Search

Eosinophilic esophagitis (EoE) is an atopic disease of the esophagus that has shown a significant increase in incidence and prevalence in the last 20 years. The etiology of EoE is unclear, and few studies explore the esophageal microbiota in EoE. The local microbiome has been implicated in the pathogenesis of several allergic and inflammatory diseases, such as asthma and eczema. In this study, we performed a systematic review to evaluate differences in the microbiota profile of patients with EoE compared with controls. MEDLINE, Embase, Cochrane Library, Scopus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched to identify studies investigating the microbiota composition in EoE. Three reviewers screened the articles for eligibility and quality. Seven articles underwent full-text review, and a narrative synthesis was undertaken. The microbiota of the mouth and esophagus are correlated. Patients with active EoE present increased esophageal microbial load and increased abundance in particular species, such as Haemophilus and Aggregatibacter. On the other hand, EoE patients present a decrease in Firmicutes. High microbial load and abundance of Haemophilus are observed in EoE patients, but little evidence exists to demonstrate their influence on inflammation and disease. Understanding microbial signatures in EoE might contribute to the development of novel therapeutic strategies.

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 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.

BACKGROUND Aboriginal and Torres Strait Islander women have access to and interest in mobile health (mHealth), although few culturally relevant, evidence-based mHealth programs are available. We codeveloped an mHealth program in New South Wales with Aboriginal and Torres Strait Islander women, focusing on women’s and children's health and well-being. OBJECTIVE This study aims to assess the engagement with and acceptability of the Growin’ Up Healthy Jarjums program among mothers caring for Aboriginal and Torres Strait Islander children aged METHODS Women were given access to Growin’ Up Healthy Jarjums—a web-based application, a Facebook (Meta Platforms, Inc) page, and SMS text messages—for 4 weeks. Short videos of health professionals presenting health information were tested within the application and on the Facebook page. Engagement with the application was examined through the number of log-ins, page views, and links used on the application. Engagement with the Facebook page was examined through likes, follows, comments, and the reach of posts. Engagement with the SMS text messages was examined through the number of mothers who opted out, and engagement with the videos was examined through the number of plays and videos watched and duration of the video watched. The acceptability of the program was examined through posttest interviews with mothers and focus groups with professionals. RESULTS A total of 47 participants joined the study (n=41, 87%, mothers and n=6, 13%, health professionals). Interviews were completed by 78% (32/41) of the women and 100% (6/6) health professionals. Of the 41 mothers, 31 (76%) women accessed the application, 13 (42%) scrolled the main page only, and 18 (58%) clicked on other pages. There were 48 plays and 6 completions of the 12 videos. The Facebook page received 49 page likes and 51 followers. The post with the most reach was a supportive and affirming cultural post. No participants opted out of the SMS text messages. Almost all mothers (30/32, 94%) reported that Growin’ Up Healthy Jarjums was useful, and all mothers reported that the program was culturally appropriate and easy to use. Of the 32 mothers, 6 (19%) mothers reported technical problems with accessing the application. Moreover, 44% (14/32) of mothers suggested improvements to the application. All the women reported that they would recommend the program to other families. CONCLUSIONS This study demonstrated that the Growin’ Up Healthy Jarjums program was perceived useful and culturally appropriate. SMS text messages had the highest engagement, followed by the Facebook page and then the application. This study identified areas for technical and engagement-related improvements to the application. A trial is needed to assess the effectiveness of the Growin’ Up Healthy Jarjums program at improving health outcomes.

BACKGROUND Health programs delivered through digital devices such as mobile phones (mobile health [mHealth]) have become an increasingly important component of the health care tool kit. Aboriginal and Torres Strait Islander women of reproductive age are likely to be caring for children and family members and needing health care, but little is known about their access to and interest in mHealth. OBJECTIVE The objectives of this study were to investigate Aboriginal and Torres Strait Islander women’s ownership of digital devices, access to the internet, current mHealth use, and interest and preferences for future mHealth. We examined the factors (age, remoteness, caring for a child younger than 5 years, and level of education) associated with the ownership of digital devices, use of internet, and interest in using a mobile phone to improve health. This study also examines if women are more likely to use mHealth for topics that they are less confident to talk about face-to-face with a health professional. METHODS A national web-based cross-sectional survey targeting Aboriginal and Torres Strait Islander women of reproductive age (16-49 years) was performed. Descriptive statistics were reported, and logistic regressions were used to examine the associations. RESULTS In total, 379 women completed the survey; 89.2% (338/379) owned a smartphone, 53.5% (203/379) a laptop or home computer, 35.6% (135/379) a tablet, and 93.1% (353/379) had access to the internet at home. Most women used social media (337/379, 88.9%) or the internet (285/379, 75.2%) everyday. The most common modality used on the mobile phone for health was Google (232/379, 61.2%), followed by social media (195/379, 51.5%). The most preferred modality for future programs was SMS text messaging (211/379, 55.7%) and social media (195/379, 51.4%). The most preferred topics for future mHealth programs were healthy eating (210/379, 55.4%) and cultural engagement (205/379, 54.1%). Women who were younger had greater odds of owning a smartphone, and women with tertiary education were more likely to own a tablet or laptop. Older age was associated with interest to use telehealth, and higher educational attainment was associated with interest for videoconferencing. Most women (269/379, 70.9%) used an Aboriginal medical service and overall reported high rates of confidence to discuss health topics with a health professional. Overall, women showed a similar likelihood of selecting a topic in mHealth whether they were or were not confident to talk to a health professional about that. CONCLUSIONS Our study found that Aboriginal and Torres Strait Islander women were avid users of the internet and had strong interest in mHealth. Future mHealth programs for these women should consider utilizing SMS text messaging and social media modalities and including content on nutrition and culture. A noteworthy limitation of this study was that participant recruitment was web-based (due to COVID-19 restrictions).

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.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 (PMThe 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/mProlonged 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.

Background Aboriginal and Torres Strait Islander women have access to and interest in mobile health (mHealth), although few culturally relevant, evidence-based mHealth programs are available. We codeveloped an mHealth program in New South Wales with Aboriginal and Torres Strait Islander women, focusing on women’s and children's health and well-being. Objective This study aims to assess the engagement with and acceptability of the Growin’ Up Healthy Jarjums program among mothers caring for Aboriginal and Torres Strait Islander children aged Methods Women were given access to Growin’ Up Healthy Jarjums—a web-based application, a Facebook (Meta Platforms, Inc) page, and SMS text messages—for 4 weeks. Short videos of health professionals presenting health information were tested within the application and on the Facebook page. Engagement with the application was examined through the number of log-ins, page views, and links used on the application. Engagement with the Facebook page was examined through likes, follows, comments, and the reach of posts. Engagement with the SMS text messages was examined through the number of mothers who opted out, and engagement with the videos was examined through the number of plays and videos watched and duration of the video watched. The acceptability of the program was examined through posttest interviews with mothers and focus groups with professionals. Results A total of 47 participants joined the study (n=41, 87%, mothers and n=6, 13%, health professionals). Interviews were completed by 78% (32/41) of the women and 100% (6/6) health professionals. Of the 41 mothers, 31 (76%) women accessed the application, 13 (42%) scrolled the main page only, and 18 (58%) clicked on other pages. There were 48 plays and 6 completions of the 12 videos. The Facebook page received 49 page likes and 51 followers. The post with the most reach was a supportive and affirming cultural post. No participants opted out of the SMS text messages. Almost all mothers (30/32, 94%) reported that Growin’ Up Healthy Jarjums was useful, and all mothers reported that the program was culturally appropriate and easy to use. Of the 32 mothers, 6 (19%) mothers reported technical problems with accessing the application. Moreover, 44% (14/32) of mothers suggested improvements to the application. All the women reported that they would recommend the program to other families. Conclusions This study demonstrated that the Growin’ Up Healthy Jarjums program was perceived useful and culturally appropriate. SMS text messages had the highest engagement, followed by the Facebook page and then the application. This study identified areas for technical and engagement-related improvements to the application. A trial is needed to assess the effectiveness of the Growin’ Up Healthy Jarjums program at improving health outcomes.

A high fruit and vegetable (FV) diet reduces asthma exacerbations in adults; this has not been examined in children to date.To investigate the effect of a 6-month, high FV diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial.Children (aged 3-11 years) with asthma, history of exacerbations and usual low FV intake (≤3 serves/day) were randomized to the intervention (high FV diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression.67 children were randomized between September 2015 and July 2018. FV intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (XA high FV diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

Children with asthma are at risk of acute exacerbations triggered mainly by viral infections. A diet high in fruit and vegetables (F&V), a rich source of carotenoids, may improve innate immune responses in children with asthma. Children with asthma (3–11 years) with a history of exacerbations and low F&V intake (≤3 serves/d) were randomly assigned to a high F&V diet or control (usual diet) for 6 months. Outcomes included respiratory-related adverse events and in-vitro cytokine production in peripheral blood mononuclear cells (PBMCs), treated with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS). During the trial, there were fewer subjects with ≥2 asthma exacerbations in the high F&V diet group (n = 22) compared to the control group (n = 25) (63.6% vs. 88.0%, p = 0.049). Duration and severity of exacerbations were similar between groups. LPS-induced interferon (IFN)-γ and IFN-λ production showed a small but significant increase in the high F&V group after 3 months compared to baseline (p < 0.05). Additionally, RV1B-induced IFN-λ production in PBMCs was positively associated with the change in plasma lycopene at 6 months (rs = 0.35, p = 0.015). A high F&V diet reduced asthma-related illness and modulated in vitro PBMC cytokine production in young children with asthma. Improving diet quality by increasing F&V intake could be an effective non-pharmacological strategy for preventing asthma-related illness by enhancing children’s innate immune responses.

Background Health programs delivered through digital devices such as mobile phones (mobile health [mHealth]) have become an increasingly important component of the health care tool kit. Aboriginal and Torres Strait Islander women of reproductive age are likely to be caring for children and family members and needing health care, but little is known about their access to and interest in mHealth. Objective The objectives of this study were to investigate Aboriginal and Torres Strait Islander women’s ownership of digital devices, access to the internet, current mHealth use, and interest and preferences for future mHealth. We examined the factors (age, remoteness, caring for a child younger than 5 years, and level of education) associated with the ownership of digital devices, use of internet, and interest in using a mobile phone to improve health. This study also examines if women are more likely to use mHealth for topics that they are less confident to talk about face-to-face with a health professional. Methods A national web-based cross-sectional survey targeting Aboriginal and Torres Strait Islander women of reproductive age (16-49 years) was performed. Descriptive statistics were reported, and logistic regressions were used to examine the associations. Results In total, 379 women completed the survey; 89.2% (338/379) owned a smartphone, 53.5% (203/379) a laptop or home computer, 35.6% (135/379) a tablet, and 93.1% (353/379) had access to the internet at home. Most women used social media (337/379, 88.9%) or the internet (285/379, 75.2%) everyday. The most common modality used on the mobile phone for health was Google (232/379, 61.2%), followed by social media (195/379, 51.5%). The most preferred modality for future programs was SMS text messaging (211/379, 55.7%) and social media (195/379, 51.4%). The most preferred topics for future mHealth programs were healthy eating (210/379, 55.4%) and cultural engagement (205/379, 54.1%). Women who were younger had greater odds of owning a smartphone, and women with tertiary education were more likely to own a tablet or laptop. Older age was associated with interest to use telehealth, and higher educational attainment was associated with interest for videoconferencing. Most women (269/379, 70.9%) used an Aboriginal medical service and overall reported high rates of confidence to discuss health topics with a health professional. Overall, women showed a similar likelihood of selecting a topic in mHealth whether they were or were not confident to talk to a health professional about that. Conclusions Our study found that Aboriginal and Torres Strait Islander women were avid users of the internet and had strong interest in mHealth. Future mHealth programs for these women should consider utilizing SMS text messaging and social media modalities and including content on nutrition and culture. A noteworthy limitation of this study was that participant recruitment was web-based (due to COVID-19 restrictions).

Rhinovirus (RV) infections in asthmatic patients are often associated with asthma exacerbation, characterized by worsened airways hyperreactivity and increased immune cell infiltration to the airways. The C-X-C chemokines, CXCL3 and CXCL5, regulate neutrophil trafficking to the lung via CXCR2, and their expression in the asthmatic lung is associated with steroid-insensitive type 2 inflammatory signatures. Currently, the role of CXCL3 and CXCL5 in regulating neutrophilic and type 2 responses in viral-induced asthma exacerbation is unknown. Inhibition of CXCL3 or CXCL5 with silencing RNAs in a mouse model of RV-induced exacerbation of asthma attenuated the accumulation of CXCR2+ neutrophils, eosinophils, and innate lymphoid cells in the lung and decreased production of type 2 regulatory factors IL-25, IL-33, IL-5, IL-13, CCL11, and CCL24. Suppression of inflammation was associated with decreased airways hyperreactivity, mucus hypersecretion, and collagen deposition. Similar results were obtained by employing RC-3095, which has been shown to bind to CXCR2, or by depletion of neutrophils. Our data demonstrate that CXCL3 and CXCL5 may be critical in the perpetuation of RV-induced exacerbation of asthma through the recruitment of CXCR2-positive neutrophils and by promoting type 2 inflammation. Targeting the CXCL3/CXCL5/CXCR2 axis may provide a new therapeutic approach to attenuating RV-induced exacerbations of asthma.

Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided byPregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05).

ImportanceNasal 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.ObjectiveTo determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure.Design, Setting, and ParticipantsA 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.InterventionsEnrolled 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 MeasuresThe 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.ResultsOf 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 Conclusions and RelevanceNasal 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 Registrationanzctr.org.au Identifier: ACTRN12618000210279

BACKGROUND Despite their growing popularity, there are very few mobile health (mHealth) interventions for Aboriginal and Torres Strait Islander people that are culturally safe and evidence based. A co-design approach is considered a suitable methodology for developing health interventions with Aboriginal and Torres Strait Islander people. OBJECTIVE The aim of this study was to co-design an mHealth intervention to improve health knowledge, health behaviors, and access to health services for women caring for young Aboriginal and Torres Strait Islander children. METHODS Aboriginal researchers led engagement and recruitment with health services and participants in 3 Aboriginal and Torres Strait Islander communities in New South Wales, Australia. Focus groups and interviews were facilitated by researchers and an app developer to gather information on 3 predetermined themes: design characteristics, content modules, and features and functions. Findings from the co-design led to the development of an intervention prototype. Theories of health behavior change were used to underpin intervention components. Existing publicly available evidence-based information was used to develop content. Governance was provided by an Aboriginal advisory group. RESULTS In total, 31 mothers and 11 health professionals participated in 8 co-design focus groups and 12 interviews from June 2019 to September 2019. The 6 design characteristics identified as important were credibility, Aboriginal and Torres Strait Islander designs and cultural safety, family centeredness, supportive, simple to use, and confidential. The content includes 6 modules for women’s health: Smoke-free families, Safe drinking, Feeling good, Women’s business, Eating, and Exercising. The content also includes 6 modules for children’s health: Breathing well; Sleeping; Milestones; Feeding and eating; Vaccinations and medicines; and Ears, eyes, and teeth. In addition, 6 technology features and functions were identified: content feed, social connection, reminders, rewards, communication with health professionals, and use of videos. CONCLUSIONS An mHealth intervention that included app, Facebook page, and SMS text messaging modalities was developed based on the co-design findings. The intervention incorporates health behavior change theory, evidence-based information, and the preferences of Aboriginal and Torres Strait Islander women and health professionals. A pilot study is now needed to assess the acceptability and feasibility of the intervention.

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.

Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.

BackgroundAsthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children.ObjectiveThe present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma.MethodsUsing a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1β, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout.ResultsThe frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (PConclusionOur study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.

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 a...

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. 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. 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.

Background Despite their growing popularity, there are very few mobile health (mHealth) interventions for Aboriginal and Torres Strait Islander people that are culturally safe and evidence based. A co-design approach is considered a suitable methodology for developing health interventions with Aboriginal and Torres Strait Islander people. Objective The aim of this study was to co-design an mHealth intervention to improve health knowledge, health behaviors, and access to health services for women caring for young Aboriginal and Torres Strait Islander children. Methods Aboriginal researchers led engagement and recruitment with health services and participants in 3 Aboriginal and Torres Strait Islander communities in New South Wales, Australia. Focus groups and interviews were facilitated by researchers and an app developer to gather information on 3 predetermined themes: design characteristics, content modules, and features and functions. Findings from the co-design led to the development of an intervention prototype. Theories of health behavior change were used to underpin intervention components. Existing publicly available evidence-based information was used to develop content. Governance was provided by an Aboriginal advisory group. Results In total, 31 mothers and 11 health professionals participated in 8 co-design focus groups and 12 interviews from June 2019 to September 2019. The 6 design characteristics identified as important were credibility, Aboriginal and Torres Strait Islander designs and cultural safety, family centeredness, supportive, simple to use, and confidential. The content includes 6 modules for women’s health: Smoke-free families, Safe drinking, Feeling good, Women’s business, Eating, and Exercising. The content also includes 6 modules for children’s health: Breathing well; Sleeping; Milestones; Feeding and eating; Vaccinations and medicines; and Ears, eyes, and teeth. In addition, 6 technology features and functions were identified: content feed, social connection, reminders, rewards, communication with health professionals, and use of videos. Conclusions An mHealth intervention that included app, Facebook page, and SMS text messaging modalities was developed based on the co-design findings. The intervention incorporates health behavior change theory, evidence-based information, and the preferences of Aboriginal and Torres Strait Islander women and health professionals. A pilot study is now needed to assess the acceptability and feasibility of the intervention.

IntroductionAsthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (FENO)-based asthma management improves perinatal outcomes compared to usual care.MethodsThe Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided byFENO(adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6–12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat).ResultsPregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94–1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78–1.68), SGA (OR 1.06, 95% CI 0.78–1.68), perinatal mortality (OR 3.62, 95% CI 0.80–16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89–1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69–2.05).ConclusionFENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Background Asthma exacerbations during pregnancy are associated with adverse pregnancy outcomes. Objective The aim of this study was to establish factors associated with asthma exacerbations during pregnancy. Methods We obtained data from three cohorts of pregnant women with asthma recruited in eastern Australia (2004-2019; n = 1461). Severe exacerbations were defined as episodes of asthma requiring hospitalization, an emergency department visit, or prescription of oral corticosteroids after enrollment. Baseline information on potential risk factors included demographic characteristics, asthma characteristics (eg, lung function, asthma triggers, asthma control, medication use), pregnancy factors (eg, fetal sex, parity, antenatal care type), and other maternal factors (body mass index, smoking status, mental health). Backward stepwise logistic regression and Akaike information criterion were used to determine the best-fitting model. Results A total of 135 participants experienced a severe exacerbation during pregnancy (9.2%). Medium to high ICS dose was most strongly associated with severe asthma exacerbations (adjusted odds ratio = 3.20; 95% confidence interval, 1.85-5.53). Worse asthma control, possession of a written action plan, and a history of asthma exacerbations in the year preceding pregnancy were associated with an increased rate of exacerbations. Conclusions Asthma exacerbations before pregnancy and more severe asthma at the beginning of pregnancy were associated with an increased rate of exacerbations during pregnancy. Despite Global Initiative for Asthma step 3 and 4 treatment and optimal management including a written asthma action plan, there is still a significant asthma burden in a group of women at high risk for severe exacerbations in pregnancy.

RationaleAsthma in pregnancy is associated with respiratory diseases in the offspring.ObjectiveTo investigate if maternal asthma is associated with lung function in early life.MethodsData on lung function measured at 5–6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland; Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term.Measurements and main resultsAll 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5; estimate: –3.5; 95% credible interval –6.8 to –0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5).ConclusionsMaternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.

Objective Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10‐fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Methods Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t‐distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Results Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty‐four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor‐homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age.” Conclusion Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life., Cord blood CRTh2high ILC2 populations from infants born to asthmatic mothers may influence lung function later in life. The association between cord blood CRTh2high ILC2 and foetal eosinophils numbers may indicate a role of foetal ILC2 in promoting eosinophilia, which warrants further investigation.

Background: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. FENO-based management in pregnancy reduced asthma exacerbations in a previous trial. BLT examined whether FENO-based asthma management would improve perinatal outcomes. Methods: BLT was a multi-centre, parallel group, RCT of asthma management guided by a FENO algorithm versus usual care. 1200 pregnant women with doctor diagnosed asthma and symptoms, or medication use for asthma in the previous year, were randomised to usual care (baseline assessment of asthma and no treatment changes) or FENO-based management. In the intervention group, a modified FENO algorithm was applied each 6-12 weeks (FENO used to adjust ICS dose, long acting beta agonist added when symptoms uncontrolled). A composite adverse perinatal outcome (preterm birth, intrauterine growth restriction, perinatal mortality, neonatal hospitalisation) was assessed from hospital records (primary outcome). Exacerbations in pregnancy (admission, emergency department visit, unscheduled doctor visit or oral steroid course) were assessed postpartum. Results: Baseline characteristics were similar between usual care (n=599) and FENO (n=601) groups. Intention to treat analysis found no significant difference between groups for the composite perinatal outcome (25.6% usual care, 29.4% FENO, OR 1.21 [0.94, 1.56]), all components of the composite outcome, and maternal exacerbations (19.2% usual care, 16.1% FENO, OR 0.80 [0.58, 1.10]). Conclusion: FENO-guided asthma management had no effect on perinatal outcomes. Funding: NHMRC Australia

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 β-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.

BackgroundPeanut allergy affects 3% of Australian children and has a higher risk of anaphylaxis than most food allergies. Predicting who is likely to develop anaphylaxis is still an inexact science. The fraction of exhaled nitric oxide (FeNO) shows promise as a biomarker involved in peanut allergy, as nitric oxide plays a role in inhibiting mast cell degranulation which is relevant in anaphylaxis, where mast cell degranulation plays a mediator role. The aim of this study was to assess the change in FeNO in children during peanut challenge.MethodsThirty-six children aged from 5 to 17 years were recruited for open-labelled peanut challenge. Participants had skin prick test to peanut performed, and serum collected for Ara h2 specific IgE and peanut specific IgE. FeNO was measured by portable device (NIOX VERO) prior to and throughout the peanut challenge.ResultsWhen grouped according to reaction type at peanut challenge (anaphylaxis, clinical allergy not anaphylaxis and tolerant), there were significant differences in the mean change in FeNO measurement between the anaphylaxis group and the clinical allergy, not anaphylaxis group (p = 0.005), and between the anaphylaxis group and tolerant group (p ConclusionsFeNO decreased more significantly in those who subsequently developed anaphylaxis than in those with clinical allergy, not anaphylaxis or negative peanut challenge (tolerance). As a bedside test that can be used in children, it has potential for further research into mechanisms of anaphylaxis in food allergy and potentially assists in predicting an imminent anaphylactic reaction in some patients.Trial registrationClinicalTrials.gov: PEAnut Anaphylaxis Predictors (PEAAP) NCT02424136.

Asthma is characterized by airway hyperreactivity and inflammation. In the lungs, parasympathetic and sensory nerves control airway tone and induce bronchoconstriction. Dysregulation of these nerves results in airway hyperreactivity. Humans with eosinophilic asthma have significantly increased sensory nerve density in airway epithelium, suggesting that type 2 cytokines and inflammatory cells promote nerve growth. Similarly, mice with congenital airway eosinophilia also have airway hyperreactivity and increased airway sensory nerve density. Here, we tested whether this occurs during development. We show that transgenic mice that overexpress IL-5, a cytokine required for eosinophil hematopoiesis, give birth to wild-type offspring that have significantly increased airway epithelial nerve density and airway hyperreactivity that persists into adulthood. These effects are caused by in utero exposure to maternal IL-5 and resulting fetal eosinophilia. Allergen exposure of these adult wild-type offspring results in severe airway hyperreactivity, leading to fatal reflex bronchoconstriction. Our results demonstrate that fetal exposure to IL-5 is a developmental origin of airway hyperreactivity, mediated by hyperinnervation of airway epithelium.

Additional file 1. Birth outcomes data extraction form.

Additional file 1: Figure S1. Asthma (current) v non-asthmatic FeNO change each increment. Figure S2. Asthma ever v nonasthmatic FeNO change each increment. Figure S3. ROC graph for FENO before and during challenge to predict clinical allergy. Figure S4. ROC graph for FeNO before and during challenge to predict anaphylaxis. Figure S5. ROC graph for prechallenge investigations to predict clinical allergy. Figure S6. ROC curves for prechallenge investigations to predict anaphylaxis.

Additional file 2. Acute respiratory symptoms, health care utilisation, and environment monthly survey.

Additional file 3. Respiratory questionnaire for infants (6 months).

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. χ2 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). 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.

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.

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.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).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.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.

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 (VO2max) 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 (VO2max 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.

This study compared the clinical and histopathological characteristics of children with eosinophilic esophagitis (EoE) and elevated anti-transglutaminase (TTG Ab) with those with EoE and normal TTG Ab titres.Single-center chart and blinded histopathological review of patients diagnosed with EoE for a 4-year period, who had esophageal and duodenal biopsies taken at time of endoscopy, and TTG Ab measured within 6 months of biopsy. Patients with histology-proven CD were excluded.Elevated TTG Ab was present in 19/34 (54%) of the study cohort, representing 23% of all patients diagnosed with EoE during the study period. Eight had titers6× upper limit of normal (ULN) and 4 had10× ULN. TTG Ab-positive patients were classified as having either potential CD with (n = 3, 16%) and without lymphocytic duodenosis (LD; n = 12, 63%), and no CD (n = 4, 21%) on human leukocyte antigen typing. There was an increase in duodenal eosinophils in patients with elevated TTG Ab (P = 0.01), which remained when patients with LD were excluded (P = 0.018). Of 19 patients with EoE and elevated TTG Ab, 5 responded to elimination diet involving exclusion of wheat, including 2 with a sole wheat trigger and TTG Ab10× ULN that were CD-associated human leukocyte antigen-negative.Serum TTG Ab was elevated in almost one-quarter of our total EoE cohort, and at least 20% of these patients did not have potential CD, suggesting EoE is a heterogeneous disease with differing immune mechanisms activated in some patients. These findings also support routine esophageal biopsy during upper endoscopy in children with elevated TTG Ab.

Summary In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T-helper type-2 lymphocytes (TH2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical TH2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of TH2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote TH2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of TH2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.

Summary 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)-γ 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.

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)-λ2/3 but not IFN-α or IFN-β. 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.

Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNF-related 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.

Whether breastfeeding protects against wheeze/ bronchiolitis in infants born to women with asthma is unclear. We examined the association between breastfeeding and respiratory outcomes in the first year of life in infants born to women with asthma. Two prospective cohort studies of pregnant women with asthma (N=624) and their infants, conducted between 2007-2018 (Newcastle, Australia) were analysed. Mothers completed a validated questionnaire (breastfeeding duration and exclusivity, infant respiratory events and healthcare utilisation) at 6±1 months (T1) and 12±1 months (T2) post-partum. Chi-squared tests and logistic regression models were used for analysis. Data were complete for n=607 at T1, with repeat measures on 80% (n=483) at T2. Of 607 participants: 89% (n=540) initiated breastfeeding, 54% breastfed for >6 months and at T2, 31% were still breastfeeding. Breastfeeding for >6 months vs. ‘never’ was associated with a reduced risk of wheeze (aRR 0.50, 95%CI 0.28-0.90) and bronchiolitis (aRR 0.47, 95%CI 0.24-0.92) at T1. Current breastfeeding vs. not current breastfeeding at T2 was also associated with a reduced risk of ‘wheeze ever’ (aRR 0.60, 95%CI 0.39-0.94). Breastfeeding for >6 months vs. ‘never’ was associated with a lower proportion of infants presenting to the emergency department at T2 (14% vs 30%, p=0.02). Breastfeeding in the first 6 months of life was associated with a reduced risk of parent-reported wheeze and bronchiolitis, and less healthcare utilisation, in infants born to women with asthma. Large cohorts are needed to examine the impact of longer duration breastfeeding, and exclusivity, on respiratory health in offspring.

Introduction and Aim: Severe asthma is characterised by frequent exacerbations with the majority triggered by viral infections. Treatment of severe allergic asthma with Omalizumab reduces exacerbation risk. We sought to determine how Omalizumab improved antiviral innate immune responses to influenza A (IAV) and rhinovirus (RV). Methods: We recruited 10 adults, with severe allergic asthma and 10 healthy controls. Participants were assessed at basdeline 4 and 24 weeks after treatment. Peripheral blood monocytes (PBMCs) were isolated, exposed to IAV, RV. Monocyte cell types and FceI expression was identified by flow cytometry, Response was assessed by ELISA/RNA for FceI, interferon (IFN)-a, IFN-l, IFN-g, IL-6, IL-10. Results: At base line visit subjects with severe allergic asthma compared to healthy controls demonstrated impaired IFN-α, and IFN-λ release in response to IAV (p Conclusion: Adults with severe allergic asthma demonstrate impaired systemic DC immune responses to IAV and RV. Treatment with Omalizumab, that results in reduced exacerbations is associated with reduced DC FceI expression, enhanced DC IFN-α/λ responses to viruses and this effect is seen within 4 weeks treatment.

Background: Maternal asthma is a strong risk factor for the development of respiratory disease in the offspring. Objective: To determine the effect of maternal asthma on Tidal Breathing Flow Volume Loop (TBFVL) parameters in babies at 6 weeks of age. Methods: TBFVL were measured in accordance with ERS/ATS standards using an ultrasonic flow meter (Spiroson®; EcoMedics AG). Data were merged from two cohorts, the Breathing for Life Trial (BLT) and the Bern Infant Lung Development (BILD) birth cohort. BLT is an ongoing multicentre study including children born to mothers with asthma during pregnancy. BILD is a cohort study including children born to mothers with and without asthma (90%). Results: TBFVL of 497 (83%) were acceptable for the final analysis of whom 344 infants were BLT and 252 infants were from BILD. Mean (±STD) time to peak tidal expiratory flow divided by total time expiratory flow percentage ratio (tPTEF/tE%) for the different sites were: Sydney (32.9 ±9.4), Newcastle (31.5 ±9.9) and Bern (34.9 ±10.3). Maternal asthma (parameter estimate: 2.31, p=0.023), gestational age (1.38, p Conclusion: Maternal asthma may be associated with lower tPTEF/tE% but the maternal asthma significance could be due to a centre effect. Weight gain in first 6 weeks of life is associated with a higher tPTEF/tE%. Optimising weight gain in early life could improve lung function.

Introduction: Asthma in pregnancy and tobacco smoking in pregnancy are common, and adversely affect pregnancy outcomes and respiratory health in the offspring. Aim: Our aim was to describe the effect of tobacco smoking on outcomes in offspring born to women with asthma in pregnancy who participated in the ongoing multicentre Breathing for Life trial, a controlled randomized trial comparing usual asthma management with inflammatory (Fraction of exhaled nitric oxide, FeNO)-guided asthma management. Results: Currently pregnancy outcome data are available from 400 women and of those 16.0% (64) reported having smoked tobacco any time during pregnancy. The mean exhaled (e)CO concentration in self-reported smokers was 15.8 ppm and non-smokers it was 3.6 ppm. 14.3% of women (n=48) who self-reported not to smoke had eCO levels of equal or greater than 6ppm. Preterm birth occurred in 12.1% (38 of 314) of women who reported not to smoke and in 11.9% (7 of 59) of women who smoked (p=0.9). Using an eCO level of 6ppm as recommended by Gomez et al (Prev Med 2005) as cut-off to define active smoking, preterm birth occurred in 21.1% (19 of 90) of actively smoking women and in 9.2% (26 of 284) of non-actively smoking women (p=0.002). At six weeks of age, premature infants had a lower mean time to reach peak tidal expiratory flow as a proportion of total expiratory time (tPTEF/TE): 26.2 (95% CI 23.4 to 29.0) vs. 32.4 (95% CI 31.0 to 33.9) in term babies (p=0.004). Conclusion: Active tobacco smoking identified by eCO was associated with increased rates of premature birth. Prematurity was associated with impaired lung function at six weeks of age in the offspring.