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Chronic cough in children is a common and multifaceted symptom, often requiring a comprehensive approach for accurate diagnosis and effective management. This review explores the use of spirometry, radiology (chest X-rays and computed tomography (CT) scans), and flexible bronchoscopy in the assessment of chronic cough in children through current guidelines and studies. The strengths, clinical indications, and limitations of each modality are examined. Spirometry, radiology, and in some cases flexible bronchoscopy are integral to the assessment of chronic cough in children; however, a tailored approach, leveraging the strengths of each modality and guided by clinical indications, enhances diagnostic accuracy and therapeutic outcomes of pediatric chronic cough.

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 (FEV 1 ) 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 FEV 1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV 1 (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 FEV 1 /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., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Backgrounds: Understanding factors associated with anxiety of parents/carers of children with respiratory problems is clinically important yet there is relative paucity of data. In 106 children seen in the respiratory clinic of a pediatric hospital, we evaluated (a) the determinants for parental anxiety and (b) whether the anxiety scores correlate with quality-of-life (QoL) scores in the subset with chronic cough., Methods: We opportunistically re-analyzed data of our main study that examined the benefits of using spirometry for pediatric respiratory consultation where parents completed an anxiety questionnaire (State-Trait Anxiety Inventory, STAI) pre- and postconsultation. A subset (children with chronic cough) also completed the parent-proxy quality-of-life (PC-QoL) tool. We computed the association between clinical characteristics and anxiety scores using multivariable regression and between the two patient-reported outcome measures using Spearman's correlation., Results: The majority of parents/carers were women (n = 89, 84%). Most children (mean age = 10.9 years, SD = 3.7 years) were previously seen at the clinic (n = 67, 63.2%). In multivariate regression, parental anxiety score was significantly associated with reported presence of cough [coefficient β = 17.31 (95% confidence interval 9.62, 25.1)] and lower forced expiratory volume in first second (FEV 1 )/forced vital capacity (FVC) [-3.88 (-7.05, -0.71)] at preconsultation, but associated with cough only [coefficient β = 12.04 (5.24, 18.84)] at postconsultation, all p < .05. STAI strongly correlated with PC-QoL scores at pre- but only modestly at postconsultation (r s  = -.63 and -.39, respectively, p < .05)., Conclusion: Parental anxiety levels of children attending respiratory clinics are influenced by the presence of cough and low FEV 1 /FVC of their child and are associated with poorer QoL. These highlight the need for on-going research to reduce parental anxiety focusing on cough and lung function indices., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Early childhood respiratory infections, including pneumonia, are an important global public health issue, with more than 40 million annual cases resulting in approximately 650 000 deaths. A growing number of published studies have examined the effects of early childhood lower respiratory tract infections (LRTIs) or pneumonia on lung function, particularly as part of large early-life exposure studies. To our knowledge, there is no published systematic review of these data. We searched PubMed, Embase, and Web of Science for studies published between database inception and May 12, 2022. Case-control, cohort, and cross-sectional studies were included if they reported forced expiratory volume in 1 s (FEV 1 ) or forced vital capacity (FVC) values of participants older than 5 years. Article titles and abstracts were screened in Rayyan before retrieval, assessment, and data extraction of the full text. Primary outcome measures were differences in mean FEV 1 or FVC values between exposed groups (ie, children aged ≤5 years with LRTIs) and non-exposed groups. This study is registered with PROSPERO, CRD42021265295. Database searches yielded 3070 articles, and 14 studies were included in this systematic review, providing a total of 23 276 participants, including 9969 children and 13 307 adults. Eight of 14 articles reported significant reductions in FEV 1 values, and six of 12 studies reported reductions in FVC values in children and adults with a history of early childhood LRTIs or pneumonia, compared with unexposed controls (p<0·05). Most studies reporting reductions in lung function described deficits consistent with a restrictive spirometry pattern. Only two of 14 studies reported data from low-income and middle-income countries or disadvantaged populations in middle-income and high-income countries, and there were scarce data available on the effect of LRTI severity and recurrence on lung function. LRTIs in early childhood could be associated with a restrictive spirometry pattern in later childhood and adulthood. Data are needed from low-income and middle-income nations, and from disadvantaged populations in middle-income and high-income countries in which early childhood respiratory infection burden is disproportionately high. Data are also needed on the effect of LRTI severity and recurrence on future lung function., Competing Interests: Declaration of interests ABC reports multiple grants from the Australian National Health and Medical Research Council (NHMRC), and other fees to the institution from work relating to independent data monitoring committee membership of an unlicensed vaccine (GlaxoSmithKline), an unlicensed monoclonal antibody for RSV (AstraZeneca), and a COVID-19 vaccine (Moderna), outside the submitted work; and fees to the institution from work relating to unlicensed therapies for bronchiectasis (inhaled antibiotics from Zambon and a molecule from Boehringer Ingelheim). JLP reports investigator-initiated funding from GlaxoSmithKline for unrelated research. SCD reports investigator-initiated funding from GlaxoSmithKline for unrelated research, and further investigator-initiated funding from AstraZeneca. MSM reports other grants from Children's Hospital Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: There is limited evidence on the efficacy of using spirometry routinely in paediatric practice for improving outcomes., Objective: To determine whether the routine use of spirometry alters clinical decisions and patient-related outcome measures for children managed by respiratory paediatricians., Methods: We undertook a parallel open-label randomised controlled trial involving children (aged 4-18 years) able to perform spirometry in a specialist children's hospital in Australia. Children were randomised to either routine use of spirometry (intervention) or clinical review without use of spirometry (control) for one clinic visit. The primary outcomes were the (a) proportion of children with 'any change in clinical decisions' and (b) 'change score' in clinical decisions. Secondary outcomes were change in patient-related outcome measures assessed by State-Trait Anxiety Inventory (STAI) and Parent-Proxy QoL questionnaire for paediatric chronic cough (PC-QoL)., Results: Of 136 eligible children, 106 were randomised. Compared with controls, the intervention group had significantly higher proportion of children with 'any change in clinical decisions' (n=54/54 (100%) vs n=34/52 (65.4%), p<0.001) and higher clinical decision 'change score' (median=2 (IQR 1-4) vs 1 (0-2), p<0.001). Also, improvement was significantly greater in the intervention group for overall STAI score (median=-5 (IQR -10 to -2) vs -2.5 (-8.5, 0), p=0.021) and PC-QoL social domain (median=3 (IQR 0 to 5) vs 0 (-1, 1), p=0.017)., Conclusion: The routine use of spirometry in children evaluated for respiratory issues at clinical outpatient review is beneficial for optimising clinical management and improving parent psychosocial well-being., Registration: Australia and New Zealand Clinical Trials Registry ACTRN12619001686190., Competing Interests: Competing interests: No competing interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Low diffusing capacity of the lung for carbon monoxide (D LCO ) and spirometry values are associated with increased mortality risk. However, associations between mortality risk and cardiovascular disease with the transfer coefficient of the lung for carbon monoxide (K CO ) and alveolar volume (V A ) are unknown. This cohort study: (i) evaluated whether D LCO , K CO , and V A abnormalities are independently associated with cardiovascular morbidity and/or elevated mortality risk and, (ii) compared these associations with those using spirometry values., Methods: Gas-diffusing capacity and spirometry data of 1165 adults seen at specialist respiratory outreach clinics over an 8-year period (241 with cardiovascular disease; 108 deceased) were analysed using multivariable Cox and logistic regression., Results: D LCO , K CO , and V A values below the lower limit of normal (< - 1.64 Z-scores) were associated with elevated cardiovascular disease prevalence [respective odds ratios of 1.83 (95% CI 1.31-2.55), 1.56 (95% CI 1.08-2.25), 2.20 (95% CI 1.60-3.01)] and increased all-cause mortality risk [respective hazard ratios of 2.99 (95% CI 1.83-4.90), 2.14 (95% CI 1.38-3.32), 2.75 (95% CI 1.18-2.58)], after adjustment for factors including age, personal smoking, and respiratory disease. Compared to similar levels of spirometry abnormality, D LCO , K CO , and V A were associated with similar or greater mortality risk, and similar cardiovascular disease prevalence. Analysis of only those patients with clinical normal spirometry values (n = 544) showed these associations persisted for D LCO ., Conclusion: Low D LCO , K CO , and V A measurements are associated with cardiovascular disease prevalence. As risk factors of all-cause mortality, they are more sensitive than spirometry even among patients with no diagnosed respiratory disease., (© 2022. The Author(s).)

Background: There is little data on patterns of spirometry curves in children with tracheomalacia but convex inflection on flow-volume curves (identified as the 'knee') is thought to represent tracheomalacia., Objectives: To determine (a) the prevalence of tracheomalacia in children with the 'knee' pattern on spirometry, and (b) whether spirometry parameters and visual characteristics of the 'knee' can identify presence/absence or severity of tracheomalacia., Patients/methods: We reviewed the spirometry undertaken at Queensland Children's Hospital between 2016 and 2019 and retrieved spirometry with the 'knee' pattern in the flow-volume curves. Flexible bronchoscopy videos of these children were reviewed for tracheomalacia diagnosis and severity in a blinded manner. We also evaluated several 'knee' characteristics (onset of inflection, angle of inflection, a scoop before plateau, plateau progression), spirometry parameters and tracheomalacia severity., Results: Of the 78 children with the 'knee', 51 (65.4%) had tracheomalacia. Spirometry values were significantly lower in those with tracheomalacia, compared to those without (predicted FEV 1  = 86.1% vs 99.9%, FVC = 95.1% vs 104%, FEF 25-75%  = 68.6% vs 89.6%, all p < 0.02). A scoop before plateau was significantly associated with tracheomalacia (66.7% vs 40.7%, p = 0.03). There was no significant difference in spirometry parameters or the 'knee' characteristics between children with mild versus moderate-to-severe tracheomalacia., Conclusion: Most but not all children with the 'knee' pattern have flexible bronchoscopy-defined tracheomalacia. Those with tracheomalacia had lower spirometry values and the presence of a scoop before plateau was the most characteristic feature. A prospective longitudinal study is required to determine the diagnostic value of spirometry flow-volume curve characteristics in children., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Spirometry provides a quantitative measure of lung function and its use is recommended as an adjunct to enhance pediatric respiratory healthcare in many clinical practice guidelines. However, there is limited evidence confirming the benefits (or otherwise) of using spirometry from either clinician or patient perspectives. This systematic review aimed to determine the impact of spirometry on change in clinical decision making and patient-reported outcome measures. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, www.clinicaltrials.gov, and World Health Organization International Clinical Trials Registry Platform, from inception to July 2021. We included randomized controlled trials (RCTs) comparing the use versus non-use of spirometry during standard clinical review in children aged <18 years with respiratory problems in clinics. We used Cochrane methodology. The search identified 3475 articles; 8 full-text articles were reviewed but only 1 study fulfilled the inclusion criteria. The single study involved two cluster RCTs of spirometry for children with asthma in general practice. The included study did not find any significant intergroup difference at the 12-month follow-up for asthma-related quality-of-life and clinical endpoints. However, the findings were limited by methodological weaknesses and high risks of bias. With a paucity of data, the clinical benefits of spirometry remain unclear. Thus, there is a clear need for RCTs that provide high-quality evidence to support the routine use of spirometry in children with suspected or known lung disease. Pending the availability of better evidence, we recommend that clinicians adhere to the current clinical practice recommendations., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objectives: Spirometry is easily accessible yet there is limited data in children with tracheomalacia. Availability of such data may inform clinical practice. We aimed to describe spirometry indices of children with tracheomalacia, including Empey index and flow-volume curve pattern, and determine whether these indices relate with bronchoscopic features., Methods: From the database of children with tracheomalacia diagnosed during 2016-2019, we reviewed their flexible bronchoscopy and spirometry data in a blinded manner. We specially evaluated several spirometry indices and tracheomalacia features (cross-sectional lumen reduction, malacic length, and presence of bronchomalacia) and determined their association using multivariable regression., Results: Of 53 children with tracheomalacia, the mean (SD) peak expiratory flow (PEF) was below the normal range [68.9 percent of predicted value (23.08)]. However, all other spirometry parameters were within normal range [Z-score forced expired volume in 1 s (FEV 1 ) = -1.18 (1.39), forced vital capacity (FVC) = -0.61 (1.46), forced expiratory flow between 25% and 75% of vital capacity​​​​​​ (FEF 25%-75% ) = -1.43 (1.10), FEV 1 /FVC = -1.04 (1.08)], Empey Index = 8.21 (1.59). The most common flow-volume curve pattern was the "knee" pattern (n = 39, 73.6%). Multivariable linear regression identified the presence of bronchomalacia was significantly associated with lower flows: FEV 1 [coefficient (95% CI) -0.78 (-1.54, -0.02)], FEF 25%-75% [-0.61 (-1.22, 0)], and PEF [-12.69 (-21.13, -4.25)], all p ≤ 0.05. Other bronchoscopic-defined tracheomalacia features examined (cross-sectional lumen reduction, malacic length) were not significantly associated with spirometry indices., Conclusion: The "knee" pattern in spirometry flow-volume curve is common in children with tracheomalacia but other indices, including Empey index, cannot be used to characterize tracheomalacia. Spirometry indices were not significantly associated with bronchoscopic tracheomalacia features but children with tracheobronchomalacia have significantly lower flow than those with tracheomalacia alone., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Introduction: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance., Methods and Analysis: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance., Ethics and Dissemination: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians., Trial Registration Number: ACTRN12619000564156., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 β = -0.42, [95%CI -0.79, -0.04]; FVC β = -0.62, [95%CI -1.14, -0.09]), and between three and five years (β = -0.50, [95%CI -0.88, -0.12]; β = -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.

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: FEV 1 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 FEV 1 and 15% (95% CI: 8%-21%) of FVC differences in the younger group, and 26% (95% CI: 16%-37%) of FEV 1 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., (© 2021 Wiley Periodicals LLC.)

Introduction: Although spirometry has been available for decades, it is underused in paediatric practice, other than in specialist clinics. This is unsurprising as there is limited evidence on the benefit of routine spirometry in improving clinical decision making and/or outcomes for children. We hypothesised that using spirometry for children being evaluated for respiratory diseases impacts on clinical decision making and/or improves patient-related outcome measures (PROMs) and/or quality of life (QoL), compared with not using spirometry., Methods and Analysis: We are undertaking a randomised controlled trial (commenced in March 2020) that will include 106 children (aged 4-18 years) recruited from respiratory clinics at Queensland Children's Hospital, Australia. Inclusion criteria are able to perform reliable spirometry and a parent/guardian who can complete questionnaire(s). Children (1:1 allocation) are randomised to clinical medical review with spirometry (intervention group) or without spirometry (control group) within strata of consultation status (new/review), and cough condition (present/absent). The primary outcome is change in clinical decision making. The secondary outcomes are change in PROM scores, opinions regarding spirometry and degree of diagnosis certainty. Intergroup differences of these outcomes will be determined by χ 2 test or unpaired t-test (or Mann-Whitney if not normally distributed). Change in outcomes within the control group after review of spirometry will also be assessed by McNemar's test or paired t-test/Wilcoxon signed-rank test., Ethics and Dissemination: The Human Research Ethics Committee of the Queensland Children's Hospital approved the study. The trial results will be disseminated through conference presentations, teaching avenues and publications., Trial Registration Number: ACTRN12619001686190; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (FEV 1 ) was clinically abnormal for 54% of First Nations patients (51% of non-First Nations patients), forced vital capacity (FVC) for 46% (36%), FEV 1 /FVC% for 30% (36%), and gas diffusing capacity (D LCO ) 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, FEV 1 and FVC significantly improved (mean change: zFEV 1  = 0.15 [95% CI 0.10-0.20]; zFVC = 0.25 [0.20, 0.31]), and FEV 1 /FVC% significantly reduced (mean =  - 0.10 [95%CI - 0.07 to - 0.03]), with no significant change in D LCO . Patients with COPD had lower FEV 1 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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 (FEV 1 ) 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). FEV 1 /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., Competing Interests: The authors received no specific funding for this work. AJC is supported by a National Health and Medical Research Council (NHMRC) Postgraduate Scholarship (APP2003334), had full access to all the data in the study and had final responsibility for the decision to submit for publication. JM reports grants from the Children's Hospital Foundation (RPC0772019) during the conduct of the study. ABC reports grants from the NHMRC (APP1154302) and Children's Health Foundation (top-up #50286); other fees to the institution from work relating to being a IDMC Member of an unlicensed vaccine (GSK), and an advisory member of study design for unlicensed molecule for chronic cough (Merck) outside the submitted work. TB reports grants from during the conduct of the study; AD is a paid employee of Metro North Hospital and Health Services which also administers the Indigenous Respiratory Outreach (IROC) Program for Queensland Health, and provides clinical services to IROC clinics. KF reports grants from Various competitive funding bodies, non-financial support from Industry, occasional honorariums from various Universities, various international funding bodies, and Cochrane Clinical Answers, occasional royalty from UpToDate, outside the submitted work; and Paid employee of Metro North Hospital and Health Services which also administers the IROC program for Queensland Health. MM reports other from Children's Hospital Foundation, and grants from the NHMRC during the conduct of the study., (© 2021 The Authors.)

Objectives: Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) could be useful clinical parameters in monitoring many conditions including cystic fibrosis (CF). However, current protocols for undertaking the measurements lack standardization including the number of repeated attempts to achieve best values. We aimed to (a) determine the optimum number of attempts to achieve best MIP/MEP values, and (b) evaluate if the number of attempts is consistent across two different test days., Methods: We analyzed data of a previous randomized controlled trial involving the effect of singing on respiratory muscle strength in 35 children with CF. On two different days (T1, T2) children performed MIP/MEP with at least ten attempts each to achieve < 10% repeatability., Results: All children achieved repeatable MIP/MEP values within 10-11 attempts with 24 (68.6%) and 26 (74.3%) of these achieving best values of MIP and MEP, respectively, at attempts 6-11. Median values of the pressures by three, five, eight and all attempts significantly increased with more attempts (all p < 0.05). At T2, 56% required fewer attempts to achieve best values, but 32% required more attempts, indicating that the number of attempts required was inconsistent between test days., Conclusion: It is likely that at least ten attempts (best two within < 10% variability) is required to achieve best and reliable MIP/MEP in children with CF. A larger sample size in children with CF and various conditions is required to consolidate these findings.

Background: Inequitable access to quality health care contributes to the known poorer outcomes of people living in regional/remote areas (compared with urban-based), especially for First Nations people. Integration of specialist outreach services within primary care is one strategy that can reduce the inequity when modeled to the needs and available resources of target communities., Research Question: To evaluate whether respiratory outreach clinics in regional and remote Queensland are as effective as tertiary respiratory services at improving the lung function of children., Study Design and Methods: From existing databases, we obtained spirometry data of children (aged 3-18 years) seen at Indigenous-focused outreach clinics in regional and remote Queensland and Brisbane-based pediatric tertiary hospitals over the same contemporary period (October 2010 to July 2019). We compared the change in spirometry z scores (Δz) at follow-up for both groups of children., Results: Lung function significantly improved in both groups: Tertiary hospital (n = 2,249; ΔzFEV 1  = 0.22, 95% CI, 0.17 to 0.27; ΔzFVC = 0.23, 95% CI, 0.18 to 0.28); outreach (n = 252; ΔzFEV 1  = 0.35, 95% CI, 0.22 to 0.48; ΔzFVC = 0.36, 95% CI, 0.23 to 0.50). No significant intergroup differences were found in ΔzFEV 1 (0.13; 95%CI, -0.02 to 0.28; P = .10) or ΔzFVC (0.14; 95% CI, -0.02 to 0.29; P = .08) improvement from baseline. In both groups, the proportion of children with zFEV 1 > 0 at follow-up (hospital = 31.7%; outreach = 46.8%) significantly increased (hospital P = .001; outreach P = .009) from baseline (hospital = 27.2%; outreach = 35.3%). Numbers of children with zFEV 1 > 0 significantly increased for asthma and bronchiectasis outreach subgroups, and for children with asthma in the hospital-based group., Interpretation: Comparable significant lung function improvement of children was seen in Indigenous-focused outreach remote/regional clinics and paediatric tertiary hospitals. This suggests that effective clinical care is achievable within the outreach setting., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction/aim: A validated tool for scoring bronchitis during flexible bronchoscopy (FB) is potentially useful for clinical practice and research. We aimed to develop a bronchoscopically defined bronchitis scoring system in children (BScore) based on our pilot study., Methods: Children undergoing FB were prospectively enrolled. Their FB was digitally recorded and assessed (two clinicians blinded to each other and clinical history) for six features: secretion amount (six-point scale), secretion color (BronkoTest, 0-8), mucosal oedema (0-3), ridging (0-3), erythema (0-3), and pallor (0-3) based on pre-determined criteria. We correlated (Spearman's rho) each feature with bronchoalveolar lavage (BAL) neutrophil percentage (neutrophil%). BScore was then derived using models with combinations of the six features that best related to airway BAL neutrophil%. The various models of BScore were plotted against BAL neutrophil% using receiver operating characteristic (ROC) curves., Results: We analyzed 142 out of 150 children enrolled. Eight children were excluded for unavailability of BAL cytology or FB recordings. Chronic/recurrent cough was the commonest indication for FB (75%). The median age was 3 years (IQR, 1.5-5.3 years). Secretion amount (r = 0.42) and color (r = 0.46), mucosal oedema (r = 0.42), and erythema (r = 0.30) significantly correlated with BAL neutrophil%, P < .0001. The highest area under ROC (aROC) was obtained by the addition of the scores of all features excluding pallor (aROC = 0.84; 95% CI, 0.76-0.90) with airway neutrophilia (defined as BAL neutrophil% of >10%)., Conclusion: This prospective study has developed the first validated bronchitis scoring tool in children based on bronchoscopic visual inspection of airways. Further validation in other cohorts is however required., (© 2020 Wiley Periodicals LLC.)

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., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background and Objectives: Indigenous Respiratory Outreach Care (IROC) is a culturally appropriate specialist respiratory service established to deliver multidisciplinary respiratory care to regional and remote Queensland communities. Our objective was to evaluate the impact of an outreach specialist respiratory service on the spirometry of children attending IROC clinics, particularly Indigenous children with asthma and bronchiectasis., Methods: Retrospective single-arm cohort study of 189 children who performed spirometry at twelve sites across regional and remote Queensland between October 2010 and December 2017. Each child's baseline spirometry was compared to their best spirometry at follow-up visit occurring within (1) 12 months of their most recent visit with at least 12 months of specialist care and; (2) each year of their first 3 years of care., Results: Forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) z-scores improved significantly across the whole group from baseline to follow-up (change in z-scores (Δz) of FEV 1  = 0.38, 95% CI 0.22, 0.53; ΔzFVC = 0.36, 95% CI 0.21, 0.51). In subgroup analyses, lung function significantly improved in Indigenous children (n = 141, ΔzFEV 1  = 0.37, 95% CI 0.17, 0.57; ΔzFVC = 0.36, 95% CI 0.17, 0.55) including those with asthma (n = 117, ΔzFEV 1  = 0.41, 95% CI 0.19, 0.64; ΔzFVC = 0.46, 95% CI 0.24, 0.68) and bronchiectasis (n = 38, ΔzFEV 1  = 0.33, 95% CI 0.07, 0.59; ΔzFVC = 0.26, 95% CI - 0.03, 0.53). Significant improvements in FEV 1 and FVC were observed within the first and second year of follow-up for Indigenous children, but not for non-Indigenous children., Conclusion: The IROC model of care in regional and remote settings leads to significant lung function improvement in Indigenous children with asthma and bronchiectasis.

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&#95;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 (FEV 1 ) 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., (© 2019 Asian Pacific Society of Respirology.)

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., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.

Background: Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including anti-histamines. Also, anti-histamines are advocated as an empirical treatment in adults with chronic cough., Objectives: To evaluate the effectiveness of anti-histamines in treating children with prolonged non-specific cough., Search Strategy: We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, OLDMEDLINE and EMBASE databases. The latest searches were performed in November 2007., Selection Criteria: All randomised controlled trials comparing anti-histamines with a placebo or placebo-like medication with cough as an outcome, where cough is not primarily related to an underlying respiratory disorder such as cystic fibrosis, asthma, or suppurative lung disease., Data Collection and Analysis: Two review authors independently assessed study quality and extracted data., Main Results: Three included therapeutic studies had 182 randomised participants with 162 completing the trials although in one study, children with recurrent wheeze were also included. The two included safety evaluation studies randomised 963 participants with 793 completing the trials. Clinical heterogeneity was evident and limited data prevented combining data for meta-analysis. The two larger therapeutic studies described significant improvement in both the intervention and the placebo/placebo-like arms with no significant difference between the two groups. In the study with the smallest sample size, cetirizine (a second generation anti-histamine) was significantly more efficacious than placebo in reducing chronic cough in children associated with seasonal allergic rhinitis, and the effect was seen within two weeks of therapy. Combined data from the safety evaluation studies revealed a non-significant difference between groups (OR 1.6, 95% CI 0.7 to 3.82) for cough as an adverse event but the trend favoured the placebo arm., Authors' Conclusions: This review has significant limitations. However, our finding of uncertain efficacy of anti-histamines for chronic cough are similar to that for acute cough in children. In contrast to recommendations in adults with chronic cough, anti-histamines cannot be recommended as empirical therapy for children with chronic cough. If anti-histamines were to be trialled in these children, current data suggest a clinical response (time to response) occurs within two weeks of therapy. However the use of anti-histamines in children with non-specific cough has to be balanced against the well known risk of adverse events especially in very young children.

It has been reported that asthma provoked by breathing subfreezing air during exercise is enhanced when air at BTPS is inhaled in the recovery period (1). It was concluded that the rate of airway rewarming is an important event in asthma provoked by exercise. It is also possible, however, that the enhanced response was due to hypo-osmolarity caused by condensation of water from inspired air at BTPS on the cooled mucosa. We examined, in a group of boys with asthma, the response to rapid rewarming of the airways after exercise, with and without the potential for condensation. On two test days, two exercise tests were performed 4 h apart on a cycle ergometer. On Day 1 (n = 17), the inspired air during exercise was -5 degrees C, dry. During recovery, the air was either -5 degrees C, dry or 50 degrees C, 23 mg H2O/L. On Day 2 (n = 11), the inspired air during exercise was -15 degrees C, dry, and during recovery was either -15 degrees C, dry or at BTPS. We did not find enhancement of the response with either condition designed to cause rapid airway rewarming. On Day 1 the mean (+/- 1 SD) percent fall in FEV1 was 23 +/- 22 (-5 degrees C, dry) and 24 +/- 21 (50 degrees C, 23 mg H2O/L) (r = 0.92), and on Day 2 it was 19 +/- 17 (-15 degrees C, dry) and 18 +/- 17 (BTPS) (r = 0.96).(ABSTRACT TRUNCATED AT 250 WORDS)