2024 |
Sena CRDS, Morten M, Collison AM, Shaar A, Andrade EDQ, Meredith J, et al., 'Bronchiolitis hospital admission in infancy is associated with later preschool ventilation inhomogeneity.', Pediatr Pulmonol, 59 632-641 (2024) [C1]
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Nova |
2023 |
Grace T, Fisher J, Wang C, Valkenborghs SR, Smith R, Hirst JJ, et al., 'Newcastle 1000 (NEW1000) Study: an Australian population-based prospective pregnancy cohort study design and protocol', BMJ OPEN, 13 (2023)
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2023 |
Perkes SJ, Huntriss B, Skinner N, Leece B, Dobson R, Mattes J, et al., 'Evaluation of an mHealth Intervention (Growin Up Healthy Jarjums) Designed With and for Aboriginal and Torres Strait Islander Mothers: Engagement and Acceptability Study', JMIR Pediatrics and Parenting, 6 e43673-e43673 [C1]
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Nova |
2023 |
Girkin JLN, Sokulsky LA, Starkey MR, Hansbro PM, Foster PS, Collison AM, Mattes J, 'A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6', Frontiers in Allergy, 4 [C1]
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Nova |
2023 |
Liu G, Haw TJ, Starkey MR, Philp AM, Pavlidis S, Nalkurthi C, et al., 'TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.', Nat Commun, 14 7349 (2023) [C1]
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2023 |
Dy ABC, Girkin J, Marrocco A, Collison A, Mwase C, O'Sullivan MJ, et al., 'Rhinovirus infection induces secretion of endothelin-1 from airway epithelial cells in both in vitro and in vivo models.', Respir Res, 24 205 (2023) [C1]
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Nova |
2023 |
Percival E, Collison AM, da Silva Sena CR, De Queiroz Andrade E, De Gouveia Belinelo P, Gomes GMC, et al., 'The association of exhaled nitric oxide with air pollutants in young infants of asthmatic mothers.', Environ Health, 22 84 (2023) [C1]
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2023 |
Perkes SJ, Bonevski B, Hall K, Mattes J, Chamberlain C, Bennett J, et al., 'Aboriginal and Torres Strait Islander Women s Access to and Interest in mHealth: National Web-based Cross-sectional Survey', Journal of Medical Internet Research, 25 e42660-e42660 [C1]
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Nova |
2023 |
Franklin D, Babl FE, George S, Oakley E, Borland ML, Neutze J, et al., 'Effect of Early High-Flow Nasal Oxygen vs Standard Oxygen Therapy on Length of Hospital Stay in Hospitalized Children with Acute Hypoxemic Respiratory Failure: The PARIS-2 Randomized Clinical Trial', JAMA, 329 224-234 (2023) [C1]
Importance: Nasal high-flow oxygen therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The efficacy of high-flow oxygen th... [more]
Importance: Nasal high-flow oxygen therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The efficacy of high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure without bronchiolitis is unknown. Objective: To determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted at 14 metropolitan and tertiary hospitals in Australia and New Zealand, including 1567 children aged 1 to 4 years (randomized between December 18, 2017, and March 18, 2020) requiring hospital admission for acute hypoxemic respiratory failure. The last participant follow-up was completed on March 22, 2020. Interventions: Enrolled children were randomly allocated 1:1 to high-flow oxygen therapy (n = 753) or standard oxygen therapy (n = 764). The type of oxygen therapy could not be masked, but the investigators remained blinded until the outcome data were locked. Main Outcomes and Measures: The primary outcome was length of hospital stay with the hypothesis that high-flow oxygen therapy reduces length of stay. There were 9 secondary outcomes, including length of oxygen therapy and admission to the intensive care unit. Children were analyzed according to their randomization group. Results: Of the 1567 children who were randomized, 1517 (97%) were included in the primary analysis (median age, 1.9 years [IQR, 1.4-3.0 years]; 732 [46.7%] were female) and all children completed the trial. The length of hospital stay was significantly longer in the high-flow oxygen group with a median of 1.77 days (IQR, 1.03-2.80 days) vs 1.50 days (IQR, 0.85-2.44 days) in the standard oxygen group (adjusted hazard ratio, 0.83 [95% CI, 0.75-0.92]; P <.001). Of the 9 prespecified secondary outcomes, 4 showed no significant difference. The median length of oxygen therapy was 1.07 days (IQR, 0.50-2.06 days) in the high-flow oxygen group vs 0.75 days (IQR, 0.35-1.61 days) in the standard oxygen therapy group (adjusted hazard ratio, 0.78 [95% CI, 0.70-0.86]). In the high-flow oxygen group, there were 94 admissions (12.5%) to the intensive care unit compared with 53 admissions (6.9%) in the standard oxygen group (adjusted odds ratio, 1.93 [95% CI, 1.35-2.75]). There was only 1 death and it occurred in the high-flow oxygen group. Conclusions and Relevance: Nasal high-flow oxygen used as the initial primary therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not significantly reduce the length of hospital stay compared with standard oxygen therapy. Trial Registration: anzctr.org.au Identifier: ACTRN12618000210279.
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Nova |
2022 |
Beyene T, Murphy VE, Gibson PG, McDonald VM, Van Buskirk J, Holliday EG, et al., 'The impact of prolonged landscape fire smoke exposure on women with asthma in Australia', BMC Pregnancy and Childbirth, 22 (2022) [C1]
Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and inform... [more]
Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants¿ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM2.5). Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 µg/m3 PM2.5 and 105 µg/m3 peak PM2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.
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Nova |
2022 |
Sena CRDS, Andrade EDQ, Belinelo PDG, Percival E, Prangemeier B, O'Donoghue C, et al., 'Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age', THORAX, 77 1106-1112 (2022) [C1]
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Nova |
2022 |
De Queiroz Andrade E, Bayfield KJ, Blaxland A, Wong A, De Gouveia Belinelo P, Sly PD, et al., 'Exposure to 4% SF6 during multiple breath washout affects subsequent infant tidal breathing analysis', PEDIATRIC PULMONOLOGY, 57 1089-1091 (2022)
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2022 |
Gould GS, Ryan NM, Kumar R, Stevenson LC, Carson-Chahhoud K, Oldmeadow C, et al., 'SISTAQUIT: training health care providers to help pregnant Aboriginal and Torres Strait Islander women quit smoking. A cluster randomised controlled trial', MEDICAL JOURNAL OF AUSTRALIA, 217 36-42 (2022)
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2022 |
Mallise CA, Murphy VE, Karayanidis F, Armstrong H, Whalen OM, Woolard AJ, et al., 'Parenting stress in mothers with asthma during the postpartum period', Journal of Asthma, 59 2091-2099 (2022) [C1]
Objective: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and ... [more]
Objective: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. Methods: This cohort survey-based study included mothers with (n = 157) and without (n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index¿Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. Results: Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. Conclusions: This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.
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Nova |
2022 |
Perkes SJ, Huntriss B, Skinner N, Leece B, Dobson R, Mattes J, et al., 'Development of a Maternal and Child mHealth Intervention With Aboriginal and Torres Strait Islander Mothers: Co-design Approach', JMIR FORMATIVE RESEARCH, 6 (2022) [C1]
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Nova |
2022 |
Sena CRDS, Lines O, Latheef MS, Amarasinghe GG, Quah WH, Beyene T, et al., 'Reduction in forced vital capacity in asthmatic children on days with bushfire smoke exposure in the Australian 2019/2020 bushfire', PEDIATRIC ALLERGY AND IMMUNOLOGY, 33 (2022)
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2022 |
Murphy VE, Jensen ME, Holliday EG, Giles WB, Barrett HL, Callaway LK, et al., 'Effect of asthma management with exhaled nitric oxide
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Nova |
2022 |
Hosseini B, Berthon BS, Jensen ME, McLoughlin RF, Wark PAB, Nichol K, et al., 'The Effects of Increasing Fruit and Vegetable Intake in Children with Asthma on the Modulation of Innate Immune Responses', Nutrients, 14 3087-3087 (2022) [C1]
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Nova |
2021 |
Belinelo PDG, Collison AM, Murphy VE, Robinson PD, Jesson K, Hardaker K, et al., 'Maternal asthma is associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts', THORAX, 76 996-1001 (2021) [C1]
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Nova |
2021 |
Berthon BS, McLoughlin RF, Jensen ME, Hosseini B, Williams EJ, Baines KJ, et al., 'The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial', CLINICAL AND EXPERIMENTAL ALLERGY, 51 1144-1156 (2021) [C1]
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Nova |
2021 |
Hosseini B, Berthon BS, Starkey MR, Collison A, McLoughlin RF, Williams EJ, et al., 'Children With Asthma Have Impaired Innate Immunity and Increased Numbers of Type 2 Innate Lymphoid Cells Compared With Healthy Controls', FRONTIERS IN IMMUNOLOGY, 12 (2021) [C1]
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Nova |
2021 |
Bokern MP, Robijn AL, Jensen ME, Barker D, Callaway L, Clifton V, et al., 'Factors Associated with Asthma Exacerbations During Pregnancy', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 9 4343-+ (2021) [C1]
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Nova |
2021 |
Da Silva Sena CR, Morten M, Meredith J, Kepreotes E, E Murphy V, G Gibson P, et al., 'Rhinovirus bronchiolitis, maternal asthma, and the development of asthma and lung function impairments', Pediatric Pulmonology, 56 362-370 (2021) [C1]
Background: Children with a history of rhinovirus (RV) positive bronchiolitis have a high risk of developing subsequent asthma. Maternal asthma might also increase this risk. The ... [more]
Background: Children with a history of rhinovirus (RV) positive bronchiolitis have a high risk of developing subsequent asthma. Maternal asthma might also increase this risk. The aim of this study was to investigate the combined effects of hospitalization for RV positive bronchiolitis in infancy and a history of maternal asthma on the development of asthma at preschool age. Methods: This is a prospective cohort study of 139 preschool-aged children, with a history of hospital admission for bronchiolitis in infancy, followed-up to ascertain asthma and asthma-like symptoms, skin prick allergy test positivity, and lung function measured pre- and post-bronchodilator using impulse oscillometry. Results: Children with a past hospitalization for RV positive bronchiolitis (42.4% of all) and a history of maternal asthma (36.7% of all) had the greatest prevalence and risk ratio (RR) for doctor-diagnosed asthma (prevalence 81.8% and RR 2.10, 95% confidence interval [CI] 1.37¿3.19, p =.001), use of inhaled corticosteroids (68.2% and RR 2.17, 95% CI 1.19¿3.99, p =.001) and short-acting ß-agonists in the last 12 months (95.2% and RR 1.49, 95% CI 1.17¿1.89, p =.001), as compared to those with RV negative bronchiolitis and no maternal asthma history. More children in this group had an abnormal airway resistance (33.3% and adjusted risk ratio [aRR] 3.11, 95% CI 1.03¿9.47, p =.045) and reactance (27.8% and aRR 2.11, 95% CI 1.06¿4.26, p =.035) at 5 Hz, as compared to those with RV negative bronchiolitis and no maternal asthma history. Conclusion: Hospitalization for RV positive bronchiolitis in early life combined with a history of maternal asthma identifies a subgroup of children with a high asthma burden while participants with only one of the two risk factors had intermediate risk for asthma.
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Nova |
2021 |
Martins Costa Gomes G, de Gouveia Belinelo P, Starkey MR, Murphy VE, Hansbro PM, Sly PD, et al., 'Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 10 (2021) [C1]
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Nova |
2021 |
De Queiroz Andrade E, Gomes GMC, Collison A, Grehan J, Murphy VE, Gibson P, et al., 'Variation of DNA Methylation in Newborns Associated with Exhaled Carbon Monoxide during Pregnancy', INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 18 (2021) [C1]
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Nova |
2021 |
Gomes GMC, Karmaus W, Murphy VE, Gibson PG, Percival E, Hansbro PM, et al., 'Environmental Air Pollutants Inhaled during Pregnancy Are Associated with Altered Cord Blood Immune Cell Profiles', INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 18 (2021) [C1]
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Nova |
2021 |
Murphy VE, Karmaus W, Mattes J, Brew BK, Collison A, Holliday E, et al., 'Exposure to Stress and Air Pollution from Bushfires during Pregnancy: Could Epigenetic Changes Explain Effects on the Offspring?', INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 18 (2021) [C1]
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Nova |
2021 |
Mallise CA, Murphy VE, Campbell LE, Woolard AJ, Whalen OM, Milton G, et al., 'Early Sensory and Temperament Features in Infants Born to Mothers With Asthma: A Cross-Sectional Study', Frontiers in Psychology, 12 (2021) [C1]
Maternal asthma in pregnancy is associated with an increased risk of adverse perinatal outcomes. Adverse perinatal outcomes may result in poorer infant developmental outcomes, suc... [more]
Maternal asthma in pregnancy is associated with an increased risk of adverse perinatal outcomes. Adverse perinatal outcomes may result in poorer infant developmental outcomes, such as temperament and sensory difficulties. This study aimed to (1) assess differences in temperament and sensory features between infants born to mothers with and without asthma and (2) investigate differences in these infant behaviours as a function of maternal asthma severity and asthma control. Mothers completed the Carey Temperament Scales and the Sensory Profile 2 at either 6 weeks, 6 months, or 12 months postpartum. Overall, we observed no significant differences between infants born to mothers with and without asthma in their temperament or sensory features; scores in both domains fell within the normative range. More infants in the asthma group, however, were reported to be highly distractible. When compared with normative data, infants in both groups were reported to have poor predictability of biological functions and fewer infants engaged in low levels of sensory behaviours. Some infants were observed to experience difficulties with hyper-reactivity within several domains. Maternal asthma severity and control during pregnancy were not linked to significant differences between infant temperament and sensory features. The present findings indicate that infants born to mothers with asthma are not at an increased risk overall for temperament or sensory difficulties, compared to control infants. However, a subset of infants across both groups may be at risk for attention or sensory hyper-reactivity difficulties. Further research into the developmental outcomes of infants born to mothers with asthma is warranted.
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Nova |
2021 |
Robijn AL, Barker D, Gibson PG, Giles WB, Clifton VL, Mattes J, et al., 'Factors Associated with Nonadherence to Inhaled Corticosteroids for Asthma During Pregnancy', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 9 1242-+ (2021) [C1]
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Nova |
2021 |
Jensen ME, Robijn AL, Gibson PG, Oldmeadow C, Clifton V, Giles W, et al., 'Longitudinal Analysis of Lung Function in Pregnant Women with and without Asthma', Journal of Allergy and Clinical Immunology: In Practice, 9 1578-1585.e3 (2021) [C1]
Background: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies exami... [more]
Background: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies examining lung function across gestation are limited. Also, whether spirometry values follow the same pattern during pregnancy in women with and without asthma is unknown. Objective: To investigate the effect of advancing gestation, and its interaction with asthma, on lung function in a large well-defined cohort of pregnant women. Methods: Data were obtained from prospective cohorts involving women with (n = 770) and without (n = 259) asthma (2004-2017), recruited between 12 and 22 weeks' gestation. Lung function (forced vital capacity [FVC], FEV1, FEV1:FVC%) was assessed periodically during pregnancy using spirometry. Multilevel mixed-effect regression models were used to assess changes in lung function over gestation. Results: Asthma had a significant effect on baseline lung function (FEV1%, -9%; FVC%, -3%; FEV1:FVC%, -4%). FVC% decreased with advancing gestation (-0.07%/wk; 95% CI, -0.10 to -0.04]), as did FEV1%, but only among those without asthma (women without asthma: -0.14%/wk, 95% CI, -0.22 to -0.06%; compared with women with asthma: 0.02%/wk, 95% CI, -0.01 to 0.06). FEV1:FVC% remained relatively stable for women without asthma (0.03%/wk; 95% CI, -0.08 to 0.02), but increased for women with asthma (0.06%/wk; 95% CI, 0.04 to 0.16). Conclusions: Data suggest that advancing gestation negatively affects FVC% and FEV1%. This is consistent with extrapulmonary restriction from advancing pregnancy. Yet, the presence of asthma altered the trajectories of FEV1% and FEV1:FVC%. Optimal asthma management during pregnancy might have opposed the negative effects of gestation on lung function.
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Nova |
2021 |
Collison AM, Sokulsky LA, Kepreotes E, de Siqueira AP, Morten M, Edwards MR, et al., 'miR-122 promotes virus-induced lung disease by targeting SOCS1', JCI Insight, 6 (2021) [C1]
Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the c... [more]
Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.
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Nova |
2020 |
Sokulsky LA, Garcia-Netto K, Nguyen TH, Girkin JLN, Collison A, Mattes J, et al., 'A critical role for the CXCL3/CXCL5/CXCR2 neutrophilic chemotactic axis in the regulation of type 2 responses in a model of rhinoviral-induced asthma exacerbation', Journal of Immunology, 205 2468-2478 (2020) [C1]
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Nova |
2020 |
Mattes J, Collison A, 'Fetal Eosinophils Get on the Nerves of Airways Early Origins of Bronchoconstriction', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 62 407-408 (2020)
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2020 |
Harvey SM, Murphy VE, Gibson PG, Collison A, Robinson P, Sly PD, et al., 'Maternal asthma, breastfeeding, and respiratory outcomes in the first year of life', Pediatric Pulmonology, 55 1690-1696 (2020) [C1]
Maternal asthma increases the risk of infant wheeze. Breastfeeding may offer protection but there is limited evidence in this high-risk group. We examined associations between bre... [more]
Maternal asthma increases the risk of infant wheeze. Breastfeeding may offer protection but there is limited evidence in this high-risk group. We examined associations between breastfeeding and respiratory outcomes, in infants born to women with asthma. This study was a secondary analysis of two prospective cohorts of pregnant women with asthma, and their infants, conducted between 2007 and 2018. At 6 ± 1 (T1) and 12 ± 1 (T2) months post-partum, mothers reported breastfeeding patterns and infant wheeze (primary outcome), bronchiolitis, and related medication use and healthcare utilization, via a validated questionnaire; a subgroup completed face-to-face interviews. ¿2 tests and logistic regression models, adjusting for confounders, were utilized. Data were complete for 605 participants at T1 and 486 (80%) at T2. Of 605 participants: 89% initiated breastfeeding and 38% breastfed for more than 6 months. Breastfeeding for more than 6 months vs ¿never¿ was associated with a reduced adjusted relative risk of infant wheeze at T1 (0.54, 95% confidence interval, 0.30-0.96). Bronchiolitis risk was reduced at T1 and T2 with more tha 6 months of breastfeeding vs ¿never.¿ Breastfeeding duration of 1 to 3 months, 4 to 6 months, and more than 6 months were associated with a reduced risk of infant healthcare utilization (all P <.05, vs ¿never¿), but not medication use (P >.05). Breastfeeding for more than 6 months was associated with a reduced risk of wheeze, bronchiolitis, and wheeze-related healthcare utilization in infants at risk due to maternal asthma. Notably, breastfeeding for shorter durations was associated with a reduced risk of healthcare utilization compared with none. Larger cohorts are needed to further examine the impact of breastfeeding exposure on respiratory health in infants exposed to maternal asthma.
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Nova |
2020 |
Perkes S, Bonevski B, Mattes J, Hall K, Gould GS, 'Respiratory, birth and health economic measures for use with Indigenous Australian infants in a research trial: a modified Delphi with an Indigenous panel', BMC Pediatrics, 20 (2020) [C1]
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Nova |
2020 |
Percival E, Bhatia R, Preece K, McEvoy M, Collison A, Mattes J, 'Change in exhaled nitric oxide during peanut challenge is related to severity of reaction', ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, 16 (2020) [C1]
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Nova |
2020 |
De Queiroz Andrade E, Da Silva Sena CR, Collison A, Murphy VE, Gould GS, Bonevski B, Mattes J, 'Association between active tobacco use during pregnancy and infant respiratory health: a systematic review and meta-analysis', BMJ open, 10 (2020) [C1]
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Nova |
2020 |
Whalen OM, Campbell LE, Murphy VE, Lane AE, Gibson PG, Mattes J, et al., 'Observational study of mental health in asthmatic women during the prenatal and postnatal periods', Journal of Asthma, 57 829-841 (2020) [C1]
Objective: We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asth... [more]
Objective: We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asthmatic women with and without mental health problems differ in self-management, medications knowledge, and asthma symptoms. Methods: We assessed spirometry performance and asthma symptoms in 120 women (mean age 29.8 years) before 23 weeks gestation, as part of the Breathing for Life Trial (Trial ID: ACTRN12613000202763). Prenatal depression data was obtained from medical records. At 6 weeks postpartum, we assessed general health, self-reported asthma control, depression symptoms (with the Edinburgh Postnatal Depression Scale) and adaptive functioning (with the Achenbach System of Empirically Based Assessment scales). Results: Twenty percent of our sample reported having a current mental health diagnosis, 14% reported currently receiving mental health care, while 47% reported having received mental health care in the past (and may/may not have received a diagnosis). The sample scored high on the Aggressive Behavior, Avoidant Personality, and Attention Deficit/Hyperactivity scales. Poorer self-reported postnatal asthma control was strongly correlated with elevated somatic complaints, externalizing problems, antisocial personality problems, and greater withdrawal. Prenatal spirometry or asthma severity and control were largely not associated with measures of psychopathology. Conclusions: These findings indicate that pregnant women with asthma frequently report issues with psychopathology during the prenatal and postnatal periods, and that the subjective perception of asthma control may be more related to psychopathology than objective asthma measures. However, due to sample bias, these findings are likely to be understated.
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Nova |
2020 |
Belinelo PDG, Nielsen A, Goddard B, Platt L, Sena CRDS, Robinson PD, et al., 'Clinical and lung function outcomes in a cohort of children with severe asthma', BMC PULMONARY MEDICINE, 20 (2020) [C1]
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Nova |
2020 |
Murphy VE, Jensen ME, Robijn AL, Wright TK, Mattes J, Collison A, Gibson PG, 'How Maternal BMI Modifies the Impact of Personalized Asthma Management in Pregnancy', Journal of Allergy and Clinical Immunology: In Practice, 8 219-228.e3 (2020) [C1]
Background: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wh... [more]
Background: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring. Objectives: In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (FENO)-based management on asthma exacerbations in pregnancy and offspring wheeze. Methods: A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or FENO and symptoms (FENO group). Exacerbations were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy. GWG was categorized according to Institute of Medicine guidelines. A validated parent-completed questionnaire assessed infant wheeze-related outcomes. Results: FENO-based management was associated with a significantly lower incidence rate ratio for maternal exacerbations in nonobese mothers (0.52, 95% confidence interval [CI], 0.31-0.88, P = .015, n = 129), and women with GWG within recommendations (0.35, 95% CI, 0.12-0.96, P = .042, n = 43), but not for obese mothers (0.59, 95% CI, 0.32-1.08, P = .089, n = 88), or women with excess GWG (0.58, 95% CI, 0.32-1.04, P = .07, n = 104). Recurrent bronchiolitis occurred in 5.3% (n = 1) of infants born to non-overweight mothers, 16.7% (n = 3) of infants of overweight mothers, and 21.7% (n = 5) of infants of obese mothers in the control group. In the FENO group, 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P = .031). Conclusions: The benefits of FENO-based management are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy.
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Nova |
2020 |
Collison AM, Sokulsky LA, Nightingale S, Percival E, LeFevre A, Meredith J, et al., 'In vivo targeting of miR-223 in experimental eosinophilic oesophagitis', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 9 (2020) [C1]
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Nova |
2020 |
Silva FMDCE, Oliveira EED, Ambrósio MGE, Ayupe MC, Souza VPD, Gameiro J, et al., 'High-fat diet-induced obesity worsens TH2 immune response and immunopathologic characteristics in murine model of eosinophilic oesophagitis', Clinical and Experimental Allergy, 50 244-255 (2020) [C1]
Background: Eosinophilic oesophagitis (EoE) is an emergent chronic immune-mediated disease of the oesophagus, which affects both children and adults. It is clinically characterize... [more]
Background: Eosinophilic oesophagitis (EoE) is an emergent chronic immune-mediated disease of the oesophagus, which affects both children and adults. It is clinically characterized by dysphagia, food impaction and oesophageal eosinophilia. Epidemiological studies indicate that obesity can worsen allergic symptoms; however, its effect on EoE immunopathological response has not been evaluated yet. This study aimed to assess the effect of obesity on allergic inflammation and T helper-2 profile in an EoE experimental model. Methods: Obesity was induced by high-fat feeding. After 7¿weeks of diet, male BALB/c mice were subcutaneously sensitized and orally challenged with OVA. Results: Obesity itself induced a significant mast cell and eosinophil accumulation in the oesophagus, trachea, gut and lung. After allergy induction, this number was higher, when compared to lean-allergic mice. Moreover, obese-allergic mice showed higher remodelling area, in the oesophagus, associated with higher IL-5 and TSLP mRNA expression. In contrast, FoxP3 and IL-10 were less expressed in comparison with lean-allergic mice. In addition, the amount of CD11c+MHCII+PDL1+ dendritic cells was reduced, while the number of CD11c+MHCII+CD80+ DCs and CD3+CD4+GATA3+IL-4+ cells was increased in obese-allergic mice in the spleen and lymph nodes when compared to lean-allergic mice. Conclusion: Obesity aggravated the immune histopathological characteristics in the EoE experimental model, which was associated with the reduction in the regulatory profile, and the increased inflammatory cells influx, related to the TH2 profile. Altogether, the data provide new knowledge about obesity as a risk factor, worsening EoE symptoms, and contribute for future treatment strategies for this specific profile.
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Nova |
2019 |
Kulkarni G, de Waal K, Grahame S, Collison A, Roddick L, Hilton J, et al., 'Polysomnography for the management of oxygen supplementation therapy in infants with chronic lung disease of prematurity', Journal of Maternal-Fetal and Neonatal Medicine, 32 3640-3646 (2019) [C1]
Aim: Some infants with bronchopulmonary dysplasia (BPD) may require oxygen supplementation at home but a role for overnight polysomnography (PSG) in the management of home oxygen ... [more]
Aim: Some infants with bronchopulmonary dysplasia (BPD) may require oxygen supplementation at home but a role for overnight polysomnography (PSG) in the management of home oxygen therapy has been rarely described. Methods: Forty-one infants with BPD born at less than 30 weeks gestational age were discharged with continuous home oxygen supplementation therapy between 2010 and 2013. PSG data were recorded on oxygen supplementation versus room air at median corrected age of 2 months (range 1¿5 months) (first PSG after discharge to home). Those infants who continued oxygen supplementation therapy at home had at least one more PSG before oxygen therapy was discontinued (last PSG). We also collected PSG data in 10 healthy term infants (median age 3.5 months; range 2¿4 months). Results: In infants with BPD in room air, increased numbers of central apneas, hypopneas, and SaO2 desaturations were the predominant PSG features with a median apnea¿hypopnea index (AHI) of 16.8 events per hour (range 0¿155). On oxygen supplementation therapy, median AHI dramatically improved (2.2, range 0¿22; p <.001) and was not different from control infants (2.0, range 0¿3.9; p =.31). AHI on room air at the last PSG when home oxygen was ceased was 4.1 per hour (range 0¿13.8) slightly higher than in healthy infants. Conclusion: Central sleep disordered breathing in infants with BPD dramatically normalizes with low flow nasal cannula home oxygen therapy and improves with age. Mild central sleep disordered breathing remains detectable, although much improved, when compared with healthy infants at the time when the decision to cease home oxygen therapy was made by the physician.
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Nova |
2019 |
Franklin D, Shellshear D, Babl FE, Schlapbach LJ, Oakley E, Borland ML, et al., 'Multicentre, randomised trial to investigate early nasal high-flow therapy in paediatric acute hypoxaemic respiratory failure: a protocol for a randomised controlled trial-a Paediatric Acute respiratory Intervention Study (PARIS 2)', BMJ OPEN, 9 (2019)
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2019 |
Mattes J, Gulliver T, Hilton J, Collison A, Whitehead B, 'Polysomnography in Preterm Infants with Bronchopulmonary Dysplasia for Monitoring Sleep-Disordered Breathing and Pulmonary Reserve', Current Sleep Medicine Reports, 5 56-60 (2019) [C1]
Purpose of Review: Bronchopulmonary dysplasia (BPD) has progressed over time into a syndrome with multifactorial aetiology and complex pathophysiology characterised by a developme... [more]
Purpose of Review: Bronchopulmonary dysplasia (BPD) has progressed over time into a syndrome with multifactorial aetiology and complex pathophysiology characterised by a developmental arrest of the alveolar and pulmonary vasculature compartments. BPD remains common in extremely preterm and very low birth weight infants. Maintaining appropriate oxygen blood levels in BPD infants may promote growth, reduce the risk of sudden infant death syndrome, and lower pulmonary artery pressures. There is no agreed approach on how to best titrate and wean home oxygen treatment in BPD infants. Recent Findings: In BPD infants on home oxygen therapy, sleep-disordered breathing is common and appears to be central in origin. However, obstructive apnoea events are also more common in BPD infants. The increased frequency of central apnoea events during sleep in BPD infants has been shown to decline on low-flow oxygen treatment to levels observed in healthy infants. It is hypothesised that brief respiratory pauses in sleep could result in significant oxygen desaturations in BPD infants who have a decreased pulmonary reserve. Those events are scored as central apnoea in polysomnography and are prevented by oxygen treatment. Central apnoea events may also represent disrupted control of breathing secondary to altered chemosensitivity. Summary: Polysomnography may be of clinical value to monitor sleep-disordered breathing, assess pulmonary reserves, and titrate and wean oxygen in BPD infants. Considering the increasing number of extremely preterm and very low birth weight infants with BPD, we recommend prioritising the performance of well-designed studies to gather high-level evidence into the potential role of polysomnography in the management of prematurity- and BPD-associated long-term sequelae.
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Nova |
2019 |
Bissell K, Ellwood P, Ellwood E, Chiang C-Y, Marks GB, El Sony A, et al., 'Essential Medicines at the National Level: The Global Asthma Network's Essential Asthma Medicines Survey 2014', INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 16 (2019) [C1]
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Nova |
2019 |
Jensen ME, Murphy VE, Gibson PG, Mattes J, Camargo CA, 'Vitamin D status in pregnant women with asthma and its association with adverse respiratory outcomes during infancy', Journal of Maternal-Fetal and Neonatal Medicine, 32 1820-1825 (2019) [C1]
Background: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma... [more]
Background: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. Methods: Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother¿infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D = 75 nmol/L (at one or both time-points). Results: In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26¿110) nmol/L at 16 weeks, and 65 (range 32¿116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points; 21 (40%) had 25(OH)D = 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with ¿wheeze ever¿ at 12 months, compared with 25(OH)D = 75 nmol/L (71 versus 43%, p =.04). Infant acute-care presentations (45 versus 13%, p =.02) and oral corticosteroid use (26 versus 4%, p =.03) due to ¿asthma/wheezing¿ were higher in the maternal group with 25(OH)D < 75 nmol/L, versus =75 nmol/L. Conclusions: Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.
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Nova |
2019 |
Collison AM, Li J, de Siqueira AP, Lv X, Toop HD, Morris JC, et al., 'TRAIL signals through the ubiquitin ligase MID1 to promote pulmonary fibrosis', BMC PULMONARY MEDICINE, 19 (2019) [C1]
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Nova |
2019 |
Mattes J, Szefler S, 'Mechanisms in children', ERS Monograph, 2019 231-245 (2019)
Severe asthma affects <5% of asthmatic children but carries the majority of asthma morbidity and mortality due to asthma. Although severe asthma is recognised as a heterogeneou... [more]
Severe asthma affects <5% of asthmatic children but carries the majority of asthma morbidity and mortality due to asthma. Although severe asthma is recognised as a heterogeneous disease, recent studies have identified some molecular and histopathological features that may be shared among atopic children with severe therapy-resistant asthma. These include exaggerated eosinophilic inflammation, airway remodelling and activation of the alarmin IL-33 in the subepithelial layer, as well as neutrophils in the epithelial layer of the airway wall. The emergence of treatments to specifically target cytokines and their receptors has reaffirmed the redundancy and complexity of effector functions in mounting type 2 immune responses in severe asthma. The further development of predictive and monitoring biomarkers for treatment success and failure may allow clinicians to identify children at risk for severe asthma early and to intervene effectively with currently available and novel personalised treatment approaches.
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2019 |
Nair PM, Starkey MR, Haw TJ, Liu G, Collison AM, Mattes J, et al., 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 8 (2019) [C1]
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Nova |
2019 |
Robijn AL, Jensen ME, Gibson PG, Powell H, Giles WB, Clifton VL, et al., 'Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.', The Journal of asthma : official journal of the Association for the Care of Asthma, 56 594-602 (2019) [C1]
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Nova |
2018 |
Morten M, Collison A, Murphy VE, Barker D, Oldmeadow C, Attia J, et al., 'Managing Asthma in Pregnancy (MAP) trial: FENO levels and childhood asthma', Journal of Allergy and Clinical Immunology, 142 1765-1772.e4 (2018) [C1]
Background: The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fracti... [more]
Background: The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FENO) in combination with asthma symptoms (FENO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (Australian New Zealand Clinical Trials Registry, no. 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FENO group. However, the effect of FENO-guided management on the development of asthma in the offspring is unknown. Objective: We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood. Methods: A total of 179 mothers consented to participate in the Growing into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FENO-guided asthma management on childhood asthma incidence. Results: A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2%; odds ratio [OR], 0.46, 95% CI, 0.22-0.96; P =.04). Furthermore, frequent wheeze (OR, 0.27; 95% CI, 0.09-0.87; P =.03), use of short-acting ß-agonists (OR, 0.49; 95% CI, 0.25-0.97; P =.04), and emergency department visits for asthma (OR, 0.17; 95% CI, 0.04-0.76; P =.02) in the past 12 months were less common in children born to mothers from the FENO group. Doctor-diagnosed asthma was associated with common risk alleles for early onset asthma at gene locus 17q21 (P =.01 for rs8069176; P =.03 for rs8076131), and higher airways resistance (P =.02) and FENO levels (P =.03). A causal mediation analysis suggested natural indirect effects of FENO-guided asthma management on childhood asthma through ¿any use¿ and ¿time to first change in dose¿ of inhaled corticosteroids during the MAP trial (OR: 0.83; 95% CI: 0.59-0.99, and OR: 0.90; 95% CI: 0.70-1.03, respectively). Conclusions: FENO-guided asthma management during pregnancy prevented doctor-diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.
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Nova |
2017 |
Gould GS, Lim LL, Mattes J, 'Prevention and Treatment of Smoking and Tobacco Use During Pregnancy in Selected Indigenous Communities in High-Income Countries of the United States, Canada, Australia, and New Zealand: An Evidence-Based Review', Chest, 152 853-866 (2017) [C1]
Tobacco smoking during pregnancy is the most important modifiable risk factor for adverse pregnancy outcomes and long-term health complications for mother and baby. Tobacco use du... [more]
Tobacco smoking during pregnancy is the most important modifiable risk factor for adverse pregnancy outcomes and long-term health complications for mother and baby. Tobacco use during pregnancy has decreased in high-income countries but not in Indigenous women in Australia, New Zealand, the United States, and Canada. This evidence-based review focuses on tobacco use among Indigenous pregnant women in high-income countries that share a history of European colonization. Indigenous women are more likely to use tobacco because of socioeconomic disadvantage, social norms, and poor access to culturally appropriate tobacco cessation support. Complications arising from tobacco smoking during pregnancy, such as low birth weight, prematurity, perinatal death, and sudden infant death syndrome, are much higher in Indigenous populations. Effective approaches to cessation in pregnant nonindigenous women involves behavioral counseling, with or without nicotine replacement therapy (NRT). Higher nicotine metabolism during pregnancy and poor adherence may affect therapeutic levels of NRT. Only two randomized trials were conducted among Indigenous women: neither found a statistically significant difference in cessation rates between the treatment and comparison arms. Considerations should be given to (1) whole life course approaches to reduce tobacco use in Indigenous women, (2) prohibiting tobacco promotion and reducing access to alcohol for minors to prevent smoking initiation in Indigenous youth, and (3) training health-care professionals in culturally appropriate smoking cessation care to improve access to services. It is critical to ensure acceptability and feasibility of study designs, consult with the relevant Indigenous communities, and preempt implementation challenges. Research is needed into the effect of reducing or stopping smoking during pregnancy when using NRT on subsequent maternal and infant outcomes.
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Nova |
2017 |
Kepreotes E, Whitehead B, Attia J, Oldmeadow C, Collison A, Searles A, et al., 'High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): an open, phase 4, randomised controlled trial', The Lancet, 389 930-939 (2017) [C1]
Background Bronchiolitis is the most common lung infection in infants and treatment focuses on management of respiratory distress and hypoxia. High-flow warm humidified oxygen (HF... [more]
Background Bronchiolitis is the most common lung infection in infants and treatment focuses on management of respiratory distress and hypoxia. High-flow warm humidified oxygen (HFWHO) is increasingly used, but has not been rigorously studied in randomised trials. We aimed to examine whether HFWHO provided enhanced respiratory support, thereby shortening time to weaning off oxygen. Methods In this open, phase 4, randomised controlled trial, we recruited children aged less than 24 months with moderate bronchiolitis attending the emergency department of the John Hunter Hospital or the medical unit of the John Hunter Children's Hospital in New South Wales, Australia. Patients were randomly allocated (1:1) via opaque sealed envelopes to HFWHO (maximum flow of 1 L/kg per min to a limit of 20 L/min using 1:1 air¿oxygen ratio, resulting in a maximum FiO2 of 0·6) or standard therapy (cold wall oxygen 100% via infant nasal cannulae at low flow to a maximum of 2 L/min) using a block size of four and stratifying for gestational age at birth. The primary outcome was time from randomisation to last use of oxygen therapy. All randomised children were included in the primary and secondary safety analyses. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12612000685819. Findings From July 16, 2012, to May 1, 2015, we randomly assigned 202 children to either HFWHO (101 children) or standard therapy (101 children). Median time to weaning was 24 h (95% CI 18¿28) for standard therapy and 20 h (95% CI 17¿34) for HFWHO (hazard ratio [HR] for difference in survival distributions 0·9 [95% CI 0·7¿1·2]; log rank p=0·61). Fewer children experienced treatment failure on HFWHO (14 [14%]) compared with standard therapy (33 [33%]; p=0·0016); of these children, those on HFWHO were supported for longer than were those on standard therapy before treatment failure (HR 0·3; 95% CI 0·2¿0·6; p<0·0001). 20 (61%) of 33 children who experienced treatment failure on standard therapy were rescued with HFWHO. 12 (12%) of children on standard therapy required transfer to the intensive care unit compared with 14 (14%) of those on HFWHO (difference -1%; 95% CI -7 to 16; p=0·41). Four adverse events occurred (oxygen desaturation and condensation inhalation in the HFWHO group, and two incidences of oxygen tubing disconnection in the standard therapy group); none resulted in withdrawal from the trial. No oxygen-related serious adverse events occurred. Secondary effectiveness outcomes are reported in the Results section. Interpretation HFWHO did not significantly reduce time on oxygen compared with standard therapy, suggesting that early use of HFWHO does not modify the underlying disease process in moderately severe bronchiolitis. HFWHO might have a role as a rescue therapy to reduce the proportion of children requiring high-cost intensive care. Funding Hunter Children's Research Foundation, John Hunter Hospital Charitable Trust, and the University of Newcastle Priority Research Centre GrowUpWell.
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Nova |
2017 |
Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, et al., 'MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase mediated suppression of histone deacetylase 2', Journal of Allergy and Clinical Immunology, 139 519-532 (2017) [C1]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of und... [more]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The¿mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. Objective We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Methods Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory¿tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21¿specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion We identify a previously unrecognized role for an¿miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.
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Nova |
2017 |
Girkin JL, Hatchwell LM, Collison AM, Starkey MR, Hansbro PM, Yagita H, et al., 'TRAIL signaling is proinflammatory and proviral in a murine model of rhinovirus 1B infection', American Journal of Physiology - Lung Cellular and Molecular Physiology, 312 L89-L99 (2017) [C1]
The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAI... [more]
The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-deficient (Tnfsf10-/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10-/-mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID50). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID50. HDM-challenged Tnfsf10-/-mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10-/-mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-¿2/3 but not IFN-a or IFN-ß. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.
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Nova |
2017 |
Le Fevre AK, Walker MM, Hadjiashrafy A, Bhatia R, Mattes J, Talley NJ, Nightingale S, 'Elevated Serum Tissue Transglutaminase Antibodies in Children With Eosinophilic Esophagitis.', Journal of pediatric gastroenterology and nutrition, 65 69-74 (2017) [C1]
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Nova |
2017 |
Asher I, Haahtela T, Selroos O, Ellwood P, Ellwood E, Billo NE, et al., 'Global Asthma Network survey suggests more national asthma strategies could reduce burden of asthma', Allergologia et Immunopathologia, 45 105-114 (2017) [C1]
Background Several countries or regions within countries have an effective national asthma strategy resulting in a reduction of the large burden of asthma to individuals and socie... [more]
Background Several countries or regions within countries have an effective national asthma strategy resulting in a reduction of the large burden of asthma to individuals and society. There has been no systematic appraisal of the extent of national asthma strategies in the world. Methods The Global Asthma Network (GAN) undertook an email survey of 276 Principal Investigators of GAN centres in 120 countries, in 2013¿2014. One of the questions was: ¿Has a national asthma strategy been developed in your country for the next five years? For children? For adults?¿. Results Investigators in 112 (93.3%) countries answered this question. Of these, 26 (23.2%) reported having a national asthma strategy for children and 24 (21.4%) for adults; 22 (19.6%) countries had a strategy for both children and adults; 28 (25%) had a strategy for at least one age group. In countries with a high prevalence of current wheeze, strategies were significantly more common than in low prevalence countries (11/13 (85%) and 7/31 (22.6%) respectively, p¿<¿0.001). Interpretation In 25% countries a national asthma strategy was reported. A large reduction in the global burden of asthma could be potentially achieved if more countries had an effective asthma strategy.
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Nova |
2017 |
Dunn A, Pearce K, Callister R, Collison A, Morten M, Mandaliya P, et al., 'Exercise capacity is not decreased in children who have undergone lung resection early in life for congenital thoracic malformations compared to healthy age-matched children', Pediatric Pulmonology, 52 1340-1348 (2017) [C1]
Purpose: The purpose of this study was to compare (i) the exercise capacity and (ii) lung function prior to and immediately post cardiopulmonary exercise tests (CPET) of children ... [more]
Purpose: The purpose of this study was to compare (i) the exercise capacity and (ii) lung function prior to and immediately post cardiopulmonary exercise tests (CPET) of children who underwent early life lung resection for Congenital Pulmonary Airway Malformations (CPAM) to healthy control children. Method: Eight children with CPAM (four males, age 9.6 ± 1.8 years) and eight control children without respiratory disease (three males, age 9.4 ± 1.4 years) performed a CPET on a cycle ergometer, during which maximal oxygen consumption (V¿O2max) and heart rate were measured. Prior to and immediately post CPET, lung function measures including Nitrogen Multiple Breath Washout (MBW) and spirometry were performed. Results: There were no significant between group differences in pre CPET lung function (P > 0.05) or maximal exercise capacity (V¿O2max CPAM: 39.4 mL.kg-1.min-1, Control: 40.5 mL.kg-1.min-1). Post CPET, FEV1 was significantly lower in the CPAM group, with two participants diagnosed subsequently with exercise induced bronchospasm based on post-CPET spirometry and follow-up clinical investigations. Conclusion: Early life lung resection for CPAM does not appear to have negative implications for exercise capacity later in childhood. Clinicians should be aware that dyspnoea following exercise may be due to asthma rather than residual effects of CPAM in these children.
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Nova |
2017 |
Silva FMC, Oliveira EE, Gouveia ACC, Brugiolo ASS, Alves CC, Correa JOA, et al., 'Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice', Clinical and Experimental Immunology, 189 47-59 (2017) [C1]
Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflamma... [more]
Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-¿ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity.
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Nova |
2017 |
Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, et al., 'Modeling T(H)2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma', IMMUNOLOGICAL REVIEWS, 278 20-40 (2017) [C1]
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Nova |
2016 |
Sokulsky LA, Collison AM, Nightingale S, Le Fevre A, Percival E, Starkey MR, et al., 'TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis', American Journal of Physiology - Gastrointestinal and Liver Physiology, 311 G998-G1008 (2016) [C1]
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNFrelated apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through... [more]
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNFrelated apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of the E3 ubiquitin ligase Midline (MID)-1 and subsequent downregulation of protein phosphatase 2A (PP2A), but the role of this pathway in EoE that is experimentally induced by repeated food antigen challenges has not been investigated. Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels. Wild-type and TRAIL-deficient (Tnfsf10-/-) mice were administered subcutaneous ovalbumin (OVA) followed by oral OVA challenges. In separate experiments, OVA-challenged mice were intraperitoneally administered salmeterol or dexamethasone. Esophageal biopsies from children with EoE revealed increased levels of TRAIL and MID-1 and reduced PP2A activation compared with controls. Tnfsf10-/- mice were largely protected from esophageal fibrosis, eosinophilic inflammation, and the upregulation of TSLP, IL-5, IL-13, and CCL11 when compared with wild-type mice. Salmeterol administration to wild-type mice with experimental EoE restored PP2A activity and also prevented esophageal eosinophilia, inflammatory cytokine expression, and remodeling, which was comparable to the treatment effect of dexamethasone. TRAIL and PP2A regulate inflammation and fibrosis in experimental EoE, which can be therapeutically modulated by salmeterol.
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Nova |
2016 |
Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al., 'A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease', Mucosal Immunology, 9 859-872 (2016) [C1]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective ... [more]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-Type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL + CD11b + monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
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Nova |
2016 |
Maltby S, Gibson P, Mattes J, McDonald VM, 'How to treat Severe Asthma Part 2 Management.', Australian Doctor, (2016)
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2016 |
Maltby S, Gibson P, Mattes J, McDonald VM, 'How to treat Severe Asthma Part 1 Diagnosis', Australian Doctor, (2016)
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2016 |
Lum S, Bountziouka V, Wade A, Hoo AF, Kirkby J, Moreno-Galdo A, et al., 'New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: A multicentre collaboration', Thorax, 71 276-283 (2016) [C1]
The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived f... [more]
The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices. Aim: To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation. Method: RVRTC data from healthy subjects using Jaeger BabyBody or the 'Respiratory Analysis Software Program, RASP' systems were collated from four centres internationally. Data were excluded if gestational age <37 weeks or birth weight <2.5 kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda-mu-sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF). Results: RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4-118 weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV0.5, compared with only 10% when using the new equations. Conclusions: Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up.
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Nova |
2016 |
Murphy VE, Jensen ME, Mattes J, Hensley MJ, Giles WB, Peek MJ, et al., 'The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health', BMC PREGNANCY AND CHILDBIRTH, 16 (2016)
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Nova |
2016 |
Searles A, Doran C, Attia J, Knight D, Wiggers J, Deeming S, et al., 'An approach to measuring and encouraging research translation and research impact', HEALTH RESEARCH POLICY AND SYSTEMS, 14 (2016) [C1]
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Nova |
2016 |
Judd LM, Heine RG, Menheniott TR, Buzzelli J, O Brien-Simpson N, Pavlic D, et al., 'Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice', American Journal of Physiology - Gastrointestinal and Liver Physiology, 310 G13-G25 (2016) [C1]
We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and ... [more]
We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.
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Nova |
2016 |
Lovett S, Roche J, Hunter S, Symonds I, Tomlinson N, Gagnon R, et al., 'Respective value of the traditional clinical rotation and high fidelity simulation on the acquisition of clinical reasoning skills in medical students A Randomized Controlled Trial.', MedEdPublish, 5 (2016) [C1]
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Nova |
2016 |
Percival E, Bhatia R, Preece K, McElduff P, McEvoy M, Collison A, Mattes J, 'Reproducibility of serum IgE, Ara h2 skin prick testing and fraction of exhaled nitric oxide for predicting clinical peanut allergy in children', ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, 12 (2016) [C1]
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Nova |
2015 |
Thorburn AN, McKenzie CI, Shen S, Stanley D, MacIa L, Mason LJ, et al., 'Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites', Nature Communications, 6 (2015) [C1]
Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinct... [more]
Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.
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Nova |
2015 |
Tay HL, Kaiko GE, Plank M, Li J, Maltby S, Essilfie A-T, et al., 'Correction: Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung.', PLoS pathogens, 11 e1004956 (2015) [O1]
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2015 |
Collison AM, Sokulsky LA, Sherrill JD, Nightingale S, Hatchwell L, Talley NJ, et al., 'TNF-related apoptosis-inducing ligand (TRAIL) regulates midline-1, thymic stromal lymphopoietin, inflammation, and remodeling in experimental eosinophilic esophagitis', Journal of Allergy and Clinical Immunology, 136 971-982 (2015) [C1]
Background Eosinophilic esophagitis (EoE) is an inflammatory disorder of the esophagus defined by eosinophil infiltration and tissue remodeling with resulting symptoms of esophage... [more]
Background Eosinophilic esophagitis (EoE) is an inflammatory disorder of the esophagus defined by eosinophil infiltration and tissue remodeling with resulting symptoms of esophageal dysfunction. TNF-related apoptosis-inducing ligand (TRAIL) promotes inflammation through upregulation of the E3 ubiquitin-ligase midline-1 (MID1), which binds to and deactivates the catalytic subunit of protein phosphatase 2Ac, resulting in increased nuclear factor ¿B activation. Objective We sought to elucidate the role of TRAIL in EoE. Methods We used Aspergillus fumigatus to induce EoE in TRAIL-sufficient (wild-type) and TRAIL-deficient (TRAIL-/-) mice and targeted MID1 in the esophagus with small interfering RNA. We also treated mice with recombinant thymic stromal lymphopoietin (TSLP) and TRAIL. Results TRAIL deficiency and MID1 silencing with small interfering RNA reduced esophageal eosinophil and mast cell numbers and protected against esophageal circumference enlargement, muscularis externa thickening, and collagen deposition. MID1 expression and nuclear factor ¿B activation were reduced in TRAIL-/- mice, whereas protein phosphatase 2Ac levels were increased compared with those seen in wild-type control mice. This was associated with reduced expression of CCL24, CCL11, CCL20, IL-5, IL-13, IL-25, TGFB, and TSLP. Treatment with TSLP reconstituted hallmark features of EoE in TRAIL-/- mice and recombinant TRAIL induced esophageal TSLP expression in vivo in the absence of allergen. Post hoc analysis of gene array data demonstrated significant upregulation of TRAIL and MID1 in a cohort of children with EoE compared with that seen in controls. Conclusion TRAIL regulates MID1 and TSLP, inflammation, fibrosis, smooth muscle hypertrophy, and expression of inflammatory effector chemokines and cytokines in experimental EoE.
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Nova |
2015 |
Schilter HC, Collison A, Russo RC, Foot JS, Yow TT, Vieira AT, et al., 'Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration', Respiratory Research, 16 (2015) [C1]
Background and purpose: The persistent influx of neutrophils into the lung and subsequent tissue damage are characteristics of COPD, cystic fibrosis and acute lung inflammation. V... [more]
Background and purpose: The persistent influx of neutrophils into the lung and subsequent tissue damage are characteristics of COPD, cystic fibrosis and acute lung inflammation. VAP-1/SSAO is an endothelial bound adhesion molecule with amine oxidase activity that is reported to be involved in neutrophil egress from the microvasculature during inflammation. This study explored the role of VAP-1/SSAO in neutrophilic lung mediated diseases and examined the therapeutic potential of the selective inhibitor PXS-4728A. Methods: Mice treated with PXS-4728A underwent intra-vital microscopy visualization of the cremaster muscle upon CXCL1/KC stimulation. LPS inflammation, Klebsiella pneumoniae infection, cecal ligation and puncture as well as rhinovirus exacerbated asthma models were also assessed using PXS-4728A. Results: Selective VAP-1/SSAO inhibition by PXS-4728A diminished leukocyte rolling and adherence induced by CXCL1/KC. Inhibition of VAP-1/SSAO also dampened the migration of neutrophils to the lungs in response to LPS, Klebsiella pneumoniae lung infection and CLP induced sepsis; whilst still allowing for normal neutrophil defense function, resulting in increased survival. The functional effects of this inhibition were demonstrated in the RV exacerbated asthma model, with a reduction in cellular infiltrate correlating with a reduction in airways hyperractivity. Conclusions and implications: This study demonstrates that the endothelial cell ligand VAP-1/SSAO contributes to the migration of neutrophils during acute lung inflammation, pulmonary infection and airway hyperractivity. These results highlight the potential of inhibiting of VAP-1/SSAO enzymatic function, by PXS-4728A, as a novel therapeutic approach in lung diseases that are characterized by neutrophilic pattern of inflammation.
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Nova |
2015 |
Li JJ, Tay HL, Maltby S, Xiang Y, Eyers F, Hatchwell L, et al., 'MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity', Journal of Allergy and Clinical Immunology, 136 462-473 (2015) [C1]
Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Levels of IFN-¿ and LPS are often increased in these patients.... [more]
Background Steroid-resistant asthma is a major clinical problem that is linked to activation of innate immune cells. Levels of IFN-¿ and LPS are often increased in these patients. Cooperative signaling between IFN-¿/LPS induces macrophage-dependent steroid-resistant airway hyperresponsiveness (AHR) in mouse models. MicroRNAs (miRs) are small noncoding RNAs that regulate the function of innate immune cells by controlling mRNA stability and translation. Their role in regulating glucocorticoid responsiveness and AHR remains unexplored. Objective IFN-¿ and LPS synergistically increase the expression of miR-9 in macrophages and lung tissue, suggesting a role in the mechanisms of steroid resistance. Here we demonstrate the role of miR-9 in IFN-¿/LPS-induced inhibition of dexamethasone (DEX) signaling in macrophages and in induction of steroid-resistant AHR. Methods MiRNA-9 expression was assessed by means of quantitative RT-PCR. Putative miR-9 targets were determined in silico and confirmed in luciferase reporter assays. miR-9 function was inhibited with sequence-specific antagomirs. The efficacy of DEX was assessed by quantifying glucocorticoid receptor (GR) cellular localization, protein phosphatase 2A (PP2A) activity, and AHR. Results Exposure of pulmonary macrophages to IFN-¿/LPS synergistically induced miR-9 expression; reduced levels of its target transcript, protein phosphatase 2 regulatory subunit B (B56) d isoform; attenuated PP2A activity; and inhibited DEX-induced GR nuclear translocation. Inhibition of miR-9 increased both PP2A activity and GR nuclear translocation in macrophages and restored steroid sensitivity in multiple models of steroid-resistant AHR. Pharmacologic activation of PP2A restored DEX efficacy and inhibited AHR. MiR-9 expression was increased in sputum of patients with neutrophilic but not those with eosinophilic asthma. Conclusion MiR-9 regulates GR signaling and steroid-resistant AHR. Targeting miR-9 function might be a novel approach for the treatment of steroid-resistant asthma.
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2015 |
Hatchwell L, Collison A, Girkin J, Parsons K, Li J, Zhang J, et al., 'Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia', Thorax, (2015) [C1]
© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), w... [more]
© 2015 BMJ Publishing Group Ltd & British Thoracic Society.Background Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), which is sensed by Toll-like receptors (TLR) such as TLR7. Some asthmatics have impaired interferon (IFN) responses to RV, but the underlying mechanisms of this clinically relevant observation are poorly understood. Objectives To investigate the importance of intact TLR7 signalling in vivo during RV exacerbation using mouse models of house dust mite (HDM)-induced allergic airways disease exacerbated by a superimposed RV infection. Methods Wild-type and TLR7-deficient (Tlr7<sup>-/-</sup>) BALB/c mice were intranasally sensitised and challenged with HDM prior to infection with RV1B. In some experiments, mice were administered recombinant IFN or adoptively transferred with plasmacytoid dendritic cells (pDC). Results Allergic Tlr7<sup>-/-</sup> mice displayed impaired IFN release upon RV1B infection, increased virus replication and exaggerated eosinophilic inflammation and airways hyper reactivity. Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFN? release in the absence of host TLR7 signalling. TLR7 expression in the lungs was suppressed by allergic inflammation and by interleukin (IL)-5-induced eosinophilia in the absence of allergy. Subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, despite inhaled steroids, showed reduced TLR7 and IFN?2/3 expression in endobronchial biopsies. Furthermore, TLR7 expression inversely correlated with percentage of sputum eosinophils. Conclusions This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression and antiviral responses, which provides a molecular mechanism underpinning the effect of eosinophil-targeting treatments for the prevention of asthma exacerbations.
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Nova |
2015 |
Mandaliya PH, Morten M, Kumar R, James A, Deshpande A, Murphy VE, et al., 'Ventilation inhomogeneities in children with congenital thoracic malformations', BMC Pulmonary Medicine, 15 (2015) [C1]
Background: Congenital thoracic malformations (CTM) are rare lung lesions that are managed with surgical resection or active surveillance. Methods: Nitrogen lung clearance index (... [more]
Background: Congenital thoracic malformations (CTM) are rare lung lesions that are managed with surgical resection or active surveillance. Methods: Nitrogen lung clearance index (LCI), reactance and resistance (X5Hz and R5Hz), forced expiratory volume in 1 s and forced vital capacity (FEV1 and FVC) were prospectively measured in 10 children with CTM (mean age/SD: 7.6/1.3) who had undergone surgical resection in early life and in 17 healthy children (mean age/SD: 4.8/0.4). Total lung capacity (TLC) was also conducted in children older than 7 years of age with CTM (n = 8). Results: Mean LCI was 8.0 (95% CI 7.5 to 8.5) in the CTM group and 7.3 (95% CI 7.0 to 7.6) in healthy children (p = 0.016). Mean X5Hz was -0.44kPa/l/s (95% CI -0.58 to -0.31) in the CTM group and -0.31kPa/l/s (95% CI -0.35 to -0.27) in healthy children (p = 0.02). Mean Z score for X5Hz was -2.11 (95% CI -3.59 to -0.63) in the CTM group and -0.11 (95% CI -0.55 to 0.33) in healthy children (p = 0.0008). Mean FEV1 was 1.21 L (95% CI 0.97 to 1.45) in the CTM group and 1.02 L (95% CI 0.90 to 1.15) in healthy children (p = 0.22). Mean % predicted FEV1 was 83% (95% CI 74 to 92) in the CTM group and 97% (95% CI 87 to 107) in healthy children (p < 0.05). Mean % predicted TLC in CTM children was 121.3% (95% CI 88.45 to 154.1). Mean LCI was inversely correlated with height z-scores in the CTM group (rs = -0.88, p = 0.002) but not in healthy children (rs = 0.22, p = 0.4). Conclusions: Children with CTM have impaired lung function as demonstrated by the significant differences in LCI, reactance and FEV1 but not FVC, resistance and TLC. These findings may be of clinical relevance as ventilation inhomogeneities are closely correlated with somatic growth in this study.
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Nova |
2015 |
Girkin J, Hatchwell L, Foster P, Johnston SL, Bartlett N, Collison A, Mattes J, 'CCL7 and IRF-7 mediate hallmark inflammatory and IFN responses following rhinovirus 1B infection', Journal of Immunology, 194 4924-4930 (2015) [C1]
Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B-infected naive BALB/c mice (nonallergi... [more]
Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B-infected naive BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7 among the most upregulated mRNA transcripts in the lung. To investigate their roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced activation of NF-¿B p65 and p50 subunits, as well as airway hyperreactivity (AHR) in nonallergic mice. However, neither NF-¿B subunit activation nor AHR was abolished with infection of allergic mice after neutralizing CCL7, despite a reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small interfering RNA primarily suppressed IFN-a and IFN-b levels during infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7 in RV-induced inflammation and IFN responses and link NF-¿B signaling to the development of AHR.
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Nova |
2015 |
Tay HL, Kaiko GE, Plank M, Li JJ, Maltby S, Essilfie AT, et al., 'Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung', PLoS Pathogens, 11 (2015) [C1]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibio... [more]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.
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2014 |
Starkey MR, Nguyen DH, Essilfie AT, Kim RY, Hatchwell LM, Collison AM, et al., 'Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease.', Mucosal Immunol, 7 478-488 (2014) [C1]
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2014 |
Mattes J, Gibson PG, 'The early origins of copd in severe asthma: The one thing that leads to another or the two things that come together?', Thorax, 69 789-790 (2014) [C3]
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Nova |
2014 |
Mattes J, Murphy VE, Powell H, Gibson PG, 'Prenatal origins of bronchiolitis: Protective effect of optimised asthma management during pregnancy', Thorax, 69 383-384 (2014) [C1]
Objective Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy. Recurrent episodes of bronchiolitis are stro... [more]
Objective Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy. Recurrent episodes of bronchiolitis are strongly associated with the development of childhood asthma. Methods We conducted a follow-up study of infants born to women with asthma who completed a double-blind randomised controlled trial during pregnancy. In this trial, pregnant women with asthma were assigned to treatment adjustment by an algorithm using clinical symptoms (clinical group) or the fraction of exhaled nitric oxide (FeNO group) and we showed that the FeNO group had significantly lower asthma exacerbation rates in pregnancy. Results 146 infants attended the 12-month follow-up visit. Infants born to mothers from the FeNO group were significantly less likely to have recurrent episodes of bronchiolitis in the first year of life (OR 0.08, 95% CI 0.01 to 0.62; p=0.016) as compared with the clinical group. Conclusions Optimised management of asthma during pregnancy may reduce recurrent episodes of bronchiolitis in infancy, which could potentially modulate the risk to develop or the severity of emerging childhood asthma.
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2014 |
Hatchwell L, Girkin J, Morten M, Collison A, Mattes J, Foster PS, et al., 'Salmeterol attenuates chemotactic responses in rhinovirus-induced exacerbation of allergic airways disease by modulating protein phosphatase 2A', Journal of Allergy and Clinical Immunology, (2014) [C1]
Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning... [more]
Background: ß-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning mechanisms remain poorly understood. Recently, a direct interaction between formoterol and protein phosphatase 2A (PP2A) has been described in¿vitro. Objective: We sought to elucidate the molecular mechanisms by which ß-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD). Methods: Mice were sensitized and then challenged with house dust mite to induce AAD while receiving treatment with salmeterol, formoterol, or salbutamol. Mice were also infected with rhinovirus 1B to exacerbate lung inflammation and therapeutically administered salmeterol, dexamethasone, or the PP2A-activating drug (S)-2-amino-4-(4-[heptyloxy]phenyl)-2-methylbutan-1-ol (AAL[S]). Results: Systemic or intranasal administration of salmeterol protected against the development of allergen- and rhinovirus-induced airway hyperreactivity and decreased eosinophil recruitment to the lungs as effectively as dexamethasone. Formoterol and salbutamol also showed anti-inflammatory properties. Salmeterol, but not dexamethasone, increased PP2A activity, which reduced CCL11, CCL20, and CXCL2 expression and reduced levels of phosphorylated extracellular signal-regulated kinase 1 and active nuclear factor ¿B subunits in the lungs. The anti-inflammatory effect of salmeterol was blocked by targeting the catalytic subunit of PP2A with small RNA interference. Conversely, increasing PP2A activity with AAL(S) abolished rhinovirus-induced airway hyperreactivity, eosinophil influx, and CCL11, CCL20, and CXCL2 expression. Salmeterol also directly activated immunoprecipitated PP2A in¿vitro isolated from human airway epithelial cells. Conclusions: Salmeterol exerts anti-inflammatory effects by increasing PP2A activity in AAD and rhinovirus-induced lung inflammation, which might potentially account for some of its clinical benefits. © 2013 American Academy of Allergy, Asthma & Immunology.
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Nova |
2014 |
Tay HL, Plank M, Collison A, Mattes J, Kumar RK, Foster PS, 'MicroRNA: Potential biomarkers and therapeutic targets for allergic asthma?', Annals of Medicine, 46 633-639 (2014) [C1]
MicroRNAs are small non-coding RNAs that bind to multiple target mRNAs to control gene expression post-transcriptionally by inhibiting translation. In mammalian cells, microRNAs p... [more]
MicroRNAs are small non-coding RNAs that bind to multiple target mRNAs to control gene expression post-transcriptionally by inhibiting translation. In mammalian cells, microRNAs play important roles in a diverse array of cellular processes (e.g. cell proliferation and differentiation). However, alterations in their levels may compromise cellular function, predisposing to disease. In this review, we discuss microRNAs that have been linked with pathogenesis of asthma and propose functional roles in the regulation of disease. MicroRNAs have the potential to be biomarkers for asthma and provide the platform for the development of new classes of therapeutic compounds.
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2014 |
Murphy VE, Mattes J, Powell H, Baines KJ, Gibson PG, 'Respiratory viral infections in pregnant women with asthma are associated with wheezing in the first 12 months of life', Pediatric Allergy and Immunology, 25 151-158 (2014) [C1]
Background: There are few studies investigating the relationship between respiratory viral infection in pregnancy and asthma in the offspring, and none among mothers with asthma. ... [more]
Background: There are few studies investigating the relationship between respiratory viral infection in pregnancy and asthma in the offspring, and none among mothers with asthma. Infants of mothers with asthma are more likely to wheeze and have a higher risk of developing asthma than infants of non-asthmatic mothers. Methods: A prospective cohort study of viral infection in pregnancy was conducted between 2007 and 2009, and a subgroup of infants of mothers with asthma was followed up at 6 and 12 months of age. During common colds, nasal and throat swabs were collected from mothers and respiratory viruses detected by polymerase chain reaction. Respiratory health of infants was assessed by parent-completed questionnaire. Results: Twelve-month-old infants whose mothers had confirmed viral infections in pregnancy (n = 26) reported more frequent wheeze (40% had 4-12 wheeze attacks compared with 0%), sleep disturbed by wheeze (1 night per week or more in 60% vs. 11%), beta agonist treatment for wheeze (27% vs. 0%), prolonged colds (2 wk or longer 31% vs. 0%), more eczema (40% vs. 6.3%), and parent-perceived asthma (32% vs. 0%), compared with infants whose mothers had common colds without laboratory-confirmed viral infection (n = 16). Conclusions: This study demonstrates a relationship between maternal respiratory viral infection in pregnancy and wheezing illness in infants of mothers with asthma. Viral infections are the most common cause of asthma exacerbations in pregnancy, and infants of asthmatic mothers are at increased risk of asthma themselves. Further research is needed to elucidate the mechanisms involved. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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2014 |
Preece K, Bhatia R, Belcher J, Patchett K, McElduff P, Collison A, Mattes J, 'The fraction of exhaled nitric oxide improves prediction of clinical allergic reaction to peanut challenge in children', CLINICAL AND EXPERIMENTAL ALLERGY, 44 371-380 (2014) [C1]
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Nova |
2014 |
Pinnock R, Monagle P, Couper J, Wright I, Asher I, Jones P, et al., 'Dedicated paediatric teaching remains critical to the undergraduate medical curriculum', JOURNAL OF PAEDIATRICS AND CHILD HEALTH, 50 949-951 (2014) [C3]
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2014 |
Wark PAB, Murphy V, Mattes J, 'The interaction between mother and fetus and the development of allergic asthma', Expert Review of Respiratory Medicine, 8 57-66 (2014) [C1]
The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in suscep... [more]
The rising prevalence of asthma and atopic disease in industrialized countries in the last 50 years has raised important questions about how and why the disease develops in susceptible populations. Most asthma begins in childhood in association with allergic sensitization and the development of a TH2 phenotype. It is recognized that asthma arises in the context of a complex interaction between genetic factors and the evolving immune system of the infant and the environment to which it is exposed, which now includes its in utero exposure. Early life exposures that lead to allergen sensitization and airway damage, especially in the form of viral respiratory tract infections, may lead to disease induction that commence the process that leads in some to asthma. Asthma models and early life observations suggest that repeated exposure to allergens and viral infection perpetuate a state of chronic airway inflammation leading to a maladaptive innate immune response that fails to resolve, characterized by chronic airway inflammation, airway remodeling and airway hyperresponsiveness. This article will concentrate on the development of asthma in the context of early life and maternal influences, including the effect of asthma on both the fetus and the mother. © 2014 Informa UK Ltd.
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2014 |
Hansbro PM, Starkey MR, Mattes J, Horvat JC, 'Pulmonary immunity during respiratory infections in early life and the development of severe asthma', Annals of the American Thoracic Society, 11 S297-S302 (2014) [C1]
Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation... [more]
Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) to normally innocuous antigens. Combination therapies with inhaled corticosteroids and bronchodilators effectively manage mild to moderate asthma, but there are no cures, and patients with severe asthma do not respond to these treatments. The inception of asthma is linked to respiratory viral (respiratory syncytial virus, rhinovirus) and bacterial (Chlamydia, Mycoplasma) infections. The examination of mouse models of early-life infections and allergic airway disease (AAD) provides valuable insights into the mechanisms of disease inception that may lead to the development of more effective therapeutics. For example, early-life, but not adult, Chlamydia respiratory infections in mice permanently modify immunity and lung physiology. This increases the severity of AAD by promoting IL-13 expression, mucus hypersecretion, and AHR. We have identified novel roles for tumor necrosis factor-related apoptosisinducing ligand (TRAIL) and IL-13 in promoting infection-induced pathology in early life and subsequent chronic lung disease. Genetic deletion of TRAIL or IL-13 variously protected against neonatal infection-induced inflammation, mucus hypersecretion, altered lung structure, AHR, and impaired lung function. Therapeutic neutralization of these factors prevented infection-induced severe AAD. Other novel mechanisms and avenues for intervention are also being explored. Such studies indicate the immunological mechanisms that may underpin the association between early-life respiratory infections and the development of more severe asthma and may facilitate the development of tailored preventions and treatments.
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Nova |
2014 |
Gunawardhana LP, Baines KJ, Mattes J, Murphy VE, Simpson JL, Gibson PG, 'Differential DNA methylation profiles of infants exposed to maternal asthma during pregnancy', Pediatric Pulmonology, 49 852-862 (2014) [C1]
Background Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important... [more]
Background Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important in asthma development. Fetal exposure to maternal asthma during critical periods of in utero development may lead to epigenetic alterations that predispose infants to a greater risk of developing asthma themselves. We investigated alterations in the DNA methylation profile of peripheral blood from infants exposed to maternal asthma during pregnancy. Methods Peripheral blood was collected from 12-month-old infants born to women with (n = 25) and without (n = 15) doctor diagnosed asthma during pregnancy. Genomic DNA was extracted, bisulfite converted, and hybridized to Infinium Methylation 27 arrays (Illumina), containing over27,000 CpGs from 14,495 genes. CpG loci in only autosomal genes were classified as differentially methylated at the 99% level (P < 0.01, |DiffScore| > 22 and delta beta >0.06). Results There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper-methylated loci of FAM181A, MRI1, PIWIL1, CHFR, DEFA1, MRPL28, AURKA, and hypo-methylated loci of NALP1L5, MAP8KIP3, ACAT2, and PM20D1 in maternal asthma. Methylation of MAPK8IP3 was significantly negatively correlated with maternal blood eosinophils (r = -0.38; P = 0.022), maternal eNO (r = -0.44; P = 0.005), and maternal serum total IgE (r = -0.39, P = 0.015). Methylation of AURKA negatively correlated with maternal hemoglobin (r = -0.43; P = 0.008), infants height (r = -0.51; P < 0.001) and weight (r = -0.36; P = 0.021). Methylation of PM20D1 was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of PM20D1 was lower and MRI1 was higher in infants born to atopic mothers without asthma. Conclusions In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development. © 2013 Wiley Periodicals, Inc.
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Nova |
2014 |
Collison A, Li J, Pereira De Siqueira A, Zhang J, Toop HD, Morris JC, et al., 'Tumor necrosis factor-related apoptosis-inducing ligand regulates hallmark features of airways remodeling in allergic airways disease', American Journal of Respiratory Cell and Molecular Biology, 51 86-93 (2014) [C1]
Allergic asthma is a complex disease characterized by acute inflammation of the airways that over time leads to the development of significant structural changes termed remodeling... [more]
Allergic asthma is a complex disease characterized by acute inflammation of the airways that over time leads to the development of significant structural changes termed remodeling. TNF-related apoptosis-inducing ligand (TRAIL) has an important regulatory role in acute allergic airways inflammation through up-regulation of the E3 ubiquitin ligase Midline-1 (MID-1), which limits protein phosphatase 2A (PP2A) activity and downstream dephosphorylation of proinflammatory signaling molecules. The relevance of TRAIL in the development of airways remodeling has yet to be determined. In this study, the lungs of wild-type (WT) BALB/c and Tnfsf10 knockout (TRAIL-/-) mice were chronically exposed to ovalbumin (OVA) for 12 weeks to induce hallmark features of chronic allergic airways disease, including airways hyperreactivity (AHR), subepithelial collagen deposition, goblet cell hyperplasia, and smooth muscle hypertrophy. TRAIL-/- mice were largely protected from the development of AHR and peribronchial eosinophilia and had reduced levels of mast cells in the airways. This correlated with lower levels of cytokines, including IL-4, -5, -10, and -13, and with lower levels of proinflammatory chemokines from cultured cells isolated from the draining lymph nodes. TRAIL-/- mice were also protected from the characteristic features of airways remodeling, including peribronchial fibrosis, smooth muscle hypertrophy, and mucus hypersecretion, which correlated with reduced TGF-ß1 levels in the lungs. MID-1 expression was reduced in TRAIL-/- mice and up-regulated in allergic WT mice. Raising PP2A activity using 2-amino-4-(4-heptyloyphenol)-2-methylbutan-1-ol in allergic WT mice reduced eosinophilia, TGF-ß1, and peribronchial fibrosis. This study shows that TRAIL promotes airways remodeling in an OVA-induced model of chronic allergic airways disease. Targeting TRAIL and its downstream proin flammatory signaling pathway involving PP2A may be of therapeutic bene fit in reducing the hallmark features of airways remodeling observed in chronic allergic airways inflammation. Copyright © 2014 by the American Thoracic Society.
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2013 |
de Souza Alves CC, Collison A, Hatchwell L, Plank M, Morten M, Foster PS, et al., 'Inhibiting AKT phosphorylation employing non-cytotoxic anthraquinones ameliorates TH2 mediated allergic airways disease and rhinovirus exacerbation.', PLoS One, 8 e79565 (2013) [C1]
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Nova |
2013 |
Foster PS, Plank MW, Collison AM, Tay HL, Kaiko GE, Li J, et al., 'The emerging role of microRNAs in regulating immune and inflammatory responses in the lung', Immunological Reviews, 253 198-215 (2013) [C1]
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Nova |
2013 |
Plank M, Maltby S, Mattes J, Foster PS, 'Targeting translational control as a novel way to treat inflammatory disease: the emerging role of microRNAs.', Clinical and Experimental Allergy, 43 981-999 (2013)
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Nova |
2013 |
Barry J, Loh Z, Collison A, Mazzone S, Lalwani A, Zhang V, et al., 'Absence of Toll-IL-1 Receptor 8/Single Immunoglobulin IL-1 Receptor-Related Molecule Reduces House Dust Mite-Induced Allergic Airway Inflammation in Mice', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 49 481-490 (2013) [C1]
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Nova |
2013 |
Collison AM, Hatchwell LM, Verrills NM, Wark PA, Pereira De Siqueira AL, Tooze MK, et al., 'The E3 ubiquitin ligase midline 1 promotes allergen and rhinovirus-induced asthma by inhibiting protein phosphatase 2A activity', Nature Medicine, 19 232-237 (2013) [C1]
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Nova |
2013 |
Collison A, Siegle JS, Hansbro NG, Kwok C-T, Herbert C, Mattes J, et al., 'Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma', DISEASE MODELS & MECHANISMS, 6 993-1000 (2013) [C1]
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Nova |
2013 |
Starkey MR, Essilfie A-T, Horvat JC, Kim RY, Nguyen DH, Beagley KW, et al., 'Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease', Mucosal Immunology, 6 569-579 (2013) [C1]
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Nova |
2012 |
Starkey MR, Kim RY, Beckett EL, Schilter HC, Shim D, Essilfie A-T, et al., 'Chlamydia muridarum lung infection in infants alters hematopoietic cells to promote allergic airway disease in mice', PLoS One, 7 (2012) [C1]
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2011 |
Collison AM, Herbert C, Siegle JS, Mattes J, Foster PS, Kumar RK, 'Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target', BMC Pulmonary Medicine, 11 29 (2011) [C1]
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Nova |
2011 |
Collison AM, Mattes J, Plank MW, Foster PS, 'Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment', Journal of Allergy and Clinical Immunology, 128 160-U251 (2011) [C1]
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Nova |
2011 |
Weckmann M, Kopp MV, Heinzmann A, Mattes J, 'Haplotypes covering the TNFSF10 gene are associated with bronchial asthma', Pediatric Allergy and Immunology, 22 25-30 (2011) [C1]
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Nova |
2011 |
Kumar RK, Siegle JS, Kaiko GE, Herbert C, Mattes JE, Foster PS, 'Responses of airway epithelium to environmental injury: role in the induction phase of childhood asthma.', Journal of allergy, 2011 257017 (2011)
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2009 |
Tran HA, Song S, Crock PA, Mattes J, Howard K, 'The A, B, C, D of hypercalcaemia in Down syndrome', BMJ Case Reports, (2009) [C1]
Hypercalcaemia in infants with Down syndrome is an uncommon condition with only five previous case reports. The patients often present in the toddler years with the classical tria... [more]
Hypercalcaemia in infants with Down syndrome is an uncommon condition with only five previous case reports. The patients often present in the toddler years with the classical triad of Down syndrome, biochemical hypercalcaemia, and nephrocalcinosis. We present the sixth case and second male with this condition and further review the clinical details of this under-recognised condition and stratify the diagnostic criteria. The management mandates a reduction in calcium intake as a first step. The natural history of the various aspects of this condition is also considered.
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2009 |
Mattes J, Collison AM, Plank MW, Phipps S, Foster PS, 'Antagonism of microRNA-126 suppresses the effector function of T(H)2 cells and the development of allergic airways disease', Proceedings of the National Academy of Sciences of the United States of America, 106 18704-18709 (2009) [C1]
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Nova |
2009 |
Collison AM, Foster PS, Mattes J, 'Emerging role of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) as a key regulator of inflammatory responses', Clinical and Experimental Pharmacology and Physiology, 36 1049-1053 (2009) [C1]
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Nova |
2009 |
Foster PS, Mattes J, 'IL-21 comes of age', Immunology and Cell Biology, 87 359-360 (2009) [C2]
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Nova |
2009 |
Phipps S, Lam CE, Kaiko GE, Foo A, Collison AM, Mattes J, et al., 'Toll/IL-1 signaling is critical for house dust mite-specific Th1 and Th2 responses', American Journal of Respiratory and Critical Care Medicine, 179 883-893 (2009) [C1]
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Nova |
2008 |
Mattes J, Collison AM, Foster PS, 'Emerging role of microRNAs in disease pathogenesis and strategies for therapeutic modulation', Current Opinion in Molecular Therapeutics, 10 150-157 (2008) [C1]
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Nova |
2008 |
Yang M, Mattes J, 'Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs', Pharmacology & Therapeutics, 117 94-104 (2008) [C1]
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Nova |
2007 |
Mattes J, Yang M, Foster PS, 'Regulation of microRNA by antagomirs: a new class of pharmacological antagonists for the specific regulation of gene function?', American Journal of Respiratory and Cellular Molecular Biology, 36 8-12 (2007) [C1]
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2007 |
Weckmann M, Collison A, Simpson JL, Kopp MV, Wark PA, Smyth MJ, et al., 'Critical link between TRAIL and CCL20 for the activation of T(H)2 cells and the expression of allergic airway disease', Nature Medicine, 13 1308-1315 (2007) [C1]
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2007 |
Huck B, Neumann-Haefelin D, Schmitt-Graeff A, Weckmann M, Mattes J, Ehl S, Falcone V, 'Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus', Respiratory Research, 8 (2007) [C1]
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2007 |
Mattes J, Whitehead BF, Liehr T, Wilkinson I, Bear J, Fagan KA, et al., 'Paternal uniparental isodisomy for chromosome 14 with mosaicism for a supernumerary marker chromosome 14', American Journal of Medical Genetics Part A, 143A 2165-2171 (2007) [C1]
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2006 |
Yang M, Mattes J, Hansbro PM, Foster PS, 'Employment of microRNA profiles and RNA interference and antagomirs for the characterization and treatment of respiratory disease', Drug Discovery Today: Therapeutic Strategies, 3 325-332 (2006) [C1]
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Nova |
2005 |
Prescott VE, Campbell PM, Moore A, Mattes J, Rothenberg ME, Foster PS, et al., 'Transgenic expression of bean alpha-amylase inhibitor in peas results in altered structure and immunogenicity', Journal of Agricultural and Food Chemistry, 53 9023-9030 (2005) [C1]
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2004 |
Clark K, Simson L, Newcombe N, Koskinen AML, Mattes J, Lee NA, et al., 'Eosinophil degranulation in the allergic lung of mice primarily occurs in the airway lumen', Journal of Leukocyte Biology, 75 1001-1009 (2004) [C1]
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2004 |
Ihorst G, Frischer T, Horak F, Schumacher M, Kopp M, Forster J, et al., 'Long- and medium-term ozone effects on lung growth including a broad spectrum of exposure', EUROPEAN RESPIRATORY JOURNAL, 23 292-299 (2004)
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2004 |
Storm Van's Gravesande K, Mattes J, Endlicher A, Alving K, Ihorst G, Kühr J, 'Effect of two doses of budesonide on exhaled nitric oxide and urinary EPX excretion in asthmatic children', Pneumologie, 58 483-488 (2004)
The use of objective outcome measures that assess airway inflammation in pediatric asthma can provide a good evaluation of asthma severity and treatment response. In this double-b... [more]
The use of objective outcome measures that assess airway inflammation in pediatric asthma can provide a good evaluation of asthma severity and treatment response. In this double-blind and randomized study the effects of 200 µg of budesonide and 800 µg of budesonide on markers of inflammation (exhaled nitric oxide (eNO), eosinophil protein X (EPX) excretion in urine) and on lung function (FEV 1) were prospectively investigated in 24 ICS-naive children with mild persistent to moderate persistent asthma over a period of eight weeks. After eight weeks of treatment 200 µg and 800 µg of budesonide led to a significant decrease (p < 0.025) in eNO [median (90% interval): 200 µg: -17.2 ppb (-54.6 to 0.9); 800 µg: -13.2 ppb (-44.6 to -1.7)]. A significant change in urinary EPX excretion was only observed in the high dose group [200 µg: -10.3 µg/mmol creatinine (-116.2 to 50.5), p = 0.9; 800 µg: -49.2 µg/mmol creatinine (-231.0 to 48.7), p = 0.02]. However, a significant difference between the change from baseline after 8 weeks of either group was found neither for eNO (p = 0.66) nor for EPX excretion (p = 0.04). In conclusion, our data demonstrate that 800 µg budesonide per day did not show any advantage in reduction of airway inflammation, measured by eNO and urinary EPX excretion, in children with mild persistent to moderate persistent asthma.
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2004 |
Ngoumou G, Schaefer DO, Mattes J, Kopp MV, 'Interleukin-18 enhances the production of interferon-gamma (IFN-gamma) by allergen-specific and unspecific stimulated cord blood mononuclear cells', CYTOKINE, 25 172-178 (2004)
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2003 |
Mattes J, Foster P, 'Regulation of eosinophil migration and Th2 cell function by IL-5 and eotaxin', Current Drug Targets, 2 169-174 (2003) [C1]
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2003 |
Foster PS, Yang M, Mattes J, Kumar R, Webb D, 'Interleukin-13 and allergy', Modern Aspects of Immunobiology, 3 8 (2003)
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2003 |
Mattes J, Hulett M, Xie W, Hogan S, Rothenburg ME, Foster P, Parish C, 'Immunotherapy of cytotoxic T cell resistant tumors by T helper 2 cells: an eotaxin and STAT6 dependent process', Journal of Experimental Medicine, 197 387-393 (2003) [C1]
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2003 |
Kruse S, Kuehr J, Moseler M, Kropp MV, Kurz T, Deichmann KA, et al., 'Polymorphisms in the IL18 gene are associated with specific sensitization to common allergens and allergic rhinitis', Journal of Allergy and Clinical Immunology, 111 117-122 (2003) [C1]
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2003 |
Lange J, Ngoumou G, Berkenheide S, Moseler M, Mattes J, Kuehr J, Kopp MV, 'High interleukin-13 production by phytohaemagglutinin- and Der p 1-stimulated cord blood mononuclear cells is associated with the subsequent development of atopic dermatitis at the age of 3 years', CLINICAL AND EXPERIMENTAL ALLERGY, 33 1537-1543 (2003)
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2002 |
Mattes J, Yang M, Mahalinggam S, Kuehr J, Webb DC, Simson L, et al., 'Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and cotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma.', J Exp Med. 195:1433-44, 1433-1444 (2002) [C1]
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2002 |
Mattes J, Gravesande KSV, Moeller C, Moseler M, Brandis M, Kuehr J, 'Circadian variation of exhaled nitric oxide and urinary eosinophil protein X in asthmatic and healthy children', PEDIATRIC RESEARCH, 51 190-194 (2002)
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2002 |
Foster PS, Hogan S, Yang M, Mattes J, Young I, Matthaei K, et al., 'Interleukin-5 and eosinophils as therapeutic targets for asthma', Trends in Molecular Medicine, 8 162-167 (2002) [C2]
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2002 |
Karmaus W, Arshad H, Mattes J, 'Re: "Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years" - Reply', AMERICAN JOURNAL OF EPIDEMIOLOGY, 156 883-884 (2002)
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2001 |
Karmaus W, Arshad H, Mattes J, 'Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years', AMERICAN JOURNAL OF EPIDEMIOLOGY, 154 909-915 (2001)
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2001 |
Hertz M, Mahalingam S, Dalum I, Klysner S, Mattes J, Neisig A, et al., 'Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma', Journal of Immunology, 167 3792-3799 (2001) [C1]
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2001 |
Mackenzie J, Mattes J, Dent L, Foster PS, 'Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function', Journal of Immunology, 167 3146-3155 (2001) [C1]
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2001 |
Mattes J, Yang M, Siqueira A, Clark K, Mackenzie J, McKenzie A, et al., 'IL-13 induces airways hyperreactivity independently of the IL-4R{alpha} chain in the allergic lung', Journal of Immunology, 167 1683-1692 (2001) [C1]
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2001 |
Foster PS, Mould A, Yang M, Mackenzie J, Mattes J, Hogan S, et al., 'Elemental signals regulating eosinophil accumulation in the lung', Immunological Reviews, 179 173-181 (2001) [C2]
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2000 |
Webb D, McKenzie A, Koskinen A, Yang M, Mattes J, Foster PS, 'Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity', Journal of Immunology, 165 108-113 (2000) [C1]
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2000 |
Mattes J, van's Gravesande KS, Moeller C, Kuehr J, 'Circadian variation of urinary EPX in asthmatic and healthy children', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 105 S193-S193 (2000)
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2000 |
van Gravesande KS, Mattes J, Grossklauss E, Zurmuhl A, Moseler M, Kuhr J, 'Preventive effect of 2 and 10 mg of sodium cromoglycate on exercise-induced bronchoconstriction', EUROPEAN JOURNAL OF PEDIATRICS, 159 759-763 (2000)
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2000 |
Reining U, Mattes J, Storm Van's Gravesande K, Ihorst G, Kühr J, 'Reproducibility in the induced sputum in childhood', Pneumologie, 54 185-190 (2000)
In asthmatic children sputum-induction with hypertonic saline is useful to quantify the eosinophilic inflammation. However, only few data are available about feasibility and safet... [more]
In asthmatic children sputum-induction with hypertonic saline is useful to quantify the eosinophilic inflammation. However, only few data are available about feasibility and safety of the procedure in children. Therefore, taking 9 non-atopic healthy control children (mean age 11,8 years) and 34 asthmatic children (mean age 11,4 years), inhaling n = 25 Budesonid (400-1200 µg/die) and n = 9 DNCG (60 mg/die), sputum induction was performed twice within 6 weeks. Briefly, 10 minutes after inhalation of 200 µg salbutamol subjects inhaled hypertonic saline (3, 4 and 5%) for in all 30 minutes, while all 5 minutes lung function was checked and expectoration of sputum was supported. Adequate sputum plugs were separated from contaminating saliva and processed immediately employing native chamber and cytospin cell count as well as measurement of eosinophilic: cationic protein (ECP). Sputum-induction could be performed in 84 out of 86 planed tests (97,7%) without any objective clinical adverse effects. The mean fall in FEV1 was 3,0%, the maximum 11,0%. The reproducibility of eosinophil, neutrophil and lymphocyte differential cell count (5-95%-values Test1: 0,0- 4.2%, 0,8 - 11,4%, and 3.2 - 35,1%, respectively) was moderate for eosinophils and neutrophils (Intraclass-Correlation-Coefficient (ICC) 0,41) as well as for lymphocytes (ICC = 0,49). For ECP 5-95%-values Test1: 39,8-8000.0 µg/l) only a fair reproducibility (ICC = 0,24) was found. The ICC levels for total cell count (ICC = 0,31) and for weight of the sputum plug (ICC = 0,30) were also fair. Based on the procedure presented induced sputum is a feasible and safe method in childhood. The differential sputum cell count of eosinophils, neutrophils and lymphocytes can be recommended as parameters with moderate reproducibility.
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1999 |
Mattes J, Gravesande KS, Reining U, Alving K, Ihorst G, Henschen M, Kuehr J, 'NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma', EUROPEAN RESPIRATORY JOURNAL, 13 1391-1395 (1999)
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1999 |
Mattes J, Karmaus W, 'The use of antibiotics in the first year of life and development of asthma: which comes first?', CLINICAL AND EXPERIMENTAL ALLERGY, 29 729-732 (1999)
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1999 |
van's Gravesande KS, Mattes J, Gruntjens T, Kopp M, Seydewitz HH, Moseler M, Kuehr J, 'Circadian variation of urinary eosinophil protein X in asthmatic and healthy children', CLINICAL AND EXPERIMENTAL ALLERGY, 29 1497-1501 (1999)
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1999 |
Bohnet W, Bar G, Strauch E, Ihorst G, Mattes J, Schneider C, et al., 'Short-term effect of particular matter (PM10) on pulmonary function in schoolchildren over two years', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159 A772-A772 (1999) |
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1999 |
Mattes J, Baer G, Schneider C, Bohnet W, Ihorst G, Strauch E, et al., 'Association between respiratory symptoms and ambient ozone levels over two summers in 765 schoolchildren', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159 A772-A772 (1999) |
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1999 |
Mattes J, Baer G, Schneider C, Bohnet W, Ihorst G, Strauch E, et al., 'Correlation between personal and fixed-site ozone measurements in schoolchildren', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159 A772-A772 (1999) |
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1999 |
Mattes J, van Gravesande KS, Reining U, Alving K, Ihorst G, Heuschen M, Kuehr J, 'Nitric oxide in exhaled air is correlated with eosinophilic airway inflammation in children with chronic asthma', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159 A862-A862 (1999) |
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1999 |
Gravesande KSV, Langenbacher E, Mattes J, Zurmuehl A, Beck W, Moseler M, Knehr J, 'Sodium cromoglycate (SCG) reduces the excretion of eosinophil protein X (EPX) in children with exercise induced asthma', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159 A911-A911 (1999) |
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1999 |
Mattes J, Karmaus W, Gravesande KSV, Moseler M, Forster J, Kuehr J, 'Pulmonary function in children of school age is related to the number of siblings in their family', PEDIATRIC PULMONOLOGY, 28 414-417 (1999)
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1998 |
Mattes J, Karmaus W, Moseler M, Frischer T, Kuehr J, 'Accumulation of atopic disorders within families: a sibling effect only in the offspring of atopic fathers', CLINICAL AND EXPERIMENTAL ALLERGY, 28 1480-1486 (1998)
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