Asthma is one of the most common chronic diseases affecting pregnant women with variable prevalence around the world. Hormonally mediated and physical changes to the respiratory system occur during pregnancy and can impact asthma status unpredictably—some women improve, some worsen and some are stable. Increased maternal and foetal adverse outcomes are observed with uncontrolled asthma. Medication non-adherence increases in pregnancy, often because of concerns regarding the effect of medications on the developing foetus and is a major contributor to loss of asthma control. Certain comorbidities, particularly metabolic comorbidities, are more common in pregnant women with asthma and are increasingly understood to impact asthma and pregnancy outcomes. There is reassuring observational data to suggest the safety of omalizumab and dupilumab in pregnancy, but more studies are needed. This review highlights the current evidence regarding epidemiology, pregnancy-related respiratory changes, comorbidities and treatment of asthma in pregnancy.

BackgroundThis study is aimed at identifying early-life modifiable factors associated with allergic rhinitis to assist in reducing the public health burden of allergic rhinitis on young children and their families.MethodsChildren of mothers with asthma in the Breathing for Life Trial cohort were followed over 4 years. Potential risk and preventative exposures (outdoor, home environment and early life) were measured at 12 months using a validated parent-reported questionnaire. Validated questionnaires and a skin prick test were administered to collect outcome data at 4 years-allergic rhinitis symptoms (n = 285), hay fever (n = 276), airborne allergen sensitisation (n = 142) and persistent rhinitis (n = 285). Multivariate logistic regression assessed associations, and population attributable fractions (PAFs) and prevented fractions for the population (PFPs) were calculated.ResultsParent-reported bronchiolitis before 12 months of age was associated with allergic rhinitis symptoms (adjOR 1.95, 95% CI 1.07-3.57, PAF 17.6%). Additionally, hospitalised bronchiolitis was associated with hay fever (PAF 13.5%). Cat ownership was associated with lower odds for allergic rhinitis symptoms and persistent allergic rhinitis (PFP 17% and 24.2%, respectively), and dog ownership was associated with lower odds for hay fever (PFP 23.7%). Additionally, gas cooking was associated with reduced persistent allergic rhinitis (PFP 22.5%) and total breastfeeding for 4-6 months with reduced hay fever (PFP 14.9%). Associations with traffic frequency, second-hand smoking, type of heating and childcare attendance were not significant.ConclusionEarly respiratory infection and cat and dog exposure were identified as potentially modifiable exposures to reduce the risk of childhood allergic rhinitis.

BACKGROUND:Vitamin D supplementation may improve asthma by modulating inflammation, but its effects in preschoolers with virus-induced asthma remain underexplored. OBJECTIVE:To measure the association between serum 25-hydroxyvitamin D (25(OH)D) and inflammatory biomarkers and the impact of vitamin D supplementation on these biomarkers. METHODS:We conducted a nested study within a 7-month randomized placebo-controlled trial. Children aged 1 to 5 years with virus-induced asthma received vitamin D3 in 2 oral boluses (100,000 IU) 3.5 months apart, with a daily (400 IU) supplement, or placebo boluses and daily supplement. Serum 25(OH)D and C-reactive protein (CRP) were measured at baseline, 3.5 months, and 7 months, whereas blood cells were measured at baseline and 7 months. Primary outcomes were CRP across time points and change from baseline in CRP at 3.5 and 7 months, analyzed using generalized estimating equation and mixed-effects models. RESULTS:Among 236 (118 Vitamin D: 118 placebo) children (64.4% male), no significant association was observed between CRP and 25(OH)D. However, neutrophils were inversely associated with 25(OH)D (adjusted β [95% CI]= -0.016 (-0.027 to -0.005) × 10⁹ cells/L, n = 198). Compared with placebo, vitamin D supplementation led to a greater reduction from baseline in CRP over time (adjusted β [95% CI] = -3.154 [-5.978 to -0.330] mg/L, n = 174), and neutrophils at 7 months (adjusted β [95% CI] = -0.657 [-1.288 to -0.026] × 10⁹ cells/L, n = 110). No associations were observed with other blood cell biomarkers. CONCLUSION:In preschoolers with virus-induced asthma, serum 25(OH)D was inversely associated with neutrophils, and vitamin D supplementation significantly reduced CRP and neutrophils over time, suggesting modulation of neutrophilic inflammation. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03365687.

BACKGROUND:Climate change is contributing to more frequent wildfires. Exposure to wildfire smoke during pregnancy increases the risk of adverse neonatal outcomes. Pregnant women with asthma and their newborns are particularly at risk of negative effects from wildfire smoke exposure and remain understudied. Determining critical windows of exposure during pregnancy could help inform mitigation strategies for this high-risk group. OBJECTIVE:This study aimed to assess the association of prenatal wildfire smoke exposure with adverse neonatal outcomes in mothers with asthma and to determine which period of pregnancy is most critical. STUDY DESIGN:This was a multicenter cohort study (Breathing for Life Trial) including mothers and newborns from 6 antenatal clinics across 4 cities in Australia (Sydney, Brisbane, Newcastle, Canberra). Pregnant women (n=1275) with asthma were recruited at 12 to 23 weeks of gestation. Chronic lung disease (other than asthma), miscarriages, and perinatal deaths were excluded. Prenatal wildfire smoke exposure days and daily wildfire-related particulate matter ≤2.5 μm concentrations were determined by residence. Exposure over pregnancy was assessed in 3 ways: (1) cumulative days of wildfire smoke (0, 1-4, 5-9, ≥10 days); (2) wildfire smoke-affected days and wildfire-related particulate matter ≤2.5 μm as continuous variables for each gestational month; and (3) a natural experiment comparing exposure during the 2019-2020 summer extreme wildfire period with historical controls. Neonatal outcomes included birthweight, low birthweight (<2500 g), gestational length, preterm birth (<37 weeks), neonatal intensive care unit admission, and cesarean delivery. RESULTS:The mean age of women was 30.7 years (SD, 5.5), 85% were White, 15% were smokers, and 69% were overweight or obese. The prenatal mean daily particulate matter ≤2.5 μm concentration (all sources) was 7.6 μg/m3 (SD, 1.42); the median daily wildfire-related particulate matter ≤2.5 μm concentration was 0.1 μg/m3 (range, 0-7.7 μg/m3); and the median number of prenatal cumulative days of wildfire smoke exposure was 3 (range, 0-71 days). Prenatal exposure to ≥10 cumulative wildfire smoke days was associated with low birthweight (adjusted odds ratio, 4.2; 95% confidence interval, 1.2-13.9), preterm birth (adjusted odds ratio, 2.8; 95% confidence interval, 1.1-7.2), and neonatal intensive care unit admission (adjusted odds ratio, 5.0; 95% confidence interval, 1.4-17.8). Exposure to wildfire-related particulate matter ≤2.5 μm in the second and third gestational months was associated with preterm birth, small for gestational age, and neonatal intensive care unit admission. In the natural experiment, prenatal exposure was associated with low birthweight (adjusted odds ratio, 2.6; 95% confidence interval, 1.1-6.2), preterm birth (adjusted odds ratio, 2.5; 95% confidence interval, 1.2-5.2), and neonatal intensive care unit admission (adjusted odds ratio, 4.8; 95% confidence interval, 2.0-11.2). CONCLUSION:In pregnant women with asthma, prenatal exposure to wildfire smoke early in pregnancy increases the risk of adverse neonatal outcomes. Measures to reduce wildfire smoke exposure early in pregnancy could be beneficial.

Introduction Asthma is one of the most prevalent long-term health conditions affecting pregnant women. Poorly controlled asthma during pregnancy is associated with adverse maternal and fetal outcomes and may predispose offspring to long-term respiratory morbidity. The current ‘one size fits all’ approach to asthma management during pregnancy is not optimally effective for approximately half of the pregnant women with asthma. A personalised medicine approach to managing airways disease is required. The treatable traits approach focuses on the identification and treatment of traits in the pulmonary, extra-pulmonary and behavioural domains, which are identifiable, measurable, clinically relevant (linked to exacerbation risk or poor asthma control) and treatable. This manuscript outlines the protocol for the Treatable Traits for Asthma Management in Pregnancy (TTAP) study. The purpose of the TTAP study is to prospectively determine the prevalence of a range of treatable traits from these three domains in pregnant women with asthma and determine which traits are associated with exacerbation risk, poor asthma control and poor asthma-related quality of life. Additionally, this study will assess differences in trait prevalence and clinical relevance in pregnant women from regional versus metropolitan hospitals in Australia and in different antenatal models of care.Methods and analysis The TTAP study is a multicentre, prospective observational cohort study. Study participants are pregnant women with asthma attending antenatal clinics at 10 metropolitan and regional hospitals (public and private) in NSW and Victoria, Australia. Assessment of traits from the pulmonary, extrapulmonary and behavioural domains as well as asthma outcomes is conducted at three gestational timepoints: 12–16 weeks, 22–26 weeks and 32–36 weeks of pregnancy. A follow-up assessment of asthma outcomes is conducted at 2–4 weeks postpartum. The outcomes assessed are asthma exacerbations requiring medical intervention (primary outcome), asthma symptom control and asthma-related quality of life. Traits and outcomes will be assessed using questionnaires, direct questioning, measurement of biomarkers, physical measurements and assessment of routinely collected data from medical records.Ethics and dissemination The Hunter New England Human Ethics Committee (2024/ETH01289) has approved the TTAP study protocol. Outcomes will be published in peer-reviewed journals, presented at scientific conferences and disseminated online to participants, clinicians and other pregnant women with asthma and their families via the Asthma in Pregnancy Toolkit website https://asthmapregnancytoolkit.org.au/.

BACKGROUND:Asthma and gestational diabetes mellitus (GDM) are prevalent in pregnancy, with asthma previously associated with an increased GDM risk. Each independently increases the risk of adverse perinatal outcomes, but the effect of dual exposure is unknown. OBJECTIVE:To compare clinical, demographic, and perinatal outcome data between women with and without asthma, who do and do not develop GDM. METHODS:Data for singleton births to mothers aged 18 years or older were extracted from electronic records across 2 Australian Health Districts (2018-2020). The effects of asthma and/or GDM on perinatal outcomes were estimated using generalized estimating equations. RESULTS:Of 40,149 pregnancies, 9.6% had asthma only, 9.6% had GDM only, and 1.4% had asthma and GDM. Asthma was not associated with GDM risk, following adjustment for confounders (adjusted relative risk [aRR] 1.04; 95% confidence interval [95% CI] 0.96-1.13). Compared with neither exposure, asthma and/or GDM was associated with an increased risk for each cesarean birth and infant respiratory distress. Asthma was also associated with an increased risk of preterm birth (aRR 1.15; 95% CI 1.03-1.29), low birth weight (aRR 1.15; 95% CI 1.03-1.29), and congenital anomalies (aRR 1.15; 95% CI 1.03-1.29). There was also an increased risk of hypertensive disorders of pregnancy (aRR 1.36; 95% CI 1.05-1.77) with dual exposure. No multiplicative interactions between asthma and GDM were detected. CONCLUSIONS:Asthma and/or GDM increased the risk of adverse perinatal outcomes, but no synergistic effect was observed for asthma+GDM exposure. Asthma was not associated with an increased risk of GDM after adjusting for important confounders, including obesity.

INTRODUCTION:Poor respiratory health in childhood is common, and asthma is the most common chronic disease among children, for which there is no known cure. Maternal intake of vitamins (A, C, E) may be a modifiable nutritional exposure to reduce adverse respiratory health in offspring. OBJECTIVE:We aimed to systematically review the evidence for the association between maternal vitamin (A, C, E) intake during pregnancy (via questionnaire or blood assay) and respiratory outcomes in the offspring. METHODS:Studies identified through electronic databases were eligible if they assessed maternal levels and/or intake of vitamins A, C and/or E via dietary intake or supplements in pregnancy and respiratory outcomes in the first 5 years of life. Meta-analyses were conducted where possible. Outcomes included wheeze, cough, asthma, infant respiratory distress syndrome (RDS), respiratory tract infection (RTI) and lung function measurement. RESULTS:Of 1170 articles screened, 12 observational studies and six RCTs met the inclusion criteria (total sample size n = 58,769). Meta-analysis could not be performed for vitamin A; however, there was no evidence to suggest that maternal vitamin A intake improves early life respiratory outcomes in offspring. Two RCTs found that vitamin C supplementation (500 mg/day vs. placebo) reduced the incidence of wheeze at 12 months (n = 206 children) and 5 years (n = 213 children) in pregnancies exposed to smoking. In meta-analyses, maternal intake in the highest vitamin E quartile versus lowest reduced the odds of wheeze at 2 years by 36% (aOR: 0.64, 95% CI: 0.47-0.87, n = 2 observational studies, very low certainty); this was not true for vitamin C intake (aOR: 0.85, 95% CI: 0.63-1.16, n = 2 observational studies, very low certainty). Vitamin supplementation (C + E) was not associated with infant RDS (OR: 1.15, 95% CI: 0.80-1.64, n = 2 studies, moderate certainty) relative to placebo. CONCLUSION:There may be some benefit to vitamin C supplementation during pregnancy in the context of maternal smoking or higher maternal vitamin E intake during pregnancy, for reducing the risk of childhood wheeze in early life. This emerging evidence warrants further studies to enable translation into dietary guidelines.

Background Improved maternal asthma management in pregnancy may reduce recurrent bronchiolitis and wheeze outcomes in infancy. We assessed whether infant bronchiolitis and wheeze outcomes are influenced by inflammation-guided management intervention, inhaled corticosteroid (ICS) use or exacerbations in pregnancy. Methods A randomised controlled trial (RCT) secondary analysis and observational cohort analysis using the same study population was carried out. Pregnant women (12–23 weeks’ gestation) from six centres in Australia were recruited and randomised to inflammation-guided asthma management or usual care between 2013 and 2023. ICS use and asthma exacerbations were reported during pregnancy and postnatally. When infants were 6 (n=691) and 12 (n=606) months of age, respiratory information was collected from parents and medical records. Associations for the RCT and observational analyses were assessed with logistic regression. Results Guided asthma management in pregnancy was not associated with bronchiolitis or wheeze-related outcomes, for example for recurrent bronchiolitis at 12 months, the intervention OR was 1.04 (95% CI 0.62–1.73). In the observational analyses, ICS use in pregnancy was not associated with respiratory outcomes; however, asthma exacerbations in pregnancy were associated with at least one bronchiolitis episode (adjusted odds ratio (adjOR) 2.20, 95% CI 1.28–3.76) or croup episode (adjOR 4.34, 95% CI 1.89–9.96) at 6 months, and wheeze (adjOR 1.80, 95% CI 1.14–2.84) and increasing wheeze episodes at 12 months (adjOR 1.81, 95% CI 1.17–2.79). Conclusion Although there was no evidence that guided asthma management or ICS use in pregnancy reduces infant bronchiolitis or wheeze, maternal asthma exacerbations are an important risk factor for these outcomes. Further research is needed to reduce exacerbations in pregnancy.

Asthma is one of the most common chronic diseases affecting pregnant women with variable prevalence around the world. Hormonally mediated and physical changes to the respiratory system occur during pregnancy and can impact asthma status unpredictably—some women improve, some worsen and some are stable. Increased maternal and foetal adverse outcomes are observed with uncontrolled asthma. Medication non‐adherence increases in pregnancy, often because of concerns regarding the effect of medications on the developing foetus and is a major contributor to loss of asthma control. Certain comorbidities, particularly metabolic comorbidities, are more common in pregnant women with asthma and are increasingly understood to impact asthma and pregnancy outcomes. There is reassuring observational data to suggest the safety of omalizumab and dupilumab in pregnancy, but more studies are needed. This review highlights the current evidence regarding epidemiology, pregnancy‐related respiratory changes, comorbidities and treatment of asthma in pregnancy.

BACKGROUND:Optimal management of asthma during pregnancy is an important element in improving maternal and neonatal outcomes. Asthma effects 12.7 % of pregnant women in Australia. Despite consistent management recommendations available via clinical practice guidelines for asthma in pregnancy, pregnant women with asthma are not receiving guideline recommended care. This study builds on previous research and aims to explore the asthma management experiences of pregnant women with asthma. Specifically, to gain insight into pregnant women's understanding of their asthma; previous and current exposure to asthma education; and attitudes towards their asthma management and medication use. METHODS:This qualitative descriptive study involved individual semi-structured interviews with pregnant women with asthma. Data were transcribed and analysed using content analysis. The participants were recruited from those enrolled in the Breathing For Life Trial (BLT), an RCT of inflammation-guided asthma management in pregnancy versus usual care. RESULTS:A total of 24 women were interviewed between June 2018 and May 2020. Three main themes: "Did not think asthma was an issue", "If I'm not getting oxygen in then neither is my baby" and "Beyond pregnancy care" were identified along with 9 sub-themes which showed asthma knowledge, attitude and medication adherence variation depending on experiences with asthma management. CONCLUSIONS:This study highlighted the varied experiences of this cohort of pregnant women with asthma and identified the need for ongoing consistent asthma management to improve the knowledge, attitude, and medication adherence of women with asthma before during and after pregnancy, and in turn improve maternal and neonatal outcomes.

Maternal asthma increases the risk of adverse perinatal and respiratory outcomes in their infants (1) ; breastfeeding may mitigate the risk of respiratory outcomes, including wheeze (2,3) . However, breastfeeding rates are lower in women with asthma (3) compared to general population data and no studies have examined early data on breastfeeding outcomes in this population. This study aimed to examine infant breastfeeding outcomes in the early postnatal period, including breastfeeding initiation, by maternal asthma exposure and whether any differences were due to adverse perinatal outcomes. Data were extracted from electronic obstetric records (e-Maternity) for pregnant women aged ≥ 18 years with singleton births who attended antenatal clinics in two local health districts in New South Wales, Australia, between 2018 and 2020. The association between breastfeeding outcomes and the exposure (maternal asthma) were estimated using multivariable logistic regression, adjusting for maternal confounders (body mass index, age, ethnicity, smoking, Socio-Economic Index for Areas). Secondly, selected perinatal outcomes were added individually to the models to examine if the effect of asthma on breastfeeding outcomes was mediated via these variable/s. Of 41,297 births, 4553 (11%) were to women with asthma. A lower proportion of the maternal asthma group intended to breastfeed compared to the no asthma group (87% vs 90%, p < 0.001); this was not significant in multivariable models, after adjusting for confounders (adjusted Odds Ratio [adjOR] 0.93, 95% Confidence Interval [CI] 0.84 to 1.03). Breastfeeding initiation was lower in the maternal asthma vs no asthma group (80 vs 84%, p < 0.001), as was infant breastfeeding at discharge from hospital (66% vs 71%, p < 0.001; mean length of stay 2.11 days vs 1.97 days) and at post-partum follow-up (56% vs 63%, p < 0.001). A higher proportion of the maternal asthma group had breastfeeding issues as an inpatient, compared to the no asthma group (44% vs 39%, p < 0.001). In multivariable models, maternal asthma was associated with 12% lower odds of breastfeeding initiation (adjOR 0.88, 95% CI 0.80 to 0.96); 11% and 9% lower odds, respectively, of the infant receiving breastmilk only at birth (adjOR 0.89, 95% CI 0.81 to 0.97) and at the postpartum follow-up (adjOR 0.91, 95% CI 0.83 to 0.99); and 12% higher odds of breastfeeding issues (adjOR 1.12, 95% CI 1.04 to 1.20). None of the potential mediators examined (low birthweight, preterm birth, caesarean section, neonatal intensive care unit admission) changed the effect size of asthma exposure by more than 10% on the OR scale for the selected outcomes (breastfeeding initiation, breastfeeding issues, breastfeeding at postpartum). In this population data analysis, maternal asthma increased the odds of poor breastfeeding outcomes in the immediate postpartum period, but these associations did not appear to be mediated via adverse birth outcomes.

Objectives The Breathing for Life Trial (BLT) was a multicentre randomised controlled trial testing the hypothesis that a fractional exhaled nitric oxide-based intervention to guide asthma therapy in pregnancy improves perinatal outcomes. While BLT was negative based on selected outcomes, the conduct of the trial over 7 years showed potential for assessing the broader research impacts and returns on investment in BLT. The aim of this study was to retrospectively assess and report on the impact and value of BLT to show accountability for the research investment in what was deemed a ‘negative’ trial.Methods The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred method. FAIT combines three validated methods, including a modified Payback framework, an economic analysis of return on investment and a narrative account of the impact generated from the research. Data collection was done via document analysis of BLT administrative and research records and review of relevant websites/databases.Results BLT delivered a return on investment of $6.7 million in leveraged grants, fellowships and consultancies and conservatively returned $2.44 for every dollar invested. The research trained and upskilled 18 midwives and obstetricians in evidence-based asthma management in pregnancy and improved research capability of six PhD students. Specialised equipment purchased by BLT is now being repurposed to undertake other research in regional Australia, saving further research investment. Of the 1200 mothers who were part of BLT, 508 now have written asthma plans, 268 had a clinically significant improvement in their asthma control score and the proportion who improved their asthma plan knowledge increased by 58 percentage points from 12 to 70%.Conclusion This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report more broadly on the impact of and returns on research investment in a clinical trial.Trial registration number ACTRN12613000202763; Post results.

Asthma is one of the most common chronic diseases affecting pregnant women with variable prevalence around the world. Hormonally mediated and physical changes to the respiratory system occur during pregnancy and can impact asthma status unpredictably-some women improve, some worsen and some are stable. Increased maternal and foetal adverse outcomes are observed with uncontrolled asthma. Medication non-adherence increases in pregnancy, often because of concerns regarding the effect of medications on the developing foetus and is a major contributor to loss of asthma control. Certain comorbidities, particularly metabolic comorbidities, are more common in pregnant women with asthma and are increasingly understood to impact asthma and pregnancy outcomes. There is reassuring observational data to suggest the safety of omalizumab and dupilumab in pregnancy, but more studies are needed. This review highlights the current evidence regarding epidemiology, pregnancy-related respiratory changes, comorbidities and treatment of asthma in pregnancy.

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.

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 m g/m 3 , 24-hour equivalent) or moderate (100 m g/m 3 , 24-hour equivalent) concentrations of LFS PM (10 m m and below [PM 10 ]) were administered daily for 3 (short-term) and 14 (longterm) 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 PM 10 were administered for 3 days. Cardiac function and gene expression were assessed. Results: Short- and long-term LFS PM 10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM 10 airway exposure also decreased gas diffusion. Short-term LFS PM 10 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 PM 10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM 10 airway exposure on respiratory and cardiovascular disease outcomes.