Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma.

BACKGROUND: Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood. OBJECTIVE: We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes. METHODS: LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 µg/m3, 24-hour equivalent) or moderate (100 µg/m3, 24-hour equivalent) concentrations of LFS PM (10 µm and below [PM10]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM10 were administered for 3 days. Cardiac function and gene expression were assessed. RESULTS: Short- and long-term LFS PM10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM10 airway exposure also decreased gas diffusion. Short-term LFS PM10 airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies. CONCLUSIONS: We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM10 airway exposure on respiratory and cardiovascular disease outcomes.

Beliefs about medicines and adherence to asthma medications during pregnancy.

OBJECTIVE: Discontinuation of, and non-adherence to, inhaled corticosteroids (ICS) for asthma treatment is a significant issue in pregnancy. This study characterized beliefs about medicines in pregnant women with asthma and investigated associations with ICS adherence. METHODS: Pregnant women with relatively mild asthma (n = 302) were grouped according to ICS use and self-reported adherence (≥80% doses taken). They completed questions about dislike of asthma medications and the validated Beliefs about Medicines Questionnaire (BMQ), which consists of ten questions about asthma medicines ("necessity" questions about maintaining health, or "concern" questions about adverse effects), and eight general medicine questions, scored on five-point Likert scales. The Necessity Concerns differential (N-C) was calculated, with positive scores indicating that the patient perceives the benefits of medicines to outweigh the risks. RESULTS: ICS was used by 87 (29%) women, with 49 (56%) self-reporting adherence. Of the 22% who disliked taking asthma medications during pregnancy, 20% had the belief that the medication was unsafe. ICS users had a significantly higher BMQ necessity score and higher necessity-concern differential score than nonusers; when adjusted for covariates, ICS non-adherence was associated with a lower necessity score (p = 0.015). Women adherent to ICS were more likely to agree to "my health at present depends on my asthma medication" compared to non-adherent ICS users. CONCLUSIONS: ICS non-adherence was not associated with having relatively more concerns about asthma medicines; however, ICS users were more likely to perceive that the benefits of medication use outweighed any risks. Interventions to improve asthma medication adherence in pregnancy are needed.

Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (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). RESULTS: Pregnant 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). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Exacerbations of asthma following step-up and step-down inhaled corticosteroid and long acting beta agonist therapy in the managing asthma in pregnancy study.

OBJECTIVE: Guidelines for asthma management contain a consensus recommendation that inhaled corticosteroid (ICS) dose should not be stepped down in pregnancy. However, this is not consistent with consumer preferences and pharmacological principles to minimize medication exposure during pregnancy. We investigated exacerbations after changes to ICS and long acting beta agonist (LABA) therapy in pregnant women with asthma. METHODS: Pregnant women (n = 220) were recruited to a randomized controlled trial (RCT) where maintenance treatment was adjusted monthly based on either symptoms (control group), or fractional exhaled nitric oxide (FeNO, to alter ICS) and symptoms (to alter LABA, FeNO group). Exacerbations were monitored prospectively. RESULTS: ICS were used by 137 (62.3%) women at some time during pregnancy. ICS dose remained unchanged in 16 women (11.7%, 95% confidence interval [CI] 7-18%), increased in 37 women (27%, 95%CI 20-35%), decreased in 34 women (24.8%, 95%CI 18%-33%), or both increased and decreased in 50 women (36.5%, 95%CI 29-45%). Exacerbations occurred within 14 days of ICS step-down in 11 women (13%, 95%CI 7.5%-22%). This was not significantly different from exacerbations occurring within 14 days of step-up, in 7 women (8.1%, 95%CI 4%-16%, P = 0.294). There were no differences between management groups. Exacerbations occurred within 14 days of step-down in 14.7% (95%CI 7%-30%) of women in the control group, and in 12% (95%CI 6%-24%) of women in the FENO group. CONCLUSIONS: ICS step-down could be considered when eosinophilic inflammation or symptoms are low, and may be a useful management approach for women, doctors, and midwives wishing to minimize ICS exposure during pregnancy.

The impact of prolonged landscape fire smoke exposure on women with asthma in Australia.

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.

A cross-sectional survey of Australian healthcare professionals' confidence, evidence-based knowledge and guideline use for antenatal asthma management.

BACKGROUND: Asthma is one of the most common chronic health conditions experienced during pregnancy and is associated with numerous adverse maternal and perinatal outcomes. AIMS: To better understand the confidence, evidence-based knowledge and guideline use among healthcare professionals around Australia commonly involved in providing antenatal care for women with asthma. MATERIALS AND METHODS: An online, cross-sectional survey was developed and distributed to maternity carers (obstetricians and midwives), primary carers (general practitioners and general practice nurses) and respiratory specialists (respiratory physicians and respiratory nurses). Self-reported confidence and use of clinical guidelines were recorded. Evidence-based knowledge was assessed with 13 questions relating to four clinical scenarios that covered recommendations from national and international guidelines. RESULTS: Primary carers and respiratory specialists were more confident in providing antenatal asthma care, more likely to use clinical guidelines and scored significantly higher in evidence-based knowledge of antenatal asthma management than maternity carers (P < 0.01 and P < 0.001, respectively). There was no significant difference in evidence-based knowledge among healthcare professionals from metropolitan, regional and rural backgrounds. However, healthcare professionals who used clinical guidelines scored significantly higher than those who did not (P < 0.0001). CONCLUSION: Greater utilisation of clinical guidelines could improve the evidence-based knowledge of maternity carers. However, the absence of antenatal asthma management in obstetric- and maternity-specific guidelines poses a potential barrier that needs to be addressed. Furthermore, the development of multidisciplinary antenatal clinics, staffed by respiratory nurses and/or physicians, could improve outcomes for pregnant women with asthma who are not undertaking shared care.

The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial.

BACKGROUND: A high fruit and vegetable (F&V) diet reduces asthma exacerbations in adults; this has not been examined in children to date. OBJECTIVE: To investigate the effect of a 6-month, high F&V diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial. METHODS: Children (aged 3-11 years) with asthma, history of exacerbations and usual low F&V intake (≤3 serves/day) were randomized to the intervention (high F&V 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. RESULTS: 67 children were randomized between September 2015 and July 2018. F&V 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 (X5 ∆: 0.76 [0.04, 1.48] p = 0.038, X20 ∆: 0.93 [0.23, 1.64] p = 0.009) and changes in faecal microbiota were observed though there was no difference between groups in systemic inflammation or molecular mechanisms. In the control group, CRP and HDAC enzyme activity increased, while GPR41 expression decreased. No adverse events attributable to the interventions were observed. CONCLUSION & CLINICAL RELEVANCE: A high F&V 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.

Fractional exhaled nitric oxide-based asthma management: The feasibility of its implementation into antenatal care in New South Wales, Australia.

BACKGROUND: The use of fractional exhaled nitric oxide (FeNO)-based asthma management during pregnancy can significantly reduce asthma exacerbations in non-smoking pregnant women. The feasibility of implementing this strategy into antenatal care has not been explored. AIMS: To examine the feasibility of implementing FeNO-based asthma management into antenatal clinics in New South Wales (NSW) Australia. MATERIALS AND METHODS: Semi-structured face-to-face interviews with video elicitation were conducted with healthcare professionals (HCPs) providing antenatal care in one of two hospital-based antenatal clinics in NSW, Australia. The video shown demonstrated the use of the FeNO instrument and other aspects of the management strategy, in antenatal care. Interviews were recorded, transcribed and analysed using qualitative content analysis. RESULTS: A total of 20 interviews were conducted with 15 midwives, four obstetricians, and one general practitioner. Two main themes and ten sub-themes arose: Getting a number (sub-themes: engaging, technically easy, objective, predictive, reassuring); and Resourcing (sub-themes: time and timing, systems, staff, education and cost). Comments included: 'It's easy, fast and effective' and 'the main barrier is time'. All HCPs felt capable of facilitating the FeNO-based management strategy, with appropriate education, and were willing to undertake this strategy, saying: '…it would be perfectly acceptable for a midwife or doctor to do it'; also, 'they don't necessarily need to see a physician, it's something that midwives would take on generally…'. CONCLUSION: Participants in this study considered FeNO-based asthma management for pregnant women to be a feasible addition to antenatal care following appropriate provision of resources and education.

Inhaled corticosteroid use during pregnancy among women with asthma: A systematic review and meta-analysis.

BACKGROUND: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. METHODS: We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). RESULTS: A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N = 45; Aim 2, N = 13; and Aim 3, N = 5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). CONCLUSIONS: The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.

Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.

OBJECTIVE: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. METHODS: Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. RESULTS: At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education. CONCLUSIONS: There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

Asthma during Pregnancy: Exacerbations, Management, and Health Outcomes for Mother and Infant.

One in 10 pregnant women worldwide has asthma and of these, 10% will have a severe exacerbation requiring oral corticosteroids (OCSs) in pregnancy. This review of recent publications in the field will describe the effects of exacerbation on maternal and neonatal health, the use of asthma medications during pregnancy, and will suggest novel management approaches for asthma in pregnancy. Pregnancy results in unpredictable changes in the disease; therefore, regular monitoring of symptoms is recommended. Uncontrolled asthma is frequently described in cohorts of pregnant women with asthma, and some recent studies show associations with adverse perinatal outcomes, as previously demonstrated with exacerbations. Guidelines for the management of asthma recommend the continued use of inhaled corticosteroids (ICSs) in pregnancy, with budesonide having a particularly good safety profile. Recent data suggest small effects of asthma and/or asthma medication use on congenital malformations; however, there is less data available on the safety of ICS/long-acting ß agonist combinations, which are increasingly used for maintenance treatment. Novel management strategies are needed to address the complex needs of pregnant women with asthma. These include medication nonadherence and the presence of numerous comorbidities which can affect asthma, such as rhinitis, cigarette smoking, obesity, and mental health issues. Inflammation-based management has been shown to be effective in reducing exacerbations in pregnancy and may also improve perinatal outcomes. The involvement of a multidisciplinary team and the assessment of comorbidities have potential to improve the health of mothers and their offspring.

Caregiver's functional status during a young child's asthma exacerbation: A validated instrument.

BACKGROUND: Few instruments exist to measure caregivers' functional status during a young child's asthma exacerbation. OBJECTIVE: We sought to develop and validate a measure of caregivers' functional status during a preschooler's asthma exacerbation. METHODS: The psychometric properties of the 21-item questionnaire Effects of a Young Child's Asthma Flare-up on the Parents (ECAP) were tested in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with virus-induced asthma. Caregivers completed the ECAP questionnaire on the last day their child exhibited symptoms of an upper respiratory tract infection or asthma exacerbation (episode). The mean of each item, scored on a scale of 1 (best) to 7 (worst), provided the ECAP score. RESULTS: Ninety-three preschoolers (2.5 ± 1.0 years old; 62.4% male) experienced 878 episodes. Feasibility (80% questionnaire return rate; 90% completion) and internal consistency (Cronbach α = 0.97) were high. Of 628 episodes with a completed ECAP questionnaire, 621 (98.9%) had data on exacerbations, and 609 (97.0%) had data on health care use. The ECAP score was significantly higher for children experiencing an asthma exacerbation versus those who were not (mean difference, 0.8; 95% CI, 0.6-1.0) and for episodes resulting versus not resulting in an emergency visit (mean difference, 1.2; 95% CI, 1.0-1.4), systemic corticosteroid use (mean difference, 1.4; 95% CI, 1.1-1.7), or hospitalization (mean difference, 1.9; 95% CI, 1.4-2.5). The ECAP score was significantly lower in children treated with fluticasone versus those treated with placebo (mean difference, -0.7; 95% CI, -1.1 to -0.3). CONCLUSIONS: The 21-item ECAP questionnaire, showing high feasibility, internal consistency, discriminative validity, and responsiveness, has the psychometric properties to serve as a validated outcome to measure the burden of preschoolers' asthma exacerbations on their caregivers' functional status.

Asthma Flare-up Diary for Young Children to monitor the severity of exacerbations.

BACKGROUND: Few instruments exist to ascertain the severity of a preschool-aged child's asthma exacerbations managed at home. OBJECTIVE: We sought to develop and validate a functional status instrument to assess asthma exacerbation severity in preschoolers. METHODS: The parent-completed Asthma Flare-up Diary for Young Children (ADYC), which was developed systematically, comprises 17 items, each scored from 1 (best) to 7 (worst). The ADYC was completed daily from the onset of an upper respiratory tract infection (URTI) until asthma symptom resolution; the cumulative daily score was reported. The ADYC was examined for key psychometric properties in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with URTI-induced asthma. RESULTS: In 121 children aged 2.7 ± 1.1 years (59.5% male), the ADYC's internal consistency (Cronbach α = .97), feasibility (97% completion), and test-retest reliability (r = 0.71; 95% CI, 0.59-0.80) were demonstrated. The ADYC was responsive to change between 2 consecutive days (Guyatt statistic = 0.77) with a minimal important difference of 0.22 (0.17-0.27). Of 871 episodes, the cumulative ADYC score was significantly higher during exacerbations than during URTIs (mean difference [MD], 7.6; 95% CI, 6.4-8.9) and for exacerbations with an acute-care visit (MD, 9.1; 95% CI, 7.6-10.7), systemic corticosteroids (MD, 10.1; 95% CI, 8.3-12.0), and hospitalization (MD, 6.8; 95% CI, 2.9-10.7) versus those without. In children receiving fluticasone, the ADYC score was significantly lower versus that in the placebo group (MD, 5.1; 95% CI, 1.8-8.3). CONCLUSIONS: The 17-item ADYC proved feasible, responsive to day-to-day changes, and discriminative across exacerbations of different severities. In a trial testing effective therapy in preschoolers, it identified a significant reduction in asthma exacerbation severity.

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.

BACKGROUND: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. METHODS/DESIGN: BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12-22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3-6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required. DISCUSSION: This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .

Macrophage activation, age and sex effects of immunometabolism in obese asthma.

Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma. Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines. Plasma CRP (p<0.01) and leptin (p<0.01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=-0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02). Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level.

Lean mass, not fat mass, is associated with lung function in male and female children with asthma.

BACKGROUND: Whether body composition is associated with lung function in asthmatic children has not been investigated. This study aimed to primarily investigate whether BMI z-score and body composition were associated with respiratory function in asthmatic children. METHODS: In a cross-sectional study, male (n = 27; mean age: 11.9 y (SD: 2.3)) and female (n = 21; mean age: 13.6 y (SD: 2.2)) asthmatic children underwent clinical assessment. RESULTS: BMI z-score was associated with forced expiratory volume in 1 s (FEV1; r = 0.458), forced vital capacity (FVC; r = 0.477), and total lung capacity (TLC; r = 0.451) in males only (P < 0.05). Total lean mass was associated with FEV1 (r = 0.655), FVC (r = 0.562), and TLC (r = 0.635) in males, as was thoracic lean mass (FEV1 (r = 0.573), FVC (r = 0.526), and TLC (r = 0.497); P < 0.05). TLC was associated with total (r = 0.522) and thoracic (r = 0.532) lean mass in females (P < 0.05). Fat mass was not associated with lung function in this group. CONCLUSION: Lean mass, not fat mass, is associated with lung function in children with asthma. The positive association between BMI z-score and respiratory function in male children is driven by lean mass. Although body weight can be easily monitored in the clinical setting, body composition can provide important information. Future research exploring lean mass and lung function associations could inform future interventions.

Personal strategies to reduce the effects of landscape fire smoke on asthma-related outcomes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Landscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes. METHODS AND ANALYSIS: We will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: This study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022341120.

Adverse neonatal outcomes in pregnant women with asthma: An updated systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma. OBJECTIVE: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes. SEARCH STRATEGY: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma. DATA COLLECTION AND ANALYSIS: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined. MAIN RESULTS: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance. CONCLUSIONS: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma.

Airway and systemic inflammation in obese children with asthma.

Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8-17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.

Increased sleep latency and reduced sleep duration in children with asthma.

STUDY OBJECTIVE: Sleep disturbance is reported to be more prevalent in children and adolescents with asthma than those without. However, this has not been described adequately using objective measures. The aim of this study was to objectively characterise sleep disturbance in asthmatic and non-asthmatic children and adolescents. METHODS: A retrospective analysis of polysomnography recordings from children aged 5-17 years old, with (n = 113) and without asthma (n = 104), referred for a sleep study over the period 2005-2010 at the Paediatric Sleep Unit, John Hunter Children's Hospital in Newcastle, NSW Australia, was carried out. RESULTS: Polysomnographic recordings were analysed to compare sleep quality and quantity between asthmatic and non-asthmatic children. Sleep latency was significantly longer in asthmatic children compared to controls. However, this result was significant for females only (46.2 (5.6) vs 33.2 (2.7) min, p < 0.05). Male asthmatics had significantly shorter sleep duration (425.9 (5.4) vs 441.8 (5.4) min, p < 0.05) than male controls. CONCLUSIONS: Sleep disturbance exists in children with asthma and manifests differently in males and females. Further investigation into the clinical implication of increased sleep latency and reduced sleep duration upon daytime functioning and lifestyle behaviours in children and adolescents with asthma is warranted.