Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-Risk Settings: A Randomized Controlled Trial.

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.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

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.

Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation.

Bronchiectasis, particularly in children, is an increasingly recognised yet neglected chronic lung disorder affecting individuals in both low-to-middle and high-income countries. It has a high disease burden and there is substantial inequity within and between settings. Furthermore, compared with other chronic lung diseases, considerably fewer resources are available for children with bronchiectasis. The need to prevent bronchiectasis and to reduce its burden also synchronously aligns with its high prevalence and economic costs to health services and society. Like many chronic lung diseases, bronchiectasis often originates early in childhood, highlighting the importance of reducing the disease burden in children. Concerted efforts are therefore needed to improve disease detection, clinical management and equity of care. Modifiable factors in the causal pathways of bronchiectasis, such as preventing severe and recurrent lower respiratory infections should be addressed, whilst also acknowledging the role played by social determinants of health. Here, we highlight the importance of early recognition/detection and optimal management of bronchiectasis in children, and outline our research, which is attempting to address important clinical knowledge gaps discussed in a recent workshop. The research is grouped under three themes focussing upon primary prevention, improving diagnosis and disease characterisation, and providing better management. Our hope is that others in multiple settings will undertake additional studies in this neglected field to further improve the lives of people with bronchiectasis. We also provide a resource list with links to help inform consumers and healthcare professionals about bronchiectasis and its recognition and management.

Transition of pediatric patients with bronchiectasis to adult medical care in the Northern Territory: A retrospective chart audit.

Background: Bronchiectasis is increasingly being recognized to exist in all settings with a high burden of disease seen in First Nations populations. With increasing numbers of pediatric patients with chronic illnesses surviving into adulthood, there is more awareness on examining the transition from pediatric to adult medical care services. We undertook a retrospective medical chart audit to describe what processes, timeframes, and supports were in place for the transition of young people (≥14 years) with bronchiectasis from pediatric to adult services in the Northern Territory (NT), Australia. Methods: Participants were identified from a larger prospective study of children investigated for bronchiectasis at the Royal Darwin Hospital, NT, from 2007 to 2022. Young people were included if they were aged ≥14 years on October 1, 2022, with a radiological diagnosis of bronchiectasis on high-resolution computed tomography scan. Electronic and paper-based hospital medical records and electronic records from NT government health clinics and, where possible, general practitioner and other medical service attendance were reviewed. We recorded any written evidence of transition planning and hospital engagement from age ≥14 to 20 years. Results: One hundred and two participants were included, 53% were males, and most were First Nations people (95%) and lived in a remote location (90.2%). Nine (8.8%) participants had some form of documented evidence of transition planning or discharge from pediatric services. Twenty-six participants had turned 18 years, yet there was no evidence in the medical records of any young person attending an adult respiratory clinic at the Royal Darwin Hospital or being seen by the adult outreach respiratory clinic. Conclusion: This study demonstrates an important gap in the documentation of delivery of care, and the need to develop an evidence-based transition framework for the transition of young people with bronchiectasis from pediatric to adult medical care services in the NT.

Listening to First Nations women's voices, hearing requests for continuity of carer, trusted knowledge and family involvement: A qualitative study in urban Darwin.

PROBLEM: Australian First Nations women are more likely to commence care later in pregnancy and underutilise maternal health services than non-First Nations women. BACKGROUND: Disrespectful maternity care is a major barrier to care-seeking in pregnancy, often resulting in later commencement and underutilisation of care. AIM: We aimed to identify barriers and enablers to pregnancy-related care-seeking for Australian First Nations women living in the Darwin region through yarning about their experiences of pregnancy care. METHODS: Ten Australian First Nations women shared stories about their pregnancy care journeys. Yarns took place at a time and location determined by the women, with recruitment continuing until saturation was reached. FINDINGS: Emerging themes included a desire for continuity of carer, particularly with midwives; access to trustworthy information, enabling informed decision-making; and a need to have family involved in all aspects of care. No specific barriers were identified within this cohort DISCUSSION: Universal access to continuity of carer models would provide women with the relational care they are asking for as well as address other identified needs, such as a desire for information relevant to their pregnancy; and space for partners/family members to be involved. The themes that emerged provide a picture of what a positive, respectful pregnancy care experience could be for First Nations women within the Darwin Region, thus enabling care-seeking in pregnancy. CONCLUSION: Although the public sector and Aboriginal Controlled Community Health Organisations currently provide continuity of carer models, robust systems ensuring these models are made available to all women are lacking.

Interventions to improve enablers and/or overcome barriers to seeking care during pregnancy, birthing and postnatal period for women living with vulnerabilities in high-income countries: A systematic review and meta-analysis.

OBJECTIVE: To reduce maternal morbidity and mortality, World Health Organization recommendations include: commencing pregnancy care before 12-weeks', at least eight antenatal and four postnatal visits, and attendance of skilled care at birthing. While lower adherence to the recommendation predominates in low- and middle-income countries, it also occurs in some settings in high-income countries. Globally, various strategies are used to optimise maternity care, in line with these recommendations. This systemic review aimed to determine if enhanced care improves maternal care-seeking, thus improving clinical outcomes for women and babies living with vulnerabilities, in high-income countries. DESIGN, SETTING AND PARTICIPANTS: We searched the Cochrane Central Registers of Controlled Trials and Cochrane Pregnancy and Childbirth, MEDLINE, CINAHL, Proquest Dissertation and Thesis and reference lists of relevant articles. The latest search was performed June 20, 2022. Randomised controlled trials, non-randomised intervention trials and cohort studies comparing effects of interventions designed to increase utilisation of maternal health services with routine care, for women at increased risk of maternal mortality and severe maternal morbidity in high-income countries were included. Two authors selected, extracted, assessed and analysed data. Additional information was sought from study authors. This systematic review and meta-analysis was registered with PROSPERO(CRD42021256811). FINDINGS: Nine studies with 5,729 participants were included. Interventions to enhance care significantly increased utilisation of health services, increasing attendance at antenatal classes (Odds Ratio[OR]=15·23, 95%Confidence Interval[CI] 10·73-21·61, p<0·0001) and postnatal visits by 6-8 weeks (OR=2·66, 95%CI 1·94-3·64, p<0·0001), compared to routine care. Infants in the intervention groups were significantly less likely to be: born preterm (OR=0·68, 95%CI 0·56-0·82, p<0·0001); low birthweight (OR=0·78, 95%CI 0·64-0·95, p = 0·01) or; require neonatal intensive care (OR=0·80, 95%CI 0·66-0·96, p = 0·02). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Among women living with vulnerabilities in high-income countries, interventions to enhance care increases utilisation of maternal health services and improves outcomes.

Multi-lingual "Asthma APP" improves health knowledge of asthma among Australian First Nations carers of children with asthma.

Background: Among Australian First Nations people, asthma is associated with worse morbidity and mortality than non-First Nations people. Improving the delivery of health education that is innovative and culturally relevant to linguistically diverse populations is needed. Digital platforms, such as mobile applications (APP), have the potential to improve evidence-based health education, particularly in settings where access to specialist services is limited and turnover of staff is high, such as in remote Australia. In response to consumer needs, we developed a multi-lingual Asthma APP from our existing asthma flipchart, with a "voice-over" in seven local First Nations languages and English, using a mixture of static and interactive formats. In this study, we evaluated (a) the functionality and usability of the APP with First Nations health professionals with and without asthma and (b) whether the APP improves health knowledge and understanding of asthma among First Nations carers of children with asthma. Methods: In total, 7 First Nations health professionals participated in semi-structured interviews prior to the evaluation with 80 First Nations carers of children with asthma from the Northern Territory and Queensland, Australia. Carers underwent pre- and post-education questionnaires (maximum score = 25), where the post-questionnaire was administered immediately post the APP education session. Results: Health professionals found that APP was easy to navigate and culturally appropriate. Among the 80 carers, most were mothers (86%), aged between 26 and 50 years (75%) and 61% lived in remote settings (>100 km from a tertiary hospital). Most carers chose English audio (76%) with the remainder choosing one of the First Nations languages. Overall, asthma knowledge significantly improved post-education (median scores pre = 21 [interquartile range (IQR), 19-22; post = 24 (IQR 22-24), p = 0.05]. Conclusion: The First Nations-specific multi-lingual Asthma APP was easy to use and acceptable for the use by health professionals that also significantly improved short-term asthma knowledge among First Nations carers of children with asthma. The Asthma APP is an innovative and culturally acceptable method of delivering evidence-based, health education to culturally and linguistically diverse populations among Australian First Nations people.

Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. METHODS AND ANALYSIS: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. ETHICS AND DISSEMINATION: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. TRIAL REGISTRATION NUMBER: ACTRN12619000564156.

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial.

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.

How does the Canadian Acute Respiratory Illness and Flu Scale relate to other scales in pediatric asthma exacerbations?

OBJECTIVES: In children with asthma exacerbations, we evaluated the relationship between Canadian Acute Respiratory Illness and Flu Scale (CARIFS) scores and (a) Asthma Diary Scale (ADS) scores for 14 days; (b) Pediatric Asthma Caregiver's Quality of Life (QoL) Questionnaire (PACQLQ) scores on days 1, 7 and 14; (c) viral detection. We hypothesized that in children with acute asthma, CARIFS scores correlate with ADS and PACQLQ scores over time and that viruses have little impact on CARIFS scores. METHODS: In children aged 2-16 years who presented with acute asthma to the Emergency Departments of 2 hospitals, we documented the clinical history, examination, asthma severity at baseline and on presentation. Eighteen respiratory pathogens were determined by PCR on nasopharyngeal aspirate (NPA) collected on recruitment. The parent(s) recorded their child's daily CARIFS and ADS and weekly PACQLQ for 14 days. We used Spearman's correlation to relate the scores of 108 children. RESULTS: CARIFS scores correlated well with ADS scores throughout 14 days (rs ranged 0.30-0.67). CARIFS and PACQLQ scores correlated -0.28, -0.14 and -0.44 on days 1, 7 and 14 respectively. There was no significant difference in CARIFS scores between children whose NPAs were PCR virus-positive or -negative over 14 days. CONCLUSIONS: CARIFS and ADS scores correlated well as a disease severity measure during the recovery period in children with acute asthma and this was not influenced by the virus state. The ADS may be used as an alternative in selected situations. The CARIFS reflects different aspects to acute asthma severity and QoL.

Utility of a personalised Bronchiectasis Action Management Plan (BAMP) for children with bronchiectasis: protocol for a multicentre, double-blind parallel, superiority randomised controlled trial.

INTRODUCTION: Bronchiectasis is no longer considered rare or irreversible in children, yet it remains relatively under-researched and neglected in respiratory health globally. Bronchiectasis (including chronic suppurative lung disease) causes substantial morbidity for patients and significant impact on caregivers, especially during acute respiratory exacerbations. In other chronic respiratory diseases (eg, asthma), empowering consumers with an individualised plan for management of acute exacerbations improves clinical outcomes. However, in the absence of any such data specific to bronchiectasis, action management plans are rarely currently used in children or adults with bronchiectasis. We hypothesise that providing an individualised bronchiectasis action management plan (BAMP) to children with bronchiectasis reduces non-scheduled doctor consultations, compared with not having a BAMP. METHODS AND ANALYSIS: This multicentre, parallel, double-blind, randomised trial involving three urban Australian hospitals commenced in June 2018 and will include 198 children, aged <19 years with bronchiectasis who had 2 or more exacerbations in the previous 18 months. Children will be randomised to having an individualised BAMP or standard care (a decoy clinic letter). Primary caregivers will then be followed up monthly for 12 months. The primary outcome is the rate of acute non-scheduled doctor visits for respiratory exacerbations by 12 months. The main secondary outcomes are cough-specific quality of life scores at 6 and 12 months, overall exacerbation rate over 12 months, and proportion of children who received timely influenza vaccination by 30 May annually. ETHICS AND DISSEMINATION: The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Heath Research and Queensland Children's Hospital approved the study. The results of the trial will be submitted for publication and the BAMP made available free online. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register ACTRN12618000604202.

Clinical and research priorities for children and young people with bronchiectasis: an international roadmap.

The global burden of children and young people (CYP) with bronchiectasis is being recognised increasingly. They experience a poor quality of life and recurrent respiratory exacerbations requiring additional treatment, including hospitalisation. However, there are no published data on patient-driven clinical needs and/or research priorities for paediatric bronchiectasis. Parent/patient-driven views are required to understand the clinical needs and research priorities to inform changes that benefit CYP with bronchiectasis and reduce their disease burden. The European Lung Foundation and the European Respiratory Society Task Force for paediatric bronchiectasis created an international roadmap of clinical and research priorities to guide, and as an extension of, the clinical practice guideline. This roadmap was based on two global web-based surveys. The first survey (10 languages) was completed by 225 respondents (parents of CYP with bronchiectasis and adults with bronchiectasis diagnosed in childhood) from 21 countries. The parent/patient survey encompassed both clinical and research priorities. The second survey, completed by 258 health practitioners from 54 countries, was limited to research priorities. The two highest clinical needs expressed by parents/patients were: having an action management plan for flare-ups/exacerbations and access to physiotherapists. The two highest health practitioners' research priorities related to eradication of airway pathogens and optimal airway clearance techniques. Based on both surveys, the top 10 research priorities were derived, and unanimous consensus statements were formulated from these priorities. This document addresses parents'/patients' clinical and research priorities from both the parents'/patients' and clinicians' perspectives and will help guide research and clinical efforts to improve the lives of people with bronchiectasis.

Comparison of Profiles of First Nations and Non-First Nations Children With Bronchiectasis Over Two 5-Year Periods in the Northern Territory, Australia.

BACKGROUND: Although the burden of bronchiectasis is recognized globally, pediatric data are limited, particularly on trends over the years. Also, no published data exists regarding whether vitamin D deficiency or insufficiency and human T-cell lymphotropic virus type 1 (HTLV-1) infection, both found to be related to severe bronchiectasis in First Nations adults, also are important in children with bronchiectasis. RESEARCH QUESTION: Among children with bronchiectasis, (1) have the clinical and BAL profiles changed between two 5-year periods (period 1, 2007-2011; period 2, 2012-2016) and (b) are vitamin D deficiency or insufficiency, HTLV-1 infection, or both associated with radiologic severity of bronchiectasis? STUDY DESIGN AND METHODS: We analyzed the data from children with bronchiectasis prospectively enrolled at Royal Darwin Hospital, Australia, at the first diagnosis; that is, no child was included in both periods. Data collected include demographics, BAL, routine investigation bloods, and high-resolution CT scan of the chest evaluated using the Bhalla and modified Bhalla scores. RESULTS: The median age of the 299 children was 2.2 years (interquartile range, 1.5-3.7 years). One hundred sixty-eight (56%) were male and most were First Nations (92%). Overall, bronchiectasis was high over time, particularly among First Nations children. In the later period, numbers of non-First Nations children more than tripled, but did not reach statistical significance. In period 2 compared with period 1, fewer First Nations children demonstrated chronic cough (period 1, 61%; period 2, 47%; P = .03), and were younger, First Nations children were less likely to have received azithromycin (period 1, 42%; period 2, 21%; P < .001), and the BAL fluid of First Nations children showed lower Haemophilus influenzae and Moraxella catarrhalis infection. HTLV-1 infection was not detected, and vitamin D deficiency or insufficiency did not correlate with severity of bronchiectasis. INTERPRETATION: Bronchiectasis remains high particularly among First Nations children. Important changes in their profiles that arguably reflect improvements were present, but overall, the profiles remained similar. Although vitamin D deficiency was uncommon, its role in children with bronchiectasis requires further evaluation. HTLV-1 infection was nonexistent and is unlikely to play any role in First Nations children with bronchiectasis.

European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis.

There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality of life for the child/adolescent and their parents, recurrent exacerbations, and costs to the family and health systems. Optimal treatment improves clinical outcomes. Several national guidelines exist, but there are no international guidelines.The European Respiratory Society (ERS) Task Force for the management of paediatric bronchiectasis sought to identify evidence-based management (investigation and treatment) strategies. It used the ERS standardised methodology that included a systematic review of the literature and application of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to define the quality of the evidence and level of recommendations.A multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, immunology, methodology, patient advocacy and parents of children/adolescents with bronchiectasis considered the most relevant clinical questions (for both clinicians and patients) related to managing paediatric bronchiectasis. 14 key clinical questions (seven PICO (Patient, Intervention, Comparison, Outcome) and seven narrative) were generated. The outcomes for each PICO were decided by voting by the panel and parent/patient advisory group.This guideline addresses the definition, diagnostic approach and antibiotic treatment of exacerbations, pathogen eradication, long-term antibiotic therapy, asthma-type therapies (inhaled corticosteroids and bronchodilators), mucoactive drugs, airway clearance, investigation of underlying causes of bronchiectasis, disease monitoring, factors to consider before surgical treatment, and the reversibility and prevention of bronchiectasis in children/adolescents. Benchmarking quality of care for children/adolescents with bronchiectasis to improve clinical outcomes and evidence gaps for future research could be based on these recommendations.

Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia.

BACKGROUND: Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. METHODS: For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012-May 2017) with the 7vPCV period (June 2007-May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. FINDINGS: Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p<0.001); ST19A decreased from 36.4% to 12.4%. No cases of ST1 empyema were identified in the 13vPCV period versus 14.5% in the 7vPCV period. INTERPRETATION: 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.

Can Acute Cough Characteristics From Sound Recordings Differentiate Common Respiratory Illnesses in Children?: A Comparative Prospective Study.

BACKGROUND: Acute respiratory illnesses cause substantial morbidity worldwide. Cough is a common symptom in these childhood respiratory illnesses, but no large cohort data are available on whether various cough characteristics can differentiate between these etiologies. RESEARCH QUESTION: Can various clinically based cough characteristics (frequency [daytime/ nighttime], the sound itself, or type [wet/dry]) be used to differentiate common etiologies (asthma, bronchiolitis, pneumonia, other acute respiratory infections) of acute cough in children? STUDY DESIGN AND METHODS: Between 2017 and 2019, children aged 2 weeks to ≤16 years, hospitalized with asthma, bronchiolitis, pneumonia, other acute respiratory infections, or control subjects were enrolled. Spontaneous coughs were digitally recorded over 24 hours except for the control subjects, who provided three voluntary coughs. Coughs were extracted and frequency defined (coughs/hour). Cough sounds and type were assessed independently by two observers blinded to the clinical data. Cough scored by a respiratory specialist was compared with discharge diagnosis using agreement (Cohen's kappa coefficient [қ]), sensitivity, and specificity. Caregiver-reported cough scores were related with objective cough frequency using Spearman coefficient (rs). RESULTS: A cohort of 148 children (n = 118 with respiratory illnesses, n = 30 control subjects), median age = 2.0 years (interquartile range, 0.7-3.9), 58% males, and 50% First Nations children were enrolled. In those with respiratory illnesses, caregiver-reported cough scores and wet cough (range, 42%-63%) was similar. Overall agreement in diagnosis between the respiratory specialist and discharge diagnosis was slight (қ = 0.13; 95% CI, 0.03 to 0.22). Among diagnoses, specificity (8%-74%) and sensitivity (53%-100%) varied. Interrater agreement in cough type (wet/dry) between blinded observers was almost perfect (қ = 0.89; 95% CI, 0.81 to 0.97). Objective cough frequency was significantly correlated with reported cough scores using visual analog scale (rs = 0.43; bias-corrected 95% CI, 0.25 to 0.56) and verbal categorical description daytime score (rs = 0.39; bias-corrected 95% CI, 0.22 to 0.54). INTERPRETATION: Cough characteristics alone are not distinct enough to accurately differentiate between common acute respiratory illnesses in children.

Determinants of cough and caregivers' quality of life in pediatric asthma exacerbations.

OBJECTIVES: In hospitalized and nonhospitalized children with asthma exacerbations, we evaluated the determinants of (a) prolonged cough on day-14 and (b) asthma quality of life (QoL) questionnaires for parents (PACQLQ) on day-21. We hypothesized that children with more severe acute asthma are more likely to have prolonged cough and/or poorer PACQLQ during the recovery phase. DESIGN: Prospective cohort study performed during 2009-2011. METHODOLOGY: Two hundred and forty-four children aged 2-16 years presenting with acute asthma to the Emergency Departments of two hospitals were recruited. Clinical history, examination, baseline asthma severity, and acute asthma severity on presentation were documented. Validated daily cough diaries and weekly PACQLQ were recorded for 14 and 21 days, respectively. RESULTS: 34.4% and 32.2% of children who returned the daytime and nighttime cough diaries respectively had a prolonged cough. Those on regular inhaled corticosteroids (ICS) were significantly more likely to have a daytime or nighttime cough score of ≥1 on day-14 (odds ratio [ORadjusted ] = 4.70, 95% confidence interval [CI] 1.65, 13.35, p = .004 and ORadjusted = 2.65, 95% CI 1.05, 6.69, p = .040, respectively). PACQLQ on day-21 was significantly poorer in younger children (mean difference [MD] = -0.04 per year, 95% CI -0.08, -0.01, p = .016), those on ICS (MD = -0.31, 95% CI -0.52, -0.09, p = .005), leukotriene antagonists (MD = -0.42, 95% CI -0.83, -0.02, p = .040) and in those who had an unplanned visit for asthma on day-21 (MD = -1.20, 95% CI -1.61, -0.78, p = .0001). CONCLUSIONS: Post an acute asthma exacerbation, children on regular ICS were more likely to have prolonged cough and poorer QoL. While this may be reflective of asthma severity or control, its association deserves further evaluation.

Electronic cigarettes: A position statement from the Thoracic Society of Australia and New Zealand.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators.

A decade on: Follow-up findings of indigenous children with bronchiectasis.

OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010. METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans. RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values. CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

The point prevalence of respiratory syncytial virus in hospital and community-based studies in children from Northern Australia: studies in a 'high-risk' population.

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory infections globally, accounting for high morbidity and mortality burden among children aged less than 5 years. As candidate RSV vaccine trials in pregnant women and infants are underway a greater understanding of RSV epidemiology is now needed, especially in paediatric populations with high rates of acute and chronic respiratory disease. The objective was to identify RSV prevalence in children living in northern Australia, a region with a high respiratory disease burden. METHODS: Data were sourced from 11 prospective studies (four hospital and seven community-based) of infants and children with acute and chronic respiratory illnesses, as well as otitis media, conducted between 1996 and 2017 inclusive. The data from northern Australian children in these trials were extracted and, where available and consented, their nasopharyngeal swabs (biobanked at -80ºC) were tested by polymerase chain reaction assays for RSV-A and B, 16 other viruses and atypical respiratory bacterial pathogens. RESULTS: Overall, 1127 children were included. Their median age was 1.8 years (interquartile range 0.5-4.9); 58% were male and 90% Indigenous, with 81% from remote communities. After human rhinoviruses (HRV), RSV was the second most prevalent virus (15%, 95% confidence interval (CI) 13-18). RSV prevalence was greatest amongst children aged less than 2 years hospitalised with bronchiolitis (47%, 95%CI 41.4-52.4), with more than two-thirds with RSV aged less than 6 months. In contrast, the prevalence of RSV was only 1-3.5% in other age groups and settings. In one-third of RSV cases, another respiratory virus was also detected. Individual viruses other than RSV and HRV were uncommon (0-9%). CONCLUSION: Combined data from 11 hospital and community-based studies of children aged less than 18 years who lived in communities with a high burden of acute and chronic respiratory illness showed that RSV was second only to HRV as the most prevalent virus detected across all settings. RSV was the most frequently detected virus in infants hospitalised with bronchiolitis, including those aged less than 6 months. In contrast, RSV was uncommonly detected in children in community settings. In northern Australia, effective maternal and infant RSV vaccines could substantially reduce RSV bronchiolitis-related hospitalisations, including admissions of Indigenous infants from remote communities.