Radiographic Outcomes in Pediatric Bronchiectasis and Factors Associated with Reversibility.

Rationale: Conventionally considered irreversible, bronchiectasis has been demonstrated to be reversible in children in small studies. However, the factors associated with radiographic reversibility of bronchiectasis have yet to be defined. Objectives: In a large cohort of children with bronchiectasis, we aimed to determine: 1) if and to what extent bronchiectasis is reversible and 2) factors associated with radiographic chest high-resolution computed tomography (cHRCT) resolution. Methods: We identified children with bronchiectasis who had a repeat multidetector cHRCT scan between 2010 and 2021. We excluded those with cystic fibrosis, surgical pulmonary resection, traction bronchiectasis only, or lobar opacification. Measurements and Main Results: cHRCT scans were scored using the modified Reiff score (MRS) with a pediatric correction. Resolution was defined as an absence of abnormal bronchoarterial ratio (>0.8) on the second cHRCT scan. We included 142 children (median age, 5 years; IQR, 2.6-7.4). Inter- and intrarater agreement in MRSs was excellent (weighted κ = 0.83-0.86 and 0.95, respectively). There was radiographic resolution in 57 of 142 patients (40.1%), improvement in 56 of 142 (39.4%), and no change or worsening in 29 of 142 (20.4%). Pseudomonas aeruginosa (PsA) was absolutely associated with a lack of resolution. On multivariable regression, in those without PsA cultured, younger age at the time of diagnosis (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-0.99), lower MRS (RR, 0.89; 95% CI, 0.82-0.97), and lower annual rate of exacerbations requiring intravenous antibiotic therapy (RR, 0.60; 95% CI, 0.37-0.98) increased the likelihood of radiographic resolution. Conclusions: This first large cohort confirms that bronchiectasis in children is often reversible with appropriate management. Younger children and those with lesser radiographic severity at diagnosis were most likely to exhibit radiographic reversibility, whereas those with PsA infection were least likely.

Rasch validation of the short form (8 item) PC-QoL questionnaire and applicability of use as a health state classification system for a new preference-based measure.

BACKGROUND: The parent-proxy paediatric chronic cough quality of life questionnaire (PC-QoL) is a commonly used measure of spillover quality of life in parents of children with chronic cough. To date, spillover health utility in these parents is not routinely estimated largely due to the lack of a suitable instrument. Their perspective is not included in economic evaluations of interventions for their children. We explored developing a health state classification system based on the PC-QoL for measuring health utility spill over in this population. METHODS: This study included PC-QoL 8-item responses of 653 parents participating in a prospective cohort study about paediatric chronic cough. Exploratory factor analysis (EFA) and Rasch analysis were used to examine dimensionality and select potential items and level structure. RESULTS: EFA indicated that the PC-QoL had one underlying domain. Rasch analysis indicated threshold disordering in all items which improved when items were collapsed from seven to four levels. Two demonstrated differential item functioning (DIF) by diagnosis or ethnicity and were excluded from the final scale. This scale satisfied Rasch assumptions of local independence and unidimensionality and demonstrated acceptable fit to the Rasch model. It was presented to and modified by an expert panel and a consumer panel. The resulting classification system had six items, each with four levels. DISCUSSION: The PC-QoL can conform to a Rasch model with minor modifications. It may be a good basis for the classification system of a child cough-specific PBM. A valuation study is required to estimate preference weights for each item and to estimate health utility in parents of children with chronic cough.

European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

Cost of hospitalization for bronchiectasis exacerbation in children.

BACKGROUND AND OBJECTIVE: Despite paediatric bronchiectasis being recognized increasingly worldwide, prior reports of hospitalization costs for bronchiectasis in children are lacking. This study aimed to (i) identify health service costs of hospitalizations and (ii) factors associated with these costs in children admitted to an Australian paediatric hospital following an acute exacerbation of their bronchiectasis. METHODS: Demographic and hospital resource use data were prospectively recorded for 100 hospitalizations in 80 children aged <18 years admitted consecutively to the QCH, Brisbane, Australia. Costs (2016 AUD) were obtained from the hospital's Finance Department. Linear regressions, with bootstrap resampling to quantify uncertainty, were used to estimate factors affecting cost of hospitalization. RESULTS: The 100 hospitalizations (48 males) had a median (IQR) age of 6.04 (4.04-9.85) years. Their mean (SD) LOS was 12.30 (4.60) days. The mean (SD) direct health service cost was AUD 30 182 (13 998) per hospitalization. The greatest contributor to costs was health professional wages, accounting for 70% of the cost per episode. LOS, younger age at admission and number of bronchiectatic lobes affected were associated with higher costs, whilst HITH service was associated with lower cost. The cost to families on average was AUD 2669.50 (SD: 991.50) per hospitalization when accounting for lost wages and opportunity cost. CONCLUSION: The per episode healthcare cost burden of hospitalizations for paediatric bronchiectasis exacerbations is substantial. Interventions that prevent hospitalized exacerbations and reduce severity of childhood bronchiectasis with even moderate effectiveness are likely to result in substantial hospital costs savings.

Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial.

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

Burden and emergency department management of acute cough in children.

AIM: In children presenting to an emergency department (ED) with an acute coughing illness, the aims of this study were to: (i) describe the frequency of doctor visits and medication use; and (ii) describe management and relate it to current evidence-based guidelines. METHODS: This was a cross-sectional study in ED of a major teaching hospital (Royal Children's Hospital, Brisbane, Australia). Participants included 537 children (<15 years) presenting with acute (<2 weeks) cough, with a median age of 2.2 years (interquartile range 1.0-4.0); 61.5% were boys. Hospitalised children and those with asthma, pneumonia or chronic illnesses were excluded. Main outcome measures were: (i) frequency of pre-ED doctor visits and medication use; and (ii) comparison of management to current evidence-based recommendations related to four discharge diagnoses: bronchiolitis, 'wheeze/reactive airway disease (RAD)', croup and 'non-specific acute respiratory illness'. RESULTS: A total of 300 children (55.9%) had seen a doctor prior to their ED presentation, and use of medications pre-ED was high (53.4%). While 93.4% of children with croup were treated in accordance with guidelines, concordance was lower for children with bronchiolitis or 'wheeze/RAD'. The majority of children with a discharge diagnosis of 'wheeze/RAD' (95.6%) received bronchodilators, and 72.7% also received oral corticosteroids but were not diagnosed with asthma. More than half (55.1%) of the children with non-specific acute respiratory illness received medication(s) either prior to or during their ED presentation. CONCLUSIONS: The burden of acute cough-related illnesses in children is high, and there is a need for improved uptake of evidence-based guidelines. In addition, the large number of children diagnosed with 'wheeze/RAD' suggests asthma is likely under-diagnosed in this setting.

Health-resource use and quality of life in children with bronchiectasis: a multi-center pilot cohort study.

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 < 18-years with high-resolution chest computed-tomography confirmed bronchiectasis undergoing management in three pediatric respiratory medical clinics in Darwin and Brisbane, Australia and Auckland, New Zealand. Children with cystic fibrosis or receiving cancer treatment were excluded. Data collected included the frequency of healthcare attendances (general practice, specialists, hospital and/or emergency departments, and other), medication use, work and school/childcare absences for parents/carers and children respectively, and both parent/carer and child reported quality of life and cough severity. RESULTS: Overall, 951 child-months of observation were completed for 85 children (median age 8.7-years, interquartile range 5.4-11.3). The mean (standard deviation) number of exacerbations was 3.3 (2.2) per child-year. Thirty of 264 (11.4%) exacerbation episodes required hospitalization. Healthcare attendance and antibiotic use rates were high (30 and 50 per 100 child-months of observation respectively). A carer took leave from work for 53/236 (22.5%) routine clinic visits. Absences from school/childcare due to bronchiectasis were 24.9 children per 100 child-months. Quality of life scores for both the parent/carer and child were highly-correlated with one another, remained stable over time and were negatively associated with cough severity. CONCLUSIONS: Health resource use in this cohort of children is high, reflecting their severe disease burden. Studies are now needed to quantify the direct and societal costs of disease and to evaluate interventions that may reduce disease burden, particularly hospitalizations.

Paediatric chronic suppurative lung disease: clinical characteristics and outcomes.

UNLABELLED: We describe the clinical, bronchoscopic, bronchoalveolar lavage (BAL) and radiographic characteristics of children whose chronic wet cough did not resolve with oral antibiotics and which led to their hospitalisation for intravenous antibiotics and airway clearance therapy. Between 2010 and 2014, medical chart review identified 22 such children. Their median cough duration was 26 weeks (interquartile range (IQR) 13-52). All received oral antibiotics immediately before their hospitalisation (median 4 weeks; IQR 4-6.5). On chest examination, seven (31 %) children had auscultatory crackles. At bronchoscopy, 9 (41 %) had tracheomalacia, 18 (86 %) demonstrated airway neutrophilia (>15 %) and 12 (57 %) grew Haemophilus influenzae from their BAL fluid. They received intravenous antibiotics (mostly cefotaxime or ceftriaxone) and airway clearance therapy as inpatients (median 12.5 days (IQR 10.8-14). All were cough-free at follow-up. CONCLUSION: The children's BAL characteristics are similar to those with protracted bacterial bronchitis and bronchiectasis, but their poor clinical response to oral antibiotics and non-specific chest CT findings differentiated them from these other two disorders. The findings are consistent with chronic suppurative lung disease. Intravenous antibiotics and airway clearance therapy should therefore be considered in children whose wet cough persists despite 4 weeks of oral antibiotics and where other causes of chronic wet cough are absent. What is known on this topic? • Chronic wet cough not resolving with appropriate antibiotics increases the likelihood of bronchiectasis. • Children with chronic suppurative lung disease (CSLD) have clinical features of bronchiectasis, but lack the radiographic evidence for this diagnosis. WHAT THIS STUDY ADDS: • Children with CSLD have airway neutrophilia and predominantly Haemophilus influenzae in lower airway cultures, similar to children with protracted bacterial bronchitis and bronchiectasis. • Chronic wet cough in CSLD, unresponsive to oral antibiotics, resolves with intravenous antibiotics and airway clearance therapy.

Combination inhaled corticosteroids and long-acting beta2-agonists for children and adults with bronchiectasis.

BACKGROUND: Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis. OBJECTIVES: To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state. SEARCH METHODS: The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013. SELECTION CRITERIA: All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF). DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality. AUTHORS' CONCLUSIONS: In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.

Cough in Protracted Bacterial Bronchitis and Bronchiectasis.

Chronic cough in children is a common condition for which patients seek medical attention, and there are many etiologies. Of the various causes of chronic cough in children, protracted bacterial bronchitis (PBB) is one of the commonest causes, and bronchiectasis is one of the most serious. Together, they lie on different ends of the spectrum of chronic wet cough in children. Cough is often the only symptom present in children with PBB and bronchiectasis. This review highlights the role of cough as a marker for the presence of these conditions, as well as an outcome endpoint for treatment and research.

Ewing's sarcoma of kidney extending into IVC and RA: resection using modified cannulation strategy for CPB.

Ewing's sarcoma of the kidney is a rare tumor. Although renal carcinomas are known to involve the inferior cava, extension of the tumor up to the right atrium is not common. In the majority of cases when the tumor extends into the infrahepatic part of the inferior vena cava, it can be removed from the abdominal approach. Few patients require the use of cardiopulmonary bypass for removal of the tumor in the inferior vena cava and right atrium. The management of patients requiring resection of kidney tumors and right atrial mass is more complicated and requires a team approach consisting of oncosurgeons, cardiac surgeons, and cardiac anesthetists. The resection of the kidney tumor with a mass in the right atrium is usually done concomitantly. The cardiopulmonary bypass cannulation strategy needs to be modified in such cases.

Clinical utility of elective paediatric flexible bronchoscopy and impact on the quality of life: protocol for a single-centre, single-blind, randomised controlled trial.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there are no randomised controlled trials (RCTs) that have examined its benefits (or otherwise).Our primary aim is to determine the impact of FB on the parent-proxy quality-of-life (QoL) scores. Our secondary aims are to determine if undertaking FB leads to (a) change in management and (b) improvement of other relevant patient-reported outcome measures (PROMs). We also quantified the benefits of elective FB (using 10-point Likert scale). We hypothesised that undertaking elective FB will contribute to accurate diagnosis and therefore appropriate treatment, which will in turn improve QoL and will be deemed to be beneficial from patient and doctor perspectives. METHODS AND ANALYSIS: Our parallel single-centre, single-blind RCT (commenced in May 2020) has a planned sample size of 114 children (aged <18 years) recruited from respiratory clinics at Queensland Children's Hospital, Brisbane, Australia. Children are randomised (1:1 concealed allocation) within two strata: age (≤2 vs >2 years) and indication for FB (chronic cough vs other indications) to either (a) early arm (intervention where FB undertaken within 2 weeks) or (b) delayed (control, FB undertaken at usual wait time). Our primary outcome is the difference between groups in their change in QoL at the T2 timepoint when the intervention group has had the FB and the control group has not. Our secondary outcomes are change in management, change in PROMs, adverse events and the Likert scales. ETHICS AND DISSEMINATION: The human research ethics committee of the Queensland Children's Hospital granted ethical clearance (HREC/20/QCHQ/62394). Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation. Results will be disseminated through conference presentations, teaching avenues, workshops, websites and publications. REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12620000610932.

The utility of elective flexible bronchoscopy to improve quality of life and clinical outcomes for children: A systematic review.

INTRODUCTION: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review (SRs) aimed to determine the utility of FB on its impact in clinical decision making and quality of life (QoL). METHODS: We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organization Clinical Trials Registry Platform and Cochrane database of SRs from inception to April 20, 2023. We included SRs and randomized controlled trials (RCTs) that used parallel group design (comparing use of elective FB vs. no FB, or a wait-list approach [early FB vs. usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions. RESULTS: Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our patient, intervention, comparator, outcome measures framework. CONCLUSIONS: There is a paucity of high-quality RCT evidence to support the routine use of elective FB in children with respiratory conditions. However, available retrospective and a single prospective study demonstrate the high utility of FB in the elective pediatric setting. REGISTRATION: PROSPERO CRD42021291305.

Flexible bronchoscopy insufflated and high-flow nasal oxygen pilot trial (BUFFALO protocol pilot trial).

BACKGROUND: Hypoxaemia occurs in approximately 30% of children during anaesthesia for flexible bronchoscopy. High-flow nasal oxygen (HFNO) can prolong safe apnoea time and be used in children with abnormal airways. During flexible bronchoscopy, there is limited evidence if HFNO confers advantages over current standard practice in avoiding hypoxaemia. The aim is to investigate feasibility of HFNO use during anaesthesia for flexible bronchoscopy to reduce frequency of rescue oxygenation and hypoxaemia. METHODS: BUFFALO is a bi-centre, unmasked, randomised controlled, parallel group, protocol for a pilot trial comparing HFNO techniques to standard practice during anaesthesia. Children (n = 81) aged > 37 weeks to 16 years presenting for elective bronchoscopy who fulfil inclusion but not exclusion criteria will be randomised prior to the procedure to HFNO or standard care oxygenation post induction of anaesthesia. Maintenance of anaesthesia with HFNO requires total venous anaesthesia (TIVA) and with standard, either inhalational or TIVA at discretion of anaesthetist in charge of the patient. Outcomes will include the feasibility of recruitment and adherence to trial procedures, acceptability of the intervention of the protocol and completion rates of data collection methods. DISCUSSION: Findings of this trial will determine feasibility to plan for a larger multicentre randomised clinical trial and support the feasibility of the proposed study procedures. TRIAL REGISTRATION: BUFFALO trial was registered with Australia and New Zealand Clinical Trials Registry (TRN12621001635853) on 29 November 2021 and commenced recruitment in May 2022. https://www.anzctr.org.au/ . The primary manuscript will be submitted for publication in a peer-reviewed journal.

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.

Mitral valve replacement in patients of rheumatic heart disease associated with immune thrombocytopenia.

Immune thrombocytopenia in association with rheumatic heart disease is not commonly seen. Surgical management of rheumatic heart disease becomes more challenging in the presence of immune thrombocytopenia. The risk of complications increases manifold and judicious medical management before, during, and after surgery is imperative. We discuss two such cases, the complications we faced and the problems we anticipated before, and their prevention. Both patients were managed without using immunoglobulins or doing splenectomy. The literature on valve replacement in patients of immune thrombocytopenia and the implications of immune thrombocytopenia in the management of patients with rheumatic heart disease is also reviewed.

Excision of a giant lung bulla in a child: Repair of bronchial leaks using redundant bullous wall/membrane.

Large lung bullae are rare in children. We report a rare case of a large bulla in the right lung causing compression of the underlying lung with a shift of the mediastinum to the contralateral side. Excision of the bulla was done and a novel technique was used in the repair of bronchial air leakage sites with part of the bullous wall/membrane. The patient recovered well with re-expansion of the underlying collapsed lung.

Vein of Giacomini can lead to the recurrence of varicosities after endovenous laser ablation of varicose veins.

Endovenous laser ablation is a commonly performed intervention in the treatment of varicose veins. The technique is generally safe and has low complication rates. A case of recurrent varicose veins that had undergone endovenous laser ablation multiple times is reported. The cause of recurrence, in this case, was the vein of Giacomini, the presence of which was probably missed at the time of initial intervention. This case highlights the importance of the vein of Giacomini in causing recurrent varicosities after laser ablation.

Large mediastinal/thoracic benign teratoma presenting with haemoptysis: Report of a case and review of the literature.

The mediastinal teratomas can grow to a large size before becoming symptomatic. The symptoms are usually due to the compression of adjacent structures. A computed tomographic scan of the chest is the investigation of choice for making a provisional diagnosis and planning for further management. Removal of large mediastinal/thoracic teratoma can be associated with various intraoperative and postoperative complications, which can be life-threatening sometimes. We operated on a patient with a large mediastinal mass extending into the right thoracic cavity up to the costo-phrenic angle. The postoperative period was eventful and required judicious intensive care. The patient eventually recovered with conservative treatment. A literature search was done on PubMed using the keywords benign mediastinal teratoma. Case series/original articles published in the last two decades, that is, after the year 2000, were evaluated. As per the review of the literature, the prevalence of benign mediastinal teratoma may be higher in eastern countries. Thoracoscopic surgery is the preferred modality except for cases with adhesions or infiltration into surrounding structures.

Phenotypic Features of Pediatric Bronchiectasis Exacerbations Associated With Symptom Resolution After 14 Days of Oral Antibiotic Treatment.

BACKGROUND: Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations. RESEARCH QUESTION: Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified? STUDY DESIGN AND METHODS: Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis. RESULTS: Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Maori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days. INTERPRETATION: Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au.