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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.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?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.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.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.

Purpose Low diffusing capacity of the lung for carbon monoxide (DLCO) 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 (KCO) and alveolar volume (VA) are unknown. This cohort study: (i) evaluated whether DLCO, KCO, and VA 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 DLCO, KCO, and VA values below the lower limit of normal (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, DLCO, KCO, and VA 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 DLCO. Conclusion Low DLCO, KCO, and VA 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.

Sexual violence against women is highly prevalent on college campuses. Survivors of sexual violence often engage in coping strategies such as risky sexual behavior. The present study used a behavioral task to measure sexual risk-taking following experiences of positive or negative affect and an emotion suppression experimental manipulation. Sexually active adult female undergraduates (N = 175) completed measures of sexual traumatization and affective experiences as well as an autobiographical recall task and a delay discounting task for hypothetical sexual outcomes. Half of the participants (n = 87) were asked to suppress their emotional response to the autobiographical recall task. The findings indicate that sexual traumatization had a significant effect on risky sexual decision-making, F(1, 167) = 23.27, p.001, η

ObjectiveChildren with tracheomalacia can develop chronic lower airway infection and neutrophilic inflammation. It is plausible children with tracheomalacia are at increased risk of developing bronchiectasis. We hypothesised that compared with controls, tracheomalacia in children is associated with bronchiectasis.DesignSingle-centre, case–control study.Setting and patients45 children with chest high-resolution CT (c-HRCT) confirmed bronchiectasis (cases) and enrolled in the Australian Bronchiectasis Registry were selected randomly from Queensland, and 90 unmatched children without chronic respiratory symptoms or radiographic evidence of bronchiectasis (disease controls). Cases and controls had flexible bronchoscopy performed for clinical reasons within 4 weeks of their c-HRCT.InterventionsThe bronchoscopy videos were reviewed in a blinded manner for: (a) any tracheomalacia (any shape deformity of the trachea at end-expiration) and (b) tracheomalacia defined by the European Respiratory Society (ERS) statement (>50% expiratory reduction in the cross-sectional luminal area).Main outcome measures and resultsCases were younger (median age=2.6 years, IQR 1.5–4.1) than controls (7.8 years, IQR 3.4–12.8), but well-balanced for sex (56% and 52% male, respectively). Using multivariable analysis (adjusted for age), the presence of any tracheomalacia was significantly associated with bronchiectasis (adjusted OR (ORadj)=13.2, 95% CI 3.2 to 55), while that for ERS-defined tracheomalacia further increased this risk (ORadj=24.4, 95% CI 3.4 to infinity).ConclusionBronchoscopic-defined tracheomalacia is associated with childhood bronchiectasis. While causality cannot be inferred, children with tracheomalacia should be monitored for chronic (>4 weeks) wet cough, the most common symptom of bronchiectasis, which if present should be treated and then investigated if the cough persists or is recurrent.

Acute cough in children has a significant impact on the child and family. Relevant quality of life (QoL) instruments are essential for high-quality clinical research. This study aimed to (1) revalidate the 16-item Parent-proxy Children’s Acute Cough-specific QoL questionnaire (PAC-QoL16) using a different dataset (i.e., different children), (2) confirm the minimally important difference (MID), and (3) develop and validate a short form. Three datasets from two sources were utilized, comprising of 332 children with acute cough (

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 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 and 15% (95% CI: 8%–21%) of FVC differences in the younger group, and 26% (95% CI: 16%–37%) of FEV 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.

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. 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. 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. 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.

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.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.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 (FEVThe "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.

Background: Management strategies based on airway inflammation phenotypes are increasingly used for adults with asthma. While sputum-based phenotypes are relatively stable in adults with asthma, there is little such data in childhood asthma. Hence, we aimed to evaluate the stability of sputum inflammatory phenotypes in children with asthma both in the stable and during exacerbation phases. Methods: Sputum cellularity data from two previous prospective studies involving children with asthma were re-evaluated and categorized into two inflammatory phenotypes: eosinophilic (>2.5% eosinophils) and noneosinophilic (≤2.5% eosinophils). Baseline values and follow-up sputum inflammatory phenotype classification were compared in children with asthma during stable and exacerbation phases. Results: Thirteen of 32 children (41%) with stable asthma demonstrated a change in sputum inflammatory phenotype 8 weeks later. In a different second cohort, both sputum eosinophils and neutrophils percentages increased and peaked on Day 1 of asthma exacerbation, but compared with baseline, 22% (2/9) and 13% (1/8) of these children had their sputum phenotype categorization changed on Day 1 and Day 3 of exacerbation, respectively. Conclusion: In children with asthma, sputum inflammatory phenotypes are variable in both stable and exacerbation phases, in contrast to data in adults.

IntroductionThere is limited evidence on the efficacy of using spirometry routinely in paediatric practice for improving outcomes.ObjectiveTo determine whether the routine use of spirometry alters clinical decisions and patient-related outcome measures for children managed by respiratory paediatricians.MethodsWe 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).ResultsOf 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%), pConclusionThe 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.RegistrationAustralia and New Zealand Clinical Trials Registry ACTRN12619001686190

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.

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 aged18 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.

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.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.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% of10%).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.

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. 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. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) z-scores improved significantly across the whole group from baseline to follow-up (change in z-scores (Δz) of FEV1 = 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, ΔzFEV1 = 0.37, 95% CI 0.17, 0.57; ΔzFVC = 0.36, 95% CI 0.17, 0.55) including those with asthma (n = 117, ΔzFEV1 = 0.41, 95% CI 0.19, 0.64; ΔzFVC = 0.46, 95% CI 0.24, 0.68) and bronchiectasis (n = 38, ΔzFEV1 = 0.33, 95% CI 0.07, 0.59; ΔzFVC = 0.26, 95% CI − 0.03, 0.53). Significant improvements in FEV1 and FVC were observed within the first and second year of follow-up for Indigenous children, but not for non-Indigenous children. The IROC model of care in regional and remote settings leads to significant lung function improvement in Indigenous children with asthma and bronchiectasis.

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.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.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.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 FEVsub1/sub = 86.1% vs 99.9%, FVC = 95.1% vs 104%, FEFsub25-75%/sub = 68.6% vs 89.6%, all p lt; 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.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.

Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein.Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D.Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17–40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up).Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants.Clinical Trial Registration:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.

Introduction Bronchiectasis is no longer considered rare or irreversible in children, yet it remains relatively under-researched and neglected in respiratory health globally. Bronchiectasis (including chronic suppurative lung disease) causes substantial morbidity for patients and significant impact on caregivers, especially during acute respiratory exacerbations. In other chronic respiratory diseases (eg, asthma), empowering consumers with an individualised plan for management of acute exacerbations improves clinical outcomes. However, in the absence of any such data specific to bronchiectasis, action management plans are rarely currently used in children or adults with bronchiectasis. We hypothesise that providing an individualised bronchiectasis action management plan (BAMP) to children with bronchiectasis reduces non-scheduled doctor consultations, compared with not having a BAMP. Methods and analysis This multicentre, parallel, double-blind, randomised trial involving three urban Australian hospitals commenced in June 2018 and will include 198 children, aged

Introduction: Children with chronic wet cough regularly use the health system, experience considerable variability in care, have reduced quality of life (QoL), and, left untreated, poorer health outcomes. Despite this, little is known about the associated economic burden. This study aimed to quantify the cost of chronic wet cough among Australian children from the perspectives of families and the health system. Methods: A cost of illness study was conducted at the Queensland Children's Hospital, Brisbane, using data on 91 children newly referred to a respiratory specialist between July 2015 and January 2017 with a history of chronic wet cough (>4 weeks) of unknown etiology. Administrative and parent-reported data were used to estimate costs (reported in 2019 Australian Dollars [AUD]) for up to 12 months before and following initial pulmonology consultation. QoL was assessed for the same periods. Results: Mean cost per child-month during the average 9.8 months of observation preceding pulmonology consultation was AUD689 (95% confidence interval [CI] 534–844) increasing to AUD1339 (95% CI 1051–1628) during the average 11.9 months following pulmonology consultation. This translated to a total of AUD1.9 million across the study period, with families bearing 26.4% of costs. Aspiration and bronchiectasis were associated with higher total costs. For all etiologies, cough-specific QoL improved following pulmonology consultation, while direct medical costs declined. Conclusion: Childhood chronic wet cough is associated with substantial societal costs. The observed cost decrease after specialist diagnosis suggests that early referral to a respiratory specialist may have economic benefits, in addition to the known health benefits.

Introduction/Aim: As tracheomalacia impairs mucociliary clearance, it can lead to ongoing lower airway infection and inflammation. Therefore, it is biologically plausible that children with tracheomalacia are at risk of developing bronchiectasis (BE). We assessed the association between tracheomalacia and bronchiectasis. Methods: A retrospective case control study was conducted. ‘Cases' (n=45) were children with bronchiectasis (randomly selected from the Australian Bronchiectasis Registry) and ‘controls’ (n=90) were children with no bronchiectasis, based on chest high-resolution computed tomography (HRCT) (children with oncological conditions who had FB and chest HRCT for febrile neutropenia workup). Both cases and controls had flexible bronchoscopy (FB) within a month of chest HRCT. The FB recordings were scored in a random order by expert respiratory paediatricians (blinded to the history) for presence or absence of tracheomalacia in two different ways (presence of any tracheomalacia [Any-TM] and presence of tracheomalacia according to the definition used by the European Respiratory Society (ERS) statement on tracheomalacia and bronchomalacia in children [ERS-TM]). Regression analyses was used to adjust for baseline characteristics. Results: The median age of the ‘control’ group was 93 months (IQR = 41-152) and the median age of the ‘cases’ group was 31 months (IQR = 18-49). 17 patients had tracheomalacia according to the Any-TM definition and 9 patients had tracheomalacia according to the ERS-TM definition. Multivariate analysis (table below) revealed that the ORadj of having BE was 13 (95%CI 3-55, p

IntroductionAlthough 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 analysisWe 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 χ2 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 disseminationThe 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 numberACTRN12619001686190; Pre-results.

Summary: 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

Acute cough in children has a significant impact on the child and family. Relevant quality of life (QoL) instruments are essential for high-quality clinical research. This study aimed to (1) revalidate the 16-item Parent-proxy Children's Acute Cough-specific QoL questionnaire (PAC-QoLThree datasets from two sources were utilized, comprising of 332 children with acute cough ( 2 weeks duration); the first dataset (n = 83, 54 boys; median age 2.04 years, IQR 1.08-4.06 years) was used for revalidation, the second dataset (n = 238, 141 boys; median age 2.17 years, IQR 1.21-4.21 years) was used to develop the short form, and the third dataset (n = 94, 62 boys; median age, 1.75 years, IQR 0.90-3.63 years) was used to confirm the short form. Psychometric properties were investigated.Six items were found to account for 96.4% of the variance in the PAC-QoLBoth the PAC-QoL

Background Chronic wet cough is common in pediatric pulmonology practice and is clinically important. Guidelines recommend treatment with antibiotics as their effectiveness has been proven. However, factors associated with duration of cough in response to antibiotics in children with chronic wet cough have not been prospectively examined. Objective To determine if demographic, clinical and/or bronchoalveolar lavage (BAL) factors are associated with “time to cough resolution” in children with chronic wet cough treated with antibiotics after bronchoscopy. Methods Data from children with chronic wet cough treated with antibiotics after bronchoscopy were extracted from a prospective cohort study database. Cough dairies were used to determine when the cough resolved. Associations between various factors with “time to cough resolution” were examined using regression. Results The median age of the 133 children was 2.4 years (interquartile range, 1.4‐4.9). Duration of prior cough at bronchoscopy was significantly positively related with “time to cough resolution” (β = .010; 95% confidence interval, 0.004‐0.017; P = .002). This translated to; for each month of prior cough, it took an extra 1.02 days to achieve cough resolution while on antibiotic treatment. Gender, age, diagnosis, tobacco smoke exposure, pneumonia history, blood cellularity, and BAL cellular and microbiology profiles were not significantly associated with time to cough resolution. Conclusion In children with chronic wet cough, duration of cough before antibiotic treatment is a small but significant determinant of “time to cough resolution.” Research using standardized antibiotic regimes is required to provide clinical and/or biomarkers that can further identify factors associated with the response of chronic cough to antibiotic treatment.

While publications from days gone by did not refer to PBB as such, the condition clearly existed. Historically, astute clinicians described PBB-like conditions but did not define it as a clinical entity. Field's 1940s series on paediatric bronchiectasis described the concept of a pre-bronchiectasis state [1, 3] and advocated aggressive treatment (predominantly antibiotics) for prevention and cure of bronchiectasis. In the same era, Finke [7] opened his paper with the statement “The common background of chronic bronchitis and bronchiectasis is, in the majority of cases, non-tuberculous broncho-pulmonary infection”. In that era, tools that are now widely available (e.g. flexible bronchoscopy and bronchoalveolar lavage (BAL) assessments) were non-existent. Almost 40 years ago, Taussig et al. [8] highlighted the various definitions of “childhood chronic bronchitis” doctors used, ranging from “productive cough for 3-months in a year” to “recurrent episodes of cough lasting for >2-weeks” and wheezing., Recognising the link between protracted bacterial bronchitis and bronchiectasis creates an opportunity to understand the pathobiology of early suppurative endobronchial lung disease and prospects for the development of effective and early interventions http://bit.ly/2K3ikI6

Background Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. Methods BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Results Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

Summary Background Protracted bacterial bronchitis (PBB) is a leading cause of chronic wet cough in children. The current standard treatment in European and American guidelines is 2 weeks of antibiotics, but the optimal duration of therapy is unknown. We describe the first randomised controlled trial to assess the duration of antibiotic treatment in children with chronic wet cough and suspected PBB. We hypothesise that 4 weeks of amoxicillin–clavulanate is superior to 2 weeks for improving clinical outcomes. Methods Our parallel, double-blind, placebo-controlled, randomised controlled trial was completed in four Australian hospitals. Children aged 2 months to 19 years with chronic (>4 weeks duration) wet cough, and suspected PBB were randomly assigned (1:1) using permuted block randomisation (stratified by age and site) to 4 weeks of amoxicillin–clavulanate (25–35 mg/kg twice daily oral suspension; 4-week group) or 2 weeks of amoxicillin–clavulanate followed by 2 weeks of placebo (2-week group). The children, caregivers, all the study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was clinical cure (cough resolution) by day 28. Secondary outcomes were recurrence of PBB at 6 months, time to next exacerbation, change in Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, nasal swab bacteriology, and antimicrobial resistance. Analyses followed the intention-to-treat principle. This trial is complete and registered with Australian/New Zealand Registry, ACTRN12616001725459. Findings Between March 8, 2017, and Sept 30, 2019, 106 children were randomly assigned (52 in the 4-week group, median age 2·2 years [IQR 1·3–4·1]; 54 in the 2-week group, median age 1·7 years [1·2–3·8]) with 90 children completing the 4-week treatment. By day 28, the primary endpoint of clinical cure in the 4-week group (32 [62%] of 52 patients) was not significantly different to the 2-week group (38 [70%] of 54 patients; adjusted relative risk 0·87 [95% CI 0·60 to 1·28]; p=0·49). Time to next wet cough exacerbation was significantly longer in the 4-week group than the 2-week group (median 150 days [IQR 38–181] vs 36 days [15–181]; adjusted hazard ratio 0·47 [0·25 to 0·90]; p=0·02). The rate of recurrence of PBB at 6 months was 17 (53%) of 32 patients in the 4-week group vs 28 (74%) of 38 patients in the 2-week group, but the difference between the groups was not significant (adjusted odds ratio 0·39 [0·14 to 1·04]; p=0·07). PC-QoL significantly improved from baseline to day 28 in both groups, but there was no significant difference between them (mean difference in change −0·2 [95% CI −1·0 to 0·6]; p=0·64). From day 28 to 7 months, median PC-QoL remained stable in both groups with no difference in change between them. Data on respiratory pathogens and antimicrobial resistance (paired swabs available for 48 children) were similar between groups. Adverse events occurred in 13 (25%) children in the 2-week group and ten (19%) in the 4-week group (p=0·57). Interpretation A 4-week course of amoxicillin–clavulanate for treating children with chronic wet cough and suspected PBB confers little advantage compared with a 2-week course in achieving clinical cure by 28 days. However, as a 4-week duration led to a longer cough-free period, identifying children who would benefit from a longer antibiotic course is a priority. Funding Queensland Children's Hospital Foundation.

INTRODUCTION: Cough is an important contributor to the health burden of children and their families. There are limited data describing healthcare utilization and medication use over the course of a cough illness beyond the initial presentation. Our primary objective was to describe medication and healthcare use in children with a respiratory illness with cough as a symptom over the course of the illness. METHODS: A cohort study of children aged less than 15-years presenting to three primary healthcare centers and three emergency departments with a cough illness between July 7, 2015 and October 6, 2018. Children with immunosuppression, known chronic lung diseases (except asthma) and those requiring hospitalization at screening were excluded. The primary outcomes were cough-related frequency and type of healthcare seeking and medication use up to 28 days following enrolment. RESULTS: Data for 465 children were analyzed; median age 2.2-years (interquartile range = 1.1-5.3). Cough at Day 28 persisted in 117 children (25.2%). Overall, 436 (94%) children received medications in the week before and/or 4 weeks following enrolment. Half with upper respiratory tract infections were prescribed antibiotics. Among children with no diagnosis of asthma, reactive airways disease or croup (n = 404), 16.8% were given steroids. Fifty-eight percent of children sought healthcare at least once before their baseline presentation (median = 1, range = 0-20) and 49.7% had at least one further presentation in the following 28 days. CONCLUSIONS: High healthcare utilization, inappropriate medication use, and suboptimal parent knowledge regarding cough suggests targeted education is needed to improve management and reduce cough burden.

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.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.In the combined cohort, the forced expiratory volume in 1 s (FEVRegional-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.

Introduction: The optimal duration of antibiotic treatment for children with protracted bacterial bronchitis (PBB), a common cause of chronic wet cough in children, is controversial. Effective management may reduce the risk of chronic suppurative disease (e.g. bronchiectasis). Objective: To determine whether 4-wks of amoxicillin-clavulanate is superior to 2-wks for improved clinical outcomes in children with suspected PBB. Methods: Multi-center, double-blind, placebo-controlled, RCT in Australian children aged 2-mo to 19-yrs with suspected PBB. Children were randomized to either 4-wks of amoxicillin-clavulanate or 2-wks of amoxicillin-clavulanate followed by 2-wks placebo. Follow-up was for 6-mo. Our primary outcome was cough resolution within 28-days. Recurrence of PBB, parent-proxy cough specific quality of life (PC-QoL) score at 28-days and time to first exacerbation were secondary outcomes. Results: 106 children were randomized, median age 2.0-yrs. There was no difference in cough resolution by 28-days between the groups (4-wks=61.5% vs 2-wks=71.4%) (RR 0.87, 95% CI0.59-1.29; p=0.50). Longer antibiotic treatment resulted in a non-significant increase in time to next wet cough exacerbation (150-wks vs 48-wks; p=0.094) and reduced PBB recurrence (74% vs 53%; p=0.074) in those whose cough resolved by day-28. PC-QoL improved by a median of 2.0 across both groups. Conclusion: A 4-wk course of amoxicillin-clavulanate in children with suspected PBB confers little advantage compared to a 2-wk course. A non-inferiority RCT is required to support our findings but until such data is available, children suspected of having PBB should be treated with the current standard 2-wks.

Background and objective: Long-term data on children with PBB has been identified as a research priority. We describe the 5-year outcomes for children with PBB to ascertain the presence of chronic respiratory disease (bronchiectasis, recurrent PBB and asthma) and identify the risk factors for these. Methods: Prospective cohort study was undertaken at the Queensland Children's Hospital, Brisbane, Australia, of 166 children with PBB and 28 controls (undergoing bronchoscopy for symptoms other than chronic wet cough). Monitoring was by monthly contact via research staff. Clinical review, spirometry and CT chest were performed as clinically indicated. Results: A total of 194 children were included in the analysis. Median duration of follow-up was 59 months (IQR: 50–71 months) post-index PBB episode, 67.5% had ongoing symptoms and 9.6% had bronchiectasis. Significant predictors of bronchiectasis were recurrent PBB in year 1 of follow-up (ORadj = 9.6, 95% CI: 1.8–50.1) and the presence of Haemophilus influenzae in the BAL (ORadj = 5.1, 95% CI: 1.4–19.1). Clinician-diagnosed asthma at final follow-up was present in 27.1% of children with PBB. A significant BDR (FEV1 improvement >12%) was obtained in 63.5% of the children who underwent reversibility testing. Positive allergen-specific IgE (ORadj = 14.8, 95% CI: 2.2–100.8) at baseline and bronchomalacia (ORadj = 5.9, 95% CI: 1.2–29.7) were significant predictors of asthma diagnosis. Spirometry parameters were in the normal range. Conclusion: As a significant proportion of children with PBB have ongoing symptoms at 5 years, and outcomes include bronchiectasis and asthma, they should be carefully followed up clinically. Defining biomarkers, endotypes and mechanistic studies elucidating the different outcomes are now required.

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; ΔzFEV1 = 0.22, 95% CI, 0.17 to 0.27; ΔzFVC = 0.23, 95% CI, 0.18 to 0.28); outreach (n = 252; ΔzFEV1 = 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 ΔzFEV1 (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 zFEV1 > 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 zFEV1 > 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.

Summary Background Although amoxicillin–clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis. Methods We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1–19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin–clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of −20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897). Findings We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin–clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin–clavulanate group. The risk difference showed non-inferiority (−0·3%, 95% CI −11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin–clavulanate group than in the azithromycin group (median 10 days [IQR 6–15] vs 14 days [8–16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin–clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5). Interpretation By 21 days of treatment, azithromycin is non-inferior to amoxicillin–clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance. Funding Australian National Health and Medical Research Council.

Aim: In children presenting to an emergency department (ED) with an acute coughing illness, the aims of this study were to: (i) describe the frequency of doctor visits and medication use; and (ii) describe management and relate it to current evidence-based guidelines. Methods: This was a cross-sectional study in ED of a major teaching hospital (Royal Children's Hospital, Brisbane, Australia). Participants included 537 children (

We describe the prevalence and risk factors for protracted bacterial bronchitis (PBB) following healthcare presentation for an acute cough illness in children. Data from three studies of the development of chronic cough (CC) in children were combined. PBB was defined as a wet cough of at least 4-weeks duration with no identified specific cause of cough that resolved following 2–4 weeks of appropriate antibiotics. Anterior nasal swabs were tested for 17 viruses and bacteria by polymerase chain reaction. The study included 903 children. Childcare attendance (adjusted relative risk (aRR) = 2.32, 95% CI 1.48–3.63), prior history of chronic cough (aRR = 2.63, 95% CI 1.72–4.01) and age

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.