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Background: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease., Methods: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario)., Results: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences., Conclusion: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes., Competing Interests: A.B.C., K.G., S.T.Y., R.S.W., G.B.M., P.S.M., J.W.U., and P.J.T. report grants from NHMRC and NHMRC-managed grants (Medical Research Futures Fund), during the conduct of the study. ABC is also an independent data management committee member for clinical trials for Moderna (COVID-19 and EBV vaccines) and of an unlicensed vaccine (GlaxoSmithKline) and monoclonal antibody (AstraZeneca), received fees from the institution for consulting on the study designs for Zambon and Boehringer Ingelheim, airfares for travel from the European Respiratory Society and Boehringer Ingelheim, and personal fees for being an author of two UpToDate chapters that are outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Indigenous peoples around the world bear a disproportionate burden of chronic respiratory diseases, which are associated with increased risks of morbidity and mortality. Despite the imperative to address global inequity, research focused on strengthening respiratory health in Indigenous peoples is lacking, particularly in low-income and middle-income countries. Drivers of the increased rates and severity of chronic respiratory diseases in Indigenous peoples include a high prevalence of risk factors (eg, prematurity, low birthweight, poor nutrition, air pollution, high burden of infections, and poverty) and poor access to appropriate diagnosis and care, which might be linked to colonisation and historical and current systemic racism. Efforts to tackle this disproportionate burden of chronic respiratory diseases must include both global approaches to address contributing factors, including decolonisation of health care and research, and local approaches, co-designed with Indigenous people, to ensure the provision of culturally strengthened care with more equitable prioritisation of resources. Here, we review evidence on the burden of chronic respiratory diseases in Indigenous peoples globally, summarise factors that underlie health disparities between Indigenous and non-Indigenous people, propose a framework of approaches to improve the respiratory health of Indigenous peoples, and outline future directions for clinical care and research., Competing Interests: Declaration of interests ABC reports multiple grants related to studies on Indigenous children's lung health to her institution from the Australian National Health and Medical Research Council (NHMRC); she is also the lead author of several point-of-care manuals and educational resources related to Indigenous children's lung health, for which no payments have been received. TK reports personal fees for advisory board membership from Covis Pharma Canada. GJR reports payment of a training grant to his institution from the US Maternal and Child Health Bureau of the Health Resources & Services Administration; he is also an editor of the paediatric pulmonology section of UpToDate. GGA reports a grant for a study on Indigenous lung health to his institution from the Canadian Institute of Health Research. MT reports multiple grants related to studies on Indigenous health to her institution from the NHMRC; she also established two Aboriginal-controlled primary health-care services. PJT reports multiple grants related to studies on Indigenous lung health to his institution from the NHMRC; he is also the medical director of an Aboriginal-controlled primary health-care service and has co-authored point-of-care manuals and educational resources related to Indigenous lung health, for which no payments have been received. DMG reports grant funding and consulting fees from the Wellcome Trust, unrelated to this manuscript, and support for attending conferences from the Pan African Thoracic Society; she is also Treasurer of the Pan African Thoracic Society Executive Committee. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations., Methods and Findings: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size., Conclusions: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation., Trial Registration: ClinicalTrials.gov NCT01735084 and NCT01174849., Competing Interests: AJL received funds from NHMRC paid to the institution, and GSK provided materials for immunogenicity assays. AJL received funds from Merck Sharp and Dohme for analysis of pneumococcal carriage, payment to institution. ABC served as advisor on a Data Safety Monitoring Board for an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has multiple project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. ABC received Royalties or licences as an author of cough and bronchiectasis topics, and Partial reimbursement for airfares as a speaker for European Respiratory Society. All payments were to the institution. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to Merck Sharp and Dohme Australia. All other authors (DL, CGB-J, HS-V, MJB, MDC, PVL, PSM, PJT) declare no competing interests., (Copyright: © 2024 Leach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention., Methods and Analysis: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function., Ethics and Dissemination: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations., Trial Registration Number: ACTRN12621000315819., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage., Methods: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose., Results: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%., Conclusion: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs., Competing Interests: Declaration of competing interest AJL received funds from NHMRC paid to the institution, and GSK provided materials for immunogenicity assays. AJL received funds from Merck Sharp and Dohme for analysis of pneumococcal carriage, payment to institution. ABC served as advisor on a Data Safety Monitoring Board for an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has multiple project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. ABC received Royalties or licences as an author of cough and bronchiectasis topics, and Partial reimbursement for airfares as a speaker for European Respiratory Society. All payments were to the institution. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to MSD Australia. All other authors (DL, HS-V, MB, MC, PL, PSM, PT) declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules., Methods: PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 μg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849)., Findings: Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related., Interpretation: Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children., Funding: National Health and Medical Research Council (NHMRC)., Competing Interests: Declaration of interests ABC served as advisor on an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has various project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to MSD Australia. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP., Methods: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks., Results: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance., Conclusions: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits., Competing Interests: A.B.C. is supported by a National Health and Medical Research Council practitioner fellowship (number 1154302) and Children’s Hospital Foundation Queensland (Grant 50286). The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)