Search

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.

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.

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.

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.

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

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.

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: 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 (

Objective Data on the aetiology of persistent cough at the transitional stage from sub-acute to chronic cough (>4 weeks duration) are scarce. We aimed to: - (1) identify the prevalence of chronic cough following acute respiratory illness (ARI) and; - (2) determine the diagnostic outcomes of children with chronic cough. Design Prospective cohort study Setting A tertiary paediatric emergency department (ED) in Brisbane, Australia Patients Children aged

Aim: Protracted bacterial bronchitis (PBB) is considered a potential precursor to bronchiectasis (BE) in some children. We previously showed that alveolar macrophages (AM) from children with PBB or BE have a similar significant defect in phagocytic capacity, with proinflammatory associations. We hypothesized that the mechanisms responsible for this defect involve dysregulation of the sphingosine-1-phosphate (S1P) signaling pathway, as we have found in adult inflammatory lung diseases. Method: We employed a Custom TaqMan OpenArray to investigate gene expression of S1P-generating enzymes: sphingosine kinases (SPHK) 1/2, S1P phosphatase 2 (SGPP2), S1P lyase 1 (SGPL1), S1P receptors (S1PR) 1/2/4/5; proinflammatory cytokines TNF-α (TNF) and IFNγ (IFNG), the cytotoxic mediator granzyme B (GZMB), and inflammasomes AIM2 and NLRP3, in bronchoalveolar lavage from 15 children with BE, 15 with PBB and 17 age-matched controls, and determined association with clinical/demographic variables and airway inflammation. Result: Significantly increased expression of S1PR1, S1PR2, and SPHK1 was noted in PBB and BE AM vs controls with increased SGPP2 only in PBB. TNF, IFNG, AIM2, and NLRP3 were significantly increased in both disease groups with increased GZMB only in PBB. There were no significant differences in the expression of any other S1P-related mediator between groups. There were significant positive associations between Haemophilus influenzae growth and expression of S1PR1 and NLRP3; between S1PR1 and S1PR2, NLRP3 and IFNG; between S1PR2 and AIM2, SPHK1, and SPHK2; and between SPHK1 and GZMB, IFNG, AIM2, and NLRP3. Conclusion: Children with PBB and BE share similar S1P-associated gene expression profiles. AM phagocytic dysfunction and inflammation in these children may occur due to dysregulated S1P signaling.

While once thought to be rare, bronchiectasis has been increasing globally over the last 15 years. Bronchiectasis is a major contributor to chronic lung morbidity and mortality but remains a neglected disease in respiratory health globally. Currently, few high-level evidence-based management strategies are available for children with bronchiectasis. Strategies to improve clinical outcomes associated with exacerbations are important. In other respiratory conditions such as asthma and chronic obstructive pulmonary disease, use of personalized written management plans have been shown to improve clinical outcomes. Personalized management plans have also been recommended as part of treatment plans in adults with bronchiectasis. We thus undertook a review of the current literature to determine available evidence, and to establish whether a personalized written bronchiectasis action management plan (BAMP) improves clinical outcomes in children with bronchiectasis. Our search identified 43 articles; 16 duplicates were removed and a further 23 were excluded on titles and abstracts alone. Four full-text articles were reviewed but excluded. In the absence of any published studies, it remains unknown whether the use of BAMP is beneficial for improving clinical outcomes for children with bronchiectasis. These results have highlighted this clinical gap and identified the need for high-quality research to inform practice. Until high-quality evidence is available, clinicians are advised to adhere to current national and/or international guidelines.

Introduction/Aim. Despite paediatric bronchiectasis being recognised increasingly worldwide, prior reports of hospitalisation costs for bronchiectasis in children are lacking. This study aimed to: (a) identify health service costs of hospitalisations and (b) factors associated with these costs in children admitted to an Australian paediatric hospital following an acute exacerbation of their bronchiectasis. Methods. Demographic and hospital resource use data were prospectively recorded for 100 children aged

AIM National data report respiratory illness to be the most common chronic illness in Australian Indigenous people aged

Background Bronchiectasis in children is an important, but under-researched, chronic pulmonary disorder that has negative impacts on health-related quality of life. Despite this, it does not receive the same attention as other chronic pulmonary conditions in children such as cystic fibrosis. We measured health resource use and health-related quality of life over a 12-month period in children with bronchiectasis. Methods We undertook a prospective cohort study of 85 children aged

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

Background Protracted bacterial bronchitis (PBB) and bronchiectasis are distinct diagnostic entities that share common clinical and laboratory features. It is postulated, but remains unproved, that PBB precedes a diagnosis of bronchiectasis in a subgroup of children. In a cohort of children with PBB, our objectives were to (1) determine the medium-term risk of bronchiectasis and (2) identify risk factors for bronchiectasis and recurrent episodes of PBB. Methods One hundred sixty-one children with PBB and 25 control subjects were prospectively recruited to this cohort study. A subset of 106 children was followed for 2 years. Flexible bronchoscopy, BAL, and basic immune function tests were performed. Chest CT was undertaken if clinical features were suggestive of bronchiectasis. Results Of 161 children with PBB (66% boys), 13 were diagnosed with bronchiectasis over the study period (8.1%). Almost one-half with PBB (43.5%) had recurrent episodes (> 3/y). Major risk factors for bronchiectasis included lower airway infection with Haemophilus influenzae (recovered in BAL fluid) (P = .013) and recurrent episodes of PBB (P = .003). H influenzae infection conferred a more than seven times higher risk of bronchiectasis (hazard ratio, 7.55; 95% CI, 1.66-34.28; P = .009) compared with no H influenzae infection. The majority of isolates (82%) were nontypeable H influenzae. No risk factors for recurrent PBB were identified. Conclusions PBB is associated with a future diagnosis of bronchiectasis in a subgroup of children. Lower airway infection with H influenzae and recurrent PBB are significant predictors. Clinicians should be cognizant of the relationship between PBB and bronchiectasis, and appropriate follow-up measures should be taken in those with risk factors.

Background - Cough is symptomatic of a broad range of acute and chronic pediatric respiratory illnesses. No studies in children have tested for an extended panel of upper airway respiratory viruses and bacteria to identify whether they predict cough outcomes, irrespective of clinical diagnosis at the time of acute respiratory illness (ARI). We therefore determined whether upper airway microbes independently predicted hospitalization and persistent cough 28-days later in children presenting with an ARI, including cough as a symptom. Methods - A cohort study of children aged

Background Quality of life (QoL) measures are an important patient-relevant outcome measure for clinical studies. Cough is the most common symptom that results in new medical consultations. Although adult and parent-proxy cough-specific QoL instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QoL measure for children with chronic cough exists. We report on the statistical properties of a chronic cough-specific QoL (CC-QoL) questionnaire for children. Method 130 children (median age 10 years, IQR 8–12 years; 65 girls) participated. A preliminary 37-item version was developed from conversations with children with chronic cough (>4 weeks). Children also completed generic QoL questionnaires (Pediatric QoL Inventory 4.0 (PedsQL4.0), Spence Children9s Anxiety Scale (SCAS)) and cough diary scores. Results The clinical impact method of item reduction resulted in 16 items that had excellent internal consistency (Cronbach9s α=0.94) among these items and also within each domain. Evidence for construct and criterion validity was established with significant correlations between CC-QoL subscales with cough scores, PedsQL and SCAS scores. CC-QoL scores were sensitive to change following an intervention and significant differences were noted between those children coughing and those who had ceased coughing. Minimum important difference (MID) for overall and domain CC-QoL ranged from 0.37–1.36 (distribution-based approach) to 1.11–1.58 (anchor-based approach). Conclusions Chronic cough significantly impacts the QoL of children. The CC-QoL is a reliable, valid and sensitive to change outcome measure that assesses QoL from the child9s perspective. Pending data from a confirmatory cohort, a MID for the CC-QoL of 1.1 is recommended when evaluating health status change.

Bronchiectasis is described classically as a chronic pulmonary disorder characterized by a persistent productive cough and irreversible dilatation of one or more bronchi. However, in children unable to expectorate, cough may instead be wet and intermittent and bronchial dilatation reversible in the early stages. Although still considered an orphan disease, it is being recognized increasingly as causing significant morbidity and mortality in children and adults in both affluent and developing countries. While bronchiectasis has multiple etiologies, the final common pathway involves a complex interplay between the host, respiratory pathogens and environmental factors. These interactions lead to a vicious cycle of repeated infections, airway inflammation and tissue remodelling resulting in impaired airway clearance, destruction of structural elements within the bronchial wall causing them to become dilated and small airway obstruction. In this review, the current knowledge of the epidemiology, pathobiology, clinical features, and management of bronchiectasis in children are summarized. Recent evidence has emerged to improve our understanding of this heterogeneous disease including the role of viruses, and how antibiotics, novel drugs, antiviral agents, and vaccines might be used. Importantly, the management is no longer dependent upon extrapolating from the cystic fibrosis experience. Nevertheless, substantial information gaps remain in determining the underlying disease mechanisms that initiate and sustain the pathophysiological pathways leading to bronchiectasis. National and international collaborations, standardizing definitions of clinical and research end points, and exploring novel primary prevention strategies are needed if further progress is to be made in understanding, treating and even preventing this often life-limiting disease.

Cough is the single most common reason for primary care physician visits and, when chronic, a frequent indication for specialist referrals. In children, a chronic cough (>4 weeks) is associated with increased morbidity and reduced quality of life. One common cause of childhood chronic cough is protracted bacterial bronchitis (PBB), especially in children aged

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.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.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).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.

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.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 participants18 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.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).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.

Introduction: Protracted bacterial bronchitis (PBB), the commonest cause of chronic cough in childhood, is characterised by chronic wet cough (>4 weeks duration) that usually responds to 2-wks of appropriate antibiotic therapy without evidence of an alternative cause for cough. There are no long term studies on PBB beyond 2 yrs. Objectives: Characterise the 5 yr outcomes for children with PBB. Methods: 151 children (median age 26-mo, range 4-163) requiring bronchoscopy (FB) were recruited (PBB=130, controls=21). Participants were followed up for 5 yrs (min 42 mo). Participants were monitored with monthly contact via research staff and when possible annual clinical review and spirometry. CT chest was performed if symptoms/signs suggestive of bronchiectasis were present. Asthma was defined as a doctor diagnosis. Results: Of the 130 children with PBB, 88 (68%) had trachea/bronchomalacia on FB. CT chest was performed on 59 children (max 28 mo post FB), 11 (8.5%) had bronchiectasis. The incidence of recurrent PBB (>3 episodes/yr) decreased over study time from 70 (53.8%) in Yr-1 to 8 (15.7%) in Yr-5. However 38 (60.3%) required at least one course of antibiotics for an episode of wet cough in the preceding year. At the Yr-5 evaluation, 34 children with PBB (45.9%) had a diagnosis of asthma vs 2 (14%) in the controls (p Conclusion: Children with PBB should be followed-up as a significant proportion will eventually develop bronchiectasis and/or an asthma phenotype. Identifying clinical and/or lab-based markers (e.g. molecular signatures) at the index PBB episode would be useful for predicting future risk of disease.

Cough is a frequent symptom presenting to doctors. The most common cause of childhood chronic (greater than fours weeks' duration) wet cough is protracted bacterial bronchitis (PBB) in some settings, although other more serious causes can also present this way. Timely and effective management of chronic wet or productive cough improves quality of life and clinical outcomes. Current international guidelines suggest a course of antibiotics is the first treatment of choice in the absence of signs or symptoms specific to an alternative diagnosis. This review sought to clarify the current evidence to support this recommendation.To determine the efficacy of antibiotics in treating children with prolonged wet cough (excluding children with bronchiectasis or other known underlying respiratory illness) and to assess risk of harm due to adverse events.We undertook an updated search (from 2008 onwards) using the Cochrane Airways Group Specialised Register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials registries, review articles and reference lists of relevant articles. The latest searches were performed in September 2017.We included randomised controlled trials (RCTs) comparing antibiotics with a placebo or a control group in children with chronic wet cough. We excluded cluster and cross-over trials.We used standard methods as recommended by Cochrane. We reviewed results of searches against predetermined criteria for inclusion. Two independent review authors selected, extracted and assessed the data for inclusion. We contacted authors of eligible studies for further information as needed. We analysed data as 'intention to treat.'We identified three studies as eligible for inclusion in the review. Two were in the previous review and one new study was included. We considered the older studies to be at high or unclear risk of bias whereas we judged the newly included study at low risk of bias. The studies varied in treatment duration (from 7 to 14 days) and the antibiotic used (two studies used amoxicillin/clavulanate acid and one used erythromycin).We included 190 children (171 completed), mean ages ranged from 21 months to six years, in the meta-analyses. Analysis of all three trials (190 children) found that treatment with antibiotics reduced the proportion of children not cured at follow-up (primary outcome measure) (odds ratio (OR) 0.15, 95% confidence interval (CI) 0.07 to 0.31, using intention-to -treat analysis), which translated to a number needed to treat for an additional beneficial outcome (NNTB) of 3 (95% CI 2 to 4). We identified no significant heterogeneity (for both fixed-effect and random-effects model the I² statistic was 0%). Two older trials assessed progression of illness, defined by requirement for further antibiotics (125 children), which was significantly lower in the antibiotic group (OR 0.10, 95% CI 0.03 to 0.34; NNTB 4, 95% CI 3 to 5). All three trials (190 children) reported adverse events, which were not significantly increased in the antibiotic group compared to the control group (OR 1.88, 95% CI 0.62 to 5.69). We assessed the quality of evidence GRADE rating as moderate for all outcome measures, except adverse events which we assessed as low quality.Evidence suggests antibiotics are efficacious for the treatment of children with chronic wet cough (greater than four weeks) with an NNTB of three. However, antibiotics have adverse effects and this review reported only uncertainty as to the risk of increased adverse effects when they were used in this setting. The inclusion of a more robust study strengthened the previous Cochrane review and its results.

Weather monitoring has always been an element of observatory operations. For a robotic telescope there is the added complication that software needs to understand the ever changing atmospheric observing conditions in order to respond in real time, continuously balancing the schedule for both facility calibrations (i.e., standard stars) and targeted observations according to the TAC-assigned science priorities. For the Liverpool Telescope, in the past year we have been testing a new multi-threaded approach. We have long operated a single-element, integrated-all-sky, 10 m bolometer on site. To this we have added real-time photometric monitoring of field stars around the science target and analysis of publicly accessible weather satellite images. This gives us three estimates of any night's photometricity; two ground-based looking up through the cloud (optical and thermal IR) and one satellite-based looking down at the observatory. We present a comparison of the results from the different methods and share our experiences selecting between the complementary data sets to support real-time observing decisions.

Aim: In the absence of quality indicators (QIs) for the management of chronic wet cough, our study's aim was to determine whether consensus on QIs reflecting good primary health care, prior to referral for children with chronic wet cough, can be achieved. Methods: A questionnaire consisting of 10 QIs was developed by a clinical working group based on current evidence and guidelines on the management of chronic wet cough in children. Each indicator reflected the quality of care provided to children with chronic wet cough in primary care prior to referral. A modified Delphi consensus questionnaire was undertaken involving expert paediatric respiratory clinicians and general paediatricians who graded the importance of each indicator for the purposes above. We a priori defined that consensus was considered achieved if >75% agreed on the indicator. Results: Twenty-two specialists (from Brisbane, Melbourne, Perth and Canberra) participated in the survey. The cumulative number of years of their respiratory experience was 324 and that of general clinical practice was 504. Consensus was achieved in all 10 QIs, with 6 reaching 100% agreement. Mean agreement for the 10 items was 97%. Conclusion: As complete consensus was achieved on these QIs, it can be used as a provisional clinical audit tool and can guide the development of a robust audit tool for primary care clinical practice to assist with quality improvement initiatives.

Background People with cystic fibrosis (CF) and pancreatic insufficiency are at risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A deficiency predominantly causes eye and skin problems, while excessive levels of vitamin A can harm the respiratory and skeletal systems in children and interfere with the metabolism of other fat-soluble vitamins. Most CF centres administer vitamin A as supplements to reduce the frequency of vitamin A deficiency in people with CF and to improve clinical outcomes such as growth, although the recommended dose varies between different guidelines. Thus, a systematic review on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in people with CF would help guide clinical practice. This is an update of an earlier Cochrane Review. Objectives To determine if supplementation with vitamin A, carotenes or other retinoid supplements in children and adults with CF reduces the frequency of vitamin A deficiency disorders, improves general and respiratory health and affects the frequency of vitamin A toxicity. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. Additionally we searched several ongoing trials registries, including ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number Registry. Most recent database searches: 01 June 2018. Selection criteria All randomised or quasi-randomised controlled studies comparing all preparations of oral vitamin A, carotenes or retinoids (or in combination), used as a supplement compared to placebo at any dose, for at least three months, in people with CF (diagnosed by sweat tests or genetic testing) with and without pancreatic insufficiency. Data collection and analysis Two authors individually assessed study quality and extracted data on outcome measures. The authors assessed the quality of the evidence using the GRADE system. Investigators were contacted to retrieve missing quantitative data. Main results No studies of vitamin A or other retinoid supplementation were eligible for inclusion. However, one randomised study of beta (8) carotene supplementation involving 24 people with CF who were receiving pancreatic enzyme substitution was included. The study compared successive beta-carotene supplementation periods (high dose followed by low dose) compared to placebo. The results for the low-dose supplementation period should be interpreted with caution, due to the lack of a wash-out period after the high-dose supplementation. The included study did not report on two of the review's primary outcomes (vitamin A deficiency disorders and mortality); results for our third primary outcome of growth and nutritional status (reported as z score for height) showed no difference between supplementation and placebo, mean difference (MD)-0.23 (95% confidence interval (CI) -0.89 to 0.43) (low-quality evidence). With regards to secondary outcomes, supplementation with high-dose beta-carotene for three months led to significantly fewer days of systemic antibiotics required to treat pulmonary exacerbations, compared to controls, MD-15 days (95% CI-27.60 to -2.40); however, this was not maintained in the second three-month section of the study when the level of beta-carotene supplementation was reduced, MD-8 days (95% CI -18.80 to 2.80) (low-quality evidence). There were no statistically significant effects between groups in lung function (low quality evidence) and no adverse events were observed (low-quality evidence). Supplementation affected levels of beta-carotene in plasma, but not vitamin A levels. The study did not report on quality of life or toxicity. Authors' conclusions Since no randomised or quasi-randomised controlled studies on retinoid supplementation were identified, no conclusion on the supplementation of vitamin A in people with CF can be drawn. Additionally, due to methodological limitations in the included study, also reflected in the low-quality evidence judged following the specific evidence grading system (GRADE), no clear conclusions on beta-carotene supplementation can be drawn. Until further data are available, country- or region-specific guidelines regarding these practices should be followed.

Los alimentos para peces están formulados con diversos ingredientes, donde la harina de pescado es la principal fuente de proteína. Sin embargo, este insumo tiene un alto costo que lleva a la necesidad de evaluar nuevas fuentes de proteínas y probarlas en especies marinas. Oplegnathus insignis (San Pedro, Pacific beakfish) es una especie omnívora en su etapa intermareal y carnívora en su etapa submareal, que ha sido cultivada de manera experimental, siendo necesario incorporar dietas formuladas. Este estudio reporta la experiencia en alimentación y nutrición, de juveniles de O. insignis alimentados con dietas formuladas con distintas fuentes de proteína. Se efectuó una experiencia con juveniles de O. insignis provenientes de un cultivo experimental. Se formularon cuatro alimentos, uno en base de harina de pescado (referencia) y tres modificando la fuente de proteína del alimento de referencia, intercambiando un 30% de harina de pescado, por harina de soya, harina de moluscos y harina de quinoa. Se experimentó con 180 ind de 295,6 g y de 450 días post-eclosión, distribuidos en 12 estanques rectangulares de 1,6 m³. La alimentación fue a saciedad. Se efectuaron análisis próximales de los alimentos experimentales de las heces colectadas. Se determinó los coeficientes de digestibilidad total y proteína. El alimento con mayor contenido de proteína fue el que contenía harina de moluscos. El mayor coeficiente de digestibilidad total lo tienen los alimentos con harina de pescado (68,0%) y harina de moluscos (67,1%), mientras que en los alimentos en base a harinas vegetales, la digestibilidad total para la harina de soya fue de 62,7% y para harina de quinoa de 64,1%. Estos resultados indican que es factible reemplazar un 30% de la harina de pescado por harinas de origen vegetal.

Background Endobronchial suppuration is present in children with protracted bacterial bronchitis (PBB), bronchiectasis, and cystic fibrosis (CF). However, no studies have directly compared bronchoscopy and bronchoalveolar lavage (BAL) findings across these conditions within a single center using the same techniques and with shared community pathogens. Aim To determine; (i) the bronchoscopic findings and BAL microbiology and cellularity among children with these conditions and; (ii) the relationship between bacterial pathogens, airway cellularity and aberrant macroscopic bronchoscopic findings. Methods We retrospectively reviewed all bronchoscopy data (undertaken over 6.5‐years) from our center in children (

Appropriate management of cough in children depends upon accurate assessment. The diagnosis is often unclear at the initial presentation. Acute cough is frequently caused by a viral infection, and often no specific therapy is indicated. Urgent treatment may be needed if history suggests a more serious disorder such as a foreign body or pneumonia. When treating children with chronic cough, paediatric-specific algorithms should be used . Empirical use of medicines without looking for a specific cause should be avoided. In the absence of an alternative specific cause of cough, chronic wet cough (lasting at least four weeks) is most frequently due to protracted bacterial bronchitis. Antibiotics are indicated.

Background. The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods. Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV +). Presence of bacterial infection (defined as ≥104 colony-forming units/mL) was compared between BAL HAdV+ and HAdV negative (HAdV-) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results. Species C HAdVs were identified in 23 of 24 (96%) HAdV+ children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV+ BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P =. 007) and negatively associated with Staphylococcus aureus infection (P =. 03). Young age was related to increased rates of HAdV+. Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P =. 027). Conclusions. HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV+ of the lower airways and influences the likelihood of bacterial coinfection.

After birth, piglets undergo procedures likely to cause stress. The aim of this study was to evaluate stress responses evoked by 2 combinations (More Stressful [all a] or Less Stressful [all a] or More Stressful [all b]) of alternative methods for performing the following processing procedures: 1) teeth resection (TR) – [a] clip vs. [b] grind; 2) identification (ID) – [a] ear tag vs. [b] ear notch; 3)iron administration (FE) – [a] inject vs. [b] oral; 4) castration (CA) – [a] cords cut vs. [b] cords torn; 5) taildocking (TD) – [a] cold clip vs. [b] hot clip [corrected]. Ten litters of eight 2- and 3-d-old piglets were assigned to each procedure. Within each litter 1 male and 1 female piglet was assigned to 1 of 4 possible procedures: the 2 combinations, sham procedures, and sham procedures plus blood sampling. Blood was collected before processing and at 45 min, 4 h, 48 h, 1 wk, and 2 wk afterward and assayed for cortisol and β-endorphin concentrations. Procedures were videotaped and analyzed to evaluate the time taken to perform the procedure and the number of squeals, grunts, and escape attempts. Vocalizations were analyzed to determine mean and peak frequencies and duration. Piglets were weighed before the procedure and at 24 h, 48 h, 1 wk, and 2 wk afterward. Identification, tail docking, and castration lesions were scored on a 0 to 5 scale at 24 h, 1 wk, and 2 wk postprocedure. Both combinations of methods took longer to carry out than sham procedures and resulted in more squeals, grunts, and escape attempts during the procedures and higher peak frequencies of vocalizations compared with the control treatments (P < 0.05). Cortisol concentrations 45 min after processing were also higher in the 2 combination treatments than in the sham treatments (P < 0.05). Comparing between procedure treatments, the More Stressful combination of methods took longer to carry out, resulted in higher β-endorphin concentrations at 1 wk, had higher peak frequency of vocalizations, and increased ear (P < 0.05) and tail wound (P < 0.1) lesion scores at 1 wk than the Less Stressful combination. Growth during d 2 to 7 postprocedure was lower in More Stressful piglets than control piglets (P < 0.05) but by 2 wk, growth was unaffected. Using measures of behavior, physiology, and productivity, the More Stressful combination of procedures decreased welfare relative to the Less Stressful combination; however, both combinations decreased welfare relative to controls. The time taken to carry out the procedure would appear to be an important factor in the strength of the stress response.

Aim To determine whether a child with chronic wet cough and poor response to at least 4 weeks of oral antibiotics is more likely to have bronchiectasis. Methods All chest multi-detector computerised tomography (MDCT) scans at a single paediatric tertiary hospital from April 2010 to August 2012 were reviewed retrospectively so as to identify those ordered by respiratory physicians for assessment of children with a chronic wet cough. Information regarding age, sex, ethnicity, indication for imaging and the response to at least 4 weeks of antibiotics before having the scan were recorded from their charts. The data were analysed using simple and multiple logistic regression. Results Of the 144 (87 males) eligible children, 106 (65 males, 30 Indigenous) aged 10–199 months had MDCT scan evidence of bronchiectasis. Antibiotic data were available for 129 children. Among the 105 children with persistent cough despite at least 4 weeks of antibiotics, 88 (83.8%) had bronchiectasis, while of the 24 children whose cough resolved after antibiotics, only six (25.0%) received this diagnosis (adjusted OR 20.9; 95% CI 5.36 to 81.8). Being Indigenous was also independently associated with radiographic evidence of bronchiectasis (adjusted OR 5.86; 95% CI 1.20 to 28.5). Conclusions Further investigations including a MDCT scan should be considered in a child with a chronic wet cough that persists following 4 weeks of oral antibiotics. However, while reducing the likelihood of underlying bronchiectasis, responding well to a single prolonged course of antibiotics does not exclude this diagnosis completely.