Assessment of bronchodilator response in preschoolers: A systematic review.

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

Which reference equation should we use for interpreting spirometry values for First Nations Australians? A cross-sectional study.

OBJECTIVES: To evaluate the suitability of the Global Lung Function Initiative (GLI)-2012 other/mixed and GLI-2022 global reference equations for evaluating the respiratory capacity of First Nations Australians. DESIGN, SETTING: Cross-sectional study; analysis of spirometry data collected by three prospective studies in Queensland, the Northern Territory, and Western Australia between March 2015 and December 2022. PARTICIPANTS: Opportunistically recruited First Nations participants in the Indigenous Respiratory Reference Values study (Queensland, Northern Territory; age, 3-25 years; 18 March 2015 - 24 November 2017), the Healthy Indigenous Lung Function Testing in Adults study (Queensland, Northern Territory; 18 years or older; 14 August 2019 - 15 December 2022) and the Many Healthy Lungs study (Western Australia; five years or older; 10 October 2018 - 7 November 2021). MAIN OUTCOME MEASURES: Goodness of fit to spirometry data for each GLI reference equation, based on mean Z-score and its standard deviation, and proportions of participants with respiratory parameter values within 1.64 Z-scores of the mean value. RESULTS: Acceptable and repeatable forced expiratory volume in the first second (FEV1) values were available for 2700 First Nations participants in the three trials; 1467 were classified as healthy and included in our analysis (1062 children, 405 adults). Their median age was 12 years (interquartile range, 9-19 years; range, 3-91 years), 768 (52%) were female, and 1013 were tested in rural or remote areas (69%). Acceptable and repeatable forced vital capacity (FVC) values were available for 1294 of the healthy participants (88%). The GLI-2012 other/mixed and GLI-2022 global equations provided good fits to the spirometry data; the race-neutral GLI-2022 global equation better accounted for the influence of ageing on FEV1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV1 (estimated difference, -0.34; 95% confidence interval [CI], -0.46 to -0.22) and FVC Z-scores (estimated difference, -0.45; 95% CI, -0.59 to -0.32) were lower for rural or remote than for urban participants, but their mean FEV1/FVC Z-score was higher (estimated difference, 0.14; 95% CI, 0.03-0.25). CONCLUSION: The normal spirometry values of healthy First Nations Australians may be substantially higher than previously reported. Until more spirometry data are available for people in urban areas, the race-neutral GLI-2022 global or the GLI-2012 other/mixed reference equations can be used when assessing the respiratory function of First Nations Australians.

Longitudinal tracking of intrabreath respiratory impedance in preschool children.

BACKGROUND: Longitudinal measurements of intrabreath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones. METHODS: Children from a prospective, longitudinal community-based cohort performed annual intrabreath oscillometry (IB-OSC) measurements from age 3- to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance (∆R=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance (∆X=XeE-XeI), and ∆X normalized by tidal volume (∆X/VT). RESULTS: Eighty-five children produced 374 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n = 36), transient (n = 34), or persistent (n = 15). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had +0.814 hPa s L-1 ReE (95% confidence interval [CI] +0.178 to +1.451, p = 0.015), -0.792 hPa s L-1 XeE (95% CI -1.203 to -0.381, p = 0.003), -0.538 hPa s L-1 ∆X (95% CI -0.834 to -0.242, p = 0.007) and -1.672 hPa s L-2 ∆X/VT (95% CI -2.567 to -0.777, p < 0.001). Increasing height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing. CONCLUSIONS: IB-OSC is feasible for tracking lung function growth in preschool-aged children and may allow abnormal lung function to be identified early in asymptomatic preschoolers with a history of persistent wheezing.

Changes in urinary glutathione sulfonamide (GSA) levels between admission and discharge of patients with cystic fibrosis.

There is an urgent need to develop sensitive, non-invasive biomarkers that can track airway inflammatory activity for patients with cystic fibrosis (CF). Urinary glutathione sulfonamide (GSA) levels correlate well with GSA levels in BAL samples and other markers of neutrophilic inflammation, suggesting that this biomarker may be suitable for tracking disease activity in this population. We recruited 102 children (median 11.5 years-old) and 64 adults (median 32.5 years-old) who were admitted to hospital for management of an acute pulmonary exacerbation and/or eradication of infectious agents such as Pseudomonas aeruginosa or Staphylococcus aureus. Our aim was to explore how urinary GSA levels changed across admission timepoints. Urine samples were collected at admission and discharge, and GSA measured by liquid chromatography with mass spectrometry. Paired admission-discharge results were compared using Wilcoxon signed-rank test. Paired admission-discharge samples were available for 53 children and 60 adults. A statistically significant difference was observed between admission-discharge for children and adults. Spearman's correlation analysis identified a correlation between urinary GSA levels and sex and S. aureus infection for children only. Our preliminary findings suggest that urinary GSA is responsive to the resolution of an acute pulmonary exacerbation and therefore warrants further studies in this population.

Exposure to endocrine-disrupting plasticisers and lung function in children and adolescents: A systematic review and meta-analysis.

Exposure to endocrine-disrupting plasticisers (EDPs), such as phthalates and bisphenols, has been associated with reduced lung function in children and adolescents. However, the existing literature yields conflicting results. This systematic review and meta-analysis aimed to assess the epidemiologic evidence investigating the association between EDP exposure and lung function in children and adolescents. A comprehensive search of five databases identified 25 relevant studies. We employed a random-effects meta-analysis on spirometry measures. The effect size of interest was the change in lung function in standard deviation (SD) units resulting from a two-fold increase in exposure levels. We found that certain phthalates marginally reduced lung function in children. Forced expiratory volume in 1 s (FEV1) was reduced by a two-fold increase in mono-benzyl phthalate (MBzP) (ß = -0.025 SD, 95%CI: 0.042, -0.008), mono-ethyl-oxo-hexyl phthalate (MEOHP) (ß = -0.035 SD, 95%CI: 0.057, -0.014) and mono-carboxy-nonyl phthalate (MCNP) (ß = -0.024 SD, 95%CI: 0.05, -0.003). Forced vital capacity (FVC) was decreased by a two-fold increase in MBzP (ß = -0.022 SD, 95%CI: 0.036, -0.008) and MEOHP (ß = -0.035 SD, 95%CI: 0.057, -0.014) levels. A two-fold increase in MCNP levels was associated with lower FEV1/FVC (ß = -0.023 SD, 95%CI: 0.045, -0.001). Furthermore, a two-fold increase in MEOHP levels reduced forced mid-expiratory flow (FEF25-75) (ß = -0.030 SD, 95%CI: 0.055, -0.005) and peak expiratory flow (PEF) (ß = -0.056 SD, 95%CI: 0.098, -0.014). Notably, associations were more pronounced in males. Given the potential for reverse causation bias, the association between childhood exposure to EDPs and lung function remains uncertain. Overall, our meta-analysis showed small reductions in lung function with higher phthalate exposure. However, future studies are warranted in younger age groups.

Effects of prenatal alcohol exposure on infant lung function, wheeze, and respiratory infections in Australian children.

BACKGROUND: Prenatal alcohol exposure (PAE) is a known risk factor for a range of adverse outcomes, such as facial dysmorphism, adverse birth outcomes, and neurodevelopmental changes. Preclinical research shows that PAE also inhibits lung development, lowers surfactant protein expression, has detrimental effects on alveolar macrophages, and decreases both T and B cell numbers. However, clinical evidence of respiratory impacts from PAE is limited. This study explored whether lung function, wheeze, and incidence of respiratory infections differ in children with PAE compared with unexposed children. METHODS: Data from the Barwon Infant Study (n = 1074) were examined. PAE data were extracted from maternal questionnaires at trimesters 1 and 2 (combined), and trimester 3, and included as "total standard drinks" during each trimester and total pregnancy intake, a binary yes/no for PAE, and binge drinking (>5 standard drinks in one session). Respiratory outcomes were parent-reported wheeze, lung function (measured by multiple breath washout), and parent report and medical record indicators of health service attendances for respiratory conditions. Linear and logistic regressions were performed to quantify relationships between PAE and respiratory outcomes, controlling for socioeconomic status, birthweight, sex, gestational age, and maternal smoking. RESULTS: Binge drinking was associated with increased health service attendance for respiratory condition(s) in the first 12 months of life (OR = 5.0, 95% CI (1.7, 20.7), p = 0.008). We did not find a relationship between binary PAE and binge drinking with lung function at 4 weeks of age or wheeze at 12 months. The number of standard drinks consumed in trimester two was associated with a lower lung clearance index (ß = -0.011 turnovers, 95% CI (-0.0200, -0.0013), p = 0.03), and a small increase in functional residual capacity (ß = 0.34 mL, 95% CI (0.02, 0.66), p = 0.04). CONCLUSIONS: We found an association between binge drinking and health service utilization for respiratory conditions in infancy, but no evidence that low-level PAE was associated with adverse respiratory outcomes.

Association of maternal air pollution exposure and infant lung function is modified by genetic propensity to oxidative stress.

Introduction: The association between air pollution and poor respiratory health outcomes is well established, however less is known about the biological mechanisms, especially in early life. Children are particularly at risk from air pollution, especially during the prenatal period as their organs and systems are still undergoing crucial development. Therefore, our study aims to investigate if maternal exposure to air pollution during pregnancy is associated with oxidative stress (OS) and inflammation in pregnancy or infant lung function at 4 weeks of age, and the extent to which the association is modified by an infant's genetic risk of OS. Methods: The Barwon Infant Study (BIS) is a longitudinal study of Australian children from the region of Geelong, Victoria. A total of 314 infants had available lung function and maternal OS markers. Exposure to annual air pollutants (NO 2 and PM 2.5 ) were estimated using validated, satellite-based, land-use regression models. Infant lung function was measured by multiple-breath washout, and the ratio of peak tidal expiratory flow over expiratory time was calculated at 4 weeks of age. An inflammation biomarker, glycoprotein acetyls (GlycA), was measured in maternal (36 weeks) and cord blood, and oxidative stress (OS) biomarkers, 8-hydroxyguanine (8-OHGua) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in maternal urine at 28 weeks. A genetic pathway score for OS (gPFS ox ) was calculated for each infant participant in the BIS cohort, and high risk defined as score >8. Linear regression was used to explore the association of maternal air pollution exposure with infant lung function, and potential modification by OS genotype was tested through use of interaction terms and other methods. Results: There was no evidence of a relationship between maternal exposure to air pollution and infant lung function in the whole population. We did not find an association between air pollution and GlycA or OS during pregnancy. We found evidence of an association between NO 2 and lower in functional residual capacity (FRC) for children with a high genetic risk of OS (ß=-5.3 mls, 95% CI (-9.3, -1.3), p=0.01). We also found that when NO 2 was considered in tertiles, the highest tertile of NO 2 was associated with increase in lung clearance index (LCI) (ß=0.46 turnovers, (95% CI 0.10, 0.82), p=0.01) in children with a genetic propensity to OS. Conclusion: Our study found that high prenatal levels of exposure to ambient NO 2 levels is associated with lower FRC and higher LCI in infants with a genetic propensity to oxidative stress. There was no relationship between maternal exposure to air pollution with maternal and cord blood inflammation or OS biomarkers.

Developing Fractional Exhaled Nitric Oxide Predicted and Upper Limit of Normal Values for a Disadvantaged Population.

BACKGROUND: Fractional exhaled nitric oxide (Feno), used as a biomarker, is influenced by several factors including ethnicity. Normative data are essential for interpretation, and currently single cutoff values are used in children and adults. RESEARCH QUESTION: Accounting for factors that influence Feno, (1) what are appropriate predicted and upper limit of normal (ULN) Feno values in an underserved population (First Nations Australians), (2) how do these values compare with age-based interpretive guidelines, and (3) what factors influence Feno and what is the size of the effect? STUDY DESIGN AND METHODS: Feno data of First Nations Australians (age < 16 years, n = 862; age ≥ 16 years, n = 348) were obtained. Medical history using participant questionnaires and medical records were used to define healthy participants. Flexible regression using spline functions, as used by the Global Lung Function Initiative, were used to generate predicted and ULN values. RESULTS: Look-up tables for predicted and ULN values using age (4-76 years) and height (100-200 cm) were generated and are supplied with a calculator for clinician use. In healthy First Nations children (age < 18 years), ULN values ranged between 25 and 60 parts per billion (ppb) when considering only biologically plausible age and height combinations. For healthy adults, ULN values ranged between 39 and 88 ppb. Neither the current Feno interpretation guidelines, nor the currently recommended cutoff of 50 ppb for First Nations children 16 years of age or younger were appropriate for use in this cohort. Our modelling revealed that predicted and ULN values of healthy participants varied nonlinearly with age and height. INTERPRETATION: Because single pediatric, adult, or all-age Feno cutoff values used by current interpretive guidelines to define abnormality fail to account for factors that modify Feno values, we propose predicted and ULN values for First Nations Australians 4 to 76 years of age. Creating age- and height-adjusted predicted and ULN values could be considered for other ethnicities.

Early Childhood Pneumonia Is Associated with Reduced Lung Function and Asthma in First Nations Australian Children and Young Adults.

BACKGROUND: Some but not all previous studies report that pneumonia in children aged less than five years is associated with lower lung function and elevated risk of respiratory disease. To date, none have explored these associations in at-risk populations such as First Nations Australians, whose incidence of early childhood pneumonia is among the highest reported in the world. METHODS: This cross-sectional study included 1276 First Nations Australian children/young adults aged 5-25 years recruited from regional/remote Queensland and Northern Territory communities and schools. Associations between pneumonia and both spirometry values and asthma were investigated using linear and logistic regression. RESULTS: Early childhood pneumonia was associated with lower FEV1 and FVC Z-scores, but not FEV1/FVC% Z-scores, when occurring before age three (FEV1 ß = -0.42, [95%CI -0.79, -0.04]; FVC ß = -0.62, [95%CI -1.14, -0.09]), and between three and five years (ß = -0.50, [95%CI -0.88, -0.12]; ß = -0.63, [95%CI -1.17, -0.10]), compared to those who never had pneumonia. Similarly, pneumonia occurring when aged before age three years (OR = 3.68, 95%CI 1.96-6.93) and three to five years (OR = 4.81, 95%CI 1.46-15.8) was associated with increased risk of asthma in later childhood. CONCLUSIONS: Early childhood pneumonia is associated with lung function deficits and increased asthma risk in later childhood/early adulthood in First Nations Australians. The disproportionate impact of pneumonia on at-risk children must be addressed as a priority.

How do Cormic Index profiles contribute to differences in spirometry values between White and First Nations Australian children?

BACKGROUND: Spirometry values of First Nations Australian children are lower than White children. One explanation relates to differences in the sitting-height/standing-height ratio (Cormic Index), as this accounts for up to half the observed differences in spirometry values between White children and other ethnicities. We investigated whether the Cormic Index of First Nations children differs from White children and if this explains the lower spirometry values of First Nations children. METHODS: First Nations children (n = 619) aged 8-16 years were recruited from nine Queensland communities. Their spirometry and Cormic Index data were compared to that of White children (n = 907) aged 8-16 years from the NHANES III dataset. RESULTS: FEV1 and FVC of First Nations children was 8% lower for children aged 8-11.9 years and 9%-10% lower for children aged 12-16 years. The Cormic Index was statistically lower in the First Nations 8-11.9 years group (median = 0.515, interquartile range [IQR]: 0.506-0.525) compared with White children (0.519, IQR: 0.511-0.527), and this difference was greater in the 12-16 years group (0.505, IQR: 0.492-0.516; 0.520, IQR: 0.510-0.529). Adjusting for age, sex, and standing height, lower Cormic Index of First Nations children accounts for 14% (95% confidence interval [CI]: 7%-21%) of FEV1 and 15% (95% CI: 8%-21%) of FVC differences in the younger group, and 26% (95% CI: 16%-37%) of FEV1 and 31% (95% CI: 19%-42%) of FVC differences in the older group. CONCLUSION: Ethnic differences in Cormic Index partly account for why healthy First Nations Australian children have lower spirometry values than White children. As childhood spirometry values impact adult health, other contributing factors require attention.

Associations between lung function and future cardiovascular morbidity and overall mortality in a predominantly First Nations population: a cohort study.

BACKGROUND: Spirometric lung function impairment is an independent predictor of respiratory and cardiovascular disease, and mortality across a broad range of socioeconomic backgrounds and environmental settings. No contemporary studies have explored these relationships in a predominantly regional/remote First Nations population, whose health outcomes are worse than for non-First Nations populations, and First Nations people living in urban centres. METHODS: This was a retrospective cohort study of 1,734 adults (1,113 First Nations) referred to specialist respiratory outreach clinics in the state of Queensland, Australia from February 2012 to March 2020. Regression modelling was used to test associations between lung function and mortality and cardiovascular disease. FINDINGS: At the time of analysis (August 2020), 189 patients had died: 88 (47%) from respiratory causes and 38 (20%) from cardiovascular causes. When compared to patients with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) Z-scores of >0 to -1, patients with Z-scores <-1 were at elevated mortality risk (HR=3•2, 95%CI 1•4-7•4; HR=2•6, 95%CI 1•3-5•1), and elevated cardiovascular disease risk (OR=1•5, 95%CI 1•1-2•2; OR=1•6, 95%CI 1•2-2•3). FEV1/FVC% Z-scores <-1 were associated with increased overall mortality (HR=1•6, 95%CI 1•1-2•3), but not cardiovascular disease (OR=1•1, 95%CI 0•8-1•4). These associations were not affected by First Nations status. INTERPRETATION: Reduced lung function even within the clinically normal range is associated with increased mortality, and cardiovascular disease in First Nations Australians. These findings highlight the importance of lung function optimisation and inform the need for future investment to improve outcomes in First Nations populations. FUNDING: None.

Determinants and Follow-up of Lung Function Data from a Predominantly First Nations Cohort of Adults Referred to Specialist Respiratory Outreach Clinics in Regional and Remote Queensland.

PURPOSE: Northern Territory (NT)-based clinical service data suggest substantial lung function impairment amongst First Nations adults as young as 18-40 years. Our objectives were to describe the burden of disease and lung function of adults living in regional-remote Queensland, identify determinants of lung function, and evaluate the impact of a specialist respiratory outreach service on lung function. METHODS: Retrospective 8-year cohort study (February 2012-March 2020) of 1113 First Nations Australian adults (and 648 non-First Nations adults) referred to respiratory outreach clinics in regional-remote Queensland. RESULTS: In the combined cohort, the forced expiratory volume in 1 s (FEV1) was clinically abnormal for 54% of First Nations patients (51% of non-First Nations patients), forced vital capacity (FVC) for 46% (36%), FEV1/FVC% for 30% (36%), and gas diffusing capacity (DLCO) for 44% (37%). A respiratory diagnosis was assigned by a respiratory physician in 78% of First Nations (76% non-First Nations) patients. Smoking, household smoke exposure, underweight BMI, and respiratory disease were associated with reduced lung function. In the 40% of patients (709/1765) followed up, FEV1 and FVC significantly improved (mean change: zFEV1 = 0.15 [95% CI 0.10-0.20]; zFVC = 0.25 [0.20, 0.31]), and FEV1/FVC% significantly reduced (mean = - 0.10 [95%CI - 0.07 to - 0.03]), with no significant change in DLCO. Patients with COPD had lower FEV1 improvement, whilst underweight and obese patients had lower FVC improvement. CONCLUSION: Regional-remote First Nations adult Queenslanders have higher lung function than previously reported, with no lung function decline observed at follow-up visit, including for those with respiratory disease.

Impact of prenatal and early life environmental exposures on normal human development.

The global burden and pattern of disease has changed in recent decades, with fewer early childhood deaths and longer lives complicated by chronic disease. Disruption of normal human growth and development by adverse environmental exposures, especially during foetal development and early postnatal life increase life-long risk of chronic disease. The developmental timing and method of adverse exposure determines the likely impact on health and development. While many organ systems are structurally and functionally mature at birth, the CNS, respiratory and immune systems are not and undergo prolonged periods of postnatal growth and development. As such, these organ systems are vulnerable to adverse effects of both prenatal and postnatal environmental exposures. While the precise mechanisms underlying chronic disease are unknown, epigenetic mechanisms and the induction of oxidative stress are likely to be involved. An understanding of these processes is necessary to develop mitigation strategies aimed at reducing chronic disease prevalence.

Respiratory health profile of Indigenous Australian children and young adults.

AIM: National data report respiratory illness to be the most common chronic illness in Australian Indigenous people aged <35 years but multi-centre data on specific diseases is sparse. Respiratory health is now known to be an independent predictor of future all-cause mortality and cardiovascular disease. We aimed to describe the respiratory health profile (clinical and spirometry data) of randomly recruited Indigenous Australian children and young adults from several sites. METHODS: As part of the Indigenous Respiratory Reference Values study, 1278 Australian Indigenous children and young adults (aged 3-25 years) were recruited from nine communities (Queensland, n = 8; Northern Territory, n = 1). Self-reported and medical records were used to ascertain respiratory history. Participants were classified as 'healthy' if there was no current/previous respiratory disease history. Spirometry was performed on all participants and assessed according to forced expiratory volume at 1 s impairment. RESULTS: Medical history data were available for 1245 (97.4%) and spirometry for 1106 participants (86.5%). Asthma and bronchitis were the most commonly reported respiratory conditions (city/regional 19.5% and rural/remote 16.8%, respectively). Participants with a history of any respiratory disease or those living in rural/remote communities had lower lung function compared to the 'healthy' group. Almost 52.0% of the entire cohort had mild-moderate forced expiratory volume at 1 s impairment (47.7% in 'healthy' group, 58.5% in 'respiratory history' group). CONCLUSION: The high prevalence of poor respiratory health among Indigenous Australian children/young adults places them at increased risk of future all-cause mortality and cardiovascular disease. Respiratory assessments including spirometry should be part of the routine evaluation of Indigenous Australians.

Global Lung Function Initiative-2012 'other/mixed' spirometry reference equation provides the best overall fit for Australian Aboriginal and/or Torres Strait Islander children and young adults.

BACKGROUND AND OBJECTIVE: Ethnic-specific reference equations are recommended when performing spirometry. In the absence of appropriate reference equations for Australian Aboriginal and/or Torres Strait Islanders (Indigenous), we determined whether any of the existing Global Lung Function Initiative (GLI)-2012 equations were suitable for use in Indigenous children/young adults. METHODS: We performed spirometry on 1278 participants (3-25 years) who were identified as Aboriginal, Torres Strait Islander or 'both'. Questionnaires and medical records were used to identify 'healthy' participants. GLI2012_DataConversion software was used to apply the 'Caucasian', 'African-American' and 'other/mixed' equations. RESULTS: We included 930 healthy participants. Mean z-scores for forced expiratory volume in 1 s (FEV1 ) and forced vital capacity (FVC) were lower than the Caucasian predicted values (range: -0.53 to -0.60) and higher than African-American (range: 0.70 to 0.78) but similar to other/mixed (range: 0.00 to 0.08). The distribution of healthy participants around the upper and lower limits of normal (~5%) fit well for the other/mixed equation compared to the Caucasian and African-American equations. CONCLUSION: Of the available GLI-2012 reference equations, the other/mixed reference equation provides the best overall fit for Indigenous Australian children and young adults (3-25 years). Healthy data from additional communities and adults around Australia will be required to confirm generalizability of findings.

How does parent/self-reporting of common respiratory conditions compare with medical records among Aboriginal and Torres Strait Islander (Indigenous) children and young adults?

AIM: Self-reporting and/or data from medical records are frequently used in studies to ascertain health history. Data on the discrepancies between these information sources is lacking for Indigenous Australians. This study reports such data for selected respiratory and atopic conditions common among Indigenous Australians. METHODS: Data were extracted from the Indigenous respiratory reference value study, a multicentre cross-sectional study of Indigenous children and young adults (3-25 years) between June 2015 and November 2017. Only those living in rural/remote regions were included. Self-reported history was collected from parents (if participants <18 years) or participants. Medical records were manually reviewed. Participants with incomplete data (missing self-reported and/or medical record information) were excluded. Agreement between sources was examined using Cohen's kappa. RESULTS: Of 1097 participants, 889 (97.1% <18 years) had sufficient self-reported and medical record histories for comparison. Asthma was self-reported by 15.7% of participants and was reported in medical records for 10.3% (κ = 0.53, 95% confidence interval (CI) 0.45-0.61). For bronchiectasis, the reported rates were 1.5 and 0.7% (κ = 0.52, 95% CI 0.25-0.80), pneumonia 1.1 and 5.8% (κ = 0.15, 95% CI 0.02-0.27), allergic rhinitis 6.6 and 0.6% (κ = 0.05, 95% CI -0.03, 0.13) and eczema 5.8 and 6.2% (κ = 0.30, 95% CI 0.18-0.42). CONCLUSIONS: Within our cohort, agreement was moderate for asthma and bronchiectasis, fair for eczema and poor for pneumonia and allergic rhinitis. These results highlight the challenges associated with how best to obtain an accurate health history within Australian Indigenous rural/remote communities. Generalisability of findings and contributions of poor health knowledge and/or poor medical record documentation need further exploration.

Fractional Exhaled Nitric Oxide Values in Indigenous Australians 3 to 16 Years of Age.

BACKGROUND: Fractional exhaled nitric oxide (Feno) levels can identify eosinophilic asthma phenotypes. We aimed to determine Feno values of healthy Aboriginal and/or Torres Strait Islander (Indigenous) Australians, differences between these Indigenous ethnic groups, and appropriateness of published cutoff values. METHODS: We measured Feno levels in 1,036 Indigenous Australians (3-16 years of age). Participants were classified into healthy (ie, no asthma or atopy history) or asthmatic and/or atopic groups. RESULTS: Median Feno values and distribution did not differ between Indigenous ethnicities. For healthy participants < 12 years of age (n = 390), 7.2% of our cohort fell into the inflammatory zone of the American Thoracic Society (ATS), National Institute for Health and Care Excellence (NICE), and British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines (cutoff 35 parts per billion [ppb]), but only 3.8% fell into this category when using the Global Initiative for Asthma (GINA) guidelines (50 ppb). Similarly, when using the NICE and BTS/SIGN guidelines (40 ppb) for participants 12 to 16 years of age (n = 213), more healthy participants fell into the inflammatory zone compared with the ATS and GINA guidelines (50 ppb) (9.9% vs 4.7%, respectively). CONCLUSIONS: Feno values for healthy Indigenous Australians children (3-16 years of age) are likely higher than published white-based values. The GINA recommended cutoff value (> 50 ppb) appears the most appropriate for identifying healthy Indigenous children but requires confirmation from a larger study.

Does Ethnicity Influence Fractional Exhaled Nitric Oxide in Healthy Individuals?: A Systematic Review.

BACKGROUND: Fractional exhaled nitric oxide (Feno) is used clinically as a biomarker of eosinophilic airway inflammation. Awareness of the factors influencing Feno values is important for valid clinical interpretation. METHODS: We undertook a systematic review of PubMed, Cochrane Library, Scopus, and Web of Science databases and reference lists of included articles to evaluate whether ethnicity influences Feno values, and to determine if this influence affects clinical interpretation according to current guidelines. We included all studies that performed online Feno measurements on at least 25 healthy, non-Caucasian individuals, and examined the effect of ethnicity on Feno. RESULTS: From 62 potential studies, 12 studies were included. One study recruited only children (< 12 years of age), six studies recruited children and/or adolescents, four studies recruited adults only, and a single study involved children, adolescents, and adults. In total, 16 different ethnic populations representing 11 ethnicities were studied. Ethnicity was considered a significant influencing factor in 10 of the included studies. We found the geometric mean Feno to be above the normal healthy range in two studies. We also identified five studies in which at least 5% of participants had Feno results above the age-specific inflammatory ranges. CONCLUSIONS: Ethnicity influences Feno values, and for some ethnic groups this influence likely affects clinical interpretation according to current guidelines. There is a need to establish healthy Feno reference ranges for specific ethnic groups to improve clinical application.

Spirometry reference values in Indigenous Australians: a systematic review.

OBJECTIVES: To evaluate published spirometry data for Australian Aboriginal and Torres Strait Islander (Indigenous) peoples to determine (i) whether their ethnicity influenced spirometry results; and (ii) if any reliable spirometry reference values exist for Indigenous Australians. STUDY DESIGN: Systematic review of published and grey literature. DATA SOURCES: PubMed and Cochrane Library databases, references of included articles and appropriate grey literature. Last searches were conducted in April 2016. STUDY SELECTION: We included any study that performed spirometry on healthy Indigenous Australians and compared their results with those from people of European ancestry. Two authors independently screened titles and abstracts and then reviewed potentially relevant full-text articles for possible inclusion. We used PRISMA systematic review reporting methods to collate data. DATA SYNTHESIS: Of a possible 125 studies, 18 full-text articles were reviewed, but only nine fulfilled the inclusion criteria. None specified Torres Strait Islander inclusion. All studies reported lower spirometry values (as much as 30% lower) for Aboriginal people compared with non-Indigenous people. Five studies developed spirometry reference values for Indigenous Australians; however, none adhered to all participant inclusion and exclusion criteria outlined by the American Thoracic Society and European Respiratory Society. Hence, reported results and subsequent reference values may not be a true representation of spirometry values in healthy Indigenous people. CONCLUSIONS: The lower spirometry values reported for Indigenous Australians may be due to study limitations. Furthermore, there are currently no reliable spirometry reference values for Indigenous Australians that adhere to current guidelines. Developing a set of Indigenous Australian reference values will improve the accuracy of test interpretation and aid in the diagnosis of respiratory disease in this population.