Effect of fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs.

Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared FENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial - Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and FENO group mothers, with few results reaching p < 0.05. CONCLUSION:  In this sample, FENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ACTRN12613000202763. WHAT IS KNOWN: • Maternal asthma during pregnancy has been associated with increased rates of neurodevelopmental conditions in offspring, including intellectual disability and autism. WHAT IS NEW: • This is the first study to examine how managing asthma during pregnancy via a FENO-guided algorithm or usual care affects infant developmental and behavioural outcomes. While the results of the study showed no impact of the intervention, and therefore do not support the integration of FENO-based management of asthma in antenatal settings for optimal infant development, they do send a positive message about the implications of active asthma management during pregnancy on infant developmental outcomes.

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.

Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension.

BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

Characterization and inhibition of inflammasome responses in severe and non-severe asthma.

BACKGROUND: Increased airway NLRP3 inflammasome-mediated IL-1ß responses may underpin severe neutrophilic asthma. However, whether increased inflammasome activation is unique to severe asthma, is a common feature of immune cells in all inflammatory types of severe asthma, and whether inflammasome activation can be therapeutically targeted in patients, remains unknown. OBJECTIVE: To investigate the activation and inhibition of inflammasome-mediated IL-1ß responses in immune cells from patients with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with non-severe (n = 59) and severe (n = 36 stable, n = 17 exacerbating) asthma and healthy subjects (n = 39). PBMCs were stimulated with nigericin or lipopolysaccharide (LPS) alone, or in combination (LPS + nigericin), with or without the NLRP3 inhibitor MCC950, and the effects on IL-1ß release were assessed. RESULTS: PBMCs from patients with non-severe or severe asthma produced more IL-1ß in response to nigericin than those from healthy subjects. PBMCs from patients with severe asthma released more IL-1ß in response to LPS + nigericin than those from non-severe asthma. Inflammasome-induced IL-1ß release from PBMCs from patients with severe asthma was not increased during exacerbation compared to when stable. Inflammasome-induced IL-1ß release was not different between male and female, or obese and non-obese patients and correlated with eosinophil and neutrophil numbers in the airways. MCC950 effectively suppressed LPS-, nigericin-, and LPS + nigericin-induced IL-1ß release from PBMCs from all groups. CONCLUSION: An increased ability for inflammasome priming and/or activation is a common feature of systemic immune cells in both severe and non-severe asthma, highlighting inflammasome inhibition as a universal therapy for different subtypes of disease.

Absolute cardiovascular risk assessment by Australian early-career general practitioners: a cross-sectional study.

OBJECTIVE: To determine the prevalence and associations of general practice registrars' performing absolute cardio-vascular risk (ACVR) assessment (ACVRa). DESIGN: A cross-sectional study employing data (2017-2018) from the Registrar Clinical Encounters in Training project, an ongoing inception cohort study of Australian GP registrars. The outcome measure was whether an ACVRa was performed. Analyses employed univariable and multivariable regression. Analysis was conducted for all patient problems/diagnoses, then for an 'at-risk' population (specific problems/diagnoses for which ACVRa is indicated). SETTING: Three GP regional training organisations (RTOs) across three Australian states. PARTICIPANTS: GP registrars training within participating RTOs. RESULTS: 1003 registrars (response rate 96.8%) recorded details of 69 105 problems either with Aboriginal and/or Torres Strait patients aged 35 years and older or with non-Indigenous patients aged 45 years and older. Of these problems/diagnoses, 1721 (2.5% (95% CI 2.4% to 2.6%)) involved an ACVRa. An ACVRa was 'plausibly indicated' in 10 384 problems/diagnoses. Of these, 1228 (11.8% (95% CI 11.2% to 12.4%)) involved ACVRa. For 'all problems/diagnoses', on multivariable analysis female gender was associated with reduced odds of ACVRa (OR 0.61 (95% CI 0.54 to 0.68)). There was some evidence for Aboriginal and/or Torres Strait Islander people being more likely to receive ACVRa (OR 1.40 (95% CI 0.94 to 2.08), p=0.10). There were associations with variables related to continuity of care, with reduced odds of ACVRa: if the patient was new to the registrar (OR 0.65 (95% CI 0.57 to 0.75)), new to the practice (OR 0.24 (95% CI 0.15 to 0.38)) or the problem was new (OR 0.68 (95% CI 0.59 to 0.78)); and increased odds if personal follow-up was organised (OR 1.43 (95% CI 1.24 to 1.66)). For 'ACVRa indicated' problems/diagnoses, findings were similar to those for 'all problems/diagnoses'. Association with Aboriginal and/or Torres Strait Islander status, however, was significant at p<0.05 (OR 1.60 (95% CI 1.04 to 2.46)) and association with female gender was attenuated (OR 0.88 (95% CI 0.77 to 1.01)). CONCLUSION: Continuity of care is associated with registrars assessing ACVR, reinforcing the importance of care continuity in general practice. Registrars' assessment of an individual patient's ACVR is targeted to patients with individual risk factors, but this may entail ACVRa underutilisation in female patients and younger age groups.

Impact of Landscape Fire Smoke Exposure on Patients With Asthma With or Without Laryngeal Hypersensitivity.

BACKGROUND: Individuals with asthma experienced severe and prolonged symptoms after the Australian 2019 to 2020 landscape fire. Many of these symptoms, such as throat irritation, occur in the upper airway. This suggests that laryngeal hypersensitivity contributes to persistent symptoms after smoke exposure. OBJECTIVE: This study examined the relationship between laryngeal hypersensitivity and symptoms, asthma control, and health impacts on individuals exposed to landscape fire smoke. METHOD: The study was a cross-sectional survey of 240 participants in asthma registries who were exposed to smoke during the 2019 to 2020 Australian fire. The survey, completed between March and May 2020, included questions about symptoms, asthma control, and health care use, as well as the Laryngeal Hypersensitivity Questionnaire. Daily concentration levels of particulate matter less than or equal to 2.5 µm in diameter were measured over the 152-day study period. RESULTS: The 49 participants with laryngeal hypersensitivity (20%) had significantly more asthma symptoms (96% vs 79%; P = .003), cough (78% vs 22%; P < .001), and throat irritation (71% vs 38%; P < .001) during the fire period compared with those without laryngeal hypersensitivity. Participants with laryngeal hypersensitivity had greater health care use (P ≤ .02), more time off work (P = .004), and a reduced capacity to participate in usual activities (P < .001) during the fire period, as well as poorer asthma control during the follow-up (P = .001). CONCLUSIONS: Laryngeal hypersensitivity is associated with persistent symptoms, reports of lower asthma control, and increased health care use in adults with asthma who were exposed to landscape fire smoke. Management of laryngeal hypersensitivity before, during, or immediately after landscape fire smoke exposure might reduce the symptom burden and health impact.

Influenza presentations and use of neuraminidase inhibitors by Australian general practice registrars: a cross-sectional analysis from the ReCEnT study.

OBJECTIVE: This study aims to establish prevalence and associations of (1) influenza and influenza-like illness (IILI) presentations to Australian general practice (GP) registrars (trainees) and (2) the use of neuraminidase inhibitors (NAIs) by GP registrars for new presentations of IILI, for the 10 years leading up to the COVID-19 pandemic in Australia (2010-2019). DESIGN: This was a cross-sectional analysis of the Registrar Clinical Encounters in Training ongoing inception cohort study of the in-consultation experience and clinical behaviours of GP registrars. Data are collected by individual registrars three times (from 60 consecutive consultations each time) at 6 monthly intervals. Data include diagnoses/problems managed and medicines prescribed, along with multiple other variables. Univariate and multivariable logistic regression was used to establish associations of registrars seeing patients with IILI and of prescribing NAIs for IILI. SETTING: Teaching practices within the Australian general practitioner specialist vocational training programme. Practices were located in five of the six Australian states (plus one territory). PARTICIPANTS: GP registrars in each of their three compulsory 6-month GP training terms. RESULTS: From 2010 to 2019, 0.2% of diagnoses/problems seen by registrars were IILI. 15.4% of new IILI presentations were prescribed an NAI. IILI diagnoses were less likely in younger (0-14) and older (65+) age groups, and more likely in an area of higher socioeconomic advantage. There was considerable variation in NAI prescribing between regions. There was no significant association of prescribing NAIs with age or Aboriginal and/or Torres Strait Islander patients. CONCLUSIONS: IILI presentations were more likely among working-age adults and not among those groups at higher risk. Similarly, high-risk patient groups who would benefit most were not more likely to receive NAIs. The epidemiology and management of IILI has been distorted by the COVID-19 pandemic, but the burden of influenza in vulnerable populations must not be overlooked. Appropriately targeted antiviral therapy with NAIs influences outcomes for vulnerable patients. General practitioners manage the majority of IILI in Australia, and understanding GP IILI presentation and NAI prescribing patterns is a key first step to enabling sound and rational prescribing decisions for better patient outcomes.

The impact of the 2019/2020 Australian landscape fires on infant feeding and contaminants in breast milk in women with asthma.

BACKGROUND: The 2019/2020 Australian landscape fires (bushfires) resulted in prolonged extreme air pollution; little is known about the effects on breastfeeding women and their infants. This study aimed to examine the impact of prolonged landscape fires on infant feeding methods and assess the concentration of polycyclic aromatic hydrocarbons (PAHs) and elements in breast milk samples. METHODS: From May - December 2020, women with asthma, who were feeding their infants during the fires, were recruited from an existing cohort. Data on infant feeding and maternal concern during the fires were retrospectively collected. Breast milk samples were collected from a sample of women during the fire period and compared with samples collected outside of the fire period for levels of 16 PAHs (gas chromatography coupled with mass spectrometry), and 20 elements (inductively coupled plasma-mass spectrometry). RESULTS: One-hundred-and-two women who were feeding infants completed the survey, and 77 provided 92 breast milk samples. Two women reported concern about the impact of fire events on their infant feeding method, while four reported the events influenced their decision. PAHs were detected in 34% of samples collected during, versus no samples collected outside, the fire period (cross-sectional analysis); specifically, fluoranthene (median concentration 0.015 mg/kg) and pyrene (median concentration 0.008 mg/kg) were detected. Women whose samples contained fluoranthene and pyrene were exposed to higher levels of fire-related fine particulate matter and more fire days, versus women whose samples had no detectable fluoranthene and pyrene. Calcium, potassium, magnesium, sodium, sulphur, and copper were detected in all samples. No samples contained chromium, lead, nickel, barium, or aluminium. No statistically significant difference was observed in the concentration of elements between samples collected during the fire period versus outside the fire period. CONCLUSIONS: Few women had concerns about the impact of fire events on infant feeding. Detection of fluoranthene and pyrene in breast milk samples was more likely during the 2019/2020 Australian fire period; however, levels detected were much lower than levels expected to be related to adverse health outcomes.

Associations between aerobic and muscle-strengthening physical activity, sleep duration, and risk of all-cause mortality: A prospective cohort study of 282,473 U.S. adults.

PURPOSE: To examine the joint associations between meeting guidelines for physical activity (PA) and sleep duration and all-cause mortality risk among adults. METHODS: Participants were adults (n = 282,473) aged 18-84 years who participated in the 2004-2014 U.S. National Health Interview Survey. Mortality status was ascertained using the National Death Index through December 2015. Self-reported PA (Active: meeting both aerobic (AER) and muscle-strengthening (MSA) guidelines, AER only (AER), MSA only (MSA), or not meeting either AER or MSA (Inactive)) and sleep duration (Short, recommended (Rec), or Long) were classified according to guidelines, and 12 PA-sleep categories were derived. Adjusted hazard ratios and 95% confidence intervals (95%CIs) for all-cause mortality risk were estimated using Cox proportional hazards regression models. RESULTS: A total of 282,473 participants (55% females) were included; 18,793 deaths (6.7%) occurred over an average follow-up of 5.4 years. Relative to the Active-Rec group, all other PA-sleep groups were associated with increased mortality risk except for the Active-Short group (hazard ratio = 1.08; 95%CI: 0.92-1.26). The combination of long sleep with either MSA or Inactive appeared to be synergistic. For a given sleep duration, mortality risk progressively increased among participants classified as AER, MSA, and Inactive. Within each activity level, the mortality risk was greatest among adults with long sleep. CONCLUSION: Relative to adults meeting guidelines for both PA and sleep duration, adults who failed to meet guidelines for both AER and muscle strengthening PA and who also failed to meet sleep duration guidelines had elevated all-cause mortality risks. These results support interventions targeting both PA and sleep duration to reduce mortality risk.

Prospective associations between joint categories of physical activity and insomnia symptoms with onset of poor mental health in a population-based cohort.

BACKGROUND: Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety; however, few studies jointly examine these risk factors. This study aimed to prospectively examine the joint association of physical activity (PA) and insomnia symptoms with onset of poor mental health in adults. METHODS: Participants from the 2013 to 2018 annual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health (Mental Health Inventory-5 >54) in 2013, and who completed at least 1 follow-up survey (2014-2018), were included (n = 10,977). Poor mental health (Mental Health Inventory-5 ≤ 54) was assessed annually. Baseline (2013) PA was classified as high/moderate/low, and insomnia symptoms (i.e., trouble sleeping) were classified as no insomnia symptoms/insomnia symptoms, with 6 mutually exclusive PA-insomnia symptom groups derived. Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models. RESULTS: There were 2322 new cases of poor mental health (21.2%). Relative to the high PA/no insomnia symptoms group, there were higher odds (odds ratio and 95% confidence interval (95%CI)) of poor mental health among the high PA/insomnia symptoms (OR = 1.87, 95%CI: 1.57-2.23), moderate PA/insomnia symptoms (OR = 1.93, 95%CI: 1.61-2.31), low PA/insomnia symptoms (OR = 2.33, 95%CI: 1.96-2.78), and low PA/no insomnia symptoms (OR = 1.14, 95%CI: 1.01-1.29) groups. Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health, with the odds increasing as PA decreased. CONCLUSION: These findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.

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.

Cross-sectional analysis of the clinical work hours of early-career general practitioners.

BACKGROUND AND OBJECTIVES: The clinical working hours of early-career general practitioners (GPs) are an important factor in Australian GP workforce planning. This study aimed to establish the prevalence and associations of early-career GPs working full time (nine or more sessions per week) in clinical practice. METHOD: This was a cross-sectional questionnaire-based study of alumni (from six months to two years post-Fellowship) from three regional training organisations. Multivariable logistic regression was used to establish factors associated with alumni working full time. RESULTS: Of 356 currently practising early-career alumni participants, 30% worked full time. Factors associated with working full time included spouse/partner employment and family structure and any examination failure. Factors associated with working less than full time included female gender, being an Australian medical graduate, provision of other medical work and having taken additional leave during training. DISCUSSION: A high proportion of early-career GPs working part time in clinical general practice has implications for workplace planning, as GPs seek workload diversity and flexibility across their career stages.

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10-9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

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.

'Breathing Fire': Impact of Prolonged Bushfire Smoke Exposure in People with Severe Asthma.

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 µg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

Socioeconomic status of practice location and Australian GP registrars' training: a cross-sectional analysis.

BACKGROUND: Socioeconomic status (SES) is a major determinant of health. In Australia, areas of socioeconomic disadvantage are characterised by complex health needs and inequity in primary health care provision. General Practice (GP) registrars play an important role in addressing workforce needs, including equitable health care provision in areas of greater socioeconomic disadvantage. We aimed to characterize GP registrars' practice location by level of socioeconomic disadvantage, and establish associations (of registrar, practice, patient characteristics, and registrars' clinical behaviours) with GP registrars training being undertaken in areas of greater socioeconomic disadvantage. METHODS: A cross-sectional analysis from the Registrars' Clinical Encounters in Training (ReCEnT) study. ReCEnT is an ongoing, multi-centre, cohort study that documents 60 consecutive consultations by each GP registrar once in each of their three six-monthly training terms. The outcome factor was the practice location's level of socioeconomic disadvantage, defined using the Index of Relative Socio-economic Disadvantage (SEIFA-IRSD). The odds of being in the lowest quintile was compared to the other four quintiles. Independent variables related to the registrar, patient, practice, and consultation. RESULTS: A total of 1,736 registrars contributed 241,945 consultations. Significant associations of training being in areas of most disadvantage included: the registrar being full-time, being in training term 1, being in the rural training pathway; patients being Aboriginal or Torres Strait Islander, or from a non-English-speaking background; and measures of continuity of care. CONCLUSIONS: Training in areas of greater social disadvantage, as well as addressing community need, may provide GP registrars with richer learning opportunities.

Prevalence, Trends, and Correlates of Joint Patterns of Aerobic and Muscle-Strengthening Activity and Sleep Duration: A Pooled Analysis of 359,019 Adults in the National Health Interview Survey 2004-2018.

BACKGROUND: Physical activity (PA) and sleep duration have established associations with health outcomes individually but tend to co-occur and may be better targeted jointly. This study aimed to describe the cross-sectional prevalence, trends, and population characteristic correlates of activity-sleep patterns in a population-representative sample of US adults from the National Health Interview Survey (2004-2018). METHODS: Participants (N = 359,019) self-reported aerobic and muscle-strengthening activity and sleep duration. They were categorized as "meeting both"/"meeting PA only"/"meeting sleep only"/"meeting neither" of the 2018 US PA guidelines and age-based sleep duration recommendations. Trends in activity-sleep patterns were analyzed using weighted multinomial logistic regression, and correlates were identified using weighted binary Poisson regressions, with P ≤ .001 considered significant. RESULTS: "Meet sleep only" was most prevalent (46.4%) by 2018, followed by "meet neither" (30.3%), "meet both" (15.6%), and "meet PA only" (7.7%). Many significant sociodemographic, biological, and health-behavior correlates of the activity-sleep groups were identified, and the direction and magnitude of these associations differed between groups. CONCLUSIONS: Public health campaigns should emphasize the importance of both sufficient PA and sleep; target women and older adults, current smokers, and those with lower education and poorer physical and mental health; and consider specific barriers experienced by minority ethnic groups.

Onset and progression of chronic disease and disability in a large cohort of older Australian women.

OBJECTIVE: To estimate the probability of onset and progression of disease and disability, length of life with or without disease and/or disability, and incidence of mortality, and to identify factors associated with transitioning to disease and/or disability over time. STUDY DESIGN: A prospective cohort study. Data were provided by 12,432 participants (born 1921-26) of the Australian Longitudinal Study of Women's Health linked with National Death Index data from 1996 (age: 70-75) to 2016 (age: 90-95). MAIN OUTCOME MEASURES: A five-state Markov model was fitted to estimate the transition probability, length of life with or without disease and/or disability, and the association between baseline characteristics and disease/disability/mortality risk. RESULTS: Over two-thirds of women had died by age 90-95, and only 3.8% of these had died with no chronic disease and disability. Those reporting chronic disease were more likely to have experienced disability (Transition Rate Ratio: 2•72, 95%CI= 2•52-2•93) than those who died without disability. At age 70-75, the expected life without chronic disease and disability was 7•68 (95%CI: 7•52-7•80) years, life with chronic disease but no disability was 4•39 (95%CI=4•23-4•49) years, and life with disability was 3.76 (95%CI=3•66-3•92) years. The factors difficulties managing on available income (HR=1•18, 95%CI=1•02-1•38), did not complete secondary school (HR=1•19, 95%CI=1•03-1•37), and overweight/obese (HR=1•36, 95%CI=1•20-1•55) were associated with an increased risk of disability. CONCLUSIONS: Our findings provide important insights on the onset and progression of disease and disability in older women, underscoring the importance of addressing mid-/early old-life risk factors, managing chronic conditions, and delaying disability onset and progression through targeted intervention programs.