Joerg Mattes

Objectives: This study aimed to explore the perceptions of Australian healthcare providers (HCPs) of the usefulness of smart inhalers for children with asthma and considerations for their effective integration into routine care. Design: Qualitative descriptive study using semi-structured interviews. A hybrid thematic analysis approach was used to analyse the data. Setting: Healthcare services in Australia including general practice, hospitals and Local Health Districts. Participants: Eight general practitioners, six paediatric specialists and nine respiratory nurses were recruited using a unique purposive sampling strategy for each HCP group. Primary and secondary outcome measures: Perceptions of the facilitators and challenges to the adoption of smart inhalers for childhood asthma management. Results: Most HCPs had not previously used smart inhalers. Perceived benefits of smart inhalers included access to objective medication use data to inform asthma treatment decisions and enable opportunities to discuss asthma management with parents and carers. Key facilitators for implementation included evidence of clinical effectiveness, financial incentives (both in terms of subsidised smart inhaler costs for users and reimbursement for HCPs) and integration of smart inhaler data into existing medical record systems. The primary barrier to implementation identified was related to workflow issues, including available resourcing, support and time. Conclusions: HCPs expressed generally positive views about the potential of smart inhalers to improve asthma management among children. However, they also identified several practical, logistical and clinical barriers that must be addressed prior to widespread implementation of smart inhalers. Targeted strategies that address these barriers will be essential for successful implementation into routine care.

Background: Maternal asthma during pregnancy is associated with an increased risk of bronchiolitis and asthma in offspring, but the mechanisms remain poorly understood. We aimed to assess whether impaired postnatal infant lung function independently influences the risk of bronchiolitis and asthma in childhood or whether it mediates the association between maternal asthma during pregnancy and respiratory outcomes. Methods: We analysed harmonised infant lung function data from two birth cohorts: the Australian Breathing for Life Trial and the Swiss Basel-Bern Infant Lung Development. Bronchiolitis hospitalisation (verified through medical records) and asthma at age six (parent-reported) were primary outcomes. Lung function measured included the ratio of maximum tidal inspiratory flow to maximum tidal expiratory flow (MTIF/MTEF) and the time to peak tidal expiratory flow to total expiratory time ratio, tPTEF/tE. Multivariable logistic regression assessed associations, and generalised structural equation modelling was used for mediation analyses. Results: The study included 1203 term infants with 89 cases of bronchiolitis hospitalisation. Tidal breathing lung function ratios were associated with bronchiolitis hospitalisations: MTIF/MTEF adjusted ORs (aORs) 2.90, 95% CI 1.20 to 7.02, p=0.018; asthma in childhood: tPTEF/tE aOR 0.97, 95% CI 0.94 to 0.99, p=0.013 and MTIF/MTEF aOR 2.94, 95% CI 1.07 to 8.02, p=0.036. MTIF/MTEF ratio mediated 11% of the total effect of asthma during pregnancy on bronchiolitis risk, and MTIF/MTEF and tPTEF/tE ratios mediated 3% of the effect of asthma during pregnancy on childhood asthma risk. Conclusion: Postnatal lung function was associated with subsequent bronchiolitis and childhood asthma. Additionally, the effect of maternal asthma during pregnancy on the outcomes was partially mediated by impaired lung function.

Background: Prenatal exposure to air pollutants may increase the risk of adverse respiratory outcomes, particularly in offspring of asthmatic mothers. Evidence on wildfire-related PM_2.5 exposure during pregnancy remains limited. This study investigated associations between early gestational wildfire-related PM_2.5 exposure, infant lung function, and respiratory outcomes at 6 years. Methods: Gestational wildfire-related PM_2.5 exposure patterns were characterised using group-based trajectory modelling and linked to infant lung function outcomes. Infant respiratory measurements were obtained at six weeks of age during behaviourally defined quiet sleep using tidal-breathing flow–volume loops (TBFVL). Airway mechanics at six years were assessed by impulse oscillometry (IOS) following international guideline standards. Trajectory modelling of PM_2.5 during gestation was conducted in SAS (PROC TRAJ); all additional statistical analyses were performed in Stata IC 16.1. Results: Increased mean tidal inspiratory flow (MTIF, beta coefficient [β]: 10.51 mL/s, 95% CI: 3.66 to 17.36, p = 0.003) and peak tidal inspiratory flow (PTIF, β: 12.49 mL/s, 95% CI: 2.48 to 22.51, p = 0.014) were observed in infants born to mothers with higher wildfire-related PM_2.5 exposure during early gestation (n = 420; n = 411 not exposed, n = 9 exposed). β-coefficients from infant mixed models were then used as proxy indicators and applied in linear regression models and associated with higher reactance at 5 Hz frequency (n = 73) at 6 years of age (PTIF: β: 9.88 mL/s, 95% CI: 0.10 to 19.67, p = 0.048 and MTIF: β: 13.43 mL/s, 95% CI: 1.43 to 25.44, p = 0.029). PTIF was further associated with asthma diagnoses at 6 years (aOR: 1.36, 95% CI: 1.07 to 1.73, p = 0.012; n = 259; n = 116 asthma). Conclusion: Early gestational exposure to wildfire-related PM_2.5 may be linked with altered respiratory patterns in infancy and differences in airway reactance during childhood. Findings also suggest a relationship with asthma risk, although mechanisms remain uncertain.

Background: This 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. Methods: Children 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. Results: Parent‐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. Conclusion: Early respiratory infection and cat and dog exposure were identified as potentially modifiable exposures to reduce the risk of childhood allergic rhinitis.

Background Infants of asthmatic mothers have reduced lung function in early life for reasons that remain to be defined. The association between inhaled corticosteroid (ICS) use during pregnancy and lung function in the offspring has not been investigated. Objectives To investigate the association between ICS use during pregnancy and infant lung function. Methods Multivariable regression analysis of infant lung function at 4–6 weeks (tidal breathing flow volume loops and functional residual capacity (FRC)) associated with use of ICS during pregnancy. Results Among infants born to asthmatic mothers, the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF:tE), corrected for end-expiratory lung volume (FRC), was improved in offsprings whose mothers used ICS during pregnancy compared with those who did not (n=161 ICS use vs n=25 no ICS use; coefficient 0.06 /mL, 95% CI 0.01 to 0.11, p=0.014). Compared with a control group of infants born to non-asthmatic mothers, there was a lower tPTEF:tE to FRC ratio in infants born to asthmatic mothers without ICS use (n=46 no asthma vs n=25 asthma no ICS use; coefficient −0.08 /mL, 95% CI −0.01 to −0.02, p=0.012) but not in infants born to asthmatic mothers with ICS use (n=46 no asthma vs n=161 asthma ICS use; coefficient −0.02 /mL, 95% CI −0.06 to 0.03, p=0.453). Conclusions The association between maternal asthma and impaired infant lung function diminished in infants whose mothers used ICS during pregnancy. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613000202763.

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.

Background: Reduced lung function is associated with lower respiratory tract infections in early life and may predict bronchiolitis risk. Aim: To utilize tidal breathing flow-volume loops (TBFVL) from healthy infants and train-test machine learning algorithms to generate predictive models for bronchiolitis hospitalisations. Methods: TBFVL were measured at 6 weeks of corrected age in infants born to mothers with asthma using an ultrasonic flow meter (Spiroson; Eco Medics, Duernten, Switzerland). TBFVL raw data were segmented into ‘windows’ of 10 breaths to extract signal descriptive features encompassing statistical, temporal and spectral domains. Fifteen prediction models were trained using a 70:30 training-testing data split and evaluated for Area under the ROC curve (AUROC), along with accuracy, recall, precision, kappa, F1 score and Matthews correlation coefficient. Results: Three hundred and sixty-seven infants were included in the analysis, of whom 22 (6.0%) were admitted to hospital, and 47 (13%) were either admitted or presented to the hospital emergency department, for bronchiolitis during the first year of life. Forty-four signal descriptive features were selected from 2645 TBFVL segments and included along with 8 demographic features as predictors for bronchiolitis hospitalisations. The best machine learning algorithm (Extra Tree Classifier) provided an AUROC of 0.95 for hospital admissions and AUROC of 0.97 for hospital admissions and/or presentations. Conclusion: The ability to predict bronchiolitis risk in healthy infants could alleviate challenges faced by health care providers to ensure both equality and equity in accessing RSV prophylaxis.

Background. Children and adolescents with type 1 diabetes mellitus (T1DM) are frequently hospitalised for severe hypoglycaemia, hyperglycaemia, and diabetic ketoacidosis (DKA). While several risk factors have been recognised, clinically identifying these children at high risk of acute decompensation remains challenging. Objective. To develop a risk prediction model to accurately estimate the risk of acute healthcare utilisation due to severe hypoglycaemia, hyperglycaemia, and DKA in children and adolescents with T1DM. Materials and Methods. Using a retrospective dataset, baseline demographic and clinical data were collected from patients (Results. Our multivariable risk prediction model consisted of five predictors (continuous glucose monitoring device, previous acute healthcare utilisation, missed appointments, and child welfare services involvement and socioeconomic status). The model exhibited good discrimination (area under the ROC = 0.81), accurately stratified children into low-, medium-, and high-risk groups, and demonstrated significant differences between median time to healthcare utilisation. Conclusion. Our model identified patients at an increased risk of acute healthcare utilisation due to severe hypoglycaemia, hyperglycaemia, and DKA.