated with worse asthma morbidity in patients with asthma

    Directory of Open Access Journals (Sweden)

    Bouchard Anne

    2009-12-01

    Full Text Available Abstract Background Low socioeconomic status (SES has been linked to higher morbidity in patients with chronic diseases, but may be particularly relevant to asthma, as asthmatics of lower SES may have higher exposures to indoor (e.g., cockroaches, tobacco smoke and outdoor (e.g., urban pollution allergens, thus increasing risk for exacerbations. Methods This study assessed associations between adult SES (measured according to educational level and asthma morbidity, including asthma control; asthma-related emergency health service use; asthma self-efficacy, and asthma-related quality of life, in a Canadian cohort of 781 adult asthmatics. All patients underwent a sociodemographic and medical history interview and pulmonary function testing on the day of their asthma clinic visit, and completed a battery of questionnaires (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Asthma Self-Efficacy Scale. General Linear Models assessed associations between SES and each morbidity measure. Results Lower SES was associated with worse asthma control (F = 11.63, p Conclusions Results suggest that lower SES (measured according to education level, is associated with several indices of worse asthma morbidity, particularly worse asthma control, in adult asthmatics independent of disease severity. Results are consistent with previous studies linking lower SES to worse asthma in children, and add asthma to the list of chronic diseases affected by individual-level SES.

  4. A Model of Maternal Coping with Childbirth: Implications for Research and Methodology.

    Science.gov (United States)

    Nicholson, Joanne

    A conceptual model of the childbirth experience is developed which emphasizes: (1) maternal coping during labor and delivery; (2) postpartum evaluation of the experience; (3) stress and coping; (4) health and illness behavior; (5) interactions between individual physiological and psychological characteristics; and (6) physical and social…

  5. 支气管哮喘动物模型制备的研究%The Studies on Preparation of Animal Model with Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    曹珊珊

    2012-01-01

    支气管哮喘是一种常见多发病,哮喘动物实验模型的建立在研究本病的发病原因、机制及防治方面有着极其重要的意义.笔者主要就哮喘动物模型的相关内容进行了概述.%Bronchial asthma is a common and frequently encountered disease. The establishment of animal experimental model on asthma had extremely important significance in aetiological agent,mechanism and preventive treatment of asthma. A brief review relating to animal modles on asthma was summarized in this paper.

  6. An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Chang-Min Lee

    Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

  7. The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma.

    Science.gov (United States)

    Sagar, Seil; Vos, Arjan P; Morgan, Mary E; Garssen, Johan; Georgiou, Niki A; Boon, Louis; Kraneveld, Aletta D; Folkerts, Gert

    2014-04-01

    Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma.

  8. Prophylactic treatment of asthma by an ozone scavenger in a mouse model.

    Science.gov (United States)

    Bibi, Haim; Reany, Ofer; Waisman, Dan; Keinan, Ehud

    2015-01-15

    Our hypothesis that inflammation in asthma involves production of ozone by white blood cells and that ozone could be an inflammatory mediator suggests that scavengers of reactive oxygen species (ROS), for example, electron-rich olefins, could serve for prophylactic treatment of asthma. Olefins could provide chemical protection against either exogenous or endogenous ozone and other ROS. BALB/c mice pretreated by inhalation of d-limonene before an ovalbumin challenge exhibited significant attenuation of the allergic asthma symptoms. Diminution of the inflammatory process was evident by reduced levels of aldehydes, reduced counts of neutrophils in the BAL fluid and by histological tests. A surprising systemic effect was observed by decreased levels of aldehydes in the spleen, suggesting that the examination of tissues and organs that are remote from the inflammation foci could provide valuable information on the distribution of the oxidative stress and may serve as guide for targeted treatment.

  9. Asthma pharmacotherapy.

    Science.gov (United States)

    Schofield, Minka L

    2014-02-01

    Asthma is a chronic inflammatory disease of the airway that leads to airway obstruction via bronchoconstriction, edema, and mucus hypersecretion. The National Asthma Education and Prevention Program has outlined evidence-based guidelines to standardize asthma therapy and improve outcomes. The initial recommendation of choice for persistent asthmatic patients is an inhaled corticosteroid (ICS). Long-acting beta-2 agonists in combination with ICS, oral corticosteroids, leukotriene modifiers, and anti-IgE therapeutic options can be considered for patients with persistent or worsening symptoms. Many novel therapies are being developed, with an emphasis on anti-inflammatory mechanisms, gene expression, and cytokine modification.

  10. Competing risks model in screening for preeclampsia by maternal characteristics and medical history.

    Science.gov (United States)

    Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Poon, Leona C; Nicolaides, Kypros H

    2015-07-01

    The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history. This was a screening study of 120,492 singleton pregnancies at 11-13 weeks' gestation, including 2704 pregnancies (2.2%) that experienced preeclampsia. A survival-time model for the gestational age at delivery with preeclampsia was developed from variables of maternal characteristics and history. This approach assumes that, if the pregnancy was to continue indefinitely, all women would experience preeclampsia and that whether they do so or not before a specified gestational age depends on competition between delivery before or after development of preeclampsia. A 5-fold cross validation study was conducted to compare the performance of the new model with the National Institute for Health and Clinical Excellence (NICE) guidelines. In the new model, increased risk for preeclampsia, with a consequent shift in the Gaussian distribution of the gestational age at delivery with preeclampsia to the left, is provided by advancing maternal age, increasing weight, Afro-Caribbean and South Asian racial origin, medical history of chronic hypertension, diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, family history and personal history of preeclampsia, and conception by in vitro fertilization. The risk for preeclampsia decreases with increasing maternal height and in parous women with no previous preeclampsia; in the latter, the protective effect, which is related inversely to the interpregnancy interval, persists beyond 15 years. At a screen-positive rate of 11%, as defined by NICE, the new model predicted 40%, 48%, and 54% of cases of total preeclampsia and preeclampsia requiring delivery at preeclampsia. Such estimation of the a priori risk for preeclampsia is an essential first step in the use of Bayes theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of

  11. What models of maternity care do pregnant women in Ireland want?

    LENUS (Irish Health Repository)

    Byrne, C

    2012-02-01

    The introduction of new models of care in the Irish maternity services has been recommended by both advocacy groups and strategic reports. Yet there is a dearth of information about what models of care pregnant women want. We surveyed women in early pregnancy who were attending a large Dublin maternity hospital. Demographic and clinical details were recorded from the hospital chart. Of the 501 women, 351 (70%) (352 (70.3%) of women wanted shared antenatal care between their family doctor and either a hospital doctor or midwife. 228 (45.5%) preferred to have their baby delivered in a doctor-led unit, while 215 (42.9%) preferred a midwifery-led unit. Of those 215 (42.9%), 118 (55%) met criteria for suitability. There was minimal demand (1.6%) for home births. Choice was influenced by whether the woman was attending for private care or not. Safety is the most important factor for women when choosing the type of maternity care they want. Pregnant women want a wide range of choices when it comes to models of maternity care. Their choice is strongly influenced by safety considerations, and will be determined in part by risk assessment.

  12. Maternal death inquiry and response in India - the impact of contextual factors on defining an optimal model to help meet critical maternal health policy objectives

    Directory of Open Access Journals (Sweden)

    Kalter Henry D

    2011-11-01

    Full Text Available Abstract Background Maternal death reviews have been utilized in several countries as a means of identifying social and health care quality issues affecting maternal survival. From 2005 to 2009, a standardized community-based maternal death inquiry and response initiative was implemented in eight Indian states with the aim of addressing critical maternal health policy objectives. However, state-specific contextual factors strongly influenced the effort's success. This paper examines the impact and implications of the contextual factors. Methods We identified community, public health systems and governance related contextual factors thought to affect the implementation, utilization and up-scaling of the death inquiry process. Then, according to selected indicators, we documented the contextual factors' presence and their impact on the process' success in helping meet critical maternal health policy objectives in four districts of Rajasthan, Madhya Pradesh and West Bengal. Based on this assessment, we propose an optimal model for conducting community-based maternal death inquiries in India and similar settings. Results The death inquiry process led to increases in maternal death notification and investigation whether civil society or government took charge of these tasks, stimulated sharing of the findings in multiple settings and contributed to the development of numerous evidence-based local, district and statewide maternal health interventions. NGO inputs were essential where communities, public health systems and governance were weak and boosted effectiveness in stronger settings. Public health systems participation was enabled by responsive and accountable governance. Communities participated most successfully through India's established local governance Panchayat Raj Institutions. In one instance this led to the development of a multi-faceted intervention well-integrated at multiple levels. Conclusions The impact of several contextual

  13. Asthma and Hispanic Americans

    Science.gov (United States)

    ... and Data > Minority Population Profiles > Hispanic/Latino > Asthma Asthma and Hispanic Americans In 2014, 2.1 million Hispanics reported that they currently have asthma. Puerto Rican Americans have almost twice the asthma ...

  14. Asthma Triggers: Gain Control

    Science.gov (United States)

    ... Search Asthma Contact Us Share Asthma Triggers: Gain Control Breathing Freely: Controlling Asthma Triggers This video features ... Air Quality: Biological Pollutants Help Your Child Gain Control Over Asthma Top of Page Molds About Molds ...

  15. Exercise and Asthma

    Science.gov (United States)

    ... Español Text Size Email Print Share Exercise and Asthma Page Content Article Body Almost every child (and ... of Pediatrics about asthma and exercise. What is asthma Asthma is the most common chronic medical problem ...

  16. The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model.

    Directory of Open Access Journals (Sweden)

    Igor L Chernyavsky

    Full Text Available Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynamics of ASM cells over short and long terms in the normal and inflammatory environments typically observed in asthma. The degree of ASM accumulation can be explained by an increase in the rate at which ASM cells switch between non-proliferative and proliferative states, driven by episodic inflammatory events. Our model explores the idea that remodelling due to ASM hyperplasia increases with the frequency and magnitude of these inflammatory events, relative to certain sensitivity thresholds. It highlights the importance of inflammation resolution speed by showing that when resolution is slow, even a series of small exacerbation events can result in significant remodelling, which persists after the inflammatory episodes. In addition, we demonstrate how the uncertainty in long-term outcome may be quantified and used to design an optimal low-risk individual anti-proliferative treatment strategy. The model shows that the rate of clearance of ASM proliferation and recruitment factors after an acute inflammatory event is a potentially important, and hitherto unrecognised, target for anti-remodelling therapy in asthma. It also suggests new ways of quantifying inflammation severity that could improve prediction of the extent of ASM accumulation. This ASM growth model should prove useful for designing new experiments or as a building block of more detailed multi-cellular tissue-level models.

  17. Childhood Asthma

    Science.gov (United States)

    ... Education Center Fellows-in-Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice Tools Running a Practice Statements and Practice Parameters About AAAAI Advocacy Allergist / Immunologists: ...

  18. Occupational Asthma

    Science.gov (United States)

    ... Education Center Fellows-in-Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice Tools Running a Practice Statements and Practice Parameters About AAAAI Advocacy Allergist / Immunologists: ...

  19. Asthma Quiz

    Science.gov (United States)

    ... Education Center Fellows-in-Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice Tools Running a Practice Statements and Practice Parameters About AAAAI Advocacy Allergist / Immunologists: ...

  20. Childhood asthma

    African Journals Online (AJOL)

    of their lives. Definition. Asthma is clinically defined as a disease with symptoms of ... and seasonal variation in symptoms. ... “Western lifestyle” has commonly been used to explain ... influencing airway narrowing is smooth muscle contraction.

  1. Hospital- and patient-related characteristics determining maternity length of stay: a hierarchical linear model approach.

    Science.gov (United States)

    Leung, K M; Elashoff, R M; Rees, K S; Hasan, M M; Legorreta, A P

    1998-03-01

    The purpose of this study was to identify factors related to pregnancy and childbirth that might be predictive of a patient's length of stay after delivery and to model variations in length of stay. California hospital discharge data on maternity patients (n = 499,912) were analyzed. Hierarchical linear modeling was used to adjust for patient case mix and hospital characteristics and to account for the dependence of outcome variables within hospitals. Substantial variation in length of stay among patients was observed. The variation was mainly attributed to delivery type (vaginal or cesarean section), the patient's clinical risk factors, and severity of complications (if any). Furthermore, hospitals differed significantly in maternity lengths of stay even after adjustment for patient case mix. Developing risk-adjusted models for length of stay is a complex process but is essential for understanding variation. The hierarchical linear model approach described here represents a more efficient and appropriate way of studying interhospital variations than the traditional regression approach.

  2. Puerarin Attenuates Ovalbumin-Induced Lung Inflammation and Hemostatic Unbalance in Rat Asthma Model

    Directory of Open Access Journals (Sweden)

    Feng Dong

    2014-01-01

    Full Text Available Aim. We aimed to investigate and evaluate the preventive activity of puerarin on the ovalbumin-induced asthma rat model. Materials and Methods. Male Wistar rats were sensitized intraperitoneally on days 0, 7, and 14 and challenged to ovalbumin intratracheally on day 21. Groups of sensitized rats were treated randomly either with placebo, puerarin, dexamethasone, or puerarin combined with dexamethasone, from days 15 to 20. Inflammatory markers, including cell counts in bronchoalveolar lavage fluid (BALF, inflammatory cytokines, histopathology, and coagulation parameters, such as coagulation tests and the activity of coagulation factors, were analyzed. Results. Puerarin significantly inhibited the recruitment of inflammatory cells in BALF and lung tissue. At the same time, the release of IL-4, IL-10, and IFN-γ in serum and the expression of mRNAs in lung tissue homogenate were changed by puerarin. Administration of puerarin also effectively rectified the coagulation disorder in asthmatic rats, such as prothrombin time (PT (P<0.01, thrombin time (TT (P<0.05, fibrinogen (FIB (P<0.01,the activity of factor II (FII (P<0.01, the activity of factor V (FV (P<0.05, the activity of factor VII (FVII (P<0.05, the activity of factor X (FX (P<0.05, the activity of factor VIII (FVIII (P<0.01, the activity of factor IX (FIX (P<0.05, and the activity of factor XII (FXII (P<0.05. Conclusions. Our results provide a clue that puerarin was useful for the preventive of allergic airway disease in rodents.

  3. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...... were assigned to (a) control diet (CD; 1 % salt, 10 % kcal from fat), (b) high salt diet (SD; 4 % salt, 10 % kcal from fat), (c) high fat diet (HF; 1 % salt, 45 % kcal from fat) or (d) high-fat high-salt diet (HFSD; 4 % salt, 45 % kcal from fat) 21 days prior to pregnancy and during gestation......Introduction: Maternal obesity is associated with a range of pregnancy complications, including fetal growth restriction (FGR), whereby a fetus fails to reach its genetically determined growth. Placental insufficiency and reduced nutrient transport play a role in the onset of FGR. Objectives...

  4. Recognizing asthma mimics and asthma complications.

    Science.gov (United States)

    Amundson, Dennis; Seda, Gilbert; Daheshia, Massoud

    2011-10-01

    Asthma is a chronic inflammatory disorder of the airways characterized by airflow obstruction, bronchial hyperreactivity, and underlying inflammation. Two common reasons asthmatics fail standard therapy are incorrect diagnosis and failure to recognize underlying contributing factors. A correct diagnosis of asthma is of great importance to military practitioners since misdiagnosis or uncontrolled asthma affects an individual's operational readiness or determines whether one can receive a medical waiver to enlist in military service. This article presents four cases of patients with dyspnea that have conditions which mimic asthma or complicate asthma management: vocal cord dysfunction misdiagnosed as asthma, respiratory bronchiolitis interstitial lung disease mistaken as asthma, difficult-to-control asthma because of bronchiectasis and allergic bronchopulmonary aspergillosis, and difficult and fatal asthma. Asthma is contrasted to other respiratory disorders, and an outlined approach to asthma diagnosis and management is presented using the Global Initiative for Asthma guidelines.

  5. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma

    Directory of Open Access Journals (Sweden)

    Francieli Vuolo

    2015-01-01

    Full Text Available Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA. In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p. and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CBD seems to be a potential new drug to modulate inflammatory response in asthma.

  6. Allergen specific immunotherapy: The future cure for allergic asthma. Mechanisms and improvement in a mouse model

    NARCIS (Netherlands)

    Taher, Y.A.

    2007-01-01

    Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling and airway hyperresponsiveness (AHR). CD4+ T-cells, in particular T-helper type 2 (Th2) cells, play a critical role in orchestrating the disease process through the release of cytokines like IL-4

  7. Characterization of Macrophage Phenotypes in Three Murine Models of House-Dust-Mite-Induced Asthma

    NARCIS (Netherlands)

    Draijer, Christina; Robbe, Patricia; Boorsma, Carian E.; Hylkema, Machteld N.; Melgert, Barbro N.

    2013-01-01

    In asthma, an important role for innate immunity is increasingly being recognized. Key innate immune cells in the lungs are macrophages. Depending on the signals they receive, macrophages can at least have an M1, M2, or M2-like phenotype. It is unknown how these macrophage phenotypes behave with reg

  8. Cost-effectiveness of primary prevention of paediatric asthma: a decision-analytic model

    NARCIS (Netherlands)

    Ramos, G. Feljandro P.; van Asselt, Antoinette D. I.; Kuiper, Sandra; Severens, Johan L.; Maas, Tanja; Dompeling, Edward; Knottnerus, J. André; van Schayck, Onno C. P.

    2013-01-01

    Background: Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention

  9. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  10. Maternal smoking and the retinoid pathway in the developing lung

    Directory of Open Access Journals (Sweden)

    Manoli Sara E

    2012-06-01

    Full Text Available Abstract Background Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model. Methods Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week were mated to nonsmoking males. Cigarette smoke exposure continued throughout the pregnancy and after parturition. Lung tissue from the offspring was examined by mean linear intercept analysis and by quantitative PCR. Cell culture experiments using the type II cell-like cell line, A549, tested whether lipid-soluble cigarette smoke components affected binding and activation of retinoic acid response elements in vitro. Results Compared to tobacco-naïve mice, juvenile mice with tobacco toxin exposure had significantly (P  Conclusions A murine model of maternal cigarette smoking causes abnormal alveolarization in association with altered retinoic acid pathway element expression in the offspring. An in vitro cell culture model shows that lipid-soluble components of cigarette smoke decrease retinoic acid response element activation. It is feasible that disruption of retinoic acid signaling contributes to the pediatric lung dysfunction caused by maternal smoking.

  11. Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma.

    Science.gov (United States)

    Wang, Pingli; Thevenot, Paul; Saravia, Jordy; Ahlert, Terry; Cormier, Stephania A

    2011-11-01

    We identified a previously unrecognized component of airborne particulate matter (PM) formed in combustion and thermal processes, namely, environmentally persistent free radicals (EPFRs). The pulmonary health effects of EPFRs are currently unknown. In the present study, we used a model EPFR-containing pollutant-particle system referred to as MCP230. We evaluated the effects of MCP230 on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. We also investigated the adjuvant role of MCP230 on airway inflammation in a mouse model of asthma. MCP230 decreased intracellular reduced glutathione (GSH) and the GSH/oxidized glutathione ratio in BMDCs, and up-regulated the expression of costimulatory molecules CD80 and CD86 on DCs. The maturation of DCs was blocked by inhibiting oxidative stress or the uptake of MCP230. BMDCs exposed to MCP230 increased their antigen-specific T-cell proliferation in vitro. In a model of asthma, exposure to MCP230 exacerbated pulmonary inflammation, which was attributed to the increase of neutrophils and macrophages but not eosinophils. This result correlated with an increase in Th17 cells and cytokines, compared with non-MCP230-treated but ovalbumin (OVA)-challenged mice. The percentage of Th2 cells was comparable between OVA and OVA + MCP230 mice. Our data demonstrate that combustion-generated, EPFR-containing PM directly induced the maturation of DCs in an uptake-dependent and oxidative stress-dependent manner. Furthermore, EPFR-containing PM induced a Th17-biased phenotype in lung, accompanied by significant pulmonary neutrophilia. Exposure to EPFR-containing PM may constitute an important and unrecognized risk factor in the exacerbation and development of a severe asthma phenotype in humans.

  12. Influence of adolescent obesity and maternal pre-pregnancy overweight on the occurrence of tracheal asthma%青少年肥胖和母亲孕前超重对青少年支气管哮喘发病的影响

    Institute of Scientific and Technical Information of China (English)

    孔令玉; 柴若南; 刘蕾; 韩雅玲; 马德宾

    2015-01-01

    目的 明确青少年肥胖及其母亲孕前超重对青少年支气管哮喘发生的影响,并随访研究减轻体重可否协助哮喘的治疗和控制.方法 采用同期对照实验,纳入同一时期就诊的哮喘青少年507例及非哮喘青少年511例,研究其母亲及自身体质超重或肥胖的情况.将体质超重或肥胖的哮喘患儿纳入体重控制研究,在正规治疗哮喘的同时,要求其父母协助患儿正规减重,分析体重减轻对患儿哮喘控制的影响.结果 哮喘青少年组母亲孕前超重比例(115/507)明显高于非哮喘青少年组(90/511),差异有统计学意义(P<0.05);母亲孕前肥胖是青少年发生哮喘的危险因素(OR1.37,95%CI 1.01~1.87,P=0.026).同样,哮喘青少年组肥胖比例(155/507)也明显高于非哮喘青少年(102/511),差异有统计学意义(P<0.05);青少年超重或肥胖也可能导致其哮喘发生(OR 1.77, 95%CI 1.32~2.35,P<0.01).当青少年合理控制体重之后,其哮喘缓解情况明显优于体重对照组,差异有统计学意义(P=0.025).结论 母亲孕前超重及青少年肥胖均是支气管哮喘发生的危险因素,治疗哮喘的同时减轻体重可有效提高哮喘控制率.%Objective To determine the influence of adolescent obesity and maternal pre-pregnancy over-weight on the occurrence of tracheal asthma among school-age children, and study whether weight loss could assist the treatment and control of asthma. Methods In a concurrent control experiment, 507 cases of asthma adolescent pa-tients (asthma group) and 511 cases of non-asthma adolescent patients (non-asthma group) were included during the same period, with the overweight or obesity of themselves and their mothers studied. And then, asthma patients with overweight or obesity were included into the research of weight-control: parents were asked to help patients to lose weight healthily on the basis of regular treatment of asthma. The effect of weight loss on asthma control of children was

  13. Role of late maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity.

    Science.gov (United States)

    Berbel, P; Navarro, D; Ausó, E; Varea, E; Rodríguez, A E; Ballesta, J J; Salinas, M; Flores, E; Faura, C C; de Escobar, G Morreale

    2010-06-01

    Hypothyroxinemia affects 35-50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers' organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.

  14. Retrovirus-mediated delivery of an IL-4 receptor antagonist inhibits allergic responses in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This work reports the investigation of the effect of airway IL-4RA gene transfer by a recombinant retroviral vector on airway inflammation and airway responsiveness in asthmatic mice. The retrovirus-mediated delivery of IL-4RA to the airways of mice inhibited elevations of airway responsiveness and the development of allergic inflammation in asthmatic mice, and regulated the Th1/Th2 balance in OVA-sensitized and -challenged mouse models. This suggests that gene therapy is a therapeutic option for treating and controlling chronic airway inflammation and asthma symptoms.

  15. Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

    Science.gov (United States)

    Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

    2009-01-01

    Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

  16. Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

    Science.gov (United States)

    Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

    2016-01-01

    Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

  17. Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model.

    Directory of Open Access Journals (Sweden)

    Pornswan Ngamprasertwong

    Full Text Available Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK using a chronically instrumented maternal-fetal sheep model.Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check.A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated.For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart

  18. The adjuvant effect induced by di-(2-ethylhexyl) phthalate (DEHP) is mediated through oxidative stress in a mouse model of asthma.

    Science.gov (United States)

    You, Huihui; Chen, Shaohui; Mao, Lin; Li, Bing; Yuan, Ye; Li, Rui; Yang, Xu

    2014-09-01

    Di-(2-ethylhexyl) phthalate, as the most commonly used plasticizer, is considered to be related to the asthma prevalence. There are studies affirming that the DEHP has an adjuvant effect in the pathogenesis of allergy asthma. Oxidative stress is one possible pathway for DEHP-adjuvant effect. Thus, this study explored whether DEHP could induce adjuvant effect in mouse asthma model via oxidative stress pathway. Male BALB/c mice were randomly divided into six groups: (1) saline group, (2) DEHP group, (3) ovalbumin (OVA) group, (4) DEHP+OVA group, (5) OVA+vitamin E (Vit E) group, (6) DEHP+OVA+Vit E group. The exposure dose of DEHP was 30 mg/kg body weight (bw)/day. After 18 days of the exposure protocol. Reactive oxygen species (ROS), glutathione (GSH) and malonaldehyde (MDA) levels and biomarkers related to asthma model were measured. Collectively, these data indicated higher ROS and MDA levels and lower GSH contents in DEHP+OVA group than that in OVA group, while Vit E, an antioxidant, could restore ROS, MDA and GSH levels to control levels and attenuate the DEHP and/or OVA effects. Our observations suggested that there was a relationship between oxidative stress and the adjuvant effect induced by DEHP in this mouse asthma model.

  19. Ion channels in asthma.

    Science.gov (United States)

    Valverde, Miguel A; Cantero-Recasens, Gerard; Garcia-Elias, Anna; Jung, Carole; Carreras-Sureda, Amado; Vicente, Rubén

    2011-09-23

    Ion channels are specialized transmembrane proteins that permit the passive flow of ions following their electrochemical gradients. In the airways, ion channels participate in the production of epithelium-based hydroelectrolytic secretions and in the control of intracellular Ca(2+) levels that will ultimately activate almost all lung cells, either resident or circulating. Thus, ion channels have been the center of many studies aiming to understand asthma pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. In this minireview, we focus on molecular, genetic, and animal model studies associating ion channels with asthma.

  20. Comparative study analysing women's childbirth satisfaction and obstetric outcomes across two different models of maternity care.

    Science.gov (United States)

    Conesa Ferrer, Ma Belén; Canteras Jordana, Manuel; Ballesteros Meseguer, Carmen; Carrillo García, César; Martínez Roche, M Emilia

    2016-08-26

    To describe the differences in obstetrical results and women's childbirth satisfaction across 2 different models of maternity care (biomedical model and humanised birth). 2 university hospitals in south-eastern Spain from April to October 2013. A correlational descriptive study. A convenience sample of 406 women participated in the study, 204 of the biomedical model and 202 of the humanised model. The differences in obstetrical results were (biomedical model/humanised model): onset of labour (spontaneous 66/137, augmentation 70/1, p=0.0005), pain relief (epidural 172/132, no pain relief 9/40, p=0.0005), mode of delivery (normal vaginal 140/165, instrumental 48/23, p=0.004), length of labour (0-4 hours 69/93, >4 hours 133/108, p=0.011), condition of perineum (intact perineum or tear 94/178, episiotomy 100/24, p=0.0005). The total questionnaire score (100) gave a mean (M) of 78.33 and SD of 8.46 in the biomedical model of care and an M of 82.01 and SD of 7.97 in the humanised model of care (p=0.0005). In the analysis of the results per items, statistical differences were found in 8 of the 9 subscales. The highest scores were reached in the humanised model of maternity care. The humanised model of maternity care offers better obstetrical outcomes and women's satisfaction scores during the labour, birth and immediate postnatal period than does the biomedical model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Comparative study analysing women's childbirth satisfaction and obstetric outcomes across two different models of maternity care

    Science.gov (United States)

    Conesa Ferrer, Ma Belén; Canteras Jordana, Manuel; Ballesteros Meseguer, Carmen; Carrillo García, César; Martínez Roche, M Emilia

    2016-01-01

    Objectives To describe the differences in obstetrical results and women's childbirth satisfaction across 2 different models of maternity care (biomedical model and humanised birth). Setting 2 university hospitals in south-eastern Spain from April to October 2013. Design A correlational descriptive study. Participants A convenience sample of 406 women participated in the study, 204 of the biomedical model and 202 of the humanised model. Results The differences in obstetrical results were (biomedical model/humanised model): onset of labour (spontaneous 66/137, augmentation 70/1, p=0.0005), pain relief (epidural 172/132, no pain relief 9/40, p=0.0005), mode of delivery (normal vaginal 140/165, instrumental 48/23, p=0.004), length of labour (0–4 hours 69/93, >4 hours 133/108, p=0.011), condition of perineum (intact perineum or tear 94/178, episiotomy 100/24, p=0.0005). The total questionnaire score (100) gave a mean (M) of 78.33 and SD of 8.46 in the biomedical model of care and an M of 82.01 and SD of 7.97 in the humanised model of care (p=0.0005). In the analysis of the results per items, statistical differences were found in 8 of the 9 subscales. The highest scores were reached in the humanised model of maternity care. Conclusions The humanised model of maternity care offers better obstetrical outcomes and women's satisfaction scores during the labour, birth and immediate postnatal period than does the biomedical model. PMID:27566632

  2. Animal models of maternal nutrition and altered offspring bone structure – Bone development across the lifecourse

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    SA Lanham

    2011-11-01

    Full Text Available It is widely accepted that the likelihood of offspring developing heart disease, stroke, or diabetes in later life, is influenced by the their in utero environment and maternal nutrition. There is increasing epidemiological evidence that osteoporosis in the offspring may also be influenced by the mother’s nutrition during pregnancy. This review provides evidence from a range of animal models that supports the epidemiological data; suggesting that lifelong bone development and growth in offspring is determined during gestation.

  3. Maternal feeding strategies and child's food intake: considering weight and demographic influences using structural equation modeling

    OpenAIRE

    Warschburger Petra; Kröller Katja

    2009-01-01

    Abstract Background Research concerning child's food intake have considered various influencing factors, for example parental feeding strategies, demographic and weight factors. At this time, however, there are few findings that explore these factors simultaneously. Accordingly, the aim of this study was to test a structural equation model regarding the associations between maternal feeding strategies and child's food intake. Methods 556 mothers and their children between 1 and 10 years of ag...

  4. Persistent Bacteremia in Rabbit Fetuses despite Maternal Antibiotic Therapy in a Novel Intrauterine-Infection Model

    OpenAIRE

    Gras-Le Guen, C.; Debillon, T; Toquet, C; Jarry, A; Winer, N.; Jacqueline, C.; Kergueris, M. F.; Bingen, E.; Roze, J. C.; Potel, G.; Bugnon, D.

    2003-01-01

    The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, qua...

  5. Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects

    Science.gov (United States)

    Past epidemiologic studies suggest maternal ambient air pollution exposure during critical periods of the pregnancy is associated with fetal development. We introduce a multinomial probit model that allows for the joint identification of susceptible daily periods during the pregn...

  6. Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of feline asthma.

    Science.gov (United States)

    Grobman, Megan; Krumme, Stacy; Outi, Hilton; Dodam, John R; Reinero, Carol R

    2016-02-01

    Feline allergic asthma is a chronic inflammatory disorder of the lower airways that may manifest with acute, life-threatening clinical signs. Tachykinins released from sensory nerves and immune cells binding neurokinin (NK)-1, NK-2 and NK-3 receptors have been implicated in asthma pathogenesis. Maropitant, an NK-1 receptor antagonist, blocks neuroimmune pathways and may be a viable treatment option for cats in asthmatic crisis. Using an experimental chronic allergic feline asthma model, we hypothesized that a single dose of maropitant given immediately after allergen challenge would blunt clinical signs, airway hyperresponsiveness (AHR) and airway eosinophilia. Cats (n = 7) induced to have an asthmatic phenotype using Bermuda grass allergen (BGA) were enrolled in a prospective, placebo-controlled crossover design study. Cats randomly received maropitant (2 mg/kg SC) or placebo (saline SC) immediately post-BGA challenge, followed 12 h later by pulmonary mechanics testing and measurement of airway eosinophils. After a 2 week washout, cats were crossed-over to the alternate treatment. Study endpoints included subjective clinical scoring systems post-BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine and collection of bronchoalveolar lavage fluid to quantify airway eosinophilia. Data were analyzed using a Mann-Whitney rank sum test with P eosinophilia (P = 0.165) compared with placebo. A single injection of maropitant given immediately post-allergen challenge was ineffective at blunting clinical signs, AHR and airway eosinophilia, and cannot be recommended as treatment for feline status asthmaticus. © ISFM and AAFP 2015.

  7. Animal models for clinical and gestational diabetes: maternal and fetal outcomes

    Directory of Open Access Journals (Sweden)

    Kiss Ana CI

    2009-10-01

    Full Text Available Abstract Background Diabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl and mild diabetes (glycemia between 120 and 300 mg/dl on glycemia and maternal reproductive and fetal outcomes of Wistar rats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans. Methods On day 5 of life, 96 female Wistar rats were assigned to three experimental groups: control (n = 16, severe (n = 50 and mild diabetes (n = 30. At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight. Results Severe and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses. Conclusion Experimental models of severe diabetes during pregnancy

  8. Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

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    Melissa M. Bunting

    2013-01-01

    Full Text Available We investigated the role of interleukin-33 (IL-33 in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  9. Interleukin-33 drives activation of alveolar macrophages and airway inflammation in a mouse model of acute exacerbation of chronic asthma.

    Science.gov (United States)

    Bunting, Melissa M; Shadie, Alexander M; Flesher, Rylie P; Nikiforova, Valentina; Garthwaite, Linda; Tedla, Nicodemus; Herbert, Cristan; Kumar, Rakesh K

    2013-01-01

    We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  10. Bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008049 Activation ralated genes of memory CD+4 T cells in asthma patients. PI Weifeng(皮卫峰),et al. Dept Respir Med, Xinhua Hosp, Sch Med, Shanghai Jiaotong Univ, Shanghai 200092. Chin J Tuberc Respir Dis 2007;30(12):932-935. Objective To screen and identify the genes of activated memory CD+4 T cells in asthma. Methods Differential display polymerase chain reaction(DDPCR) was utilized to identify genes of memory CD+4 T cells after activation from asthmatic patients and normal individuals,

  11. Invariant NKT cells act as an adjuvant to enhance Th2 inflammatory response in an OVA-induced mouse model of asthma.

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    Hanxiang Nie

    Full Text Available Invariant natural killer T cells (iNKT cells are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail.In this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA-induced murine model of asthma.Our results demonstrate that α-Galactosylceramide (α-GalCer administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF; increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice.These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.

  12. Asthma - children

    Science.gov (United States)

    ... BS, Burks AW, et al, eds. Middleton's Allergy Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 53. Lugogo N, Que LG, Gilstrap DL, Kraft M. Asthma: clinical diagnosis and management. In: Broaddus VC, Mason RJ, Ernst JD, et ...

  13. Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma.

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    Ying Lei

    Full Text Available In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma.

  14. In vivo micro-CT assessment of airway remodeling in a flexible OVA-sensitized murine model of asthma.

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    Mathieu Lederlin

    Full Text Available Airway remodeling is a major pathological feature of asthma. Up to now, its quantification still requires invasive methods. In this study, we aimed at determining whether in vivo micro-computed tomography (micro-CT is able to demonstrate allergen-induced airway remodeling in a flexible mouse model of asthma. Sixty Balb/c mice were challenged intranasally with ovalbumin or saline at 3 different endpoints (Days 35, 75, and 110. All mice underwent plethysmography at baseline and just prior to respiratory-gated micro-CT. Mice were then sacrificed to assess bronchoalveolar lavage and lung histology. From micro-CT images (voxel size = 46×46×46 µm, the numerical values of total lung attenuation, peribronchial attenuation (PBA, and PBA normalized by total lung attenuation were extracted. Each parameter was compared between OVA and control mice and correlation coefficients were calculated between micro-CT and histological data. As compared to control animals, ovalbumin-sensitized mice exhibited inflammation alone (Day 35, remodeling alone (Day 110 or both inflammation and remodeling (Day 75. Normalized PBA was significantly greater in mice exhibiting bronchial remodeling either alone or in combination with inflammation. Normalized PBA correlated with various remodeling markers such as bronchial smooth muscle size or peribronchial fibrosis. These findings suggest that micro-CT may help monitor remodeling non-invasively in asthmatic mice when testing new drugs targeting airway remodeling in pre-clinical studies.

  15. Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma.

    Science.gov (United States)

    Al-Harbi, Naif O; Nadeem, A; Al-Harbi, Mohamed M; Imam, F; Al-Shabanah, Othman A; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M; Bahashwan, Saleh A

    2015-05-01

    Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk.

  16. Airway subepithelial fibrosis in a murine model of atopic asthma: suppression by dexamethasone or anti-interleukin-5 antibody.

    Science.gov (United States)

    Blyth, D I; Wharton, T F; Pedrick, M S; Savage, T J; Sanjar, S

    2000-08-01

    Fibrosis in the reticular layer beneath the epithelial basement membrane is a feature of airway remodeling in human asthma. We previously reported the presence of subepithelial fibrosis (SEF) in a disease model of atopic asthma in which mice were sensitized and intratracheally challenged with ovalbumin (OVA) (Blyth and colleagues, Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). Here, we describe further studies to quantify the degree of SEF after its induction by repeated exposure of the airways to allergen. The amount of subepithelial reticulin in the airways of animals challenged three times with 80 microg OVA was typically increased 1. 4-fold. The increased amount of reticulin showed no reduction after a 50-d period after the third allergen challenge. A reduction in SEF was achieved by daily treatment with dexamethasone (DEX) for 8 d during the allergen challenge period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of allergen challenge. Postchallenge treatment with DEX for 15 d resulted in significant resolution of previously established SEF. Severe nonallergic inflammation during repeated exposure of airways to lipopolysaccharide did not induce SEF. The results indicate that development of SEF is associated with eosinophil infiltration into airways, and may occur only when the inflammatory stimulus is allergic in nature.

  17. Cauchy-Matern Model of Sea Surface Wind Speed at the Lake Worth, Florida

    Directory of Open Access Journals (Sweden)

    Ming Li

    2012-01-01

    Full Text Available We study the Cauchy-Matern (CM process with long-range dependence (LRD. The closed form of its power spectrum density (PSD function is given. We apply it to model the autocovariance function (ACF and the PSD of the sea surface wind speed (wind speed for short observed in the Lake Worth, Florida, over the 1984–2006 period. The present results exhibit that the wind speed at the Lake Worth over 1984–2006 is of LRD. The present results exhibit that the CM process may yet be a novel model to fit the wind speed there.

  18. Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-κB and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma.

    Science.gov (United States)

    Yan, Guang Hai; Choi, Yun Ho

    2014-04-01

    Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-κB and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

  19. [Severe asthma].

    Science.gov (United States)

    González, Claudio D

    2016-01-01

    The objectives of this work were to investigate the frequency of severe asthma (SA) according to WHO definition and to compare SA patients' characteristics with those of non-severe asthma (NSA); secondly, to investigate the level of control reached throughout a period of regular treatment. Between 1-1-2005 and 12-31-2014, 471 medical records from patients with bronchial asthma assisted in Buenos Aires City were analyzed. SA frequency was 40.1% (189/471), being significantly higher among patients from the public health system (47.7%, 108/226 vs. 33%, 81/245, p = 0.001). SA patients were older than NSA ones (51.3 ± 17.4 vs. 42.6 ± 17.1 years, p = 0.000), presented longer time since onset of the disease (median 30 vs. 20 years, p = 0.000), lower educational levels (secondary level or higher 41.7% vs. 58.1%, p = 0.000), lower frequency of rhinitis (47% vs. 60.6%, p = 0.004), more severe levels of airway obstruction (FEV% 50.2 ± 13.7 vs. 77.7 ± 12.4, p = 0.000), more frequent antecedents of Near Fatal Asthma (11.1% vs. 2.8%, p = 0.000), higher levels of serum IgE (median of 410 vs. 279 UI/l, p = 0.01) and higher demand of systemic steroids requirements and hospitalizations (68.7% vs. 50.7%, p = 0.000 and 37.5% vs. 15.9%, p = 0.000, respectively). A 30.6% of SA patients (58/189) reached a follow-up period of 12 months, 13 (22.5%) of whom reached the controlled asthma level. The frequency of SA found seems to be considerable. Multicenter studies to investigate the levels of control reached by SA patients with access to proper treatment are recommended.

  20. hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma

    Science.gov (United States)

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Lee, Kyoung Young; Ha, Eun Hee; Moon, Keun-Ai; Kim, Seong Who; Oh, Wonil; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2017-01-01

    Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation. In addition, cytokine production was evaluated in co-cultures of hMSCs with either anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asthmatic patients or cells of the human bronchial epithelial cell line BEAS-2B to assess the response to hMSC treatment. The total number of immune cells in bronchoalveolar lavage fluid (BALF) showed a dramatic decrease in hMSC-treated asthmatic mice, and, in particular, neutrophilic infiltration was significantly attenuated. This phenomenon was accompanied by reduced CXCL15 production in the BALF. BEAS-2B cells co-cultured with hMSCs showed reduced secretion of IL-8. Moreover, decreased secretion of IL-4, IL-13 and IFN-γ was observed when human PBMCs were cultured with hMSCs, whereas IL-10 production was greatly enhanced. Our data imply that hMSCs may have a role in reducing neutrophilic airway inflammation by downregulating neutrophil chemokine production and modulating T-cell responses. PMID:28127050

  1. CHILDREN'S MENTAL HEALTH SERVICE USE AND MATERNAL MENTAL HEALTH: A PATH ANALYTIC MODEL.

    Science.gov (United States)

    Pfefferle, Susan G; Spitznagel, Edward L

    2009-03-01

    OBJECTIVE: This observational study explores pathways towards any past year use of child mental health services. METHODS: Data from the 2002 National Survey of American Families were used to explore the relationship between past month maternal mental health and past year child mental health services use. Observations were limited to the 8072 most knowledgeable adults who were the mothers of target children aged 6-11. Logistic regressions were performed to determine the odds of any child mental health service use followed by path analyses using Maximum Likelihood estimation with robust standard errors. RESULTS: Multiple factors were associated with odds of any child mental health service use. In the path analytic model poor past month maternal mental health was associated with increased aggravation which in turn was associated with increased use of mental health visits. Negative child behaviors as reported by the mother were also associated with increased maternal aggravation and increased service use. CONCLUSIONS: Parental perception of child behaviors influences treatment seeking, both directly and indirectly through parental aggravation. Parental mental health influences tolerance for child behaviors. Findings are consistent with other studies. Interventions should address the entire family and their psychosocial circumstances through collaboration between multiple service sectors.

  2. Persistent influence of maternal obesity on offspring health: Mechanisms from animal models and clinical studies.

    Science.gov (United States)

    Wankhade, Umesh D; Thakali, Keshari M; Shankar, Kartik

    2016-11-05

    The consequences of excessive maternal weight and adiposity at conception for the offspring are now well recognized. Maternal obesity increases the risk of overweight and obesity even in children born with appropriate-for-gestational age (AGA) birth weights. Studies in animal models have employed both caloric excess and manipulation of macronutrients (especially high-fat) to mimic hypercaloric intake present in obesity. Findings from these studies show transmission of susceptibility to obesity, metabolic dysfunction, alterations in glucose homeostasis, hepatic steatosis, skeletal muscle metabolism and neuroendocrine changes in the offspring. This review summarizes the essential literature in this area in both experimental and clinical domains and focuses on the translatable aspects of these experimental studies. Moreover this review highlights emerging mechanisms broadly explaining maternal obesity-associated developmental programming. The roles of early developmental alterations and placental adaptations are also reviewed. Increasing evidence also points to changes in the epigenome and other emerging mechanisms such as alterations in the microbiome that may contribute to persistent changes in the offspring. Finally, we examine potential interventions that have been employed in clinical cohorts.

  3. Niflumic Acid Inhibits Goblet Cell Degranulation in a Guinea Pig Asthma Model

    OpenAIRE

    Mitsuko Kondo; Junko Nakata; Naoki Arai; Takehiro Izumo; Etsuko Tagaya; Kiyoshi Takeyama; Jun Tamaoki; Atsushi Nagai

    2012-01-01

    Background: Human Ca2+-activated Cl ion channel 1 (hCLCAl) is expressed in goblet cell hyperplasia in the airway of asthmatics, and murine CLCA3 is associated with antigen-sensitized and IL-13-induced goblet cell metaplasia in mice. However, the role of CLCA in goblet cell degranulation is not fully investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits goblet cell metaplasia, but the effect of NFA on goblet cell degranulation has not been determined in an asthma mo...

  4. Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeon, Seong Gyu [Department of Life Science, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan, College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jong Hoon [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Won, Moo Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

  5. Rosuvastatin attenuates mucus secretion in a murine model of chronic asthma by inhibiting the gamma-aminobutyric acid type A receptor

    Institute of Scientific and Technical Information of China (English)

    ZHU Tao; ZHANG Wei; WANG Dao-xin; HUANG Ni-wen; BO Hong; DENG Wang; DENG Jia

    2012-01-01

    Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction,pulmonary inflammation and airway remodeling.Current standard therapies for asthma provide symptomatic control,but fail to target the underlying disease pathology.Furthermore,no therapeutic agent is effective in preventing airway remodeling.A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity.In this study,we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma.Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma.The recruitment of inflammatory cells into bronchoalveolar lavage fluid (BALF) and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin (H&E) staining.ELISA was used for measuring the levels of IL-4,IL-5,IL-13 and TNF-α in BALF.Periodic acid-Schiff (PAS) staining was used for mucus secretion.Gamma-aminobutyric acid type A receptor (GABAAR)32 expression was measured by means of immunohistochemistry,reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.Results Rosuvastatin reduced the number of total inflammatory cells,lymphocytes,macrophages,neutrophils,and eosinophils recruited into BALF,the levels of IL-4,IL-5,IL-13 and TNF-α in BALF,along with the histological mucus index (HMI) and GABAAR β2 expression.Changes occurred in a dose-dependent manner.Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma,rosuvastatin may be a useful therapeutic agent for treatment of asthma.

  6. Phosphatidylinositol 3-kinases pathway mediates lung caspase-1 activation and high mobility group box 1 production in a toluene-diisocyanate induced murine asthma model.

    Science.gov (United States)

    Liang, Junjie; Zhao, Haijin; Yao, Lihong; Tang, Haixiong; Dong, Hangming; Wu, Yue; Liu, Laiyu; Zou, Fei; Cai, Shaoxi

    2015-07-02

    We have previously demonstrated that downregulating HMGB1 decreases airway neutrophil inflammation in a toluene-diisocyanate (TDI)-induced murine asthma model, yet how HMGB1 is regulated in the lung remains uncertain. In this study, we intended to explore whether PI3K signaling pathway mediates pulmonary HMGB1 production in TDI-induced asthma model and the possible roles of NLRP3 inflammasome and caspase-1 in this process. BALB/c mice were sensitized and challenged with TDI to establish a TDI-induced asthma model. LY294002, a specific inhibitor of PI3K, was given intratracheally 1h before each challenge. Here we showed that airway hypersensitivity, airway infiltration of neutrophils and eosinophils, serum IgE and IL-4 in supernatant of cervical lymphocytes in TDI induced asthmatic mice were all markedly decreased by LY294002, accompanied by suppressed pulmonary expression of HMGB1. At the same time, we observed elevated protein levels of cleaved caspase-1 and IL-1β after TDI challenge, as well as increased immunoreactivity in lung, all of which were significantly recovered by LY294002. While both the protein expression and immunodistribution of NLRP3 in the lung stayed unchanged. These data suggest that PI3K mediates lung caspase-1 activation and HMGB1 production in TDI-induced murine asthma model. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Testing cost-benefit models of parental care evolution using lizard populations differing in the expression of maternal care.

    Science.gov (United States)

    Huang, Wen-San; Pike, David A

    2013-01-01

    Parents are expected to evolve tactics to care for eggs or offspring when providing such care increases fitness above the costs incurred by this behavior. Costs to the parent include the energetic demands of protecting offspring, delaying future fecundity, and increased risk of predation. We used cost-benefit models to test the ecological conditions favoring the evolution of parental care, using lizard populations that differ in whether or not they express maternal care. We found that predators play an important role in the evolution of maternal care because: (1) evolving maternal care is unlikely when care increases predation pressure on the parents; (2) maternal care cannot evolve under low levels of predation pressure on both parents and offspring; and (3) maternal care evolves only when parents are able to successfully defend offspring from predators without increasing predation risk to themselves. Our studies of one of the only known vertebrate species to exhibit interpopulation differences in the expression of maternal care provide clear support for some of the hypothesized circumstances under which maternal care should evolve (e.g., when nests are in exposed locations, parents are able to defend the eggs from predators, and egg incubation periods are brief), but do not support others (e.g., when nest-sites are scarce, life history strategies are "risky", reproductive frequency is low, and environmental conditions are harsh). We conclude that multiple pathways can lead to the evolution of parental care from a non-caring state, even in a single population of a widespread species.

  8. Maternal separation with early weaning: a novel mouse model of early life neglect

    Directory of Open Access Journals (Sweden)

    Elwafi Hani M

    2010-09-01

    Full Text Available Abstract Background Childhood adversity is associated with increased risk for mood, anxiety, impulse control, and substance disorders. Although genetic and environmental factors contribute to the development of such disorders, the neurobiological mechanisms involved are poorly understood. A reliable mouse model of early life adversity leading to lasting behavioral changes would facilitate progress in elucidating the molecular mechanisms underlying these adverse effects. Maternal separation is a commonly used model of early life neglect, but has led to inconsistent results in the mouse. Results In an effort to develop a mouse model of early life neglect with long-lasting behavioral effects in C57BL/6 mice, we designed a new maternal separation paradigm that we call Maternal Separation with Early Weaning (MSEW. We tested the effects of MSEW on C57BL/6 mice as well as the genetically distinct DBA/2 strain and found significant MSEW effects on several behavioral tasks (i.e., the open field, elevated plus maze, and forced swim test when assessed more than two months following the MSEW procedure. Our findings are consistent with MSEW causing effects within multiple behavioral domains in both strains, and suggest increased anxiety, hyperactivity, and behavioral despair in the MSEW offspring. Analysis of pup weights and metabolic parameters showed no evidence for malnutrition in the MSEW pups. Additionally, strain differences in many of the behavioral tests suggest a role for genetic factors in the response to early life neglect. Conclusions These results suggest that MSEW may serve as a useful model to examine the complex behavioral abnormalities often apparent in individuals with histories of early life neglect, and may lead to greater understanding of these later life outcomes and offer insight into novel therapeutic strategies.

  9. Recombinant adeno-associated virus-mediated inhibiting of interleukin-4 expression in rat model of asthma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Asthma is a chronic disease characterized by reversible airway obstruction, airway hyper- responsiveness, and inflammation of airways. Th2 cells, one sort of CD4+ T lymphocytes, are currently considered to play an important role in the chronic airway inflammation of asthma. Meanwhile, a number of laboratories have clearly established the importance of the Th2-derived cytokine interleukin-4 (IL-4) in mediating the airway inflammatory response. Anti-IL-4 therapy might be beneficial in treatment of chronic asthma.

  10. The effects of early allergen/endotoxin exposure on subsequent allergic airway inflammation to allergen in mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Yeong-Ho Rha

    2010-04-01

    Full Text Available Purpose : Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR in mouse model of asthma. Methods : Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA, LPS or 1.0 μg LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; P values for significance were set to 0.05. Results : Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion : These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic

  11. Asthma in Children

    Science.gov (United States)

    ... have asthma. Nearly 9 million of them are children. Children have smaller airways than adults, which makes asthma especially serious for them. Children with asthma may experience wheezing, coughing, chest tightness, ...

  12. Asthma triggers (image)

    Science.gov (United States)

    ... things make your asthma worse. These are called asthma "triggers". Avoiding them is your first step toward feeling better. The most common asthma triggers are mold, pets, dust, grasses, pollen, cockroaches, odors ...

  13. Allergies, asthma, and dust

    Science.gov (United States)

    Reactive airway disease - dust; Bronchial asthma - dust; Triggers - dust ... Things that make allergies or asthma worse are called triggers. Dust is a common trigger. When your asthma or allergies become worse due to dust, you are ...

  14. Allergies, asthma, and molds

    Science.gov (United States)

    Reactive airway - mold; Bronchial asthma - mold; Triggers - mold; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. Mold is a common trigger. When your asthma or allergies become worse due to mold, you are ...

  15. Asthma: Basic Information

    Science.gov (United States)

    ... Air Pollution & Respiratory Health Learn How to Control Asthma Language: English Español (Spanish) Recommend on Facebook Tweet ... Treated? Select a Language Español (Spanish) What Is Asthma? Asthma is a disease that affects your lungs. ...

  16. Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study

    DEFF Research Database (Denmark)

    Lange, Peter; Çolak, Yunus; Ingebrigtsen, Truls Sylvan

    2016-01-01

    focus on individuals with asthma-COPD overlap. METHODS: We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those...... mixed-effects model. FINDINGS: We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma...

  17. Fuzzy model to estimate the number of hospitalizations for asthma and pneumonia under the effects of air pollution.

    Science.gov (United States)

    Chaves, Luciano Eustáquio; Nascimento, Luiz Fernando Costa; Rizol, Paloma Maria Silva Rocha

    2017-06-22

    Predict the number of hospitalizations for asthma and pneumonia associated with exposure to air pollutants in the city of São José dos Campos, São Paulo State. This is a computational model using fuzzy logic based on Mamdani's inference method. For the fuzzification of the input variables of particulate matter, ozone, sulfur dioxide and apparent temperature, we considered two relevancy functions for each variable with the linguistic approach: good and bad. For the output variable number of hospitalizations for asthma and pneumonia, we considered five relevancy functions: very low, low, medium, high and very high. DATASUS was our source for the number of hospitalizations in the year 2007 and the result provided by the model was correlated with the actual data of hospitalization with lag from zero to two days. The accuracy of the model was estimated by the ROC curve for each pollutant and in those lags. In the year of 2007, 1,710 hospitalizations by pneumonia and asthma were recorded in São José dos Campos, State of São Paulo, with a daily average of 4.9 hospitalizations (SD = 2.9). The model output data showed positive and significant correlation (r = 0.38) with the actual data; the accuracies evaluated for the model were higher for sulfur dioxide in lag 0 and 2 and for particulate matter in lag 1. Fuzzy modeling proved accurate for the pollutant exposure effects and hospitalization for pneumonia and asthma approach. Prever o número de internações por asma e pneumonia associadas à exposição a poluentes do ar no município em São José dos Campos, estado de São Paulo. Trata-se de um modelo computacional que utiliza a lógica fuzzy baseado na técnica de inferência de Mamdani. Para a fuzzificação das variáveis de entrada material particulado, ozônio, dióxido de enxofre e temperatura aparente foram consideradas duas funções de pertinência para cada variável com abordagem linguísticas: bom e ruim. Para a variável de saída número interna

  18. Anti-Inflammatory, Immunomodulatory, and Heme Oxygenase-1 Inhibitory Activities of Ravan Napas, a Formulation of Uighur Traditional Medicine, in a Rat Model of Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Sajida Abdureyim

    2011-01-01

    Full Text Available Ravan Napas (RN is a traditional formula used to treat pulmonary symptoms and diseases such as coughing, breathing difficulty, and asthma in traditional Uighur medicine. The purpose of this study was to investigate the anti-inflammatory, and immuno-modulatory activity of RN in a well-characterized animal model of allergic asthma. Rats were sensitized with intraperitoneal (ip ovalbumin (OVA and alum, and then challenged with OVA aerosols. The asthma model rats were treated with RN; saline- and dexamethasone- (DXM- treated rats served as normal and model controls. The bronchoalveolar lavage fluid (BALF cellular differential and the concentrations of sICAM-1, IL-4, IL-5, TNF-α, INF-γ, and IgE in serum were measured. Lung sections underwent histological analysis. The immunohistochemistry S-P method was used to measure the expression of ICAM-1 and HO-1 in the lung. RN significantly reduced the number of inflammatory cells in BALF and lung tissues, decreased sICAM-1, IL-4, IL-5, TNF-α, and IgE in serum, and increased serum INF-γ. There was a marked suppression of ICAM-1 and HO-1 expression in the lung. Our results suggest that RN may have an anti-inflammatory and immuneregulatory effect on allergic bronchial asthma by modulating the balance between Th1/Th2 cytokines.

  19. Genetic parameters of calving ease using sire-maternal grandsire model in Korean Holsteins

    Directory of Open Access Journals (Sweden)

    Mahboob Alam

    2017-09-01

    Full Text Available Objective Calving ease (CE is a complex reproductive trait of economic importance in dairy cattle. This study was aimed to investigate the genetic merits of CE for Holsteins in Korea. Methods A total of 297,614 field records of CE, from 2000 to 2015, from first parity Holstein heifers were recorded initially. After necessary data pruning such as age at first calving (18 to 42 mo, gestation length, and presence of sire information, final datasets for CE consisted of 147,526 and 132,080 records for service sire calving ease (SCE and daughter calving ease (DCE evaluations, respectively. The CE categories were ordered and scores ranged from CE1 to CE5 (CE1, easy; CE2, slight assistance; CE3, moderate assistance; CE4, difficult calving; CE5, extreme difficulty calving. A linear transformation of CE score was obtained on each category using Snell procedure, and a scaling factor was applied to attain the spread between 0 (CE5 and 100% (CE1. A sire-maternal grandsire model analysis was performed using ASREML 3.0 software package. Results The estimated direct heritability (h2 from SCE and DCE evaluations were 0.11±0.01 and 0.08±0.01, respectively. Maternal h2 estimates were 0.05±0.02 and 0.04±0.01 from SCE and DCE approaches, respectively. Estimates of genetic correlations between direct and maternal genetic components were −0.68±0.09 (SCE and −0.71±0.09 (DCE. The average direct genetic effect increased over time, whereas average maternal effect was low and consistent. The estimated direct predicted transmitting ability (PTA was desirable and increasing over time, but the maternal PTA was undesirable and decreasing. Conclusion The evidence on sufficient genetic variances in this study could reflect a possible selection improvement over time regarding ease of calving. It is expected that the estimated genetic parameters could be a valuable resource to formulate sire selection and breeding plans which would be directed towards the reduction of

  20. Asthma essentials

    Directory of Open Access Journals (Sweden)

    Timothy Greene

    2013-12-01

    Full Text Available Asthma is a chronic, reversible obstructive disease that when in exacerbation can present to the emergency department in a spectrum of severity. Prompt recognition of the potentially severely ill asthmatic requires a careful history and physical exam while considering alternative diagnoses for the presenting symptoms. Early administration of salbutamol and corticosteroids is indicated in almost all patients with other medications such as ipratropium and magnesium and supportive modalities like BiPAP reserved for sicker patients. The global impact of asthma is increasing, especially amongst children. While the benign clinical presentation is most common and mortality has decreased in recent decades due to improved recognition and care, the ubiquity of the condition and frequent lack of regular outpatient management contribute to the disease claiming 250,000 lives worldwide annually. The emergency physician must be prepared to assess and appropriately manage both the young child with a mild wheeze and the adult in respiratory failure.

  1. School variation in asthma: compositional or contextual?

    Directory of Open Access Journals (Sweden)

    Tracy K Richmond

    Full Text Available BACKGROUND: Childhood asthma prevalence and morbidity have been shown to vary by neighborhood. Less is known about between-school variation in asthma prevalence and whether it exists beyond what one might expect due to students at higher risk of asthma clustering within different schools. Our objective was to determine whether between-school variation in asthma prevalence exists and if so, if it is related to the differential distribution of individual risk factors for and correlates of asthma or to contextual influences of schools. METHODS: Cross-sectional analysis of 16,640 teens in grades 7-12 in Wave 1 (data collected in 1994-5 of the National Longitudinal Study of Adolescent Health. Outcome was current diagnosis of asthma as reported by respondents' parents. Two-level random effects models were used to assess the contribution of schools to the variance in asthma prevalence before and after controlling for individual attributes. RESULTS: The highest quartile schools had mean asthma prevalence of 21.9% compared to the lowest quartile schools with mean asthma prevalence of 7.1%. In our null model, the school contributed significantly to the variance in asthma (sigma(u0(2 = 0.27, CI: 0.20, 0.35. Controlling for individual, school and neighborhood attributes reduced the between-school variance modestly (sigma(u0(2 = 0.19 CI: 0.13-0.29. CONCLUSION: Significant between-school variation in current asthma prevalence exists even after controlling for the individual, school and neighborhood factors. This provides evidence for school level contextual influences on asthma. Further research is needed to determine potential mechanisms through which schools may influence asthma outcomes.

  2. Le Bonheur Childrens Hospital CHAMPS Program in Memphis, Tennessee Recognized with the 2015 National Environmental Leadership Award by EPA Memphis Program Recognized as National Model for Asthma Care During Asthma Awareness Month

    Science.gov (United States)

    05/05/15 - ATLANTA - One in ten kids in America suffers from asthma, and communities of color and low-income families are disproportionately impacted. During Asthma Awareness Month, EPA recognizes Le Bonheur Children's Hospital CHAMPS Program in Memp

  3. Feto-maternal interaction: a mathematical model simulating placental response in hypertensive disorders of pregnancy.

    Science.gov (United States)

    Luria, Oded; Bar, Jacob; Kovo, Michal; Golan, Abraham; Barnea, Ofer

    2010-10-01

    Elevated maternal blood pressure (BP) is common in pregnancies complicated by hypertensive disorders. In response, increased production and accumulation of elastin occurs in the feto-placental blood vessels. This results in increased vascular wall stiffness that increases the resistance to flow. To study the interaction between the stiffness of the fetoplacental blood vessels, fetoplacental blood flow and BP, a mathematical model of the fetoplacental vascular tree was developed. The model describes an elastic structure exposed to external pressure. Model results indicate that increased vascular stiffness in the fetal blood vessels may contribute to optimizing fetoplacental blood flow in hypertensive pregnancies. According to model predictions, uncontrolled lowering of BP following vascular adaptation may adversely affect fetoplacental blood flow.

  4. Fractional Brownian motion, the Matern process, and stochastic modeling of turbulent dispersion

    CERN Document Server

    Lilly, J M; Early, J J; Olhede, S C

    2016-01-01

    Stochastic process exhibiting power-law slopes in the frequency domain are frequently well modeled by fractional Brownian motion (fBm). In particular, the spectral slope at high frequencies is associated with the degree of small-scale roughness or fractal dimension. However, a broad class of real-world signals have a high-frequency slope, like fBm, but a plateau in the vicinity of zero frequency. This low-frequency plateau, it is shown, implies that the temporal integral of the process exhibits diffusive behavior, dispersing from its initial location at a constant rate. Such processes are not well modeled by fBm, which has a singularity at zero frequency corresponding to an unbounded rate of dispersion. A more appropriate stochastic model is a much lesser-known random process called the Matern process, which is shown herein to be a damped version of fractional Brownian motion. This article first provides a thorough introduction to fractional Brownian motion, then examines the details of the Matern process and...

  5. A longitudinal model of maternal self-efficacy, depression, and difficult temperament during toddlerhood.

    Science.gov (United States)

    Gross, D; Conrad, B; Fogg, L; Wothke, W

    1994-06-01

    The purpose of this study was to test a model of maternal self-efficacy during toddlerhood using a longitudinal sequential design. Participants were 126 mothers of 1-year olds (Cohort 1) and 126 mothers of 2-year olds (Cohort 2) who completed questionnaires measuring maternal self-efficacy, depression, and perceived difficult toddler temperament three times over 1 year. Data were analyzed using structural equation modeling and maximum likelihood estimation. Findings support a model whereby (a) the more depressed the mother feels, the more likely she is to rate her toddler's temperament as difficult, (b) the more difficult the child's temperament is perceived to be, the lower the mother's estimates of her parenting self-efficacy, (c) the lower the mother's self-efficacy, the greater her depression, and (d) the more depressed the mother feels at one point in time, the more likely she is to remain depressed 6 months later. Implications of the findings are discussed as they relate to self-efficacy theory and nursing intervention with parents of difficult toddlers.

  6. Improving Maternal Healthcare Access and Neonatal Survival through a Birthing Home Model in Rural Haiti

    Directory of Open Access Journals (Sweden)

    Elizabeth Wickstrom

    2007-10-01

    Full Text Available High neonatal mortality in Haiti is sustained by limited access to essential maternity services, particularly for Haiti’s rural population. We investigated the feasibility of a rural birthing home model to provide basic prenatal, delivery, and neonatal services for women with uncomplicated pregnancies while simultaneously providing triage and transport of women with pregnancy related complications. The model included consideration of the local context, including women’s perceptions of barriers to healthcare access and available resources to implement change. Evaluation methods included the performance of a baseline community census and collection of pregnancy histories from 791 women living in a defined area of rural Haiti. These retrospective data were compared with pregnancy outcome for 668 women subsequently receiving services at the birthing home. Of 764 reported most recent pregnancies in the baseline survey, 663(87% occurred at home with no assistance from skilled health staff. Of 668 women followed after opening of the birthing home, 514 (77% subsequently gave birth at the birthing home, 94 (14% were referred to a regional hospital for delivery, and only 60 (9% delivered at home or on the way to the birthing home. Other measures of clinical volume and patient satisfaction also indicated positive changes in health care seeking. After introduction of the birthing home, fewer neonates died than predicted by historical information or national statistics. The present experience points out the feasibility of a rural birthing home model to increase access to essential maternity services.

  7. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Larsson, Emanuel [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); University of Trieste, Trieste (Italy); Linkoeping University, SE-581 83 Linkoeping (Sweden); Tromba, Giuliana [Elettra-Sincrotrone Trieste, Strada Statale 14, km 163,5 in AREA Science Park, Basovizza (Trieste) 34149 (Italy); Markus, Andrea M. [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Alves, Frauke [University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); University Medical Center Goettingen, Robert Koch Strasse 40, Goettingen, Lower Saxony 37075 (Germany); Max Planck Institut for Experimental Medicine, Hermann-Rein-Strasse 3, Goettingen, Lower Saxony 37075 (Germany)

    2015-06-17

    Synchrotron inline phase-contrast computed tomography in combination with single-distance phase retrieval enables quantification of morphological alterations in lungs of mice with mild and severe experimental allergic airways disease in comparison with healthy controls. Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, ‘Elettra’, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

  8. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  9. Maternal serologic screening to prevent congenital toxoplasmosis: a decision-analytic economic model.

    Directory of Open Access Journals (Sweden)

    Eileen Stillwaggon

    2011-09-01

    Full Text Available OBJECTIVE: To determine a cost-minimizing option for congenital toxoplasmosis in the United States. METHODOLOGY/PRINCIPAL FINDINGS: A decision-analytic and cost-minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools-lowering test costs to about $2 per test-universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births. CONCLUSION/SIGNIFICANCE: Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities.

  10. Incidence and risk factors for exacerbations of asthma during pregnancy

    Directory of Open Access Journals (Sweden)

    Ali Z

    2013-05-01

    Full Text Available Zarqa Ali, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.Methods: A narrative literature review was carried out using the PubMed database.Results: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.Discussion: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma – better described as difficult-to-control asthma – nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.Keywords: acute exacerbations

  11. The placebo effect in asthma.

    Science.gov (United States)

    Dutile, Stefanie; Kaptchuk, Ted J; Wechsler, Michael E

    2014-08-01

    The placebo effect is a complex phenomenon occurring across a variety of clinical conditions. While much placebo research has been conducted in diseases defined by self-report such as depression, chronic pain, and irritable bowel syndrome (IBS), asthma has been proposed as a useful model because of its easily measured objective outcomes. Studies examining the placebo response in asthma have not only contributed to an understanding of the mechanisms behind the placebo response but also shed an interesting light on the current treatment and diagnosis of asthma. This paper will review current literature on placebos in general and specifically on the placebo response in asthma. It focuses on what we know about the mechanisms behind the placebo effect, whether there is a specific portion of the population who responds to placebos, which patient outcomes are influenced by the placebo effect, and whether the effect can be augmented.

  12. Breast regression protein-39 (BRP-39) promotes dendritic cell maturation in vitro and enhances Th2 inflammation in murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    Qian xu; Shou-jie CHAI; Ying-ying QIAN; Min ZHANG; Kai WANG

    2012-01-01

    Aim: To determine the roles of breast regression protein-39 (BRP-39) in regulating dendritic cell maturation and in pathology of acute asthma.Methods: Mouse bone marrow-derived dendritic cells (BMDCs) were prepared,and infected with adenovirus over-expressing BRP-39.Ovalbumin (OVA)-induced murine model of acute asthma was made in female BALB/c mice by sensitizing and challenging with chicken OVA and Imject Alum.The transfected BMDCs were adoptively transferred into OVA-treated mice via intravenous injection.Airway hyperresponsiveness (AHR),inflammation and pulmonary histopathology were characterized.Results: The expression of BRP-39 mRNA and protein was significantly increased in lung tissues of OVA-treated mice.The BMDCs infected with adenovirus BRP-39 exhibited greater maturation and higher activity in vitro.Adoptive transfer of the cells into OVA-treated mice significantly augmented OVA-induced AHR and eosinophilic inflammation.Meanwhile,BRP-39 further enhanced the production of OVA-induced Th2 cytokines IL-4,IL-5,and IL-13,but significantly attenuated OVA-induced IFN-γ production in bronchoalveolar lavage fluid.Conclusion: In OVA-induced murine model of acute asthma,BRP-39 is over-expressed in lung tissue and augments Th2 inflammatory response and AHR.BRP-39 promotes dendritic cell maturation in vitro.Therefore,BRP-39 may be a potential therapeutic target of asthma.

  13. K(Ca3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma.

    Directory of Open Access Journals (Sweden)

    Joanne Van Der Velden

    Full Text Available BACKGROUND: The Ca(2+-activated K(+ channel K(Ca3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of K(Ca3.1 modifies experimental asthma in sheep. METHODOLOGY AND PRINCIPAL FINDINGS: Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073, a selective inhibitor of the K(Ca3.1-channel, or vehicle alone (0.5% methylcellulose twice daily (orally. Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147. The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288. Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340. Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling. CONCLUSIONS: These findings suggest that K(Ca3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of K(Ca3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans.

  14. Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone Exposed Offspring

    Science.gov (United States)

    Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (ARR) in offspring. To determine if exposure to diesel exhaust during pregnancy worsened postnatal oz...

  15. Pretreatment With Inactivated Bacillus Calmette-Guerin Increases CD4+CD25+ Regulatory T Cell Function and Decreases Functional and Structural Effects of Asthma Induction in a Rat Asthma Model.

    Science.gov (United States)

    Gong, Ping; Li, Yun; Tan, Yu-Pin; Li, Hong

    2016-04-01

    Bacillus Calmette-Guerin (BCG) has been shown to have therapeutic effects on asthma through CD4+CD25+ regulatory T cells (Tregs). We sought to assess pretreatment with inactivated BCG on CD4+CD25+ Tregs and its functional and structural effects in rat asthma model. The rat asthma model was established using ovalbumin (OVA) sensitization and challenge. Ten rats were pretreated with BCG prior to OVA and received continued BCG injections during OVA challenge (BCG+OVA group), 10 rats were treated with OVA alone (OVA group), and 10 rats were treated with saline (control group). After 9 weeks, histamine dihydrochloride effect on airway resistance was measured. Number of CD4+CD25+ Tregs was measured by flow cytometry, expression of Foxp3 and CTLA-4 mRNA was measured, and serum TGF-β levels were determined. Differential cell count in bronchoalveolar lavage fluid (BALF) was determined, and lung tissue was processed and stained with hematoxylin and eosin, Masson's trichrome, and alcine blue and periodic acid Schiff's reaction to evaluate inflammatory cell infiltration, collagen deposition, and presence of goblet cells, respectively. BCG treatment led to an increase in CD4+CD25+ Tregs, as well as an increase in Foxp3 and CTLA-4 expression and serum TGF-β levels. In addition, we observed a decrease in histamine dihydrochloride-induced airway resistance, a decrease in inflammatory leukocytes in BALF, and a decrease in airway remodeling indicators in BCG+OVA-treated rats compared with OVA-treated rats. Intradermally injected inactivated BCG has the potential to improve airway inflammation, airway resistance, and airway remodeling through a mechanism that may involve CD4+CD25+ Tregs. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  16. Are animal models useful or confusing in understanding the human feto-maternal relationship? A debate.

    Science.gov (United States)

    Chaouat, Gérard; Clark, David A

    2015-04-01

    The proposition "This house agrees that the proper study of man is woman" was debated. For those negating the proposition, the alternative was that "animal models are useful in understanding the human feto-maternal relationship." Evidence for the proposition emphasized molecular and structural differences between the human and animal placenta and placentation. Evidence against the proposition and in favor of the alternative focused on functional and structural homologies, emphasizing that different molecules could be used in humans to achieve similar functional effects seen in animal (e.g., mouse) models. It was agreed that one always needed to test the validity of animal data by studying humans. The advantages and limitations of animal models were discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

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    Amatullah Hajera

    2011-02-01

    Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

  18. 支气管哮喘动物模型的研究进展%Research Progress in Animal Model of Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    吕洪臻; 黄诚

    2012-01-01

    建立支气管哮喘动物模型有助于对哮喘的研究.针对Th2型细胞驱动的变态反应动物模型研究较多,并已应用于相关药物的研究.对支气管哮喘动物模型有一定疗效的药物对人类患者疗效欠佳,这可能与选择实验的动物和诱导哮喘表型的方法有关.啮齿动物和豚鼠模型是最常使用的支气管哮喘动物模型.目前动物模型仍存在许多问题,如在免疫学和解剖学上动物与人类存在差异,大多数模型在致敏时需要佐剂,成年动物应用较多.因此,明确每种模型的相对优点和局限性十分必要.%Animal models of bronchial asthma are beneficial to the study of asthma. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of interrelated drugs. Many drugs that have been shown to have some efficacy in animal models of bronchial asthma have shown little clinical benefit in human asthmatics, which may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals. Rodents and guinea-pigs are the most popular bronchial asthma models. At present, there are a lot of problems in animal models of asthma, for example the difference in immunology and anatomy between these species and human, the requirement for adjuvant during sensitization in most models, adult animals as the primary disease model. Therefore understanding of the relative merits and limitations of each model is necessary.

  19. CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma

    Institute of Scientific and Technical Information of China (English)

    Hua-hao SHEN; Feng XU; Gen-sheng ZHANG; Shao-bin WANG; Wei-hua XU

    2006-01-01

    Aim: To explore the effect of a rat anti-mouse CC-chemokine receptor-3 (CCR3) monoclonal antibody (CCR3 mAb) on airway eosinophilia and mucus overproduction in asthmatic mice. Methods: An asthma model was sensitized and challenged by ovalbumin (OVA) in male C57BL/6 mice. Asthmatic mice were given dual administration (intraperitoneal injection and aerosol inhalation) of CCR3 mAb or nonspecific rat IgG (ns-IgG). The number of total and differential inflammatory cells in the bronchial alveolar lavage fluid (BALF) was counted. Eosinophils number, the goblet cell percentage (GCP) and airway mucus index (AMI) were measured in the lung tissues. Interleukin (IL)-5 levels in the BALF were examined. The expression of MUC5AC and the epidermal growth factor receptor (EGFR) mRNA in the lung tissues was detected by semi-quantitative RT-PCR. The results were compared among the groups. Results: CCR3 mAb significantly suppressed the increased eosinophils in the BALF and lung tissues in OVA-challenged mice compared with ns-IgG-treated mice. IL-5 levels in the BALF in CCR3 mAb and ns-IgG administration mice exhibited no obvious changes relative to OVA-challenged asthmatic mice. CCR3 mAb reduced the increased GCP and AMI after OVA challenge and decreased the enhanced expression of MUC5AC and EGFR mRNA in lung tissues in asthmatic animals. Conclusion: CCR3 mAb can significantly inhibit airway eosinophilia and mucus overproduction in asthmatic mice. Blockage of CCR3 may represent a new strategy to asthma therapy.

  20. Maternal And Neonatal Plasma MicroRNA Biomarkers For Fetal Alcohol Exposure In An Ovine Model

    Science.gov (United States)

    Balaraman, Sridevi; Lunde, E. Raine; Sawant, Onkar; Cudd, Timothy A.; Washburn, Shannon E.; Miranda, Rajesh C.

    2014-01-01

    Background Plasma or circulating miRNAs (cirmiRNAs) have potential diagnostic value as biomarkers for a range of diseases. Based on observations that ethanol altered intracellular miRNAs during development, we tested the hypothesis that plasma miRNAs were biomarkers for maternal alcohol exposure, and for past in utero exposure, in the neonate. Methods Pregnant sheep were exposed to a binge model of ethanol consumption resulting in an average peak blood alcohol content of 243 mg/dl, for a three-trimester equivalent period from gestational day (GD) 4 to GD 132. MiRNA profiles were assessed by quantitative PCR analysis in plasma, erythrocyte and leukocytes obtained from non-pregnant ewes, and plasma from pregnant ewes 24 hours following the last binge ethanol episode, and from newborn lambs, at birth on ~GD 147. Results Pregnant ewe and newborn lamb cirmiRNA profiles were similar to each other and different from non-pregnant female plasma, erythrocyte or leukocyte miRNAs. Significant changes in cirmiRNA profiles were observed in the ethanol-exposed ewe, and at birth, in the in utero, ethanol-exposed lamb. CirmiRNAs including miR-9, -15b, -19b and -20a were sensitive and specific measures of ethanol exposure in both pregnant ewe and newborn lamb. Additionally, ethanol exposure altered guide to passenger strand cirmiRNA ratios in the pregnant ewe, but not in the lamb. Conclusion Shared profiles between pregnant dam and neonate suggest possible maternal-fetal miRNA transfer. CirmiRNAs are biomarkers for alcohol exposure during pregnancy, in both mother and neonate, and may constitute an important shared endocrine biomarker that is vulnerable to the maternal environment. PMID:24588274

  1. Piecing together the maternal death puzzle through narratives: the three delays model revisited.

    Directory of Open Access Journals (Sweden)

    Viva Combs Thorsen

    Full Text Available BACKGROUND: In Malawi maternal mortality continues to be a major public health challenge. Going beyond the numbers to form a more complete view of why women die is critical to improving access to and quality of emergency obstetric care. The objective of the current study was to identify the socio-cultural and facility-based factors that contributed to maternal deaths in the district of Lilongwe, Malawi. METHODS: Retrospectively, 32 maternal death cases that occurred between January 1, 2011 and June 30, 2011 were reviewed independently by two gynecologists/obstetricians. Interviews were conducted with healthcare staff, family members, neighbors, and traditional birth attendants. Guided by the grounded theory approach, interview transcripts were analyzed manually and continuously. Emerging, recurring themes were identified and excerpts from the transcripts were categorized according to the Three Delays Model (3Ds. RESULTS: Sixteen deaths were due to direct obstetric complications, sepsis and hemorrhage being most common. Sixteen deaths were due to indirect causes with the main cause being anemia, followed by HIV and heart disease. Lack of recognizing signs, symptoms, and severity of the situation; using traditional Birth Attendant services; low female literacy level; delayed access to transport; hardship of long distance and physical terrain; delayed prompt quality emergency obstetric care; and delayed care while at the hospital due to patient refusal or concealment were observed. According to the 3Ds, the most common delay observed was in receiving treatment upon reaching the facility due to referral delays, missed diagnoses, lack of blood, lack of drugs, or inadequate care, and severe mismanagement.

  2. The effect of maternal psychopathology on parent-child agreement of child anxiety symptoms: A hierarchical linear modeling approach.

    Science.gov (United States)

    Affrunti, Nicholas W; Woodruff-Borden, Janet

    2015-05-01

    The current study examined the effects of maternal anxiety, worry, depression, child age and gender on mother and child reports of child anxiety using hierarchical linear modeling. Participants were 73 mother-child dyads with children between the ages of 7 and 10 years. Reports of child anxiety symptoms, including symptoms of specific disorders (e.g., social phobia) were obtained using concordant versions of the Screen for Anxiety and Related Emotional Disorders (SCARED). Children reported significantly higher levels of anxiety symptoms relative to their mothers. Maternal worry and depression predicted for significantly lower levels of maternal-reported child anxiety and increasing discrepant reports. Maternal anxiety predicted for higher levels of maternal-reported child anxiety and decreasing discrepant reports. Maternal depression was associated with increased child-reported child anxiety symptoms. No significant effect of child age or gender was observed. Findings may inform inconsistencies in previous studies on reporter discrepancies. Implications and future directions are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Comparing predictions made by a prediction model, clinical score, and physicians: pediatric asthma exacerbations in the emergency department.

    Science.gov (United States)

    Farion, K J; Wilk, S; Michalowski, W; O'Sullivan, D; Sayyad-Shirabad, J

    2013-01-01

    Asthma exacerbations are one of the most common medical reasons for children to be brought to the hospital emergency department (ED). Various prediction models have been proposed to support diagnosis of exacerbations and evaluation of their severity. First, to evaluate prediction models constructed from data using machine learning techniques and to select the best performing model. Second, to compare predictions from the selected model with predictions from the Pediatric Respiratory Assessment Measure (PRAM) score, and predictions made by ED physicians. A two-phase study conducted in the ED of an academic pediatric hospital. In phase 1 data collected prospectively using paper forms was used to construct and evaluate five prediction models, and the best performing model was selected. In phase 2 data collected prospectively using a mobile system was used to compare the predictions of the selected prediction model with those from PRAM and ED physicians. Area under the receiver operating characteristic curve and accuracy in phase 1; accuracy, sensitivity, specificity, positive and negative predictive values in phase 2. In phase 1 prediction models were derived from a data set of 240 patients and evaluated using 10-fold cross validation. A naive Bayes (NB) model demonstrated the best performance and it was selected for phase 2. Evaluation in phase 2 was conducted on data from 82 patients. Predictions made by the NB model were less accurate than the PRAM score and physicians (accuracy of 70.7%, 73.2% and 78.0% respectively), however, according to McNemar's test it is not possible to conclude that the differences between predictions are statistically significant. Both the PRAM score and the NB model were less accurate than physicians. The NB model can handle incomplete patient data and as such may complement the PRAM score. However, it requires further research to improve its accuracy.

  4. Occupational asthma caused by samba (Triplochiton scleroxylon wood dust in a professional maker of wooden models of airplanes: A case study

    Directory of Open Access Journals (Sweden)

    Patrycja Krawczyk-Szulc

    2014-08-01

    Full Text Available Objectives: Wood dust is a known occupational allergen that may induce, in exposed workers, respiratory diseases including asthma and allergic rhinitis. Samba (obeche, Triplochiton scleroxylon is a tropical tree, which grows in West Africa, therefore, Polish workers are rarely exposed to it. This paper describes a case of occupational asthma caused by samba wood dust. Material and Methods: The patient with suspicion of occupational asthma due to wood dust was examined at the Department of Occupational Diseases and Clinical Toxicology in the Nofer Institute of Occupational Medicine. Clinical evaluation included: analysis of occupational history, skin prick tests (SPT to common and occupational allergens, determination of serum specific IgE to occupational allergens, serial spirometry measurements, metacholine challenge test and specific inhalation challenge test with samba dust. Results: SPT and specific serum IgE assessment revealed sensitization to common and occupational allergens including samba. Spirometry measurements showed mild obstruction. Metacholine challenge test revealed a high level of bronchial hyperactivity. Specific inhalation challenge test was positive and cellular changes in nasal lavage and induced sputum confirmed allergic reaction to samba. Conclusions: IgE mediated allergy to samba wood dust was confirmed. This case report presents the first documented occupational asthma and rhinitis due to samba wood dust in wooden airplanes model maker in Poland.

  5. Mast cells play a key role in Th2 cytokine-dependent asthma model through production of adhesion molecules by liberation of TNF-α.

    Science.gov (United States)

    Chai, Ok Hee; Han, Eui-Hyeog; Lee, Hern-Ku; Song, Chang Ho

    2011-01-31

    Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-α on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-Kitw/Kitw-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-α directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-α, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-α.

  6. Asthma and obesity

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ali, Zarqa; Nilas, Lisbeth

    2012-01-01

    Obesity is a major health problem, and obesity is associated with a high incidence of asthma and poor asthma control. The aim of the present paper is to systematically review the current knowledge of the effect on overall asthma control of weight reduction in overweight and obese adults with asthma....

  7. What Is Asthma?

    Science.gov (United States)

    ... to incorporate environmental management into clinical practices and standards of care for asthma patients. Top of Page Contact Us to ask a question, provide feedback, or report a problem. Asthma Indoor Air Quality Home Page Asthma Home Take the Asthma Quiz ...

  8. Developing a Core Competency Model and Educational Framework for Primary Maternity Services: a national consensus approach.

    Science.gov (United States)

    Homer, Caroline S E; Griffiths, Marnie; Brodie, Pat M; Kildea, Sue; Curtin, Austin M; Ellwood, David A

    2012-09-01

    An appropriately educated and competent workforce is crucial to an effective health care system. The National Health Workforce Taskforce (now Health Workforce Australia) and the Maternity Services Inter-Jurisdictional Committee funded a project to develop Core Competencies and Educational Framework for Primary Maternity Services in Australia. These competencies recognise the interdisciplinary nature of maternity care in Australia where care is provided by general practitioners, obstetricians and midwives as well as other professionals. Key stakeholders from professional organisations and providers of services related to maternity care and consumers of services. A national consensus approach was undertaken using consultation processes with a Steering Committee, a wider Reference Group and public consultation. A national Core Competencies and Educational Framework for Primary Maternity Services in Australia was developed through an iterative process with a range of key stakeholders. There are a number of strategies that may assist in the integration of these into primary maternity service provider professional groups' education and practice. The Core Competencies and Educational Framework are based on an interprofessional approach to learning and primary maternity service practice. They have sought to value professional expertise and stimulate awareness and respect for the roles of all primary maternity service providers. The competencies and framework described in this paper are now a critical component of Australian maternity services as they are included in actions in the newly released National Maternity Services Plan and thus have relevance for all providers of Australian maternity services. Copyright © 2011 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  9. O cuidado materno no manejo da asma infantil contribuição da enfermagem transcultural El cuidado materno en el manejo del asma infantil - contribución de enfermería transcultural Maternal care in the management of child asthma: the contributions of transcultural nursing

    Directory of Open Access Journals (Sweden)

    Maíra Domingues Bernardes Silva

    2009-12-01

    Full Text Available O objeto deste estudo são as práticas culturais do cuidado materno no manejo da asma infantil. Objetivos: descrever o conhecimento e o cuidado materno sobre a asma infantil e analisar o cuidado materno no manejo da asma infantil. Estudo descritivo-exploratório desenvolvido a partir de questionários e entrevistas com mães de crianças com asma, no período de setembro de 2008 janeiro de 2009. Após análise temática dos dados, emergiram três categorias: 1 Conceito e manejo da asma na visão das mães cuidadoras; 2 Asma como sofrimento e risco para a vida dos filhos; 3 Plantas medicinais, simpatias e religiosidade no cuidado do filho com asma. Concluiu-se que é importante respeitarmos a cultura das mães cuidadoras das crianças com asma, para que seus valores possam ser preservados, acomodados e reestruturados junto ao cuidado profissional.El objeto de este estudio es analizar las prácticas culturales de la atención materna en el manejo del asma infantil. Objetivos: describir el conocimiento y el cuidado de la madre en relación con el asma infantil y analizar la atención materna en el manejo del asma infantil. Estudio exploratorio-descriptivo desarrollado a partir de cuestionarios y entrevistas con madres de niños con asma, en el período comprendido entre Septiembre de 2008 y Enero del 2009. Tras el análisis temático de los datos, surgieron tres categorías: 1 Concepto y manejo del asma en la visión de las madres que cuidan de sus hijos con asma, 2 El asma como sufrimiento y riesgo para la vida de los hijos, 3 Plantas medicinales, rituales y religiosidad en el cuidado del hijo con asma. Se concluyó que es importante respetar la cultura de las madres que cuidan de los niños con asma, de modo que sus valores puedan ser preservados, acomodados y reestructurados junto a la atención profesional.The object of this study is the cultural practices of maternal care in the management of childhood asthma. Objectives: to describe both

  10. Yoga for asthma.

    Science.gov (United States)

    Yang, Zu-Yao; Zhong, Hui-Bin; Mao, Chen; Yuan, Jin-Qiu; Huang, Ya-Fang; Wu, Xin-Yin; Gao, Yuan-Mei; Tang, Jin-Ling

    2016-01-01

    across studies, we used standardized mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 liters, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two

  11. A Model of Maternal and Paternal Ethnic Socialization of Mexican-American Adolescents' Self-Views.

    Science.gov (United States)

    Knight, George P; Carlo, Gustavo; Streit, Cara; White, Rebecca M B

    2017-08-30

    Data from a sample of 462 Mexican-American adolescents (M = 10.4 years, SD = .55; 48.1% girls), mothers, and fathers were used to test an ethnic socialization model of ethnic identity and self-efficacy that also considered mainstream parenting styles (e.g., authoritative parenting). Findings supported the ethnic socialization model: parents' endorsement of Mexican-American values were associated with ethnic socialization at fifth grade and seventh grade; maternal ethnic socialization at fifth grade and paternal ethnic socialization at seventh grade were associated with adolescents' ethnic identity exploration at 10th grade and, in turn, self-efficacy at 12th grade. The findings support ethnic socialization conceptions of how self-views of ethnicity develop from childhood across adolescence in Mexican-American children. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  12. Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model.

    Science.gov (United States)

    Gandley, Robin E; Jeyabalan, Arun; Desai, Ketaki; McGonigal, Stacy; Rohland, Jennifer; DeLoia, Julie A

    2010-05-01

    Smoking is associated with multiple adverse pregnancy outcomes, including fetal growth restriction. The objective of this study was to determine whether cigarette smoke exposure during pregnancy in a mouse model affects the functional properties of maternal uterine, mesenteric, and renal arteries as a possible mechanism for growth restriction. C57Bl/CJ mice were exposed to whole body sidestream smoke for 4 h/day. Smoke particle exposure was increased from day 4 of gestation until late pregnancy (day 16-19), with mean total suspended particle levels of 63 mg/m(3), representative of moderate-to-heavy smoking in humans. Uterine, mesenteric, and renal arteries from late-pregnant and virgin mice were isolated and studied in a pressure-arteriograph system (n = 23). Plasma cotinine was measured by ELISA. Fetal weights were significantly reduced in smoke-exposed compared with control fetuses (0.88 +/- 0.1 vs. 1.0 +/- 0.08 g, P pregnant mice exposed to cigarette smoke during gestation. This difference was not apparent in isolated renal arteries from pregnant mice exposed to cigarette smoke; however, relaxation was significantly reduced in renal arteries from smoke-exposed virgin mice. In conclusion, we found that passive cigarette smoke exposure is associated with impaired vascular relaxation of uterine and mesenteric arteries in pregnant mice. Functional maternal vascular perturbations during pregnancy, specifically impaired peripheral and uterine vasodilation, may contribute to a mechanism by which smoking results in fetal growth restriction.

  13. Effects of a self-management asthma educational program in Taiwan based on PRECEDE-PROCEED model for parents with asthmatic children.

    Science.gov (United States)

    Chiang, Li-Chi; Huang, Jing-Long; Yeh, Kuo-Wei; Lu, Chang-Ming

    2004-04-01

    This study was conducted to evaluate the comparative effectiveness of two different asthma educational programs. One was self-management asthma education based on the PRECEDE-PROCEED model to change the influential factors based on a previous need assessment study in Taiwan. The other consisted of regular outpatient asthma education. The purposes were: 1) to compare differences in the asthma knowledge, self-efficacy, perceived effectiveness, children's cooperation, doctor-patient communication, and self-management behaviors in the experimental and control groups before education, and 2 weeks, 3 months, and 6 months after education; and 2) to compare differences in drug use, medication utilization, asthma severity, signs/symptoms of asthma, school absenteeism, and exercise ability before education, and 2 weeks, 3 months, and 6 months after education. Parents of asthmatic children were recruited from among outpatients of Chang Gung Children's Hospital, Taoyuan, Taiwan. They were grouped by registration number: those with even numbers were assigned to the experimental group, and those with odd numbers were assigned to the control group. Measurements were collected four times from all parents by means of a questionnaire and chart review. The General Linear Model: Repeat Measurement was used to compare variance differences. The following results were found. 1) Asthma knowledge, self-efficacy, perceived effectiveness, children's cooperation, and self-management behaviors significantly improved after the self-management asthma educational program based on PRECEDE-PROCEED. Except for perceived effectiveness, all variables still had good effectiveness after 6 months of follow-up. The experimental group was better than the control group in knowledge, children's cooperation, and self-management behaviors at the 3-month follow up, as well as in knowledge and children's cooperation at the 6-month follow-up. 2) In both the experimental and control groups, the educational program

  14. Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.

    Science.gov (United States)

    Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P

    2016-12-01

    Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.

  15. Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study

    Institute of Scientific and Technical Information of China (English)

    WEI Hua-hua; ZHOU Ting; WANG Lan; ZHANG Hong-ping; FU Juan-juan; WANG Lei; JI Yu-lin; WANG Gang

    2012-01-01

    Background The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated.This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up.Methods This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n=290).The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models.Further,sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations.Results The subjects were divided into three groups,which were uncontrolled (U,n=128),partly-controlled (PC,n=111),and well controlled (C,n=51) asthma.After adjustment,the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75,respectively),unplanned visits (OR 8.03 and OR 8.21,respectively) and emergency visits (OR 20.00 and OR 22.60,respectively) over a 12-month follow-up period.The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P<0.05).The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%.Conclusion Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and oredict future risk of asthma exacerbations in clinical practice.

  16. Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

    Science.gov (United States)

    Wei, Da-Zhen; Guo, Xian-Yang; Lin, Li-Na; Lin, Meng-Xiang; Gong, Yu-Qiang; Ying, Bin-Yu; Huang, Ming-Yuan

    2016-12-01

    Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

  17. Immunomodulatory effects of oak dust exposure in a murine model of allergic asthma.

    Science.gov (United States)

    Määttä, Juha; Haapakoski, Rita; Lehto, Maili; Leino, Marina; Tillander, Sari; Husgafvel-Pursiainen, Kirsti; Wolff, Henrik; Savolainen, Kai; Alenius, Harri

    2007-09-01

    Repeated airway exposure to wood dust has been reported to cause adverse respiratory effects such as asthma and chronic bronchitis. In our recent study, we found that exposure of mice to oak dust induced more vigorous lung inflammation compared to birch dust exposure. In the present study, we assessed the immunomodulatory effects of repeated intranasal exposure to oak dust both in nonallergic and in ovalbumin-sensitized, allergic mice. Allergen-induced influx of eosinophils and lymphocytes was seen in the lungs of allergic mice. Oak dust exposure elicited infiltration of neutrophils, lymphocytes, and macrophages in nonallergic mice. Interestingly, oak dust-induced lung neutrophilia as well as oak dust-induced production of the proinflammatory cytokine TNF-alpha and chemokine CCL3 were significantly suppressed in allergic mice. On the other hand, allergen-induced expression of IL-13 mRNA and protein was significantly reduced in oak dust-exposed allergic mice. Finally, allergen-induced airway hyperreactivity to inhaled metacholine was significantly suppressed in oak dust-exposed allergic mice. The present results suggest that repeated airway exposure to oak dust can regulate pulmonary inflammation and airway responses depending on the immunological status of the animal.

  18. Occupational asthma in Japan

    OpenAIRE

    Dobashi, Kunio

    2012-01-01

    Research into occupational asthma (OA) in Japan has been led by the Japanese Society of Occupational and Environmental Allergy. The first report about allergic OA identified konjac asthma. After that, many kinds of OA have been reported. Cases of some types of OA, such as konjac asthma and sea squirt asthma, have been dramatically reduced by the efforts of medical personnel. Recently, with the development of new technologies, chemical antigen-induced asthma has increased in Japan. Due to adva...

  19. Sublingual immunotherapy for asthma.

    Science.gov (United States)

    Normansell, Rebecca; Kew, Kayleigh M; Bridgman, Amy-Louise

    2015-08-28

    Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. However, it is not clear whether the sublingual delivery route is safe and effective in asthma. To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma. We identified trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of all primary studies and review articles. The search is up to date as of 25 March 2015. We included parallel randomised controlled trials (RCTs), irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma. Two review authors independently screened the search results for included trials, extracted numerical data and assessed risk of bias, all of which were cross-checked for accuracy. We resolved disagreements by discussion.We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We rated all outcomes using GRADE (Grades of Recommendation, Assessment

  20. Predicting Children's Asthma Hospitalizations: Rural and Urban Differences in Texas

    Science.gov (United States)

    Grineski, Sara E.

    2009-01-01

    Asthma is the number one chronic health condition facing children today; however, little is known about rural-urban inequalities in asthma. This "area effects on health" study examines rural-urban differences in childhood asthma hospitalizations within the state of Texas using negative binomial regression models. Effects associated with…

  1. Predicting Children's Asthma Hospitalizations: Rural and Urban Differences in Texas

    Science.gov (United States)

    Grineski, Sara E.

    2009-01-01

    Asthma is the number one chronic health condition facing children today; however, little is known about rural-urban inequalities in asthma. This "area effects on health" study examines rural-urban differences in childhood asthma hospitalizations within the state of Texas using negative binomial regression models. Effects associated with…

  2. Is human Type 2 diabetes maternally inherited? Insights from an animal model.

    Science.gov (United States)

    Gill-Randall, R J; Adams, D; Ollerton, R L; Alcolado, J C

    2004-07-01

    Patients with Type 2 diabetes mellitus more often report a history of an affected mother than father. However, in the few studies where both parents and offspring have been directly tested, this apparent maternal excess has not been confirmed. Rodent models of diabetes have the advantage that all parents and offspring can undergo glucose tolerance testing at a specific age in adult life. The aim of this study was to gain insights into the inheritance of human Type 2 diabetes by using a rat model. Goto Kakizaki (GK) rats (a model of Type 2 diabetes) were mated with non-diabetic Wistar rats. Offspring were produced from 20 GK female vs. Wistar male and 20 Wistar female vs. GK male crosses. Fasting blood glucose was measured at 6 weeks and 3 months of age and an intravenous glucose tolerance test (0.8 g/kg) performed at 6 months of age. Wistar mothers produced litters with almost twice as many viable offspring as GK mothers (14.1 vs. 7.4, P < 0.001). Despite the larger litter size, offspring in the two groups were of comparable weight at 6 weeks and 6 months of age. At 3 months of age, male offspring of Wistar mothers were heavier than offspring of GK mothers (415.7 g vs. 379.5 g, P = 0.016) but this difference was not sustained at 6 months of age. Fasting blood glucose at all ages and average blood glucose during the glucose tolerance test were similar in both groups. We therefore conclude that there is no evidence for maternal transmission of diabetes in the GK rat. Mothers were able to adjust their supply of milk so that offspring attained similar weights independent of litter size. The weight of the offspring remained independent of litter size into adult life.

  3. Fish and fish oil intake in relation to risk of asthma: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Huan Yang

    Full Text Available Although laboratory studies suggest that long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs may reduce risk of asthma, epidemiological data remain controversial and inconclusive. We quantitatively reviewed the epidemiological studies published through December 2012 in PubMed and EMBASE by using a fixed-effects or random-effects model. Eleven studies, comprised of 99,093 individuals (3,226 cases, were included in the final dataset. Of them, 7 studies examined associations between intake of fish or LCn3PUFA and risk of asthma: 4 studies in children (996 cases from 12,481 children and 3 in adults (1,311 cases from 82,553 individuals. Two studies (69 cases from 276 infants investigated LCn3PUFA levels in mothers' milk, and two studies assessed maternal fish consumption (786 cases from 2,832 individuals during lactation and/or plasma LCn3PUFA levels during pregnancy (64 cases from 951 infants in relation to offspring's asthma. The pooled relative risk of child asthma were 0.76 (95% CI, 0.61-0.94 for fish consumption and 0.71 (95% CI, 0.52-0.96 for LCn3PUFA intake. No statistically significant association was found in studies among adults. Epidemiological data to date indicate that fish or LCn3PUFA intake may be beneficial to prevent asthma in children. Further studies are needed to establish causal inference and to elucidate the potential mechanisms.

  4. Testing Cost-Benefit Models of Parental Care Evolution Using Lizard Populations Differing in the Expression of Maternal Care

    Science.gov (United States)

    Huang, Wen-San; Pike, David A.

    2013-01-01

    Parents are expected to evolve tactics to care for eggs or offspring when providing such care increases fitness above the costs incurred by this behavior. Costs to the parent include the energetic demands of protecting offspring, delaying future fecundity, and increased risk of predation. We used cost-benefit models to test the ecological conditions favoring the evolution of parental care, using lizard populations that differ in whether or not they express maternal care. We found that predators play an important role in the evolution of maternal care because: (1) evolving maternal care is unlikely when care increases predation pressure on the parents; (2) maternal care cannot evolve under low levels of predation pressure on both parents and offspring; and (3) maternal care evolves only when parents are able to successfully defend offspring from predators without increasing predation risk to themselves. Our studies of one of the only known vertebrate species to exhibit interpopulation differences in the expression of maternal care provide clear support for some of the hypothesized circumstances under which maternal care should evolve (e.g., when nests are in exposed locations, parents are able to defend the eggs from predators, and egg incubation periods are brief), but do not support others (e.g., when nest-sites are scarce, life history strategies are “risky”, reproductive frequency is low, and environmental conditions are harsh). We conclude that multiple pathways can lead to the evolution of parental care from a non-caring state, even in a single population of a widespread species. PMID:23408934

  5. Testing cost-benefit models of parental care evolution using lizard populations differing in the expression of maternal care.

    Directory of Open Access Journals (Sweden)

    Wen-San Huang

    Full Text Available Parents are expected to evolve tactics to care for eggs or offspring when providing such care increases fitness above the costs incurred by this behavior. Costs to the parent include the energetic demands of protecting offspring, delaying future fecundity, and increased risk of predation. We used cost-benefit models to test the ecological conditions favoring the evolution of parental care, using lizard populations that differ in whether or not they express maternal care. We found that predators play an important role in the evolution of maternal care because: (1 evolving maternal care is unlikely when care increases predation pressure on the parents; (2 maternal care cannot evolve under low levels of predation pressure on both parents and offspring; and (3 maternal care evolves only when parents are able to successfully defend offspring from predators without increasing predation risk to themselves. Our studies of one of the only known vertebrate species to exhibit interpopulation differences in the expression of maternal care provide clear support for some of the hypothesized circumstances under which maternal care should evolve (e.g., when nests are in exposed locations, parents are able to defend the eggs from predators, and egg incubation periods are brief, but do not support others (e.g., when nest-sites are scarce, life history strategies are "risky", reproductive frequency is low, and environmental conditions are harsh. We conclude that multiple pathways can lead to the evolution of parental care from a non-caring state, even in a single population of a widespread species.

  6. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  7. Maternal separation as a model of brain-gut axis dysfunction.

    LENUS (Irish Health Repository)

    O'Mahony, Siobhain M

    2011-03-01

    Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

  8. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model.

    Science.gov (United States)

    Espinoza, Julia; Montaño, Luis M; Perusquía, Mercedes

    2013-11-01

    Primates secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA); in humans, its levels are low during childhood and start declining after the fourth decade. It has been postulated that the progressive decline in DHEA levels may be related with the severity of asthma associated with age. To determine whether DHEA may regulate the airway smooth muscle (ASM) activity, isolated tracheal rings with and without epithelium from male guinea pigs were isometrically recorded to characterize the response of ASM to DHEA at different concentrations on KCl- and carbachol (CCh)-induced contraction as well as on ovalbumin (OVA)-induced contraction in sensitized guinea pigs. Additionally, we used barometric plethysmography in sensitized guinea pigs in order to compare changes of the lung resistance increased by the antigen challenge to OVA in the absence and presence of different doses of DHEA. DHEA concentration-dependently abolished the contraction to KCl, CCh and OVA, and no differences were found in preparations with and without epithelium. DHEA-induced relaxation was not modified by the suppression of protein synthesis or transcription, pharmacological inhibition of nitric oxide (NO) synthase, nor by antagonist of β2-adrenergic receptors or an inhibitor of the 3β-HSD enzyme. Likewise, Ca(2+)-induced contraction in Ca(2+)-free depolarized tissues was antagonized by DHEA, and the contraction to the L-type voltage-dependent calcium channel activator (Bay K 8644) was inhibited by DHEA. Furthermore, DHEA prevented OVA-induced increases in lung resistance. These results indicate that DHEA-induced relaxation in ASM is a nongenomic (membrane) action and is not produced after its bioconversion. The data suggest that DHEA-induced relaxation is an epithelium- and NO-independent mechanism that involves a blockade of voltage-dependent calcium channels and possible non-selective cation channels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.

    Directory of Open Access Journals (Sweden)

    Alicja Pacholewska

    Full Text Available Recurrent airway obstruction (RAO is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs. We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.

  10. A polymorphism in gasdermin B (GSDMB gene is associated with severe asthma exacerbations in childhood: A population-based birth cohort study

    Directory of Open Access Journals (Sweden)

    Aida Semic-Jusufagic

    2011-11-01

    Full Text Available Rationale. Markers on chromosome 17q12 have been associated withchildhood asthma in genome-wide association studies. Objective.We investigated the association of a single nucleotide polymorphism(SNP in GSDMB (rs7216389 on 17q12 with asthma presence andseverity in a population-based birth cohort study. Methods. Childrenwere followed from birth to age 8 years. Data on parentally-reportedsymptoms were collected using an interviewer-administered questionnaire at age 1, 3, 5 and 8 years. Atopy was assessed by skin testing at age 3, 5 and 8 years. Information on asthma/wheeze hospital admissions and severe asthma exacerbations was collected from child’s primary care medical record. Data were analyzed as a recessive genetic model, with T-allele homozygotes as the risk group. Results. Compared to C allele carriers, T-allele homozygotes of rs7216389 were significantly more likely to: wheeze at age 3, 5 and 8 years; have persistent wheeze (OR 1.69, 95% CI 1.05-2.71, p=0.03; have frequent episodes of wheezing and be on asthma medication. In a multiple logistic regression model adjusted for gender, atopic sensitisation and maternal smoking, T allele homozygotes were significantly more likely to be hospitalized (aOR 2.20 [1.22-3.99], p=0.0009 with Cox regression hazard ratio for T-allele homozygotes of 1.94 [1.13-3.33], p=0.016. Results of Cox regression analysis investigating the eff ect of genotype on the age of first severe exacerbation of asthma indicated an overall hazard ratio of severe asthma exacerbation among T-allele homozygotes of 1.53 [1.04-2.27], p=0.03. Conclusions. Th is is the fi rst population-based birth cohort study to confirm that the risk of childhood wheeze and severe asthma/wheeze exacerbations is increased among rs7216389 TT homozygotes.

  11. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models

    Science.gov (United States)

    Liu, Meng-Yun; Yang, Zhen-Yu; Dai, Wen-Kui; Huang, Jian-Qiong; Li, Yin-Hu; Zhang, Juan; Qiu, Chuang-Zhao; Wei, Chun; Zhou, Qian; Sun, Xin; Feng, Xin; Li, Dong-Fang; Wang, He-Ping; Zheng, Yue-Jie

    2017-01-01

    AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model. METHODS Ovalbumin (OVA)-induced allergic asthma and β-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured. RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed. CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation.

  12. Effects of MnTnHex-2-PyP on lung antioxidant defence system in asthma mice model.

    Directory of Open Access Journals (Sweden)

    Violeta Dancheva

    2012-12-01

    Full Text Available We aimed to study the MnTnHex-2-PyP effect on some markers of lung antioxidant defence system in mice asthma model.The study was carried out on 28 C57B1/6 mice divided into four treatment groups: group 1 - controls; group 2 - injected and inhaled with ovalbumin; group 3 - treated with MnTnHex-2-PyP and inhaled with phosphate buffered saline; group 4 - injected with ovalbumin and MnTnHex-2-PyP but also inhaled with ovalbumin. On days 24, 25 and 26, mice from groups 1 and 2 were inhaled with PBS for 30 min, and those from groups 2 and 4 were given a 1% ovalbumin solution. One hour before inhalation, and 12 hours later the animals from groups 1 and 2 were injected i.p. with 100 μl PBS, and those from groups 3 and 4 received a 100 μl MnTnHex-2-PyP solution in PBS, сontaining 0,05mg/kg. The animals were killed by exsanguination 48 hours after the last inhalation for obtaining a lung homogenate. The activities of superoxide dismutase, catalase, glutathione peroxidase and the non-protein sulphhydryl group content in the lung homogenate were investigated. Ovalbumin decreased the activities of superoxide dismutase (p=0.01, catalase (p=0.002, glutathione peroxidase and non-protein sulphhydryl groups content (p<0.001 in comparison to controls. In group 4 (ovalbumin and MnTnHex-2-PyP the activities of superoxide dismutase (p=0.044, catalase (p=0.045, glutathione peroxidase (p=0.002, and the non-protein sulphhydryl groups content (p<0.001 were significantly increased compared to ovalbumin (group 2.MnTnHex-2-PyP restored the activities of basic enzymes in the lung antioxidant defence system in ovalbumin-induced asthma mice model, 48 hours after the last nebulization.

  13. Effects of MnTnHex-2-PyP on lung antioxidant defence system in asthma mice model.

    Science.gov (United States)

    Dancheva, Violeta; Terziev, Lyudmil; Shopova, Veneta; Stavreva, Galya

    2012-12-01

    We aimed to study the MnTnHex-2-PyP effect on some markers of lung antioxidant defence system in mice asthma model.The study was carried out on 28 C57B1/6 mice divided into four treatment groups: group 1 - controls; group 2 - injected and inhaled with ovalbumin; group 3 - treated with MnTnHex-2-PyP and inhaled with phosphate buffered saline; group 4 - injected with ovalbumin and MnTnHex-2-PyP but also inhaled with ovalbumin. On days 24, 25 and 26, mice from groups 1 and 2 were inhaled with PBS for 30 min, and those from groups 2 and 4 were given a 1% ovalbumin solution. One hour before inhalation, and 12 hours later the animals from groups 1 and 2 were injected i.p. with 100 μl PBS, and those from groups 3 and 4 received a 100 μl MnTnHex-2-PyP solution in PBS, сontaining 0,05mg/kg. The animals were killed by exsanguination 48 hours after the last inhalation for obtaining a lung homogenate. The activities of superoxide dismutase, catalase, glutathione peroxidase and the non-protein sulphhydryl group content in the lung homogenate were investigated. Ovalbumin decreased the activities of superoxide dismutase (p=0.01), catalase (p=0.002), glutathione peroxidase and non-protein sulphhydryl groups content (p<0.001) in comparison to controls. In group 4 (ovalbumin and MnTnHex-2-PyP) the activities of superoxide dismutase (p=0.044), catalase (p=0.045), glutathione peroxidase (p=0.002), and the non-protein sulphhydryl groups content (p<0.001) were significantly increased compared to ovalbumin (group 2).MnTnHex-2-PyP restored the activities of basic enzymes in the lung antioxidant defence system in ovalbumin-induced asthma mice model, 48 hours after the last nebulization.

  14. The impact of secondhand smoke on asthma control among Black and Latino children

    Science.gov (United States)

    Oh, Sam S.; Tcheurekdjian, Haig; Roth, Lindsey A.; Nguyen, Elizabeth A.; Sen, Saunak; Galanter, Joshua M.; Davis, Adam; Farber, Harold J.; Gilliland, Frank D.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; LeNoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R.; Williams, L. Keoki; Borrell, Luisa N.; Burchard, Esteban G.

    2012-01-01

    Background Among people with asthma, the clinical impact and relative contribution of maternal smoking during pregnancy (in utero smoking) and current secondhand smoke exposure on asthma control is poorly documented, and there is a paucity of research involving minority populations. Objectives To examine the association between poor asthma control and in utero smoking and current secondhand smoke exposure among Latino and Black children with asthma. Methods Case-only analysis of 2 multi-center case-control studies conducted from 2008–2010 using similar protocols. We recruited 2,481 Latinos and Blacks with asthma (ages 8–17) from the mainland United States and Puerto Rico. Ordinal logistic regression was used to estimate the effect of in utero smoking and current secondhand smoke exposures on National Heart Lung and Blood Institute-defined asthma control. Results Poor asthma control among children 8–17 years of age was independently associated with in utero smoking (odds ratio; 95% confidence interval = 1.5; 1.1–2.0). In utero smoking via the mother was also associated with secondary asthma outcomes, including early onset asthma (1.7; 1.1–2.4), daytime symptoms (1.6; 1.1–2.1), and asthma-related limitation of activities (1.6; 1.2–2.2). Conclusions Maternal smoking while in utero is associated with poor asthma control in Black and Latino subjects assessed at 8–17 years of age. PMID:22552109

  15. What's an Asthma Action Plan?

    Science.gov (United States)

    ... to 2-Year-Old What's an Asthma Action Plan? KidsHealth > For Parents > What's an Asthma Action Plan? ... normal everyday activities without having asthma symptoms. Action Plans Are Unique Each person's experience with asthma is ...

  16. Preconceptional exposure to oral contraceptive pills and the risk of wheeze, asthma and rhinitis in children

    Directory of Open Access Journals (Sweden)

    Kiwako Yamamoto-Hanada

    2016-07-01

    Conclusions: Our findings suggest that maternal OCP use has a role in the development of wheeze, asthma and rhinitis in children. Extended use of OCP is likely to increase the risk of wheeze and rhinitis.

  17. Association of prenatal exposure to acetaminophen and coffee with childhood asthma

    DEFF Research Database (Denmark)

    Liu, Xiaoqin; Liew, Zeyan; Olsen, Jørn

    2016-01-01

    PurposeSome studies have suggested that maternal acetaminophen use during pregnancy is associated with asthma in the offspring, and coffee consumption may modify the toxicity of acetaminophen. We aim to examine whether pregnancy maternal acetaminophen use increases the risk for offspring asthma......, and whether such a potential association could be modified by maternal coffee consumption. MethodsWe included 63 652 live-born singletons enrolled in the Danish National Birth Cohort. Maternal acetaminophen use and coffee consumption during pregnancy were assessed prospectively via the enrolment questionnaire...... and three computer-assisted telephone interviews. Asthma cases were identified by using the Danish National Patient Register and the Danish National Prescription Registry. We estimated the hazard ratios (HRs) for asthma according to prenatal acetaminophen and coffee exposure using Cox proportional hazards...

  18. Asthma during pregnancy in a population-based study--pregnancy complications and adverse perinatal outcomes.

    Directory of Open Access Journals (Sweden)

    Gustaf Rejnö

    Full Text Available BACKGROUND: Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes. METHODS: We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression. RESULTS: In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4% pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06-1.24 and premature contractions (adj OR 1.52; 95% CI 1.29-1.80. There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23-1.34, low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13-1.33. The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes. CONCLUSION: Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve.

  19. Obesity and Asthma

    DEFF Research Database (Denmark)

    Juel, Caroline Trunk-Black; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is more prevalent in obese compared with normal weight subjects. Our aim has been to review current knowledge of the impact of obesity on asthma severity, asthma control, and response to therapy.Several studies have shown that overweight and obesity is associated with more severe asthma...... and impaired quality of life compared with normal weight individuals. Furthermore, obesity is associated with poorer asthma control, as assessed by asthma control questionnaires, limitations in daily activities, breathlessness and wheezing, use of rescue medication, unscheduled doctor visits, emergency...... department visits, and hospitalizations for acute asthma. Studies of the impact of a high body mass index (BMI) on response to asthma therapy have, however, revealed conflicting results. Most studies show that overweight and obesity is associated with less favorable response to asthma therapy with regard...

  20. Induction, duration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone.

    Science.gov (United States)

    Blyth, D I; Pedrick, M S; Savage, T J; Bright, H; Beesley, J E; Sanjar, S

    1998-07-01

    We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose-related suppression of developing GCH, while similar treatment during the period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease.

  1. Asthma in pregnancy - from immunology to clinical management

    Directory of Open Access Journals (Sweden)

    Tamási Lilla

    2010-08-01

    Full Text Available Abstract Asthma is one of the most common chronic medical conditions that may complicate pregnancy. Asthma influences the outcome of pregnancy and, vice versa, pregnancy affects asthma severity, but the underlying immunological mechanisms of this interaction are not fully understood. As a sign of pregnancy-induced immunotolerance, attenuation of allergic responses can be detected in controlled asthmatic pregnant patients; however non controlled asthmatic pregnant women show significant asthma-associated immune reactions that may, beside other factors, influence fetal growth. Generally, although uncontrolled asthma may increase the risk of adverse perinatal outcomes, women with well-controlled and adequately treated disease during pregnancy do not develop maternal or fetal complications.

  2. Maternal Psychological Control and Peer Victimization in Early Adolescence: An Application of the Family Relational Schema Model

    Science.gov (United States)

    Batanova, Milena D.; Loukas, Alexandra

    2014-01-01

    Guided by the family relational schema model, the current study examined the direct and indirect contributions of maternal psychological control to subsequent relational and overt peer victimization, via early adolescents' conduct problems, fear of negative evaluation, and depressive symptoms. Participants were 499 10- to 14-year-olds (53% female;…

  3. Maternal Modeling and the Acquisition of Fear and Avoidance in Toddlers: Influence of Stimulus Preparedness and Child Temperament

    Science.gov (United States)

    Dubi, Kathrin; Rapee, Ronald M.; Emerton, Jane L.; Schniering, Carolyn A.

    2008-01-01

    The aim of the present study was to investigate the influence of maternal modeling on the acquisition of fear and avoidance towards fear-relevant and fear-irrelevant, novel stimuli in a sample of 71 toddlers. Children were shown a rubber snake or spider (fear-relevant objects) and a rubber mushroom or flower (fear-irrelevant objects), which were…

  4. Maternal immunisation

    NARCIS (Netherlands)

    Verweij, Marcel; Lambach, Philipp; Ortiz, Justin R.; Reis, Andreas

    2016-01-01

    There has been increased interest in the potential of maternal immunisation to protect maternal, fetal, and infant health. Maternal tetanus vaccination is part of routine antenatal care and immunisation campaigns in many countries, and it has played an important part in the reduction of maternal and

  5. TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma.

    Science.gov (United States)

    Nadeem, Ahmed; Siddiqui, Nahid; Al-Harbi, Naif O; Al-Harbi, Mohammed M; Ahmad, Sheikh F

    2016-04-01

    Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma.

  6. Inhibitory effects of kaempferol-3-O-rhamnoside on ovalbumin-induced lung inflammation in a mouse model of allergic asthma.

    Science.gov (United States)

    Chung, Mi Ja; Pandey, Ramesh Prasad; Choi, Ji Won; Sohng, Jae Kyung; Choi, Doo Jin; Park, Yong Il

    2015-04-01

    The modification of natural flavonoid by glycosylation alters their physicochemical and pharmacokinetic properties, such as increased water solubility and stability, reduced toxicity, and sometimes enhanced or even new pharmacological activities. Kaempferol (KF), a plant flavonoid, and its glycosylated derivative, kaempferol-3-O-rhamnoside (K-3-rh), were evaluated and compared for their anti-inflammatory, anti-oxidant, and anti-asthmatic effects in an asthma model mouse. The results showed that K-3-rh fully maintained its anti-inflammatory and anti-asthmatic effects compared with KF in an asthma model mouse. Both KF and K-3-rh significantly reduced the elevated inflammatory cell numbers in the bronchoalveolar lavage fluid (BALF). KF and K-3-rh also significantly inhibited the increase in Th2 cytokines (IL-4, IL-5, and IL-13) and TNF-α protein levels through inhibition of the phosphorylation Akt and effectively suppressed eosinophilia in a mouse model of allergic asthma. The total immunoglobulin (Ig) E levels in the serum and BALF were also blocked by KF and K-3-rh to similar extents. K-3-rh exerts similar or even slightly higher inhibitory effects on Th2 cytokines and IgE production compared with KF, whereas K-3-rh was less effective at DPPH radical scavenging and the inhibition of ROS generation in inflammatory cells compared with KF. These results suggested that the K-3-rh, as well as KF, may also be a promising candidate for the development of health beneficial foods or therapeutic agents that can prevent or treat allergic asthma.

  7. Implementing a pediatric asthma program: enabling self-care management through education.

    Science.gov (United States)

    Navaie-Waliser, Maryam; Mersman, Cynthia; Lincoln, Priscilla

    2004-09-01

    This article provides an overview of asthma prevalence among children, presents a summary of asthma triggers based on past research, outlines the essential components of a pediatric asthma home care model implemented by a large urban home health agency, and details the types of clinical documentation needed for care plan development and monitoring of asthma in the home.

  8. Diet and asthma: looking back, moving forward

    Directory of Open Access Journals (Sweden)

    Ellwood Philippa E

    2009-06-01

    Full Text Available Abstract Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant's immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that

  9. Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

    Directory of Open Access Journals (Sweden)

    Natarajan Sudha

    2010-11-01

    .02. Conclusion Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia.

  10. Gene expression profiling in porcine maternal infanticide: a model for puerperal psychosis.

    Science.gov (United States)

    Quilter, Claire R; Gilbert, Colin L; Oliver, Gina L; Jafer, Osman; Furlong, Robert A; Blott, Sarah C; Wilson, Anna E; Sargent, Carole A; Mileham, Alan; Affara, Nabeel A

    2008-10-01

    The etiology of mental disorders remains largely unclear. Complex interactions between genetic and environmental factors are key to the development of such disorders. Puerperal psychosis is the most extreme form of postnatal mood disorder in women. Similarly, parturition in the pig can trigger extreme behavioral disturbances, including maternal infanticide. In this study, we have used a targeted cDNA microarray approach using the pig as a model to understand the genes and genetic pathways that are involved in these processes. Two subtracted cDNA libraries from porcine hypothalamus were constructed, which were enriched for genes that were over-expressed and under-expressed in the aberrant behavioral phenotype, compared to the matched control. In addition to this, a normalized library was constructed from hypothalamus and pituitary samples taken from pigs in a variety of reproductive states. The libraries were partially sequenced and combined represented approximately 5,159 different genes. Microarray analysis determined differences in gene expression between hypothalamus samples from nine matched pairs of infanticidal versus control animals, using a common reference design. Microarray analysis of variance (MAANOVA) identified 52 clones as being differentially expressed (P infanticide phenotype, a second analysis with friendly statistics package for microarray analysis (FSPMA) identified 9 genes in common to MAANOVA, and a further 16 genes. A rapid cross-species screen onto a human oligonucleotide array confirmed 3 genes and highlighted 61 more potential candidates. Some of these genes and the pathways in which they are involved were also implicated in a parallel QTL study on maternal infanticide.

  11. Identifying a window of vulnerability during fetal development in a maternal iron restriction model.

    Directory of Open Access Journals (Sweden)

    Camelia Mihaila

    Full Text Available It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring.Our data may have significant relevance for understanding the impact of suboptimal iron levels during pregnancy not only on the mother but also on the developing fetus and hence might lead to a more informed timing of iron supplementation during pregnancy.

  12. Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model.

    Science.gov (United States)

    Dando, Samantha J; Nitsos, Ilias; Newnham, John P; Jobe, Alan H; Moss, Timothy J M; Knox, Christine L

    2010-10-01

    Erythromycin is the standard antibiotic used for treatment of infection with Ureaplasma spp. during pregnancy; however, maternally administered erythromycin may be ineffective at eliminating intra-amniotic ureaplasma infections. We examined whether erythromycin would eradicate intra-amniotic ureaplasma infections in pregnant sheep. At Gestational Day (GD) 50 (term, GD 150), pregnant ewes received intra-amniotic injections of erythromycin-sensitive Ureaplasma parvum serovar 3 (n = 16) or 10B medium (n = 16). At GD 100, amniocentesis was performed; five fetal losses (ureaplasma group, n = 4; 10B group, n = 1) had occurred by this time. Remaining ewes were allocated into treatment subgroups: medium only (n = 7), medium and erythromycin (n = 8), ureaplasma only (Up; n = 6), or ureaplasma and erythromycin (Up/E; n = 6). Erythromycin was administered intramuscularly (500 mg) every 8 h for 4 days (GDs 100-104). Amniotic fluid samples were collected at GD 105. At GD 125, preterm fetuses were surgically delivered, and specimens were collected for culture and histology. Erythromycin was quantified in amniotic fluid by liquid chromatography-mass spectrometry. Ureaplasmas were isolated from the amniotic fluid, chorioamnion, and fetal lung of animals from the Up and Up/E groups, however, the numbers of U. parvum recovered were not different between these groups. Inflammation in the chorioamnion, cord, and fetal lung was increased in ureaplasma-exposed animals compared to controls but was not different between the Up and Up/E groups. Erythromycin was detected in amniotic fluid samples, although concentrations were low (<10-76 ng/ml). This study demonstrates that maternally administered erythromycin does not eradicate chronic, intra-amniotic ureaplasma infections or improve fetal outcomes in an ovine model, potentially because of the poor placental passage of erythromycin.

  13. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... helping people with asthma live healthier lives by gaining control over their asthma. Quick Links Asthma Action ... helping people with asthma live healthier lives by gaining control over their asthma. Quick Links Asthma Action ...

  14. Airway remodeling in a mouse asthma model assessed by in-vivo respiratory-gated micro-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lederlin, Mathieu; Montaudon, Michel [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); Ozier, Annaig; Begueret, Hugues; Ousova, Olga; Marthan, Roger; Berger, Patrick [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); Laurent, Francois [Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux (France); Institut National de la Sante et de la Recherche Medicale (INSERM), U885, Bordeaux (France); CHU Bordeaux, Unite d' Imagerie Thoracique, Pessac (France); CHU de Bordeaux, Hopital du Haut-Leveque, Hopital Cardiologique, Unite d' Imagerie Thoracique et Cardiovasculaire, Pessac (France)

    2010-01-15

    The aim of our study was to evaluate the feasibility of non-invasive respiratory-gated micro-computed tomography (micro-CT) for assessment of airway remodelling in a mouse asthma model. Six female BALB/c mice were challenged intranasally with ovalbumin. A control group of six mice received saline inhalation. All mice underwent plethysmographic study and micro-CT. For each mouse, peribronchial attenuation values of 12 bronchi were measured, from which a peribronchial density index (PBDI) was computed. Mice were then sacrificed and lungs examined histologically. Final analysis involved 10 out of 12 mice. Agreement of measurements across observers and over time was very good (intraclass correlation coefficients: 0.94-0.98). There was a significant difference in PBDI between asthmatic and control mice (-210 vs. -338.9 HU, P=0.008). PBDI values were correlated to bronchial muscle area (r=0.72, P=0.018). This study shows that respiratory-gated micro-CT may allow non-invasive monitoring of bronchial remodelling in asthmatic mice and evaluation of innovative treatment effects. (orig.)

  15. Swim test immobility in a genetic rat model of depression is modified by maternal environment: a cross-foster study.

    Science.gov (United States)

    Friedman, Elliot; Berman, Marissa; Overstreet, David

    2006-03-01

    The Flinders sensitive line (FSL) genetic animal model of depression exhibits marked immobility during forced swimming, an accepted index of depressive like behavior in rodent depression models. The present experiment tested the hypothesis that swim test behavior in the FSL rats is influenced in part by early experience, specifically maternal environment. Male FSL and control Flinders resistant line (FRL) pups were cross fostered onto dams of the same or complementary strain. Nest quality and dam behavior during pup retrieval were measured on PN5 and PN8, and swim test behavior assessed in the adult males on PN60. FSL rats reared by foster FRL dams were significantly less immobile than FSL rats raised by FSL dams, but still significantly more immobile that the two FRL groups, which did not differ from each other. FSL dams took significantly longer to retrieve their pups and dropped them more often than the FRL control dams. Moreover, strain differences in maternal retrieval behavior significantly predicted later swim test immobility in the FSL animals. These findings suggest that swim test immobility in the FSL rats is modified by maternal environment. In contrast, the FRL control rats were relatively insensitive to the influence of maternal environment. The FSL model offers promise for understanding the interactions of genetic vulnerabilities and environmental influences in the etiology of clinical depression.

  16. Effects of the flavanone combination hesperetin-naringenin, and orange and grapefruit juices, on airway inflammation and remodeling in a murine asthma model.

    Science.gov (United States)

    Seyedrezazadeh, Ensiyeh; Kolahian, Saeed; Shahbazfar, Amir-Ali; Ansarin, Khalil; Pour Moghaddam, Masoud; Sakhinia, Masoud; Sakhinia, Ebrahim; Vafa, Mohammadreza

    2015-04-01

    We investigated whether flavanones, hesperetin-naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma.

  17. Selective p38α mitogen-activated protein kinase inhibitor attenuates lung inflammation and fibrosis in IL-13 transgenic mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Jing Ying Ma

    2008-11-01

    Full Text Available Jing Ying Ma1, Satyanarayana Medicherla1, Irene Kerr, Ruban Mangadu, Andrew A Protter, Linda S Higgins1Scios Inc, Fremont, CA, USA 1Jing Ying Ma and Satyanarayana Medicherla contributed equally to this workAbstract: p38 Mitogen-activated protein kinase (MAPK plays a critical role in the activation of inflammatory cells. We investigated the anti-inflammatory effects of a p38α-selective MAPK inhibitor (SD-282 in a mouse transgenic (CC10:IL-13 asthma model. The CC-10-driven over-expression of IL-13 in the mouse lung/airway has been shown to result in a remarkable phenotype recatitulating many features of asthma and characterized by eosinophilic and mononuclear inflammation, with airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot–Leyden-like crystal, and airway sub-epitheilial fibrosis. Here we show how activated p38 MAPK can be observed in the lungs at the onset of asthma ie, around 8 weeks of age in both female and male mice. We also show that administration of a p38α MAPK selective inhibitor, SD-282 at 30 or 90 mg/kg, twice a day for a period of four weeks beginning at the onset of asthma, significantly reduced the inflammation (p < 0.001; hyperplasia of airway epithelium (p < 0.05; goblet cell metaplasia and mucus hypersecretion (p < 0.001 and reduced lung remodeling and fibrosis (p < 0.01, alleviating the severity of lung damage as measured by a composite score (p < 0.05. Furthermore, SD-282 significantly reduced activated p38 MAPK in the lymphocytes and epithelial cells (p < 0.001. Simultaneously, identical studies were conducted with an anti-fibrotic TGFβR1 kinase inhibitor (SD-208 which demonstrated anti-fibrotic but not anti-inflammatory properties. These findings suggest that the p38α-selective MAPK inhibitor may have dual therapeutic potential in attenuating both the inflammatory component and the fibrotic component of asthma and other Th2

  18. Basal or stress-induced cortisol and asthma development: the TRAILS study.

    Science.gov (United States)

    Vink, Nienke M; Boezen, H Marike; Postma, Dirkje S; Rosmalen, Judith G M

    2013-04-01

    We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a post hoc meta-analysis on results from the literature. Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case-control articles on basal cortisol in asthma. No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The meta-analysis found lower morning and evening cortisol levels in asthmatics compared to non-asthmatics; however, the summary estimates were not significant. We found no evidence supporting a role for cortisol in asthma and asthma development.

  19. Adenovirus-mediated Foxp3 expression in lung epithelial cells reduces airway inflammation in ovalbumin and cockroach-induced asthma model

    Science.gov (United States)

    Park, Soojin; Chung, Hwan-Suck; Shin, Dasom; Jung, Kyung-Hwa; Lee, Hyunil; Moon, Junghee; Bae, Hyunsu

    2016-01-01

    Foxp3 is a master regulator of CD4+CD25+ regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4+ or CD8+ cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3DTR mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma. PMID:27633092

  20. Asthma and obesity.

    Science.gov (United States)

    Boulet, L-P

    2013-01-01

    The prevalence and incidence of asthma have increased among obese children and adults, particularly among women. Obesity seems to be a predisposing factor for the development of asthma, but the underlying mechanisms of its influence are still uncertain. Various hypotheses have been proposed to explain the link between obesity and asthma such as a common genetic predisposition, developmental changes, altered lung mechanics, the presence of a systemic inflammatory process, and an increased prevalence of associated comorbid conditions. Over-diagnosis of asthma does not seem to be more frequent in obese compared to non-obese subjects, but the added effects of obesity on respiratory symptoms can affect asthma control assessment. Obesity can make asthma more difficult to control and is associated with a reduced beneficial effect of asthma medications. This could be due to a change in asthma phenotype, particularly evidenced as a less eosinophilic type of airway inflammation combined to the added effects of changes in lung mechanics. Weight loss is associated with a universal improvement of asthma and should be part of asthma management in the obese patient. Additional research should be conducted to better determine how obesity influences the development and clinical expression of asthma, establish the optimal management of asthma in this population and determine how obesity affects long-term asthma outcomes in these patients.

  1. Maternity Leave Policies

    Science.gov (United States)

    Strang, Lucy; Broeks, Miriam

    2017-01-01

    Abstract Over recent years many European Union countries have made changes to the design of the maternity leave provision. These policy developments reflect calls for greater gender equality in the workforce and more equal share of childcare responsibilities. However, while research shows that long period of leave can have negative effects on women's labour market attachment and career advancements, early return to work can be seen as a factor preventing exclusive breastfeeding, and therefore, potentially having negative health impacts for babies. Indeed, the World Health Organisation recommends exclusive breastfeeding up to 6 months of age to provide babies with the nutrition for healthy growth and brain development, protection from life-threatening ailments, obesity and non-communicable diseases such as asthma and diabetes. Therefore, labour market demands on women may be at odds with the health benefits for children gained by longer periods of maternity leave. The aim of this article is to examine the relationship between leave provision and health benefits for children. We examine maternity and parental leave provision across European countries and its potential impact on the breastfeeding of very young babies (up to 6-months of age). We also consider economic factors of potential extension of maternity leave provision to 6 months, such as costs to businesses, effects on the female labour market attachment, and wider consequences (benefits and costs) for individuals, families, employers and the wider society. PMID:28983432

  2. Predicting asthma control: the role of psychological triggers.

    Science.gov (United States)

    Ritz, Thomas; Bobb, Carol; Griffiths, Chris

    2014-01-01

    Asthma triggers have been linked to adverse health outcomes in asthma, but little is known about their association with asthma control. Because trigger avoidance is an integral part of successful asthma management, psychological triggers in particular may be associated with suboptimal asthma control, given the difficulty of controlling them. We examined cross-sectional and longitudinal associations of perceived asthma triggers with self-report of asthma control impairment, symptoms, and spirometric lung function (forced expiratory volume in the 1st second, [FEV1]) in 179 adult primary care asthma patients. Perceived asthma triggers explained up to 42.5% of the variance in asthma control and symptoms, but not in FEV1 alone. Allergic triggers explained up to 12.1% of the asthma control and symptom variance, three nonallergic trigger types, air pollution/irritants, physical activity, and infection, explained up to 26.2% over and above allergic triggers, and psychological triggers up to 9.5% over and above all other triggers. Psychological triggers alone explained up to 33.9% of the variance and were the only trigger class that was consistently significant in all final multiple regression models predicting control and symptoms. Psychological triggers also predicted lower asthma control 3-6 months later, although controlling for initial asthma control eliminated this association. In free reports of individually relevant triggers, only psychological triggers were associated with suboptimal asthma control. Trigger factors are important predictors of self-reported asthma control and symptoms but not actual lung function. Particular attention should be directed to psychological triggers as indicators of patients' perceptions of suboptimal asthma control.

  3. Changes in asthma-like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model.

    Science.gov (United States)

    Zhang, X D; Hubbs, A F; Siegel, P D

    2009-11-01

    Organic acid anhydride-induced occupational asthma is considered to be IgE-mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application. The objectives of this study were (1) to develop a model of non-occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol-induced airway responses in this model. TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10-min aerosol challenge to 40 mg/m(3) TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18-24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured. Rats produced dose-dependent specific IgE titres after exposure and developed early-phase (EAR) and late-phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18-24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18-24 months and was not significantly different from the response on day 35. These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.

  4. Obesity and asthma: co-morbidity or causal relationship?

    Science.gov (United States)

    van Huisstede, A; Braunstahl, G J

    2010-09-01

    There is substantial evidence that obesity and asthma are related. "Obese asthma" may be a unique phenotype of asthma, characterized by decreased lung volumes, greater symptoms for a given degree of lung function impairment, destabilization or lack of asthma control, lack of eosinophilic inflammation and a different response to controller medication. Whether this relationship between obesity and asthma is causal or represents co-morbidity due to other factors is unclear. In previous reviews concerning the relationship between obesity and asthma, five hypotheses were put forth. One of these hypotheses is that a low grade systemic inflammation caused by adipokines from the fat tissue causes or enhances bronchial inflammation. In animal models, there is an increasing amount of evidence for the role of adipokines derived from fat tissue in the relationship between obesity and asthma. The data are conflicting in humans. Since obesity is a component of the metabolic syndrome and the metabolic syndrome is also a form of systemic inflammation, it is to be expected that there is a relationship between metabolic syndrome and asthma. The few data that are available show that there is no relationship between metabolic syndrome and asthma, but there is one between the metabolic syndrome and asthma-like symptoms. Further research is needed to confirm the relationship between obesity and asthma in humans, where a rigorous approach in the diagnosis of asthma is essential.

  5. Smoking and asthma

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000504.htm Smoking and asthma To use the sharing features on ... your allergies or asthma worse are called triggers. Smoking is a trigger for many people who have ...

  6. Exercise-induced asthma

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000036.htm Exercise-induced asthma To use the sharing features on this page, ... such as running, basketball, or soccer. Use Your Asthma Medicine Before you Exercise Take your short-acting, ...

  7. Exercise-Induced Asthma

    Science.gov (United States)

    ... management of exercise-induced bronchoconstriction: A practice parameter. Annals of Allergy, Asthma & Immunology. 2010;105:S1. Krafczyk ... up exercise on exercise-induced bronchoconstriction. Medicine and Science in Sports and Exercise. 2012;44:383. Asthma ...

  8. Psychopathology in difficult asthma

    NARCIS (Netherlands)

    Prins, L.C.; van Son, M.J.M.; Keimpema, A.R.; van Ranst, D; Pommer, A; Meijer, J.W.; Pop, V.J.M.

    2015-01-01

    OBJECTIVE: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed

  9. Test Your Asthma Knowledge

    Science.gov (United States)

    ... narrowing of the bronchi. This can make breathing difficult, particularly expiration (exhaling) and can cause a feeling of tightness in the chest. Answer: D. All of these can make asthma worse. But some things that make asthma worse ...

  10. Allergies, asthma, and pollen

    Science.gov (United States)

    Reactive airway - pollen; Bronchial asthma - pollen; Triggers - pollen; Allergic rhinitis - pollen ... Things that make allergies or asthma worse are called triggers. It is important to know your triggers because avoiding them is your first step toward feeling better. ...

  11. Asthma - child - discharge

    Science.gov (United States)

    Pediatric asthma - discharge; Wheezing - discharge; Reactive airway disease - discharge ... Your child has asthma , which causes the airways of the lungs to swell and narrow. In the hospital, the doctors and nurses helped ...

  12. Psychopathology in difficult asthma

    NARCIS (Netherlands)

    Prins, L.C.; van Son, M.J.M.; Keimpema, A.R.; van Ranst, D; Pommer, A; Meijer, J.W.; Pop, V.J.M.

    2015-01-01

    OBJECTIVE: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed

  13. Common Asthma Triggers

    Science.gov (United States)

    ... Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Common Asthma Triggers Recommend on Facebook Tweet Share Compartir ... t avoid the triggers. Some of the most common triggers are: Tobacco Smoke Tobacco smoke is unhealthy ...

  14. Fatal asthma or anaphylaxis?

    OpenAIRE

    Rainbow, J; Browne, G

    2002-01-01

    The incidence of anaphylaxis is under-reported. Children with asthma are frequently atopic and prone to allergic reactions. Parents and clinicians may attribute wheeze of rapid onset to acute severe asthma, rather than recognising an anaphylactic event. Two cases of fatal anaphylaxis are reported who were initially diagnosed as acute severe asthma, and responded poorly to bronchodilator treatment. Survivors of "acute asphyxic asthma" should be screened for reactions to common allergens that p...

  15. Identifying asthma triggers.

    Science.gov (United States)

    McCarty, Justin C; Ferguson, Berrylin J

    2014-02-01

    Asthma has many triggers including rhinosinusitis; allergy; irritants; medications (aspirin in aspirin-exacerbated respiratory disease); and obesity. Paradoxic vocal fold dysfunction mimics asthma and may be present along with asthma. This article reviews each of these triggers, outlining methods of recognizing the trigger and then its management. In many patients more than one trigger may be present. Full appreciation of the complexity of these relationships and targeted therapy to the trigger is needed to best care for the patient with asthma.

  16. Genetics of asthma

    DEFF Research Database (Denmark)

    Thomsen, Simon F

    2015-01-01

    Asthma runs in families, and children of asthmatic parents are at increased risk of asthma. Prediction of disease risk is pivotal for the clinician when counselling atopic families. However, this is not always an easy task bearing in mind the vast and ever-increasing knowledge about asthma genetics...... of methods and advances in asthma genetics in an attempt to help the clinician keep track of the most important knowledge in the field....

  17. Antiasthmatic Effects of Eugenol in a Mouse Model of Allergic Asthma by Regulation of Vitamin D3 Upregulated Protein 1/NF-κB Pathway.

    Science.gov (United States)

    Pan, Chenglin; Dong, Zewu

    2015-08-01

    The aim of the study was to investigate the antiasthmatic effects of eugenol (EUG) and the possible mechanisms. Asthma model was established by ovalbumin induction. A total of 50 mice were randomly assigned to five experimental groups: control, OVA, OVA + dexamethasone (2 mg/kg), OVA + EUG (10 mg/kg), and OVA + EUG (20 mg/kg). Airway resistance (Raw) were measured, histological studies were evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and interleukin-5 (IL-5) were evaluated by enzyme-linked immunosorbent assay (ELISA), Vitamin D3 upregulated protein 1 (VDUP1), IκBα, P-IκBα, NF-κBP65, and p-NF-κBP65 were measured by Western blotting. Our study demonstrated that EUG inhibited OVA-induced increases in Raw and eosinophil count; IL-4 and IL-5 were recovered. Histological studies demonstrated that EUG substantially inhibited OVA-induced eosinophilia in the lung tissue. Western blotting studies demonstrated that EUG substantially inhibited P-IκBα, NF-κBP65, and p-NF-κBP65 protein levels and increased VDUP1 and IκBα protein levels. These findings suggest that EUG may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

  18. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  19. Low-intensity aerobic exercise training attenuates airway inflammation and remodeling in a rat model of steroid-resistant asthma

    Institute of Scientific and Technical Information of China (English)

    Qin Qingwu; Chen Xi; Feng Juntao; Qin Ling; Hu Chengping

    2014-01-01

    Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma (SSA).The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma (SRA) and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin (IL)-25,IL-33,thymic stromal lymphopoietin (TSLP),high mobility group box-1 (HMGB1),and IL-17 in bronchoalveolar lavage fluid (BALF),and the role of dexamethasone (DXM) were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation ((29.5±4.1)% of the total cell numbers in BALF),whereas SSA rats developed eosinophil-dominated airway inflammation ((24.0±6.1)% of the total cell numbers in BALF).Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 ((33.6±10.3) vs.(104.8±24.9) pg/ml),IL-33 ((87.5±25.0) vs.(226.6±40.7) pg/ml),and TSLP ((1 933.2±899.5) vs.(7 224.0±992.1) pg/ml),and higher levels of HMGB1 ((21.2±4.5) vs.(5.4±1.6) ng/ml) and IL-17 ((780.5±261.7) vs.(291.4±76.4) pg/ml) in BALF (all P <0.05).However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats

  20. Antifungals in severe asthma

    NARCIS (Netherlands)

    Parulekar, Amit D.; Diamant, Zuzana; Hanania, Nicola A.

    2015-01-01

    Purpose of review Despite guideline-based treatment, many patients with severe asthma continue to have uncontrolled disease. Fungal allergy is being increasingly recognized in the pathogenesis of severe asthma. Limited data exist on the approach to treatment of fungal asthma. This review summarizes

  1. Asthma and Pregnancy

    Science.gov (United States)

    ... in the airways of the lungs. When an asthma attack occurs, it is difficult for air to pass through the lungs which ... others have not. In these studies, it is difficult to determine whether the problems noted were due to the mother’s asthma, the medicines needed to control the asthma, or ...

  2. Severe asthma in children.

    Science.gov (United States)

    Guilbert, Theresa W; Bacharier, Leonard B; Fitzpatrick, Anne M

    2014-01-01

    Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of inhaled corticosteroids or oral corticosteroids. Children with severe asthma may fall into 2 categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, or poor adherence due to adverse psychological or environmental factors. In contrast, treatment resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline-based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting β-agonists and other add-on therapies, such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control, including reviewing the diagnosis and removing causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future.

  3. Pesticide Exposure and Asthma

    OpenAIRE

    Kurt, Burak; Akbaba, Muhsin

    2017-01-01

    Exposureto pesticides can trigger or exacerbate asthma, induce bronchospasm, orincrease bronchial hyperreactivity. Pesticides that inhibit cholinesterase canprovoke bronchospasm through increased cholinergic activity. At high doses,certain pesticides can act as airway irritants. Low levels that areinsufficient to cause acute poisoning can trigger severe reactions in thosewithout a previous diagnosis of asthma. Pesticides linked to asthma, wheezing,and hyperreactive airway disease include: 1. ...

  4. Allergy in severe asthma

    NARCIS (Netherlands)

    Del Giacco, Stefano R.; Bakirtas, A.; Bel, E.; Custovic, A.; Diamant, Z.; Hamelmann, E.; Heffler, E.; Kalayci, O.; Saglani, S.; Sergejeva, S.; Seys, S.; Simpson, A.; Bjermer, Leif

    2017-01-01

    It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-

  5. School and Asthma

    Science.gov (United States)

    ... What Happens in the Operating Room? School and Asthma KidsHealth > For Kids > School and Asthma A A A What's in this article? Have ... La escuela y el asma If you have asthma , you probably have a routine at home for ...

  6. Exercise-Induced Asthma

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Exercise-Induced Asthma KidsHealth > For Parents > Exercise-Induced Asthma A A ... previous continue Tips for Kids With Exercise-Induced Asthma For the most part, kids with exercise-induced ...

  7. Traveling and Asthma

    Science.gov (United States)

    ... What Happens in the Operating Room? Traveling and Asthma KidsHealth > For Kids > Traveling and Asthma A A A What's in this article? Pack ... Or how about sleepover camp? If you have asthma , you'll be packing more than your clothes ...

  8. Do Allergies Cause Asthma?

    Science.gov (United States)

    ... Happens in the Operating Room? Do Allergies Cause Asthma? KidsHealth > For Kids > Do Allergies Cause Asthma? A A A en español ¿Las alergias provocan ... kinds of allergies are more likely to have asthma. Do you have allergies that affect your nose ...

  9. Severe asthma in children

    Science.gov (United States)

    Guilbert, TW; Bacharier, LB; Fitzpatrick, AM

    2015-01-01

    Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of ICS or oral corticosteroids. Children with severe asthma may fall into two categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, poor adherence due to adverse psychological or environmental factors. In contrast, treatment-resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting beta-agonists and other add on therapies such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control including reviewing the diagnosis and the removal of causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future. PMID:25213041

  10. Obesity and asthma

    DEFF Research Database (Denmark)

    Ali, Zarqa; Ulrik, Charlotte Suppli

    2013-01-01

    Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed...... association between obesity and asthma....

  11. Management of asthma in pregnant women by general practitioners: A cross sectional survey

    Directory of Open Access Journals (Sweden)

    Abramson Michael J

    2011-11-01

    Full Text Available Abstract Background Poorly controlled asthma can lead to maternal and fetal complications. Despite the known risks of poorly controlled asthma during pregnancy and the need for stepping up therapy when appropriate, there are concerns that management is suboptimal in primary care. Our objective was to investigate the management of asthma during pregnancy by general practitioners providing shared maternity care. Methods A pre-piloted, anonymous mail survey was sent to all general practitioners (n = 842 involved in shared maternity care at six maternity hospitals in Victoria, Australia. Respondents were asked about their perceived safety of individual asthma medications during pregnancy. Approach to asthma management during pregnancy was further explored using scenarios of pregnant women with stable and deteriorating asthma and poor medication adherence. Results Inhaled corticosteroids (ICS were perceived to be the safest and were the preferred preventive medication in first trimester (74.1%, whilst leukotriene receptor antagonists were the least preferred (2.9%. A quarter (25.8% of respondents would stop or decrease patients' ICS doses during pregnancy, even when their asthma was well controlled by current therapy. In addition, 12.1% of respondents were not sure how to manage deteriorating asthma during pregnancy and opted to refer to another health professional. Almost half the respondents (48.9% reported encountering medication nonadherence during pregnancy. Conclusion A lack of confidence and/or knowledge among general practitioners in managing deteriorating asthma in pregnancy was observed despite a good understanding of the safety of asthma medications during pregnancy, compliance with evidence-based guidelines in the selection of preventive medications, and self reported good asthma knowledge.

  12. The experience of being an Asthma Amigo in a program to decrease asthma episodes in Hispanic children.

    Science.gov (United States)

    Lobar, Sandra; Brooten, Dorothy; Youngblut, JoAnne M; Hernandez, Laura; Herrera-Perdigon, Jennifer; Royal, Scott; Robins, Christine

    2008-10-01

    Asthma is the most common chronic illness among Latino children in urban areas. It is especially problematic for schools serving low-income and minority populations. The purpose of this study was to describe the experience of being an Asthma Amigo, a community-based educator who delivered asthma education to a Hispanic community in a train-the-trainer educational model. Focus group process evaluation was used to assess participant experiences and program strengths and weaknesses. Findings suggested that being an Asthma Amigo helped in gaining entrée into the community and in spreading the message of asthma triggers and prevention.

  13. LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction.

    Science.gov (United States)

    Chen, Xi; Li, Xiao-Ming; Gu, Wen; Wang, Di; Chen, Yi; Guo, Xue-Jun

    2017-03-01

    Low expression of linker for activation of T cells (LAT) is observed in asthma. LAT and its downstream regulator, phospholipase C-gamma 1 (PLC-γ1) play important roles in the T cell antigen receptor signaling pathway, and their interaction is associated with CD4(+) cell polarization. Here, we investigated whether LAT can alleviate the imbalance among CD4(+) cell subgroups and the possible mechanism. An ovalbumin-induced allergic asthma mouse model was established and LAT plasmid was delivered. The pathological changes in lung were evaluated by hematoxylin and eosin and periodic acid-Schiff staining. The typical cytokines released by T helper 2 (Th2) and regulatory T (Treg) cells were measured using enzyme-linked immunosorbent assay and the number of Th1, Th2, and Treg cells were determined using flow cytometry. Lung CD4(+) T cells were isolated by magnetic isolation. The mRNA expression of LAT and PLC-γ1 was determined by real-time PCR. Co-Immunoprecipitation was performed to confirm the interaction between LAT and PLC-γ1. The protein expression of LAT, PLC-γ1 and corresponding downstream signaling factors were determined by western blotting. The delivery of LAT DNA to the lung could suppress an overactive Th2 response by decreasing allergic response and Th2 cytokine secretion, and by increasing Treg cytokine secretion. The Th2/Treg imbalance in lung and decreased phosphorylated PLC-γ1 expression in lung CD4(+) T cells were rectified by LAT DNA delivery. Excessive activation of the Raf-MEK-ERK and PI3K-AKT-CREB pathways after asthma is attenuated by LAT. The site-specific delivery of LAT DNA to the lung could suppress an overactive Th2 response and rectify the Th2/Treg imbalance in asthmatic mouse model. LAT-PLC-γ1 interaction may contribute to LAT activity in vivo and LAT protects against asthma partly via Raf-MEK-ERK and PI3K-AKT-CREB pathways. The delivery of LAT DNA could offer a novel and safe strategy for asthma prevention. Copyright © 2016 Elsevier B

  14. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    Science.gov (United States)

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Suboptimal care and maternal mortality among foreign-born women in Sweden: maternal death audit with application of the 'migration three delays' model.

    Science.gov (United States)

    Esscher, Annika; Binder-Finnema, Pauline; Bødker, Birgit; Högberg, Ulf; Mulic-Lutvica, Ajlana; Essén, Birgitta

    2014-04-12

    Several European countries report differences in risk of maternal mortality between immigrants from low- and middle-income countries and host country women. The present study identified suboptimal factors related to care-seeking, accessibility, and quality of care for maternal deaths that occurred in Sweden from 1988-2010. A subset of maternal death records (n = 75) among foreign-born women from low- and middle-income countries and Swedish-born women were audited using structured implicit review. One case of foreign-born maternal death was matched with two native born Swedish cases of maternal death. An assessment protocol was developed that applied both the 'migration three delays' framework and a modified version of the Confidential Enquiry from the United Kingdom. The main outcomes were major and minor suboptimal factors associated with maternal death in this high-income, low-maternal mortality context. Major and minor suboptimal factors were associated with a majority of maternal deaths and significantly more often to foreign-born women (p = 0.01). The main delays to care-seeking were non-compliance among foreign-born women and communication barriers, such as incongruent language and suboptimal interpreter system or usage. Inadequate care occurred more often among the foreign-born (p = 0.04), whereas delays in consultation/referral and miscommunication between health care providers where equally common between the two groups. Suboptimal care factors, major and minor, were present in more than 2/3 of maternal deaths in this high-income setting. Those related to migration were associated to miscommunication, lack of professional interpreters, and limited knowledge about rare diseases and pregnancy complications. Increased insight into a migration perspective is advocated for maternity clinicians who provide care to foreign-born women.

  16. Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model.

    Science.gov (United States)

    Hassiakos, D; Eleftheriades, M; Papastefanou, I; Lambrinoudaki, I; Kappou, D; Lavranos, D; Akalestos, A; Aravantinos, L; Pervanidou, P; Chrousos, G

    2016-01-01

    The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, poral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

  17. Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

    Science.gov (United States)

    De la Fuente, M; Llorente, R; Baeza, I; De Castro, N M; Arranz, L; Cruces, J; Viveros, M P

    2009-02-01

    Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

  18. Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring

    Directory of Open Access Journals (Sweden)

    Clare M. Reynolds

    2017-09-01

    Full Text Available Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut–brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

  19. Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

    Science.gov (United States)

    Ruskin, David N.; Murphy, Michelle I.; Slade, Sierra L.; Masino, Susan A.

    2017-01-01

    Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD. PMID:28166277

  20. Obesity and asthma.

    Science.gov (United States)

    Gibson, Peter G

    2013-12-01

    There is a global epidemic of asthma and obesity that is concentrated in Westernized and developed countries. A causal association in some people with asthma is suggested by observations that obesity precedes the onset of asthma and that bariatric surgery for morbid obesity can resolve asthma. The obese asthma phenotype features poor asthma control, limited response to corticosteroids, and an exaggeration of the physiological effects of obesity on lung function, which includes a reduction in expiratory reserve volume and airway closure occurring during tidal breathing. Obesity has important implications for asthma treatment. Increasing corticosteroid doses based on poor asthma control, as currently recommended in guidelines, may lead to overtreatment with corticosteroids in obese asthma. Enhanced bronchodilation, particularly of the small airways, may reduce the component of airway closure due to increased bronchomotor tone and suggests that greater emphasis should be placed on long-acting bronchodilators in obese asthma. The societal implications of this are important: with increasing obesity there will be increasing asthma from obesity, and the need to identify successful individual and societal weight-control strategies becomes a key goal.

  1. [Cytokines and asthma].

    Science.gov (United States)

    Gani, F; Senna, G; Piglia, P; Grosso, B; Mezzelani, P; Pozzi, E

    1998-10-01

    Asthma is a chronic inflammatory lung disease in which eosinophils are one of the most important involved cells. These cells accumulate in the lung because of cytokines, which are able to regulate cellular responses. The role of cytokines is well known in allergic asthma: IL4, IL5, IL3, GMCSF are the principally cytokine involved. IL4 regulate IgE synthesis while IL5, (and IL3) cause the activation and accumulation of eosinophils. In non allergic asthma, whilst only IL5 seemed to be important recent data, shows that also IL4 plays an important role. Therefore nowadays no relevant difference seems to exist between allergic and non allergic asthma; instead the primer is different: the allergen in allergic asthma and often an unknown factor in the non allergic asthma. Recently other cytokines have been proved to play a role in the pathogenesis of asthma. IL8 is chemotactic not only for neutrophils but also for eosinophils and might cause chronic inflammation in severe asthma. IL13 works like IL4, while RANTES seems to be a more important chemotactic agent than IL5. Finally IL10, which immunoregulates T lymphocyte responses, may reduce asthma inflammation. In conclusion cytokine made us to learn more about the pathogenesis of asthma even if we do not yet know when and how asthma inflammation develops.

  2. Guideline-defining asthma clinical trials of the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network.

    Science.gov (United States)

    Denlinger, Loren C; Sorkness, Christine A; Chinchilli, Vernon M; Lemanske, Robert F

    2007-01-01

    Because of an increasing prevalence, morbidity, and mortality associated with asthma, the National Heart, Lung, and Blood Institute created the Asthma Clinical Research Network and the Childhood Asthma Research and Education Network to improve public health. The objectives of these clinical research networks are to conduct multiple, well-designed clinical trials for rapid evaluation of new and existing therapeutic approaches to asthma and to disseminate laboratory and clinical findings to the health care community. These trials comprise a large proportion of the data driving the treatment guidelines established and reviewed by the National Asthma Education and Prevention Program. This article will review the basic design and major findings of selected Asthma Clinical Research Network and Childhood Asthma Research and Education Network trials involving both adults and children with asthma. Collectively, these studies have helped refine the therapeutic role of existing controller medications, establish standard models for side-effect evaluation and risk-benefit models, validate symptom-based assessments for asthma control, and identify baseline characteristics that might predict individual patient responses. Remaining challenges include shaping the role of novel therapeutics in future guidelines, incorporating pharmacogenomic data in treatment decisions, and establishing better implementation strategies for translation to community settings, all with the goal of reducing the asthma burden on society.

  3. Vitamin A deficiency decreases and high dietary vitamin A increases disease severity in the mouse model of asthma

    Science.gov (United States)

    The Th1/ Th2 paradigm has become an important issue in the pathogenesis of asthma, characterized by normal Th-1 and elevated Th-2 cytokine expression, resulting in a Th2 predominance. Vitamin A deficiency (VAD) produces a significant Th1 bias, while high-level dietary vitamin A supplementation promo...

  4. Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma

    NARCIS (Netherlands)

    R.G.J. Klein Wolterink (Roel); A. Kleinjan (Alex); M. van Nimwegen (Menno); I.M. Bergen (Ingrid); M.J.W. de Bruijn (Marjolein); Y. Levani (Yelvi); R.W. Hendriks (Rudi)

    2012-01-01

    textabstractAllergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune resp-onse. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of

  5. PRESSURE-VOLUME ANALYSIS OF THE LUNG WITH AN EXPONENTIAL AND LINEAR-EXPONENTIAL MODEL IN ASTHMA AND COPD

    NARCIS (Netherlands)

    BOGAARD, JM; OVERBEEK, SE; VERBRAAK, AFM; VONS, C; FOLGERING, HTM; VANDERMARK, TW; ROOS, CM; STERK, PJ

    1995-01-01

    The prevalence of abnormalities in lung elasticity in patients with asthma or chronic obstructive pulmonary disease (COPD) is still unclear, This might be due to uncertainties concerning the method of analysis of quasistatic deflation long pressure-volume curves. Pressure-volume curves were obtained

  6. Obesity and asthma

    DEFF Research Database (Denmark)

    Sivapalan, Pradeesh; Diamant, Zuzana; Ulrik, Charlotte Suppli

    2015-01-01

    PURPOSE OF REVIEW: Obesity has significant impact on asthma incidence and manifestations. The purpose of the review is to discuss recent observations regarding the association between obesity and asthma focusing on underlying mechanisms, clinical presentation, response to therapy and effect...... of weight reduction. RECENT FINDINGS: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities...... have been linked to both obesity and asthma, and may, therefore, contribute to the obese-asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma. SUMMARY: Compared with normal-weight patients, obese...

  7. Epigenetics of asthma.

    Science.gov (United States)

    Durham, Andrew L; Wiegman, Coen; Adcock, Ian M

    2011-11-01

    Asthma is caused by both heritable and environmental factors. It has become clear that genetic studies do not adequately explain the heritability and susceptibility to asthma. The study of epigenetics, heritable non-coding changes to DNA may help to explain the heritable component of asthma. Additionally, epigenetic modifications can be influenced by the environment, including pollution and cigarette smoking, which are known asthma risk factors. These environmental trigger-induced epigenetic changes may be involved in skewing the immune system towards a Th2 phenotype following in utero exposure and thereby enhancing the risk of asthma. Alternatively, they may directly or indirectly modulate the immune and inflammatory processes in asthmatics via effects on treatment responsiveness. The study of epigenetics may therefore play an important role in our understanding and possible treatment of asthma and other allergic diseases. This article is part of a Special Issue entitled: Biochemistry of Asthma.

  8. Job strain and the risk of severe asthma exacerbations

    DEFF Research Database (Denmark)

    Heikkilä, K; Madsen, I E H; Nyberg, S T;

    2014-01-01

    BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations...... asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years......, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95...

  9. Effect of High Fat Dietary Intake during Maternal Gestation on Offspring Ovarian Health in a Pig Model

    Science.gov (United States)

    Xu, Mengmeng; Che, Long; Yang, Zhenguo; Zhang, Pan; Shi, Jiankai; Li, Jian; Lin, Yan; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De; Xu, Shengyu

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest a high fat diet. We therefore determined the association of a maternal high fat diet in pregnancy with offspring ovarian health during the gestation and postnatal female offspring in pig a model. Thirty-two Yorkshire gilts with similar bodyweights mated at the third estrus were randomly assigned to two nutrition levels of either a control (CON, crude fat: 7.27%) or a high fat diet (HFD, crude fat: 11.78%). Ovary samples were collected during the fetal (Day 55 (g55) and Day 90 of gestation (g90)) and offspring (prepuberty Day 160 (d160) and age at puberty) period to detect ovary development, antioxidant status and apoptosis cells. Maternal HFD did not influence notch signaling gene expression, which regulates primordial follicle formation and transformation, and ovarian histological effect at g55 and g90. However, maternal HFD reduced the numbers of large follicles at d160 and small follicle numbers upon puberty compared to CON in offspring. The results also revealed that the antioxidant index of total antioxidative capability (T-AOC), cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPx) activities and mRNA expression were higher in the CON than the HFD at g90 and d160, whereas, malondialdehyde (MDA) concentration was decreased in the CON. Maternal HFD increased the inhibitor of the apoptosis-related gene of B-cell lymphoma-2 (bcl2) mRNA expression at g90 and d160, whereas, pro-apoptotic-related gene bcl-2 assaciated X protein (bax) was reduced. These data show that the maternal high fat diet does not delay fetal ovarian development, but it changes ovarian health by the induction of oxidative stress and accelerating cell apoptosis in offspring. PMID:27529279

  10. Effect of High Fat Dietary Intake during Maternal Gestation on Offspring Ovarian Health in a Pig Model

    Directory of Open Access Journals (Sweden)

    Mengmeng Xu

    2016-08-01

    Full Text Available Excessive fat intake is a global health concern as women of childbearing age increasingly ingest a high fat diet. We therefore determined the association of a maternal high fat diet in pregnancy with offspring ovarian health during the gestation and postnatal female offspring in pig a model. Thirty-two Yorkshire gilts with similar bodyweights mated at the third estrus were randomly assigned to two nutrition levels of either a control (CON, crude fat: 7.27% or a high fat diet (HFD, crude fat: 11.78%. Ovary samples were collected during the fetal (Day 55 (g55 and Day 90 of gestation (g90 and offspring (prepuberty Day 160 (d160 and age at puberty period to detect ovary development, antioxidant status and apoptosis cells. Maternal HFD did not influence notch signaling gene expression, which regulates primordial follicle formation and transformation, and ovarian histological effect at g55 and g90. However, maternal HFD reduced the numbers of large follicles at d160 and small follicle numbers upon puberty compared to CON in offspring. The results also revealed that the antioxidant index of total antioxidative capability (T-AOC, cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, glutathione peroxidase (GPx activities and mRNA expression were higher in the CON than the HFD at g90 and d160, whereas, malondialdehyde (MDA concentration was decreased in the CON. Maternal HFD increased the inhibitor of the apoptosis-related gene of B-cell lymphoma-2 (bcl2 mRNA expression at g90 and d160, whereas, pro-apoptotic-related gene bcl-2 assaciated X protein (bax was reduced. These data show that the maternal high fat diet does not delay fetal ovarian development, but it changes ovarian health by the induction of oxidative stress and accelerating cell apoptosis in offspring.

  11. Effect of High Fat Dietary Intake during Maternal Gestation on Offspring Ovarian Health in a Pig Model.

    Science.gov (United States)

    Xu, Mengmeng; Che, Long; Yang, Zhenguo; Zhang, Pan; Shi, Jiankai; Li, Jian; Lin, Yan; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De; Xu, Shengyu

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest a high fat diet. We therefore determined the association of a maternal high fat diet in pregnancy with offspring ovarian health during the gestation and postnatal female offspring in pig a model. Thirty-two Yorkshire gilts with similar bodyweights mated at the third estrus were randomly assigned to two nutrition levels of either a control (CON, crude fat: 7.27%) or a high fat diet (HFD, crude fat: 11.78%). Ovary samples were collected during the fetal (Day 55 (g55) and Day 90 of gestation (g90)) and offspring (prepuberty Day 160 (d160) and age at puberty) period to detect ovary development, antioxidant status and apoptosis cells. Maternal HFD did not influence notch signaling gene expression, which regulates primordial follicle formation and transformation, and ovarian histological effect at g55 and g90. However, maternal HFD reduced the numbers of large follicles at d160 and small follicle numbers upon puberty compared to CON in offspring. The results also revealed that the antioxidant index of total antioxidative capability (T-AOC), cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPx) activities and mRNA expression were higher in the CON than the HFD at g90 and d160, whereas, malondialdehyde (MDA) concentration was decreased in the CON. Maternal HFD increased the inhibitor of the apoptosis-related gene of B-cell lymphoma-2 (bcl2) mRNA expression at g90 and d160, whereas, pro-apoptotic-related gene bcl-2 assaciated X protein (bax) was reduced. These data show that the maternal high fat diet does not delay fetal ovarian development, but it changes ovarian health by the induction of oxidative stress and accelerating cell apoptosis in offspring.

  12. Relationship between women's characteristics and continuum of care for maternal health in Kenya: Complex survey analysis using structural equation modeling.

    Science.gov (United States)

    Owili, Patrick Opiyo; Muga, Miriam Adoyo; Chou, Yiing-Jenq; Hsu, Yi-Hsin Elsa; Huang, Nicole; Chien, Li-Yin

    2016-08-11

    The objective of this study was to understand and estimate the complex relationships in the continuum of care for maternal health to provide information to improve maternal and newborn health outcomes. Women (n = 4,082) aged 15-49 years in the 2008/2009 Kenya Demographic and Health Survey data were used to explore the complex relationships in the continuum of care for maternal health (i.e., before, during, and after delivery) using structural equation modeling. Results showed that the use of antenatal care was significantly positively related to the use of delivery care (β = 0.06; adjusted odds ratio [AOR] = 1.06; 95% confidence interval [CI]: 1.02-1.10) but not postnatal care, while delivery care was associated with postnatal care (β = 0.68; AOR = 1.97; 95% CI: 1.75-2.22). Socioeconomic status was significantly related to all elements in the continuum of care for maternal health; barriers to delivery of care and personal characteristics were only associated with the use of delivery care (β = 0.34; AOR = 1.40; 95% CI: 1.30-1.52) and postnatal care (β = 0.03; AOR = 1.03; 95% CI: 1.01-1.05), respectively. The three periods of maternal health care were related to each other. Developing a referral system of continuity of care is critical in the Sustainable Development Goals era.

  13. 1,25-Dihydroxyvitamin D3 pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model

    Institute of Scientific and Technical Information of China (English)

    MA Jian-xin; XIA Jun-bo; CHENG Xiao-ming; WANG Chang-zheng

    2010-01-01

    Background Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25(OH)2D3 pretreatment for immunotherapy.Methods Seventy-five BALB/c mice were randomly divided into five groups (15 mice per group). The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin (OVA, 10 μg) and aluminium hydroxide (2 mg)as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25(OH)2D3 served as a pretreatment, subcutaneous injection of OVA (100 μg) as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage (BAL) fluid were assayed.Levels of serum OVA-specific immunoglobulin E (slgE) and IFN-Y, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA.Results After 1,25(OH)2D3 pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals (eosinophils:(7.46±1.34)×104/ml vs. (13.41±1.67)×104/ml, P <0.05). In addition, levels of IL-4 ((36.g1±7.87) pg/ml vs. (43.70±6.42)pg/ml, P >0.05) and IL-5 ((41.97±7.93) pg/ml vs. (60.14±8.35) pg/ml, P <0.05) in BAL fluid and serum slgE ((0.42±0.05)vs. (0.75±0.06) OD units, P <0.05) were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased ((67.74±6.57) pg/ml vs. (44.62±8.81) pg/ml, P <0.05).Conclusions These results indicated that 1,25(OH)2D3 pretreatment enhanced the inhibitory effects of immunotherapy on allergic

  14. A statistical model for estimating maternal-zygotic interactions and parent-of-origin effects of QTLs for seed development.

    Directory of Open Access Journals (Sweden)

    Yanchun Li

    Full Text Available Proper development of a seed requires coordinated exchanges of signals among the three components that develop side by side in the seed. One of these is the maternal integument that encloses the other two zygotic components, i.e., the diploid embryo and its nurturing annex, the triploid endosperm. Although the formation of the embryo and endosperm contains the contributions of both maternal and paternal parents, maternally and paternally derived alleles may be expressed differently, leading to a so-called parent-of-origin or imprinting effect. Currently, the nature of how genes from the maternal and zygotic genomes interact to affect seed development remains largely unknown. Here, we present a novel statistical model for estimating the main and interaction effects of quantitative trait loci (QTLs that are derived from different genomes and further testing the imprinting effects of these QTLs on seed development. The experimental design used is based on reciprocal backcrosses toward both parents, so that the inheritance of parent-specific alleles could be traced. The computing model and algorithm were implemented with the maximum likelihood approach. The new strategy presented was applied to study the mode of inheritance for QTLs that control endoreduplication traits in maize endosperm. Monte Carlo simulation studies were performed to investigate the statistical properties of the new model with the data simulated under different imprinting degrees. The false positive rate of imprinting QTL discovery by the model was examined by analyzing the simulated data that contain no imprinting QTL. The reciprocal design and a series of analytical and testing strategies proposed provide a standard procedure for genomic mapping of QTLs involved in the genetic control of complex seed development traits in flowering plants.

  15. MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.

    Directory of Open Access Journals (Sweden)

    Nancy Garbacki

    Full Text Available BACKGROUND: miRNAs are now recognized as key regulator elements in gene expression. Although they have been associated with a number of human diseases, their implication in acute and chronic asthma and their association with lung remodelling have never been thoroughly investigated. METHODOLOGY/PRINCIPAL FINDINGS: In order to establish a miRNAs expression profile in lung tissue, mice were sensitized and challenged with ovalbumin mimicking acute, intermediate and chronic human asthma. Levels of lung miRNAs were profiled by microarray and in silico analyses were performed to identify potential mRNA targets and to point out signalling pathways and biological processes regulated by miRNA-dependent mechanisms. Fifty-eight, 66 and 75 miRNAs were found to be significantly modulated at short-, intermediate- and long-term challenge, respectively. Inverse correlation with the expression of potential mRNA targets identified mmu-miR-146b, -223, -29b, -29c, -483, -574-5p, -672 and -690 as the best candidates for an active implication in asthma pathogenesis. A functional validation assay was performed by cotransfecting in human lung fibroblasts (WI26 synthetic miRNAs and engineered expression constructs containing the coding sequence of luciferase upstream of the 3'UTR of various potential mRNA targets. The bioinformatics analysis identified miRNA-linked regulation of several signalling pathways, as matrix metalloproteinases, inflammatory response and TGF-β signalling, and biological processes, including apoptosis and inflammation. CONCLUSIONS/SIGNIFICANCE: This study highlights that specific miRNAs are likely to be involved in asthma disease and could represent a valuable resource both for biological makers identification and for unveiling mechanisms underlying the pathogenesis of asthma.

  16. [Association between unplanned pregnancy and adolescence onset asthma].

    Science.gov (United States)

    Vázquez-Nava, Francisco; Gil-Lara, Bertoldo; Cruz-Torres, Leoncio; Vázquez-Rodríguez, Carlos F; Vázquez-Rodríguez, Eliza M; Felizardo-Ávalos, Jorge; Llanes-Castillo, Arturo; Córdova-Fernández, José A

    2013-01-01

    The association between asthma and pregnancy has been documented previously. The relationship between unplanned pregnancy and onset asthma in adolescence has not been studied. To determine the association between unplanned pregnancy and adolescence onset asthma. A cross-sectional study was done gathering information about asthma, unplanned pregnancy, family atopy and active or passive smoking in 3,130 adolescents aged 13-19 years. Asthma diagnosis was established through a selfquestionnaire based on the International Study of Asthma and Allergy in Childhood. Odds ratios for asthma were determined using logistic regression model and chi-squared test. Mean age of the participants was 16.37 ± 1.93 years. The prevalence of active smoking was 16.1%, of passive smoking 40% and of family atopy 9.8%. From the pregnant adolescents (785), 59.5% reported had planned not to have a child before pregnancy. Prevalence of wheezing during the year prior to the study was 9.3% and of wheezing during the pregnancy 2%. The prevalence of adolescence onset asthma was 5.4%. The age of initiation of asthma in the adolescence was 14.75 ± 1.60 years. The analysis showed that unplanned pregnancy has a slight risk for the development of asthma during adolescence. (Crude OR=1.03; CI 95% 1.02-1.05; p=0.000). Unplanned pregnancy, family atopy, active smoking and smoking friends are associated with the onset-asthma in the adolescence.

  17. S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress.

    Science.gov (United States)

    Yoon, Sun-Young; Hong, Gyong Hwa; Kwon, Hyouk-Soo; Park, Sunjoo; Park, So Young; Shin, Bomi; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2016-06-03

    Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

  18. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    Science.gov (United States)

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  19. [Epigenetics in allergic diseases and asthma].

    Science.gov (United States)

    Castro-Rodríguez, José A; Krause, Bernardo J; Uauy, Ricardo; Casanello, Paola

    2016-01-01

    Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Effects of Radix Adenophorae and Cyclosporine A on an OVA-Induced Murine Model of Asthma by Suppressing to T Cells Activity, Eosinophilia, and Bronchial Hyperresponsiveness

    Directory of Open Access Journals (Sweden)

    Seong-Soo Roh

    2008-01-01

    Full Text Available The present study is performed to investigate the inhibitory effects of Radix Adenophorae extract (RAE on ovalbumin-induced asthma murine model. To study the anti-inflammatory and antiasthmatic effects of RAE, we examined the development of pulmonary eosinophilic inflammation and inhibitory effects of T cells in murine by RAE and cyclosporine A (CsA. We examined determination of airway hyperresponsiveness, flow cytometric analysis (FACS, enzyme-linked immunosorbent assay (ELISA, quantitative real time (PCR, hematoxylin-eosin staining, and Masson trichrome staining in lung tissue, lung weight, total cells, and eosinophil numbers in lung tissue. We demonstrated how RAE suppressed development on inflammation and decreased airway damage.

  1. Uncontrolled asthma and its risk factors in Chinese children: A cross-sectional observational study.

    Science.gov (United States)

    Xiang, Li; Zhao, Jing; Zheng, Yuejie; Liu, Hanmin; Hong, Jianguo; Bao, Yixiao; Chen, Aihuan; Deng, Li; Ji, Wei; Zhong, Nanshan; Shen, Kunling

    2016-09-01

    Asthma afflicts many children in China but information about asthma management among Chinese pediatric asthma patients is limited. This study aims to evaluate asthma control among Chinese pediatric patients and identify risk factors associated with uncontrolled asthma. A total of 4223 patients with persistent asthma aged 2-16 years from 42 tertiary hospitals across all regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA) criteria were used to assess asthma control for children aged 12-16 years, 4-11 years and 2-3 years, respectively. Uncontrolled asthma was defined as ACT or C-ACT score ≤19 or GINA-defined uncontrolled asthma. Risk factors associated with uncontrolled asthma were identified using multivariate logistic regression models. Asthma was uncontrolled in 19.9% of the subjects. High rates of uncontrolled asthma were found in subjects with treatment non-adherence (44.1%), concomitant allergic rhinitis (AR) (23.3%), disease duration ≥ 1.5 years (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled asthma was much higher in the treatment non-adherence group compared to the complete adherence group (OR = 5.79, p asthma. About 20% of Chinese pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR were the most significant risk factors. Tailored measures aimed at improving treatment adherence and diagnosis and treatment of AR should be adopted to improve the level of asthma control in Chinese children.

  2. Potential of PEGylated Toll-Like Receptor 7 Ligands for Controlling Inflammation and Functional Changes in Mouse Models of Asthma and Silicosis.

    Science.gov (United States)

    Ferreira, Tatiana Paula Teixeira; Mariano, Lívia Lacerda; Ghilosso-Bortolini, Roberta; de Arantes, Ana Carolina Santos; Fernandes, Andrey Junior; Berni, Michelle; Cecchinato, Valentina; Uguccioni, Mariagrazia; Maj, Roberto; Barberis, Alcide; Silva, Patricia Machado Rodrigues E; Martins, Marco Aurélio

    2016-01-01

    Prior investigations show that signaling activation through pattern recognition receptors can directly impact a number of inflammatory lung diseases. While toll-like receptor (TLR) 7 agonists have raised interest for their ability to inhibit allergen-induced pathological changes in experimental asthma conditions, the putative benefit of this treatment is limited by adverse effects. Our aim was to evaluate the therapeutic potential of two PEGylated purine-like compounds, TMX-302 and TMX-306, characterized by TLR7 partial agonistic activity; therefore, the compounds are expected to induce lower local and systemic adverse reactions. In vitro approaches and translation to murine models of obstructive and restrictive lung diseases were explored. In vitro studies with human PBMCs showed that both TMX-302 and TMX-306 marginally affects cytokine production as compared with equivalent concentrations of the TLR7 full agonist, TMX-202. The PEGylated compounds did not induce monocyte-derived DC maturation or B cell proliferation, differently from what observed after stimulation with TMX-202. Impact of PEGylated ligands on lung function and inflammatory changes was studied in animal models of acute lung injury, asthma, and silicosis following Lipopolysaccharide (LPS), allergen (ovalbumin), and silica inhalation, respectively. Subcutaneous injection of TMX-302 prevented LPS- and allergen-induced airway hyper-reactivity (AHR), leukocyte infiltration, and production of pro-inflammatory cytokines in the lung. However, intranasal instillation of TMX-302 led to neutrophil infiltration and failed to prevent allergen-induced AHR, despite inhibiting leukocyte counts in the BAL. Aerosolized TMX-306 given prophylactically, but not therapeutically, inhibited pivotal asthma features. Interventional treatment with intranasal instillation of TMX-306 significantly reduced the pulmonary fibrogranulomatous response and the number of silica particles in lung interstitial space in silicotic mice

  3. Oxidative and nitrosative events in asthma.

    Science.gov (United States)

    Andreadis, Athena A; Hazen, Stanley L; Comhair, Suzy A A; Erzurum, Serpil C

    2003-08-01

    Asthma affects over 15 million individuals in the United States, with over 1.5 million emergency room visits, 500,000 hospitalizations, and 5500 deaths each year, many of which are children. Airway inflammation is the proximate cause of the recurrent episodes of airflow limitation in asthma. Research applying molecular biology, chemistry, and cell biology to human asthma and model systems of asthma over the last decade has revealed that numerous biologically active proinflammatory mediators lead to increased production of reactive oxygen species (ROS) and the gaseous molecule nitric oxide (NO). Persistently increased ROS and NO in asthma lead to reactive nitrogen species (RNS) formation and subsequent oxidation and nitration of proteins, which may cause alterations in protein function that are biologically relevant to airway injury/inflammation. Eosinophil peroxidase and myeloperoxidase, leukocyte-derived enzymes, amplify oxidative events and are another enzymatic source of NO-derived oxidants and nitrotyrosine formation in asthma. Concomitant with increased generation of oxidative and nitrosative molecules in asthma, loss of protective antioxidant defense, specifically superoxide dismutase (SOD), contributes to the overall toxic environment of the asthmatic airway. This review discusses the rapidly accruing data linking oxidative and nitrosative events as critical participants in the acute and chronic inflammation of asthmatic airways.

  4. Preeclampsia Associates with Asthma, Allergy, and Eczema in Childhood

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Sevelsted, Astrid; Anderson, Ulrik D

    2017-01-01

    .55 to -0.06]; P = 0.0348), and allergic rhinitis (adjusted odds ratio, 4.83 [95% CI, 1.58-14.78]; P = 0.0057) in the 7-year-old children. Furthermore, the children had an increased risk of sensitization to both aeroallergens and food allergens, and increased amount of total IgE during childhood......RATIONALE: Preeclampsia reflects an unusual increase in systemic inflammation during pregnancy. OBJECTIVES: We studied associations between preeclampsia and asthma, allergy, and eczema in Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) and in national registries. METHODS....... In the registry-based cohort, 3.7% (n = 62,728) were born to mothers with preeclampsia. Preeclampsia was associated with increased risk of asthma, eczema, and aeroallergen and food allergy, especially pronounced after a duration of preeclampsia of 14 days or more. Maternal asthma increased the risk...

  5. Risk factors for asthma among children in Maputo (Mozambique).

    Science.gov (United States)

    Mavale-Manuel, S; Alexandre, F; Duarte, N; Albuquerque, O; Scheinmann, P; Poisson-Salomon, A S; de Blic, J

    2004-04-01

    Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique). This case-control study included 199 age-matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast-feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child. The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P history of asthma (OR = 26.8, CI = 10.8-68.2, P history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.

  6. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Science.gov (United States)

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  7. An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma

    Science.gov (United States)

    Xu, Huixin; Jiang, Haojun; Xie, Weiwei; Chen, Fang; Zeng, Peng; Li, Xuchao; Xie, Yifan; Liu, Hongtai; Huang, Guodong; Chen, Dayang; Liu, Ping; Jiang, Hui; Zhang, Xiuqing

    2016-01-01

    Background With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses. Methods In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%. Results Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome. PMID:27662469

  8. Maternal prepregnancy obesity is an independent risk factor for frequent wheezing in infants by age 14 months.

    Science.gov (United States)

    Guerra, Stefano; Sartini, Claudio; Mendez, Michelle; Morales, Eva; Guxens, Mònica; Basterrechea, Mikel; Arranz, Leonor; Sunyer, Jordi

    2013-01-01

    Maternal prepregnancy obesity has been linked to the offspring's risk for subsequent asthma. We determined whether maternal obesity is associated with increased risk of wheezing phenotypes early in life. We used data on 1107 mother-child pairs from two birth cohorts from the INMA-INfancia y Medio Ambiente project. Maternal height was measured and prepregnancy weight self-reported at enrolment (on average at 13.7 ± 2 weeks of gestation). Maternal prepregnancy body mass index was categorised as underweight, normal, overweight and obese according to WHO recommendations. Information on child's wheezing was obtained through questionnaires up to the age of 14 (± 1) months. Wheezing was classified as infrequent (<4 reported wheezing episodes) or frequent (≥ 4 episodes). Weight and length of infants were measured by trained study staff at 14.6 (± 1) months of age and weight-for-length z-scores computed. Although maternal obesity did not increase the risk of the child to have any or infrequent wheezing, children of obese mothers were more likely to have frequent wheezing than children of normal-weight mothers (11.8% vs. 3.8%; P = 0.002). In fully adjusted multinomial logistic regression models, including infants' weight-for-length z-scores and other covariates, maternal prepregnancy obesity was associated with increased risk of frequent [adjusted relative risk (RR) 4.18, 95% confidence interval (CI) 1.55, 11.3] but not infrequent (RR 1.05 [95% CI 0.55, 2.01]) wheezing in their children. Maternal prepregnancy obesity is independently associated with an increased risk of frequent wheezing in the infant by the age of 14 months. These findings add evidence on the potential effects of in utero exposures on asthma-related phenotypes. © 2012 Blackwell Publishing Ltd.

  9. Race and asthma control in the pediatric population of Hawaii.

    Science.gov (United States)

    Wu, Brian H; Cabana, Michael D; Hilton, Joan F; Ly, Ngoc P

    2011-05-01

    The racially unique population of Hawaii has one of the highest prevalences of childhood asthma in America. We estimate the prevalence of impaired asthma control among asthmatic children in Hawaii and determine which factors are associated with impaired control. We analyzed data from 477 asthmatic children living in Hawaii participating in the 2006-2008 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Surveys. Impaired asthma control was modeled after 2007 National Asthma Education and Prevention Program guidelines. Univariate and multivariate analyses were used to identify factors associated with impaired asthma control. Children (53.8%) with asthma were either part or full Native Hawaiian/Pacific Islander. While 35.6% of asthmatic children met criteria for impaired asthma control, being part or full Native Hawaiian/Pacific Islander was not associated with impaired control. Only 31.1% of children with impaired control reported the use of inhaled corticosteroids despite >80% having had a routine checkup for asthma in the past year and receipt of asthma education from a healthcare provider. A large proportion of asthmatic children in Hawaii have impaired asthma control that does not appear to be associated with race but may be associated with inadequate pharmacologic therapy. While a significant percentage reported receiving routine asthma care and asthma education, a minority reported using inhaled corticosteroids. Reasons for this discrepancy between asthma assessment and treatment are unclear. However, additional education on part of the physician, community, and healthcare system are likely to improve management and reduce morbidity in this population. Copyright © 2010 Wiley-Liss, Inc.

  10. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heidi Marjonen

    Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in

  11. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I ...

  12. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I ...

  13. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I ...

  14. Revealing the burden of maternal mortality: a probabilistic model for determining pregnancy-related causes of death from verbal autopsies

    Directory of Open Access Journals (Sweden)

    Desta Teklay

    2007-02-01

    Full Text Available Abstract Background Substantial reductions in maternal mortality are called for in Millennium Development Goal 5 (MDG-5, thus assuming that maternal mortality is measurable. A key difficulty is attributing causes of death for the many women who die unaided in developing countries. Verbal autopsy (VA can elicit circumstances of death, but data need to be interpreted reliably and consistently to serve as global indicators. Recent developments in probabilistic modelling of VA interpretation are adapted and assessed here for the specific circumstances of pregnancy-related death. Methods A preliminary version of the InterVA-M probabilistic VA interpretation model was developed and refined with adult female VA data from several sources, and then assessed against 258 additional VA interviews from Burkina Faso. Likely causes of death produced by the model were compared with causes previously determined by local physicians. Distinction was made between free-text and closed-question data in the VA interviews, to assess the added value of free-text material on the model's output. Results Following rationalisation between the model and physician interpretations, cause-specific mortality fractions were broadly similar. Case-by-case agreement between the model and any of the reviewing physicians reached approximately 60%, rising to approximately 80% when cases with a discrepancy were reviewed by an additional physician. Cardiovascular disease and malaria showed the largest differences between the methods, and the attribution of infections related to pregnancy also varied. The model estimated 30% of deaths to be pregnancy-related, of which half were due to direct causes. Data derived from free-text made no appreciable difference. Conclusion InterVA-M represents a potentially valuable new tool for measuring maternal mortality in an efficient, consistent and standardised way. Further development, refinement and validation are planned. It could become a routine

  15. Genetics Home Reference: allergic asthma

    Science.gov (United States)

    ... allergic asthma Merck Manual Consumer Version: Asthma Merck Manual Consumer Version: Asthma in Children TeensHealth from Nemours: Allergy Center World Allergy Organization World Allergy Organization: The Allergic March Patient Support ...

  16. Community Asthma Initiative to Improve Health Outcomes and Reduce Disparities Among Children with Asthma.

    Science.gov (United States)

    Woods, Elizabeth R; Bhaumik, Urmi; Sommer, Susan J; Chan, Elaine; Tsopelas, Lindsay; Fleegler, Eric W; Lorenzi, Margarita; Klements, Elizabeth M; Dickerson, Deborah U; Nethersole, Shari; Dulin, Rick

    2016-02-12

    Black and Hispanic children are hospitalized with complications of asthma at much higher rates than white children. The Boston Children's Hospital Community Asthma Initiative (CAI) provides asthma case management and home visits for children from low-income neighborhoods in Boston, Massachusetts, to address racial/ethnic health disparities in pediatric asthma outcomes. CAI objectives were to evaluate 1) case management data by parent/guardian report for health outcomes and 2) hospital administrative data for comparison between intervention and comparison groups. Data from parent/guardian reports indicate that CAI decreased the number of children with any (one or more) asthma-related hospitalizations (decrease of 79% at 12 months) and any asthma-related emergency department visits (decrease of 56% at 12 months) among children served, most of whom were non-Hispanic black or Hispanic. Hospital administrative data also indicate that the number of asthma-related hospitalizations per child significantly decreased among CAI participants compared with a comparison group. The CAI model has been replicated in other cities and states with adaptations to local cultural and systems variations. Health outcome and cost data have been used to contribute to a business case to educate legislators and insurers about outcomes and costs for this enhanced approach to care. Strong partnerships with public health, community, and housing agencies have allowed CAI to leverage its outcomes to expand systemic changes locally and statewide to reduce asthma morbidity.

  17. Asthma in the Elderly

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2009-01-01

    Full Text Available Bronchial asthma is a common problem with enormous medical and economics impacts. It is an inflammatory disease of the airways associated with intermittent episodes of bronchospasm. Asthma is not uncommon in the elderly patients. Prevalence of asthma is similar in older and younger adults. Asthma in the elderly patient is underdiagnosed because of false perceptions by both patient and physician. The high incidence of comorbid conditions in the elderly patient makes the diagnosis and management more difficult. Correct diagnosis is demonstrated with spirometry. The goals of asthma treatment are to achieve and maintain control of symptoms and to prevent development of irreversible airflow limitation. Asthma drugs are preferably inhaled because this route minimizes systemic absorption and, thus, improves the ratio of the therapeutic benefit to the potential side-effects in elderly patients.

  18. Late-Onset Asthma

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2017-01-01

    Late-onset asthma is common, associated with poor outcome, underdiagnosed and undertreated, possibly due to the modifying effect of ageing on disease expression. Although the diagnostic work-up in elderly individuals suspected of having asthma follows the same steps as in younger individuals (case......, to objectively confirm asthma. If necessary, a trial of oral or inhaled corticosteroid might be necessary. Asthma can be diagnosed when increased airflow variability is identified in a symptomatic patient, and if the patient does not have a history of exposure, primarily smoking, known to cause chronic...... obstructive pulmonary disease, the diagnosis is asthma even if the patient does not have fully reversible airflow obstruction. Pharmacological therapy in patients with late-onset asthma follows international guidelines, including treatment with the lowest effective dose of inhaled corticosteroid to minimize...

  19. Asthma and obesity

    DEFF Research Database (Denmark)

    Ulrik, Charlotte S

    2016-01-01

    PURPOSE OF REVIEW: Obesity has significant negative impact on asthma control and risk of exacerbations. The purpose of this review is to discuss recent studies evaluating the effects of weight reduction on asthma control in obese adults. RECENT FINDINGS: Clinical studies have shown that weight...... reduction in obese patients is associated with improvements in symptoms, use of controller medication, and asthma-related quality of life together with a reduction in the risk for severe exacerbations. Furthermore, several studies have also revealed improvements in lung function and airway responsiveness...... reduction in obese adults with asthma leads to an overall improvement in asthma control, including airway hyperresponsiveness and inflammation. Weight reduction should be a cornerstone in the management of obese patients with asthma....

  20. Improving outcomes for underserved adolescents with asthma.

    Science.gov (United States)

    Britto, Maria T; Vockell, Anna-Liisa B; Munafo, Jennifer Knopf; Schoettker, Pamela J; Wimberg, Janet A; Pruett, Raymond; Yi, Michael S; Byczkowski, Terri L

    2014-02-01

    Asthma is the most common chronic disease of childhood. Treatment adherence by adolescents is often poor, and their outcomes are worse than those of younger patients. We conducted a quality improvement initiative to improve asthma control and outcomes for high-risk adolescents treated in a primary care setting. Interventions were guided by the Chronic Care Model and focused on standardized and evidence-based care, care coordination and active outreach, self-management support, and community connections. Patients with optimally well-controlled asthma increased from ∼10% to 30%. Patients receiving the evidence-based care bundle (condition/severity characterized in chart and, for patients with persistent asthma, an action plan and controller medications at the most recent visit) increased from 38% to at or near 100%. Patients receiving the required self-management bundle (patient self-assessment, stage-of-readiness tool, and personal action plan) increased from 0% to ∼90%. Patients and parents who were confident in their ability to manage their or their adolescent's asthma increased from 70% to ∼85%. Patient satisfaction and the mean proportion of patients with asthma-related emergency department visits or hospitalizations remained stable at desirable levels. Implementing interventions focused on standardized and evidence-based care, self-management support, care coordination and active outreach, linkage to community resources, and enhanced follow-up for patients with chronically not-well-controlled asthma resulted in sustained improvement in asthma control in adolescent patients. Additional interventions are likely needed for patients with chronically poor asthma control.

  1. Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7.

    Directory of Open Access Journals (Sweden)

    Camila Leindecker Stumm

    Full Text Available A key event in chronic allergic asthma is the TGF-β-induced activation of fibroblasts into α-SMA-positive myofibroblasts which synthesize type-I collagen. In the present study we investigated the effect of the anti-fibrotic molecule BMP-7 in asthma. Balb/c mice were immunized i.p. with ovalbumin in alum and challenged every 2 days with ovalbumin aerosol (two or six challenges for acute and chronic protocols, respectively. The lung was evaluated for: α-SMA and type-I collagen by immunohistochemistry; BMP-7 and TGF- β1 gene expression by qRT-PCR; type-I collagen and Smads 2 and 3 by immunoblotting; mucus by PSA staining. Type-I collagen around bronchi, α-SMA, mucus secretion, TGF- β1 and BMP-7 gene expression were all increased in asthma. The TGF- β1/BMP-7 ratio was higher in the chronic group and correlated with higher levels of collagen. Fibroblasts isolated from asthmatic and healthy lungs produced type-I collagen upon stimulation with TGF- β1 via phosphorylation of Smad-2, Smad-3. Pre-treatment of the fibroblasts with BMP-7 reduced collagen production and Smads phosphorylation. Intranasal treatment of asthmatic mice with recombinant BMP-7 during the immunization protocol reduced lung inflammation and type I collagen deposition. These results suggest a protective role for BMP-7 in lung allergic inflammation, opposing the pro-fibrotic effects of TGF- β1.

  2. Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model

    Directory of Open Access Journals (Sweden)

    Wolff Henrik

    2010-11-01

    Full Text Available Abstract Background Nanotechnology and engineered nanomaterials (ENM are here to stay. Recent evidence suggests that exposure to environmental particulate matter exacerbates symptoms of asthma. In the present study we investigated the modulatory effects of titanium dioxide particle exposure in an experimental allergic asthma. Methods Nonallergic (healthy and ovalbumin-sensitized (asthmatic mice were exposed via inhalation to two different sizes of titanium dioxide particles, nanosized (nTiO2 and fine (fTiO2, for 2 hours a day, three days a week, for four weeks at a concentration of 10 mg/m3. Different endpoints were analysed to evaluate the immunological status of the mice. Results Healthy mice elicited pulmonary neutrophilia accompanied by significantly increased chemokine CXCL5 expression when exposed to nTiO2. Surprisingly, allergic pulmonary inflammation was dramatically suppressed in asthmatic mice which were exposed to nTiO2 or fTiO2 particles - i.e. the levels of leucocytes, cytokines, chemokines and antibodies characteristic to allergic asthma were substantially decreased. Conclusions Our results suggest that repeated airway exposure to TiO2 particles modulates the airway inflammation depending on the immunological status of the exposed mice.

  3. Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.

    Science.gov (United States)

    DeVries, Avery; Wlasiuk, Gabriela; Miller, Susan J; Bosco, Anthony; Stern, Debra A; Lohman, I Carla; Rothers, Janet; Jones, Anya C; Nicodemus-Johnson, Jessie; Vasquez, Monica M; Curtin, John A; Simpson, Angela; Custovic, Adnan; Jackson, Daniel J; Gern, James E; Lemanske, Robert F; Guerra, Stefano; Wright, Anne L; Ober, Carole; Halonen, Marilyn; Vercelli, Donata

    2017-08-01

    The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. We used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell-derived IL-1β levels were measured by means of ELISA. Neonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator. The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Analysis on related risk factors for bronchial asthma in children and maternal pregnancy and neonatal periods%儿童支气管哮喘与母孕期及新生儿期相关危险因素分析

    Institute of Scientific and Technical Information of China (English)

    黄晓玲; 刘佳; 张小芳

    2015-01-01

    目的:对儿童支气管哮喘与母孕期及新生儿期相关危险因素进行分析。方法以2012年3月至2014年1月确诊并治疗的127例儿童支气管哮喘患儿为观察组;随机选择同期的152例正常儿童作为对照组。对所有入选对象母孕期及新生儿期的相关资料进行调查。结果单因素分析结果提示观察组和对照组早孕期发热、孕早期服药史、妊娠高血压综合征、1分钟 Apgar 评分<7分、出生体重<2500 g、孕龄<37周、剖宫产率相比差异有统计学意义( P <0.05);对单因素分析有意义的因素进行多因素分析,结果提示早孕期发热、胎龄<37周及剖宫产结束分娩是儿童支气管哮喘发生的独立危险因素。结论早孕期发热、胎龄<37周及剖宫产结束分娩是儿童支气管哮喘发生的独立危险因素。了解这些因素,早期进行干预对降低儿童支气管哮喘的发生率有重要的意义。%Objective To analyze related risk factors of bronchial asthma in children and maternal and neonatal periods. Methods A to-tal of 127 pediatric patients with bronchial asthma during March 2012 to January 2014 were diagnosed and listed in observation group,and 152 nor-mal children in the same period were randomly selected as control group. All relevant information on selected objects during pregnancy and neonatal period had been studied. Results Single factor analysis indicated that the difference in early pregnancy period,fever,history of medication,preg-nancy induced hypertension syndrome,1 minute Apgar scores < 7,birth weight < 2 500 g,gestational age < 37 weeks and the rate of cesarean section compared between these 2 groups was statistically significant( P < 0. 05);the result of multi - factors analysis suggested that fever in early pregnancy period,gestational age < 37 weeks and caesarean birth were independent risk factors for bronchial asthma in children. Conclusion Fe-ver in early pregnancy period

  5. The laminin β1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2010-12-01

    Full Text Available Abstract Background Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hypercontractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR. The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established. Methods Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro. Results Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA. Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline- and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR. Conclusion These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide.

  6. Gestational Medication Use, Birth Conditions, and Early Postnatal Exposures for Childhood Asthma

    Directory of Open Access Journals (Sweden)

    Yang-Ching Chen

    2012-01-01

    Full Text Available Our aim is to explore (1 whether gestational medication use, mode of delivery, and early postnatal exposure correlate with childhood asthma, (2 the dose responsiveness of such exposure, and (3 their links to early- and late-onset asthma. We conducted a matched case-control study based on the Taiwan Children Health Study, which was a nationwide survey that recruited 12-to-14-year-old school children in 14 communities. 579 mothers of the participants were interviewed by telephone. Exclusive breastfeeding protected children from asthma. Notably, childhood asthma was significantly associated with maternal medication use during pregnancy, vacuum use during vaginal delivery, recurrent respiratory tract infections, hospitalization, main caregiver cared for other children, and early daycare attendance. Exposure to these factors led to dose responsiveness in relationships to asthma. Most of the exposures revealed a greater impact on early-onset asthma, except for vacuum use and daycare attendance.

  7. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    Science.gov (United States)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

  8. Linking obesity and asthma.

    Science.gov (United States)

    Sutherland, E Rand

    2014-04-01

    A growing body of literature suggests that obesity has a significant impact on asthma risk, phenotype, and prognosis. Epidemiological studies have clearly demonstrated that asthma is more likely to occur in obese patients, and health status is impaired in obese individuals with asthma, with obese asthmatics experiencing more symptoms, worse quality of life, increased healthcare use, and increased asthma severity. However, obesity has well-described effects on lung function and mechanics that can lead to symptoms of dyspnea without causing the pathophysiologic changes of asthma. Adding to the challenges of evaluating this association, some studies have failed to demonstrate a robust relationship between obesity and traditional biomarkers of airway inflammation in adult asthmatics, leading to the conclusion that obesity does not necessarily worsen airway inflammation in asthma. In this regard, emerging data suggest that nonatopic mechanisms may be relevant in obese asthmatics, and that these mechanisms may have a direct impact on the response of obese asthmatics to asthma therapies, most notably inhaled glucocorticoids. This article will review selected aspects of the contributions of obesity-related airway and systemic inflammation to asthma, with a focus on the impact of obesity as a modifier of risk, prognosis, and therapeutic response in asthma.

  9. Asthma among mink workers

    DEFF Research Database (Denmark)

    Grøntved, Berit; Carstensen, Ole; Petersen, Rolf

    2014-01-01

    We report two cases of asthma among mink workers. The first case is about a mink farmer who had asthma that was difficult to treat. In the medical history there was no clear relation to work, and no conclusive work relation with peak flow monitoring. He had a positive histamine release test to mink...... urine. The second case is about a mink farm worker, who had an asthma attack when handling mink furs. Peak flow monitoring showed a clear relation to this work, but there were no signs of allergy. We conclude that these two cases suggest an increased risk of asthma among mink workers....

  10. Pharmacogenomics of pediatric asthma

    Directory of Open Access Journals (Sweden)

    Gupta Sarika

    2010-01-01

    Full Text Available Context: Asthma is a complex disease with multiple genetic and environmental factors contributing to it. A component of this complexity is a highly variable response to pharmacological therapy. Pharmacogenomics is the study of the role of genetic determinants in the variable response to therapy. A number of examples of possible pharmacogenomic approaches that may prove of value in the management of asthma are discussed below. Evidence Acquisition: A search of PubMed, Google scholar, E-Medicine, BMJ and Mbase was done using the key words "pharmacogenomics of asthma", "pharmacogenomics of β-agonist, glucocorticoids, leukotriene modifiers, theophylline, muscarinic antagonists in asthma". Results: Presently, there are limited examples of gene polymorphism that can influence response to asthma therapy. Polymorphisms that alter response to asthma therapy include Arg16Gly, Gln27Glu, Thr164Ile for β-agonist receptor, polymorphism of glucocorticoid receptor gene, CRHR1 variants and polymorphism of LTC4S, ALOX5. Polymorphic variants of muscarinic receptors, PDE4 and CYP450 gene variants. Conclusion: It was concluded that genetic variation can improve the response to asthma therapy. However, no gene polymorphism has been associated with consistent results in different populations. Therefore, asthma pharmacogenomic studies in different populations with a large number of subjects are required to make possible tailoring the asthma therapy according to the genetic characteristic of individual patient.

  11. Asthma, sports, and death.

    Science.gov (United States)

    DiDario, A Geoffrey; Becker, Jack M

    2005-01-01

    The impact of asthma on the general population has been described in detail in medical literature. However, asthma also has a significant impact on the pediatric and adult athlete. This is rarely reported in either the lay press or the medical literature. In 2003, Becker and coworkers conducted a retrospective analysis of the incidence of asthma as a direct cause of death in competitive athletes across the United States between 1993 and 2000. They sought to raise awareness that severe asthma exacerbations and even death can occur during sports from asthma in athletes, while still supporting the concept of maximal participation in sporting activities. To their knowledge, this remains the only published study looking specifically at this issue. Fortunately, fatal asthma events are infrequent in either the adult or the pediatric populations. Those rare cases involving athletes are commonly highlighted in the lay press when they do occur, e.g., when the victim is a college football player such as Rashidi Wheeler. Wheeler died of a fatal asthma exacerbation on August 3, 2002, during a conditioning drill as a member of the Northwestern University football team. Although he was known to have chronic asthma with no obvious barriers to health care, he nevertheless succumbed to his condition. Here, we report a similar, although less well-known, case of an adolescent who died as a direct result of an asthma exacerbation during a high school physical education class. We also offer a brief review of the literature regarding morbidity and mortality in athletes.

  12. Justicia procumbens Extract (DW2008) Selectively Suppresses Th2 Cytokines in Splenocytes and Ameliorates Ovalbumin-Induced Airway Inflammation in a Mouse Model of Asthma.

    Science.gov (United States)

    Youm, Jihyun; Lee, Hyunyong; Chang, Hwan Bong; Jeon, Jihyun; Yoon, Mi Hee; Woo, Ji Young; Choi, Min-Soo; Hwang, Yunha; Seong, Seungkyoo; Na, Kyuheum; Yoon, Joobyoung

    2017-01-01

    DW2008 is an anhydrous ethanol extract of Justicia procumbens produced by Dong-Wha Pharmaceutical, Inc., Co. as a candidate anti-asthmatic drug. In this study, DW2008 selectively reduced T helper 2 (Th2) cytokines in mouse splenocytes and ameliorated ovalbumin-induced airway inflammation by downregulating pulmonary infiltration of differential inflammatory cells and Th2 cytokines more than a decoction or ethanol extract of J. procumbens did in a mouse asthma model. DW2008 also significantly inhibited airway hyperresponsiveness and reduced the thickness of the airway epithelium. HPLC analysis showed that the major peaks (justicidin A and B) of DW2008 were higher than those of the other extracts. Justicidin A and B significantly suppressed Th2 cytokine levels in mouse spleen cells and exhibited a protective effect in ovalbumin-induced airway inflammation. Our findings indicate that DW2008 effectively inhibits allergic airway inflammatory reactions and airway hyperresponsiveness in a mouse model of asthma, suggesting its potential as an anti-asthmatic agent.

  13. Quantification of maternal offloading of organic contaminants in elasmobranchs using the histotrophic round stingray (Urobatis halleri) as a model.

    Science.gov (United States)

    Lyons, Kady; Lowe, Christopher G

    2013-01-01

    Maternal offloading is one route by which young animals may accumulate persistent organic pollutants, such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), but has not been well documented in elasmobranchs despite their propensity to accumulate high concentrations of contaminants. Using the round stingray (Urobatis halleri) as a coastal elasmobranch model, we examined maternal offloading processes at two stages in the stingray's entire reproductive cycle. Post-ovulated and near-term pregnant female stingrays were sampled from southern California, and organic contaminants were measured in the ova and embryonic tissues and compared to concentrations measured in corresponding female livers to determine route and extent of transfer. Total organic contaminant loads measured in ovulated eggs were about two times lower than loads measured in embryos (p contaminants throughout pregnancy. Contaminant loads measured in pups showed a positive relationship with mother's contaminant concentrations (p contaminant load using contaminants measured in the liver as a proxy. However, histotrophy is only one form of supplemental provisioning utilized by elasmobranchs and variation in reproductive modes likely influences the extent to which female elasmobranchs may maternally offload contaminants.

  14. The role of CRAC channel in asthma.

    Science.gov (United States)

    Kaur, Manminder; Birrell, Mark A; Dekkak, Bilel; Reynolds, Sophie; Wong, Sissie; De Alba, Jorge; Raemdonck, Kristof; Hall, Simon; Simpson, Karen; Begg, Malcolm; Belvisi, Maria G; Singh, Dave

    2015-12-01

    Asthma is increasing globally and current treatments only manage a proportion of patients. There is an urgent need to develop new therapies. Lymphocytes are thought to play a central role in the pathophysiology of asthma through the production of inflammatory mediators. This is thought to be via the transcription factor NFAT which in turn can be activated through Ca(2+) release-activated Ca(2+) (CRAC) channels. The aim of this work was to investigate the role of CRAC in clinical and pre-clinical models of allergic asthma. Initial data demonstrated that the NFAT pathway is increased in stimulated lymphocytes from asthmatics. To confirm a role for the channel we showed that a selective inhibitor, Synta 66, blocked mediator production from lymphocytes. Synta 66 inhibited CD2/3/28 induced IL-2, IL-7, IL-13 & IFNΥ in a concentration-dependent manner in healthy and severe asthma donors, with over 60% inhibition observed for all cytokines. NFAT pathway was also increased in a pre-clinical asthma model. In this model we have demonstrated that CRAC played a central role in the airway inflammation and late asthmatic response (LAR). In conclusion, our data provides evidence that suggests targeting CRAC channels could be of therapeutic benefit for asthma sufferers.

  15. Prenatal Particulate Air Pollution and Asthma Onset in Urban Children. Identifying Sensitive Windows and Sex Differences.

    Science.gov (United States)

    Hsu, Hsiao-Hsien Leon; Chiu, Yueh-Hsiu Mathilda; Coull, Brent A; Kloog, Itai; Schwartz, Joel; Lee, Alison; Wright, Robert O; Wright, Rosalind J

    2015-11-01

    The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may differ based on timing of exposure. We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort. Analyses included 736 full-term (≥37 wk) children. Each mother's daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined. Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education (66%), and did not smoke in pregnancy (80%). In the sample as a whole, distributed lag models adjusting for child age, sex, and maternal factors (education, race and ethnicity, smoking, stress, atopy, prepregnancy obesity) showed that increased PM2.5 exposure levels at 16-25 weeks gestation were significantly associated with early childhood asthma development. An interaction between PM2.5 and sex was significant (P = 0.01) with sex-stratified analyses showing that the association exists only for boys. Higher prenatal PM2.5 exposure at midgestation was associated with asthma development by age 6 years in boys. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms.

  16. Acute Fetal Demise with First Trimester Maternal Infection Resulting from Listeria monocytogenes in a Nonhuman Primate Model

    Science.gov (United States)

    Wolfe, Bryce; Wiepz, Gregory J.; Schotzko, Michele; Bondarenko, Gennadiy I.; Durning, Maureen; Simmons, Heather A.; Mejia, Andres; Faith, Nancy G.; Sampene, Emmanuel; Suresh, Marulasiddappa; Kathariou, Sophia; Czuprynski, Charles J.

    2017-01-01

    ABSTRACT Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques (Macaca fascicularis) received a single intragastric inoculation between days 36 and 46 of gestation with 107 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy. PMID:28223455

  17. Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences.

    Science.gov (United States)

    Grier, Mark D; Carson, Robert P; Lagrange, Andre H

    2015-09-15

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by a number of neurological problems, including developmental delay, movement disorders, and epilepsy. AS results from the loss of UBE3A (an imprinted gene) expressed from the maternal chromosome in neurons. Given the ubiquitous expression of Ube3a and the devastating nature of AS, the role of environmental and maternal effects has been largely ignored. Severe ataxia, anxiety-like behaviors and learning deficits are well-documented in patients and AS mice. More recently, clinical imaging studies of AS patients suggest myelination may be delayed or reduced. Utilizing a mouse model of AS, we found disrupted expression of cortical myelin proteins, the magnitude of which is influenced by maternal status, in that the aberrant myelination in the AS pups of AS affected mothers were more pronounced than those seen in AS pups raised by unaffected (Ube3a (m+/p-)) Carrier mothers. Furthermore, feeding the breeding mothers a higher fat (11% vs 5%) diet normalizes these myelin defects. These effects are not limited to myelin proteins. Since AS mice have abnormal stress responses, including altered glucocorticoid receptor (GR) expression, we measured GR expression in pups from Carrier and affected AS mothers. AS pups had higher GR expression than their WT littermates. However, we also found an effect of maternal status, with reduced GR levels in pups from affected mothers compared to genotypically identical pups raised by unaffected Carrier mothers. Taken together, our findings suggest that the phenotypes observed in AS mice may be modulated by factors independent of Ube3a genotype. Published by Elsevier B.V.

  18. 芝麻素抗哮喘炎症作用研究%Sesamin attenuates inflammation response in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    李良昌; 朴红梅; 延光海; 秦向征; 李光昭

    2015-01-01

      正常组相比,炎症细胞计数、IL-4、IL-5、IL-13水平增高,而IFN-γ的表达明显降低(P<0.05),IκBα磷酸化和NF-κB核转位明显增加(P<0.05);芝麻素高剂量组明显降低炎症细胞计数、IL-4、IL-5、IL-13水平,提高 IFN-γ的表达( P <0.05),同时抑制IκBα磷酸化和NF-κB核转位(P<0.05)。结论芝麻素通过抑制NF-κB激活,减轻哮喘炎症反应。%Aim To investigate the effects of sesamin on inflammation response of asthma and to explore its possible mechanism of action. Methods Forty male BALB/c mice were randomly divided into five groups with 8 mice in each group: normal group, ovalbumin ( OVA) group, sesamin low dose group, sesamin high dose group and dexamethasone( DXM) group. Asthma model mice were induced by OVA in vivo. The left lung was isolated for pathological examination. Experi-ment of ELISA and Western blot were used to deter-mine the effect of sesamin on IL-4 , IL-5 , IL-13 and IFN-γ expression. Hematoxylin and eosin stain was used to investigate pathological examination in lung tis-sue. Western blot was performed to detect the IκBαphosphorylation and NF-κB nuclear translocation. Re-sults The mice developed the following pathophysio-logical features of asthma: increased numbers of in- flammatory cells, increased levels of IL-4, IL-5 and IL-13 , decreased level of IFN-γ in bronchoalveolar lavage fluids ( BALF ) and lung tissues ( P <0. 05 ) , and increased IκBα phosphorylation and NF-κB nucle-ar translocation in lung tissues ( P <0. 05 ) . Adminis-tration of sesamin markedly reduced airway inflammato-ry cell recruitment, reduced the production of IL-4, IL-5 , IL-13 and increased IFN-γ in BALF and lung tissues( P <0. 05 ) . The increased IκBα phosphoryla-tion and NF-κB nuclear translocation after OVA inhala-tion were inhibited by the administration of sesamin. Conclusion Sesamin attenuates inflammation re-sponse of asthma through suppression of NF-κB activa-tion.

  19. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: As