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Bronchiectasis is a chronic respiratory disorder characterized by the dilation and damage of bronchial walls due to recurrent and prolonged episodes of inflammation and infection. The diagnosis of bronchiectasis requires objective measurement of abnormal bronchial dilation. It is confirmed radiologically using a chest tomography (C.T.). scan where the pathognomonic feature is increased broncho-arterial ratio (BAR) (>0.8 in children) and, often accompanied by other features such as bronchial wall thickening (W.T.). Developing image processing-based methods facilitates quicker interpretation of the scans and enable detailed evaluations according to the lobes and segments. However, challenges, such as inclined and oblique orientations of structures, and partial volume effect, can complicate accurate measurements in the upper and middle lobes using the same algorithms. Therefore, the accurate detection and measurement of airway and artery regions for BAR and wall thickness in each lobe require specialized image processing/machine learning methods and approaches. Here, we adopt a step-by-step approach and propose methods for three steps: 1. Separating right lower lobe (RLL) region from full-length C.T. scans using tracheal bifurcation (Carina) point as a central marker; 2. Updated technique to locate inner diameter of airways and outer diameter of arteries for BAR measurement; and 3. Measuring airway wall thickness (W.T.) by identifying the outer and inner diameter of airway boundaries (perimeter). Our analysis of 13 high resolution C.T. scans (HRCT) with varying thicknesses (0.67mm, 1mm, 2mm) demonstrates that the frame containing the tracheal bifurcation can be detected accurately in most cases, with a deviation of ±2 frames in some cases. Similarly, a Windows app is developed for measuring inner airway diameter, artery diameter, BAR, and wall thickness, allowing users to draw bounding around visible discrete B.A. pairs in the RLL region. Measurements of 10 B.A. pairs revealed accurate results comparable to those of a human reader, with deviations of ±0.10-0.15mm observed across all measurements. Additional studies and validation are necessary to consolidate inter- and intra-rater variability and enhance the proposed methods.

Bronchiectasis, one of the most neglected chronic lung conditions, has a high individual disease burden and economic cost and causes poor quality of life in children/adolescents and adults. Advances in image quality and a dramatic reduction in acquisition times, multiple high-resolution chest tomography (HRCT) acquisitions, and reconstructions of the lung have resulted in accurate categorization and determination of the extent of lung parenchyma and airway abnormality. For bronchiectasis, the diagnosis is confirmed using the key feature of abnormally increased broncho-arterial (B.A.) ratio (BAR), with or without other abnormalities, e.g., bronchial wall thickening, lack of bronchial tapering, and mucus plugging. Most of these features require shape analysis of the airway and artery regions to perform various assessments that can have inter-rater variability and are time-consuming. This challenge is amplified in pediatric patients due to age-related anatomical variations. The anatomical differences and variations in airway structures between Infants, Early Childhood, and middle Childhood can impact how the images can be processed and analyzed. To address this, we proposed two novel image-processing methods to detect and measure the B.A. pairs. The first method uses an optimized connected component labelling (CCL) algorithm to construct bounding boxes around the objects (airway, artery) and extract the regions of interest (ROIs) for potential B.A. pairs. The second method allows us to calculate 4 or 6 diameters for each object in the ROIs and use their mean value as the final diameter, demonstrating agreement with manual readings. Evaluating against a diverse set of HRCT scans from various categories validates the significance and practical utility of our proposed methods in detecting and measuring the disjointed B.A. pairs to assess increased BAR.

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Abstract In microbiome fields of study, meta-analyses have proven to be a valuable tool for identifying the technical drivers of variation among studies and results of investigations in several diseases, such as those of the gut and sinuses. Meta-analyses also represent a powerful and efficient approach to leverage existing scientific data to both reaffirm existing findings and generate new hypotheses within the field. However, there are currently limited data in other fields, such as the paediatric respiratory tract, where extension of original data becomes even more critical due to samples often being difficult to obtain and process for a range of both technical and ethical reasons. Performing such analyses in an evolving field comes with challenges related to data accessibility and heterogeneity. This is particularly the case in paediatric respiratory microbiomics — a field in which best microbiome-related practices are not yet firmly established, clinical heterogeneity abounds and ethical challenges can complicate sharing of patient data. Having recently conducted a large-scale, individual participant data meta-analysis of the paediatric respiratory microbiota (n = 2624 children from 20 studies), we discuss here some of the unique barriers facing these studies and open and invite a dialogue towards future opportunities. Video Abstract

Abstract Introduction Pulmonary rehabilitation is recommended for people with bronchiectasis. Various education topics are included in these programmes, but the content is largely guided by the needs of people with other respiratory conditions. Objectives With the education topics applicable to people with bronchiectasis unclear, we aimed to explore the perspective of adults with this condition on relevant educational topics in a pulmonary rehabilitation context. Methods Participants from the Australian Bronchiectasis Registry were invited to undertake a semi‐structured interview. Interview transcripts were coded independently, with themes established by consensus (two researchers). Results Twenty‐one people participated. The major themes were greater clarity on the underlying cause of bronchiectasis and prognosis. Most sought knowledge about self‐management strategies and treatments to address extra‐pulmonary symptoms. Participants requested more information on physiotherapy options and the role of exercise and physical activity outside of pulmonary rehabilitation. Preferences were mixed for the education delivery model. Conclusions We have identified unmet educational topics of interest for people with bronchiectasis. Our study provides a framework for education topics desired by adults with bronchiectasis within a pulmonary rehabilitation setting. The topics identified will guide development of an education curriculum for pulmonary rehabilitation that is more fit‐for‐purpose for people with bronchiectasis.

Abstract Background In children, chronic wet cough may be a sign of underlying lung disease, including protracted bacterial bronchitis (PBB) and bronchiectasis. Chronic (> 4 weeks in duration) wet cough (without indicators pointing to alternative causes) that responds to antibiotic treatment is diagnostic of PBB. Timely recognition and management of PBB can prevent disease progression to irreversible bronchiectasis with lifelong consequences. However, detection and management require timely health-seeking by carers and effective management by clinicians. We aim to improve (a) carer health-seeking for chronic wet cough in their child and (b) management of chronic wet cough in children by clinicians. We hypothesise that implementing a culturally integrated program, which is informed by barriers and facilitators identified by carers and health practitioners, will result in improved lung health of First Nations children, and in the future, a reduced the burden of bronchiectasis through the prevention of the progression of protracted bacterial bronchitis to bronchiectasis. Methods This study is a multi-centre, pseudorandomised, stepped wedge design. The intervention is the implementation of a program. The program has two components: a knowledge dissemination component and an implementation component. The implementation is adapted to each study site using a combined Aboriginal Participatory Action Research and an Implementation Science approach, guided by the Consolidated Framework of Implementation Research. There are three categories of outcome measures related to (i) health (ii) cost, and (iii) implementation. We will measure health-seeking as the proportion of parents seeking help for their child in a 6-month period before the intervention and the same 6-month period (i.e., the same six calendar months) thereafter. The parent-proxy, Cough-specific Quality of Life (PC-QoL) will be the primary health-related outcome measure. Discussion We hypothesise that a tailored intervention at each site will result in improved health-seeking for carers of children with a chronic wet cough and improved clinician management of chronic wet cough. In addition, we expect this will result in improved lung health outcomes for children with a chronic wet cough. Trial registration Australian New Zealand Clinical Trials Registry; ACTRN12622000430730 , registered 16 March 2022, Retrospectively registered.

BackgroundBronchiectasis 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.MethodsParticipants 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.ResultsOne 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.ConclusionThis 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.

Abstract Background Globally, bronchiectasis (BE) unrelated to cystic fibrosis (CF) is recognized as a major cause of respiratory morbidity, mortality, and healthcare utilization. Children with BE regularly experience exacerbations of their condition resulting in frequent hospitalizations and decreased health-related quality of life (HR-QoL). Guidelines for the treatment and management of BE call for regular exercise as a means of improving aerobic fitness and HR-QoL. Moreover, research in adults with BE has shown that exercise can reduce the frequency of exacerbations, a potent predictor of future lung function decline and respiratory morbidity. Yet, to date, the health benefits resulting from therapeutic exercise have not been investigated in children with BE. The BREATH, Bronchiectasis - Exercise as Therapy, trial will test the efficacy of a novel 8-week, play-based therapeutic exercise program to reduce the frequency of acute exacerbations over 12 months in children with BE (aged ≥ 4 and < 13 years). Secondary aims are to determine the cost-effectiveness of the intervention and assess the program’s impact on aerobic fitness, fundamental movement skill (FMS) proficiency, habitual physical activity, HR-QoL, and lung function. Methods This multi-center, observer-blinded, parallel-group (1:1 allocation), randomized controlled trial (RCT) will be conducted at three sites. One hundred and seventy-four children ≥ 4 and < 13 years of age with BE will be randomized to a developmentally appropriate, play-based therapeutic exercise program (eight, 60-min weekly sessions, supplemented by a home-based program) or usual care. After completing the baseline assessments, the number of exacerbations and secondary outcomes will be assessed immediately post-intervention, after 6 months of follow-up, and after 12 months of follow-up. Monthly, parental contact and medical review will document acute respiratory exacerbations and parameters for cost-effectiveness outcomes. Discussion The BREATH trial is the first fully powered RCT to test the effects of a therapeutic exercise on exacerbation frequency, fitness, movement competence, and HR-QoL in children with bronchiectasis. By implementing a developmentally appropriate, play-based exercise program tailored to the individual needs of children with bronchiectasis, the results have the potential for a major paradigm shift in the way in which therapeutic exercise is prescribed and implemented in children with chronic respiratory conditions. The exercise program can be readily translated. It does not require expensive equipment and can be delivered in a variety of settings, including the participant’s home. The program has strong potential for translation to other pediatric patient groups with similar needs for exercise therapy, including those with obesity, childhood cancers, and neurological conditions such as cerebral palsy. Trial registration Australian and New Zealand Clinical Trials Register (ANZCTR) ACTRN12619001008112

Abstract Background First Nations children hospitalised with acute lower respiratory infections (ALRIs) are at increased risk of future bronchiectasis (up to 15–19%) within 24-months post-hospitalisation. An identified predictive factor is persistent wet cough a month after hospitalisation and this is likely related to protracted bacterial bronchitis which can progress to bronchiectasis, if untreated. Thus, screening for, and optimally managing, persistent wet cough one-month post-hospitalisation potentially prevents bronchiectasis in First Nations’ children. Our study aims to improve the post-hospitalisation medical follow-up for First Nations children hospitalised with ALRIs and thus lead to improved respiratory health. We hypothesize that implementation of a strategy, conducted in a culturally secure manner, that is informed by barriers and facilitators identified by both parents and health care providers, will improve medical follow-up and management of First Nations children hospitalized with ALRIs. Methods Our trial is a multi-centre, pseudo-randomized stepped wedge design where the implementation of the strategy is tailored for each study site through a combined Participatory Action Research and implementation science approach informed by the Consolidated Framework of Implementation Research. Outcome measures will consist of three categories related to (i) health, (ii) economics and (iii) implementation. The primary outcome measure will be Cough-specific Quality of Life (PC-QoL). Outcomes will be measures at each study site/cluster in three different stages i.e., (i) nil-intervention control group, (ii) health information only control group and (iii) post-intervention group. Discussion If our hypothesis is correct, our study findings will translate to improved health outcomes (cough related quality of life) in children who have persistent wet cough a month after hospitalization for an ALRI. Trial registration ACTRN12622000224729, prospectively registered 8 February 2022, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382886&isReview=true .

Abstract The purpose of this paper is to highlight a perspective for decolonizing research with Australian First Nations and provide a framework for successful and sustained knowledge translation by drawing on the recent work conducted by a research group, in five remote communities in North-Western Australia. The perspective is discussed in light of national and international calls for meaningful and dedicated engagement with First Nations people in research, policy and practice, to help close the health gap between First Nations and other Australians.

BackgroundCurrent bronchiectasis management guidelines recommend regular physical activity but a large proportion of children with bronchiectasis do not meet public health recommendations which call for 60 min or more of moderate-to-vigorous intensity physical activity daily. Knowing the factors that influence physical activity in children with bronchiectasis is necessary for the development of effective interventions to increase physical activity in this patient group. The objective of this study was to identify facilitators and barriers to physical activity in children with bronchiectasis unrelated to cystic fibrosis (CF) from the perspectives of children and their parents.Materials and methodsThis was a qualitative study informed by the theoretical domains framework (TDF). Children aged 7–15 years (8.8 years, 8.4–11.0) (median, interquartile range) and parents (45.8 years, 39.7–48.3) completed separate, semi-structured interviews (n = 21). Recordings were transcribed verbatim, and barriers and facilitators related to each TDF domain deductively coded. Emergent themes were inductively derived via consensus moderation.ResultsFrom the perspectives of children, fun with friends, organized sport and activities, and family co-participation in physical activity emerged as facilitators. Inability to keep up with their peers and time on technology emerged as barriers. From the perspectives of parents, instrumental and logistic support for physical activity and supportive social and physical activity environments emerged as facilitators, while management of symptoms associated with bronchiectasis emerged as a barrier.ConclusionPrograms to increase physical activity in children with bronchiectasis should be fun, accessible, provide opportunities for social interaction and address barriers related to exercise tolerance, perceived competence, and presence of respiratory symptoms.

The global burden of bronchiectasis in children and adolescents is being recognised increasingly. However, marked inequity exists between, and within, settings and countries for resources and standards of care afforded to children and adolescents with bronchiectasis compared with those with other chronic lung diseases. The European Respiratory Society (ERS) clinical practice guideline for the management of bronchiectasis in children and adolescents was published recently. Here we present an international consensus of quality standards of care for children and adolescents with bronchiectasis based upon this guideline. The panel used a standardised approach that included a Delphi process with 201 respondents from the parents and patients’ survey, and 299 physicians (across 54 countries) who care for children and adolescents with bronchiectasis. The seven quality standards of care statements developed by the panel address the current absence of quality standards for clinical care related to paediatric bronchiectasis. These internationally derived, clinician-, parent- and patient-informed, consensus-based quality standards statements can be used by parents and patients to access and advocate for quality care for their children and themselves, respectively. They can also be used by healthcare professionals to advocate for their patients, and by health services as a monitoring tool, to help optimise health outcomes.

BackgroundIn the absence of randomized controlled trials (RCTs) on the benefits of therapeutic exercise programs involving children with bronchiectasis, we undertook a pilot RCT to evaluate the effects of a play-based therapeutic exercise program on fundamental movement skill (FMS) proficiency. The effects of the program on cardiorespiratory fitness, perceived competence, and health-related quality of life (HR-QoL) were examined as secondary outcomes.MethodsChildren [median (IQR) age: 6.8 (5.3–8.8) years] with bronchiectasis unrelated to cystic fibrosis were randomized to a 7-week therapeutic exercise program (n = 11) or wait-list control (n = 10). The exercise program comprised 7 × 60-min weekly sessions and was supplemented by a home-based program 2-days/week. Participants were assessed on: FMS (locomotor and object control skills) using the Test of Gross Motor Development 2nd Edition (TGMD-2); cardiovascular fitness by calculating the percent change in heart rate (%ΔHR) from rest to completion of the first stage of a submaximal treadmill test; perceived competence using Harter’s athletic competence subscale; and QoL with the PedsQL.ResultsSignificant group by time interactions were observed for locomotor and object control skills. Children completing the therapeutic exercise program exhibited significant improvements in both locomotor (pre 29.0 ± 2.0, post 35.2 ± 2.2, p = 0.01) and object control (pre 27.0 ± 2.0, post 35.5 ± 2.2, p = 0.01) skills, with no significant change in controls (pre 31.6 ± 2.1, post 31.8 ± 2.3 and pre 31.0 ± 2.1, post 32.3 ± 2.3, respectively). Among children completing the program, %ΔHR declined by 6% points, while %ΔHR declined only marginally among controls (0.9% points), but the group by time interaction was not statistically significant. The program had a small positive impact on competence perceptions (Cohen’s d = 0.2) and HR-QoL (Cohen’s d = 0.3).ConclusionThis pilot RCT provides preliminary evidence for the efficacy of a play-based therapeutic exercise program to improve proficiency in FMS and fitness in children with bronchiectasis. The results are sufficiently positive to warrant conducting a larger RCT testing the efficacy of the exercise program in children with bronchiectasis and/or other chronic respiratory conditions.

Abstract Background Bronchiectasis is a major contributor to respiratory morbidity and healthcare utilization in children. Children with bronchiectasis exhibit low levels of physical activity (PA) and poor fundamental movement skills (FMS) may be a contributing factor. However, there are no data on FMS’s in this population. The current study assessed FMS proficiency in children with bronchiectasis and examined associations with objectively measured PA. Methods Forty-six children with bronchiectasis (mean age 7.5 ± 2.6 year, 63% Male) were recruited from the Queensland Children’s Hospital, Brisbane. PA was measured using the ActiGraph GT3X + accelerometer. Raw accelerometer data were processed into daily time spent in sedentary activities, light-intensity activities and games, walking, running, and moderate-to-vigorous activities and games using a random forest (RF) PA classification algorithm specifically developed for children. Daily MVPA was calculated by summing time spent in walking, running, and moderate-to-vigorous activities and games. FMS were assessed using the Test of Gross Motor Development 2nd Edition (TGMD-2). Results Fewer than 5% of children demonstrated mastery in the run, gallop, hop, and leap; while fewer than 10% demonstrated mastery for the two-handed strike, overarm throw, and underarm throw. Only eight of the 46 children (17.4%) achieved their age equivalency for locomotor skills, while just four (8.7%) achieved their age equivalency for object control skills. One-way ANCOVA revealed that children achieving their age equivalency for FMS had significantly higher levels of MVPA than children not achieving their age equivalency (51.7 vs 36.7 min/day). When examined by the five activity classes predicted by the RF algorithm, children achieving their age equivalency exhibited significantly greater participation moderate-to-vigorous intensity activities and games (22.1 vs 10.7 min/day). No significant differences were observed for sedentary activities, light-intensity activities and games, walking, and running. Conclusion Children with bronchiectasis exhibit significant delays in their FMS development. However, those who meet their age equivalency for FMS proficiency participate in significantly more daily MVPA than children who do not meet their age-equivalency. Therapeutic exercise programs designed to improve FMS proficiency are thus likely to be beneficial in this population.

BackgroundAmong 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.MethodsIn 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.ResultsHealth 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].ConclusionThe 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.

Chronic cough is a common symptom of many underlying respiratory and non-respiratory disorders and may be associated with less serious causes, such as gastroesophageal reflux and nasal diseases. Chronic cough in children differs from that in adults with respect to its etiologies and management since it can indicate a symptom of an underlying disease in children. Guidelines for managing chronic cough in children are based on recording the history, followed by physical examination, chest radiography, and spirometry. Thus, taking accurate respiratory history for coughing helps delineate the pathophysiological basis of the cause of chronic cough. Detailed history taking enhances the evaluation and treatment, and facilitates a tailored diagnostic identification of likely diagnoses. While studies have described evidence-based red flags in children with chronic cough, the value of skilled physicians regarding history taking has received less attention for the best patient care. In the present article, we outline the major questions comprising a detailed history taking for chronic cough in children.

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

Exhaled nitric oxide fraction (FENO) values can be easily measured using portable analysers and are a surrogate marker of airway eosinophilia. FENO may be useful in diagnosing and monitoring conditions characterised by airway eosinophilia, i.e. asthma and possibly COPD. Many factors other than asthma and COPD affect FENO, especially atopy, which is associated with elevated FENO. One guideline recommends that FENO should be used as part of the diagnostic pathway for asthma diagnosis in adults and children aged >5 years. The role of FENO in monitoring asthma is even less clear, and most guidelines do not recommend its use outside of specialist asthma clinics. Currently, FENO is not recommended for diagnosis or monitoring of COPD. Although FENO is starting to find a place in the management of asthma in children and adults, considerably more research is required before the potential of FENO as an objective measurement in asthma and COPD can be realised. Key points For individuals aged ≥12 years, FENO is not recommended by all guidelines as a test to diagnose asthma (recommended only by the UK National Institute for Health and Care Excellence guideline for asthma symptoms, which are likely to respond to corticosteroid treatment). FENO may be used in conjunction with other investigations to diagnose asthma in 5–16-year-olds where there is diagnostic uncertainty, but further evidence is required. FENO is not recommended as a routine test to monitor all patients with asthma or to titrate asthma treatment. FENO is not recommended for routine clinical testing in adults with COPD. FENO may be useful to identify patients with COPD who could benefit from the use of inhaled corticosteroids (asthma–COPD overlap). Educational aims To understand what factors other than asthma and COPD affect FENO To understand the current controversies in the application of FENO to diagnosis and management of asthma in children To understand the current controversies in the application of FENO to diagnosis and management of asthma and COPD in adults

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

Bronchiectasis, characterised by chronic wet/productive cough with recurrent respiratory exacerbations and abnormal bronchial dilatation on computed tomography scans, remains an increasingly recognised but often neglected chronic pulmonary disorder in children and adolescents. An early diagnosis combined with optimal management offers the prospect, at least in some patients, of curing a condition previously considered irreversible. However, unlike in adults, until now no international paediatric guidelines existed. The recently published European Respiratory Society clinical practice guidelines for the management of children and adolescents with bronchiectasis attempts to address this clinical information gap. The guidelines were formulated by panel members comprised of experts from several relevant health fields, the European Lung Foundation and parents of children with bronchiectasis. Systematic reviews and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach guided the nature and strength of recommendations. The recommendations are grouped into clinically relevant topics: diagnosis, evaluating for underlying causes, defining exacerbations, management, systematic care, monitoring, reversibility and prevention. The guidelines seek to achieve: 1) optimal lung growth, 2) preserved lung function, 3) enhanced quality of life, 4) minimal exacerbations, 5) few or no complications, and 6) if possible, reversal of lung injury for each child/adolescent with bronchiectasis. This review presents example cases that highlight the recommendations of the clinical practice guidelines. Educational aims This article is intended for those involved in caring for children/adolescents with bronchiectasis. It aims to inform: Clinicians of the European Respiratory Society recommendations for the diagnosis and management of children/adolescents with bronchiectasis. Adolescents and parents of children/adolescents with bronchiectasis of these recommendations, so as to assist discussions with healthcare teams and help facilitate access to appropriate care.

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.

Abstract 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

Abstract Background Bronchiectasis is a major contributor to respiratory morbidity and health care utilization in children and youth. Current treatment guidelines for bronchiectasis recommend participation in regular physical activity (PA) to improve aerobic fitness and quality of life (QoL). However, no previous study has assessed physical activity and sedentary behavior in this patient group, and the extent to which children with bronchiectasis meet guidelines for PA is unknown. In the absence of such data, we objectively measured the PA of children with bronchiectasis and compared them to current guidelines. Methods Forty-six children with bronchiectasis between 4 to 14 years (mean age 7.5 ± 2.6 years) were recruited from the Queensland Children’s Hospital, Brisbane. Daily time in sedentary, light, and moderate-to-vigorous PA (MVPA) was measured objectively over 7 days using the ActiGraph GT3X+ accelerometer and compared their values to current guidelines (minimum 60 min of MVPA daily). Compliance with the daily guideline and average daily steps counts were compared to normative data from two population–based health surveys of healthy children. Results We had complete measurements from 36 children. On average, they accumulated 48.6 min of MVPA daily and were sedentary for ~ 7 h/day. There was no statistical difference in these values between sexes or weekdays vs. weekends. Only 2 (5.6%) children met the 60-min daily MVPA recommendation compared to 42.1% of healthy children. Children with bronchiectasis accumulated 8229 steps/day (boys: 8422 ± SD 473, girls: 8037 ± 594), well below the recommended 12,000 steps/day. In comparison, daily step counts in healthy children ranged from 11,500–14,500 steps/day. Conclusion Children with bronchiectasis are insufficiently active for health benefit and would substantially benefit from programs to promote PA and reduce sedentary behavior.

Aims: To determine how respiratory pediatricians across Australia and New Zealand prescribe azithromycin for children with chronic wet cough, including recurrent protracted bacterial bronchitis, chronic suppurative lung disease (CSLD) and bronchiectasis.Methods: A prospective web-based questionnaire was emailed to members of the Pediatric Special Interest Group of the Thoracic Society of Australia and New Zealand (TSANZ) between April and May 2018. It comprised eight demographic and 15 clinically focused questions.Results: Of the 73 respiratory pediatricians listed across Australia and New Zealand, 29 (40%) responded and all prescribed azithromycin for chronic wet cough. Twelve (41%) indicated that they would consider prescribing a short-course (2–4 weeks) of azithromycin for children with a chronic wet cough. Although most respondents reported prescribing long-term (>4-weeks) azithromycin for either CSLD (n = 23, 79%) or bronchiectasis (n = 24, 83%), only nine (31%) respondents would commence treatment if in the previous 12-months these children experienced three non-hospitalized exacerbations and just 12 (41%) would do so if there had been two hospitalisations for severe exacerbations during the same period in accordance with the TSANZ national guidelines. A lower threshold for prescribing azithromycin was described for Indigenous children or if co-morbidities were present. None prescribed azithromycin for >24-months. Macrolide-resistance was reported in Streptococcus pneumoniae and Staphylococcus aureus.Conclusion: Although Australian and New Zealand respiratory pediatricians in this survey prescribed azithromycin for chronic wet cough most often in children with either CSLD or bronchiectasis, many did so outside the current national guidelines. Reasons for this need exploring.

Background and Objective: Data on the predictors of chronic cough development in young children are scarce. Our primary objective was to examine the factors associated with young children developing a chronic cough, with a focus on childcare attendance.Methods: A secondary analysis of data collected in a prospective cohort study of children presenting to three emergency departments and three primary healthcare centers in southeast Queensland, Australia. Eligible children where those aged

We aimed to determine the efficacy of the 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to

Background Chronic wet cough, the most common symptom of a disease spectrum that encompasses protracted bacterial bronchitis (PBB) and bronchiectasis, is common among Aboriginal children. In the absence of any community prevalence data, and with the high burden of respiratory disease and the European Respiratory Society task force's recommendation to identify disease burden, we determined the prevalence of chronic wet cough and PBB in young Aboriginal children in four remote communities in north Western Australia. Methods A whole-population, prospective study was conducted. Aboriginal children aged ≤7 years were clinically assessed for chronic wet cough by paediatric respiratory clinicians between July 2018 and May 2019. Where children had a wet cough but parents reported a short or uncertain cough duration, children were followed up 1 month later. A medical record audit 6 weeks to 3 months later was used to determine those children with chronic wet cough who had PBB (based on response to antibiotics). Results Of the 203 children, 191 (94%; median age 3.5 years, range 0–7 years) were enrolled. At the initial visit, chronic wet cough was present in 21 (11%), absent in 143 (75%) and unknown in 27 (14%). By follow-up, the total prevalence of chronic wet cough was 13% (95% CI 8–19%) and 10% (95% CI 7–17%) for PBB. Chronic wet cough was more common in the two communities with unsealed roads (19%) compared to the two with sealed roads (7%). Conclusion Given the relatively high prevalence, strategies to address reasons for and treatment of chronic wet cough and PBB in young Aboriginal children in remote north Western Australia are required.

Abstract Background Culture-independent sequencing methods are increasingly used to investigate the microbiota associated with human mucosal surfaces, including sites that have low bacterial load in healthy individuals (e.g. the lungs). Standard microbiota methods developed for analysis of high bacterial load specimens (e.g. stool) may require modification when bacterial load is low, as background contamination derived from sterile laboratory reagents and kits can dominate sequence data when few bacteria are present. Main body Bacterial load in respiratory specimens may vary depending on the specimen type, specimen volume, the anatomic site sampled and clinical parameters. This review discusses methodological issues inherent to analysis of low bacterial load specimens and recommends strategies for successful respiratory microbiota studies. The range of methods currently used to process DNA from low bacterial load specimens, and the strategies used to identify and exclude background contamination are also discussed. Conclusion Microbiota studies that include low bacterial load specimens require additional tests to ensure that background contamination does not bias the results or interpretation. Several methods are currently used to analyse the microbiota in low bacterial load respiratory specimens; however, there is scant literature comparing the effectiveness and biases of different methods. Further research is needed to define optimal methods for analysing the microbiota in low bacterial load specimens.

Abstract Objective Haemophilus haemolyticus can be misidentified as nontypeable Haemophilus influenzae (NTHi) due to their phenotypic similarities in microbiological culture. This study aimed to determine the prevalence of misidentified NTHi in respiratory specimens from children living in northern Australia. Results Among respiratory specimens collected in studies between 2010 and 2013, retrospective PCR analysis found that routine culture misidentified H. haemolyticus as NTHi in 0.3% (3/879) of nasal specimens, 25% (14/55) of bronchoalveolar lavage and 40% (12/30) of throat specimens. Therefore, in this population, PCR-based NTHi diagnostics are indicated for throat and bronchoalveolar specimens, but not for nasal specimens.

Abstract Background Respiratory morbidity in Australian Indigenous children is higher than their non-Indigenous counterparts, irrespective of urban or remote residence. There are limited studies addressing acute respiratory illness (ARI) in urban Indigenous children, particularly those that address the upper airway microbiome and its relationship to disease. We aimed to describe the prevalence of upper airway viruses and bacteria in symptomatic and asymptomatic urban-based Australian Indigenous children aged less than 5 years. Methods A cross-sectional analysis of data collected at baseline in an ongoing prospective cohort study of urban Aboriginal and Torres Strait Islander children registered with a primary health care service in the northern suburbs of Brisbane, Australia. Clinical, demographic and epidemiological data and bilateral anterior nasal swabs were collected on enrolment. Polymerase chain reaction was performed on nasal swabs to detect 17 respiratory viruses and 7 bacteria. The primary outcome was the prevalence of these microbes at enrolment. Logistic regression was performed to investigate differences in microbe prevalence between children with and without acute respiratory illness with cough as a symptom (ARIwC) at time of specimen collection. Results Between February 2013 and October 2015, 164 children were enrolled. The median age at enrolment was 18.0 months (IQR 7.2–34.3), 49.4% were boys and 56 children (34.2%) had ARIwC. Overall, 133/164 (81%) nasal swabs were positive for at least one organism; 131 (79.9%) for any bacteria, 59 (36.2%) for any virus and 57 (34.8%) for both viruses and bacteria. Co-detection of viruses and bacteria was more common in females than males (61.4% vs 38.6%, p = 0.044). No microbes, alone or in combination, were significantly associated with the presence of ARIwC. Conclusions The prevalence of upper airways microbes in asymptomatic children is similar to non-Indigenous children with ARIwC from the same region. Determining the aetiology of ARIwC in this community is complicated by the high prevalence of multiple respiratory pathogens in the upper airways. Study registration Australia New Zealand Clinical Trial Registry Registration Number: 12,614,001,214,628. Retrospectively registered.

The causes of chronic cough in children are mainly dependent on the setting and age of the child. Protracted bacterial bronchitis is a frequent cause of morbidity in childhood, and antibiotic treatment is beneficial. Prompt recognition and early treatment is important both to prevent inappropriate use of asthma medications and also progression to bronchiectasis, but the diagnosis should not be made uncritically, because chronic wet cough is not necessarily due to lower airway disease. Upper Airway Cough Syndrome (UACS) is considered by some to cause chronic cough in childhood. Underlying UACS are many common conditions, including allergic rhinitis, adenoiditis and rhinosinusitis. Diagnosis relies on a combination of clinical criteria that are relatively sensitive but non-specific. The role of nasal endoscopy in children with chronic cough and signs suggesting UACS is unclear. Nasal saline solution irrigation is commonly used in UACS, but most studies have methodological biases, and efficacy data are scanty. Randomized controlled trials are urgently required. However, if saline washes, rather than oral antibiotics, can effectively treat some children with wet cough associated with upper airway conditions, antibiotic resistance could potentially be reduced. There is a need to further study wet cough and not to assume it to be equivalent to lower airway infection in all children.

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.

Non-typeable Haemophilus influenzae (NTHi), an opportunistic pathogen of the upper airways of healthy children, can infect the lower airways, driving chronic lung disease. However, the molecular basis underpinning NTHi transition from a commensal to a pathogen is not clearly understood. Here, we performed comparative genomic and transcriptomic analyses of 12 paired, isogenic NTHi strains, isolated from the nasopharynx (NP) and bronchoalveolar lavage (BAL) of 11 children with chronic lung disease, to identify convergent molecular signatures associated with lung adaptation. Comparative genomic analyses of the 12 NP-BAL pairs demonstrated that five were genetically identical, with the remaining seven differing by only 1 to 3 mutations. Within-patient transcriptomic analyses identified between 2 and 58 differentially expressed genes in 8 of the 12 NP-BAL pairs, including pairs with no observable genomic changes. Whilst no convergence was observed at the gene level, functional enrichment analysis revealed significant under-representation of differentially expressed genes belonging to Coenzyme metabolism, Function unknown, Translation, ribosomal structure, and biogenesis Cluster of Orthologous Groups categories. In contrast, Carbohydrate transport and metabolism, Cell motility and secretion, Intracellular trafficking and secretion, and Energy production categories were over-represented. This observed trend amongst genetically unrelated NTHi strains provides evidence of convergent transcriptional adaptation of NTHi to pediatric airways that deserves further exploration. Understanding the pathoadaptative mechanisms that NTHi employs to infect and persist in the lower pediatric airways is essential for devising targeted diagnostics and treatments aimed at minimizing disease severity, and ultimately, preventing NTHi lung infections and subsequent chronic lung disease in children.

Introduction: Acute respiratory infections with cough (ARIwC) contribute considerably to childhood morbidity, yet few studies have examined the cost of these illnesses among Australian children. Moreover, of the few studies that have, none are inclusive of Aboriginal and/or Torres Strait Islander children, despite this population experiencing a greater burden of respiratory illnesses. This study aimed to determine the costs of ARIwC among urban Aboriginal and/or Torres Strait Islander children from the perspective of caretakers, the public healthcare system, and employers.Methods: This cost of illness study used data collected from Aboriginal and/or Torres Strait Islander children aged

Abstract Background To evaluate immunisation coverage, timeliness and predictors of delayed receipt in urban Australian Indigenous children during the first 18 months of life. Methods Cross-sectional retrospective analysis of data collected from 140 Australian Indigenous children aged

Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p

BackgroundAcute respiratory illnesses with cough (ARIwC) are predominant causes of morbidity in Australian Indigenous children; however, data on disease burden in urban communities are scarce. This study aimed to determine the incidence of ARIwC, the predictors of recurrent (≥4 episodes) ARIwC, and development of chronic cough following an ARIwC in urban, predominantly Indigenous, children aged 4 weeks. Children who developed chronic cough were reviewed by a pediatric pulmonologist. Incidence densities per child-month of observation were calculated and predictors of recurrent ARIwC and chronic cough were evaluated in logistic regression models.ResultsBetween February 2013 and November 2015, 200 children were enrolled; median age of 18.1 months, range (0.7–59.7 months) and 90% identified as Indigenous. A total of 1,722 child-months of observation were analyzed (mean/child = 8.58, 95% CI 8.18–9.0). The incidence of ARIwC was 24.8/100 child-months at risk (95% CI 22.3–27.5). Twenty-one children (10.5%) experienced recurrent ARIwC. Chronic cough was identified in 70/272 (25.7%) episodes of ARIwC. Predictors of recurrent ARIwC were presence of eczema, mold in the house, parent/carer employment status, and having an Aboriginal and Torres Strait Islander mother/non-Aboriginal and Torres Strait Islander father (compared to both parents being Aboriginal and Torres Strait Islander). Predictors of chronic cough included being aged 4 weeks duration, having an Aboriginal and Torres Strait Islander mother/non-Aboriginal and Torres Strait Islander father (compared to both parents being Aboriginal and Torres Strait Islander), and a low income. Of those with chronic cough reviewed by a pediatric pulmonologist, a significant underlying disorder was found in 14 children (obstructive sleep apnea = 1, bronchiectasis = 2, pneumonia = 2, asthma = 3, tracheomalacia = 6).DiscussionThis community of predominantly Aboriginal and Torres Strait Islander and socially disadvantaged children bear a considerable burden of ARIwC. One in 10 children will experience more than three episodes over a 12-month period and 1 in five children will develop chronic cough post ARIwC, some with a serious underlying disorder. Further larger studies that include a broader population base are needed.

Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3+ T cells and CD56+ NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.

We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)–specific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology.

BACKGROUNDTracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP), and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy).OBJECTIVESTo evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary) tracheomalacia.METHODSSearchThe Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Group's Specialized Register, Medline and Embase databases. The Cochrane Airways Group performed the latest searches in March 2012.Selection criteriaAll randomized controlled trials (RCTs) of therapies related to symptoms associated with primary or intrinsic tracheomalacia.Data collection and analysisTwo reviewers extracted data from the included study independently and resolved disagreements by consensus.MAIN RESULTSWe included one RCT that compared nebulized recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analyzed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulized rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulized rhDNase but did not reach levels of significance.AUTHORS' CONCLUSIONSThere is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulized rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.

BACKGROUNDTracheomalacia, a disorder of the large airways where the trachea is deformed or malformed during respiration, is commonly seen in tertiary paediatric practice. It is associated with a wide spectrum of respiratory symptoms from life-threatening recurrent apnoea to common respiratory symptoms such as chronic cough and wheeze. Current practice following diagnosis of tracheomalacia includes medical approaches aimed at reducing associated symptoms of tracheomalacia, ventilation modalities of continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP), and surgical approaches aimed at improving the calibre of the airway (airway stenting, aortopexy, tracheopexy).OBJECTIVESTo evaluate the efficacy of medical and surgical therapies for children with intrinsic (primary) tracheomalacia.METHODSSearchThe Cochrane Airways Group searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Airways Group's Specialized Register, Medline and Embase databases. The Cochrane Airways Group performed the latest searches in March 2012.Selection criteriaAll randomized controlled trials (RCTs) of therapies related to symptoms associated with primary or intrinsic tracheomalacia.Data collection and analysisTwo reviewers extracted data from the included study independently and resolved disagreements by consensus.MAIN RESULTSWe included one RCT that compared nebulized recombinant human deoxyribonuclease (rhDNase) with placebo in 40 children with airway malacia and a respiratory tract infection. We assessed it to be a RCT with overall low risk of bias. Data analyzed in this review showed that there was no significant difference between groups for the primary outcome of proportion cough-free at two weeks (odds ratio (OR) 1.38; 95% confidence interval (CI) 0.37 to 5.14). However, the mean change in night time cough diary scores significantly favoured the placebo group (mean difference (MD) 1.00; 95% CI 0.17 to 1.83, P = 0.02). The mean change in daytime cough diary scores from baseline was also better in the placebo group compared to those on nebulized rhDNase, but the difference between groups was not statistically significant (MD 0.70; 95% CI -0.19 to 1.59). Other outcomes (dyspnoea, and difficulty in expectorating sputum scores, and lung function tests at two weeks also favoured placebo over nebulized rhDNase but did not reach levels of significance.AUTHORS' CONCLUSIONSThere is currently an absence of evidence to support any of the therapies currently utilised for management of intrinsic tracheomalacia. It remains inconclusive whether the use of nebulized rhDNase in children with airway malacia and a respiratory tract infection worsens recovery. It is unlikely that any RCT on surgically based management will ever be available for children with severe life-threatening illness associated with tracheomalacia. For those with less severe disease, RCTs on interventions such as antibiotics and chest physiotherapy are clearly needed. Outcomes of these RCTs should include measurements of the trachea and physiological outcomes in addition to clinical outcomes.