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.

Radiographic Outcomes in Paediatric Bronchiectasis and Factors Associated with Reversibility.

RATIONALE: Conventionally considered irreversible, bronchiectasis reversibility in children has been demonstrated in small studies. However, the factors associated with radiographic reversibility in bronchiectasis have yet to be defined. OBJECTIVES: In a large cohort of children with bronchiectasis, we aimed to determine (a) if and to what extent bronchiectasis is reversible and (b) factors associated with radiographic chest high resolution computed tomography (cHRCT) resolution. METHODS: We identified children with bronchiectasis who had a repeat multidetector HRCT between 2010-2021. We excluded those with cystic fibrosis, surgical pulmonary resection, traction bronchiectasis only, or lobar opacification. MAIN RESULTS: cHRCT scans were scored using the modified Reiff-score (MRS) with a paediatric correction. Resolution was defined as absence of abnormal broncho-arterial ratio (>0.8) on the second cHRCT. We included 142 children (median age=5years: IQR 2.6-7.4), Inter- and intra-rater agreement in MRSs was excellent (weighted kappa=0.83-0.86 and 0.95 respectively). Radiographically resolution was documented in 57/142 (40.1%), improved in 56/142 (39.4%), unchanged/worse in 29/142 (20.4%). Pseudomonas aeruginosa (PsA) was absolutely associated with non-resolution. On multivariable regression, in those without PsA cultured, younger age-at-diagnosis (risk ratio (RR)=0.94, 95%CI 0.88-0.99) lower MRS (RR=0.89, 95% CI 0.82-0.97) and lower annual exacerbation rate requiring intravenous antibiotics (RR=0.60, 95%CI 0.37-0.98) increased the likelihood of radiographic resolution. CONCLUSIONS: This first large cohort confirms bronchiectasis in children is often reversible with appropriate management. Younger aged children and those with lesser radiographic severity at diagnosis were most likely to achieve radiographic reversibility whilst those with PsA infection were least likely.

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.

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.

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.

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.

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.

The Economic Burden of Bronchiectasis: A Systematic Review.

BACKGROUND: Bronchiectasis, a previously neglected condition, now has renewed research interest. There are a few systematic reviews that have reported on the economic and societal burden of bronchiectasis in adults, but none have reported on children. We undertook this systematic review to estimate the economic burden of bronchiectasis in children and adults. RESEARCH QUESTION: What is the health care resource utilization and economic burden of bronchiectasis in adults and children? STUDY DESIGN AND METHODS: We performed a systematic review identifying publications from Embase, PubMed, Web of Science, Cochrane (trials, reviews, and editorials), and EconLit about the economic burden and health care utilization in adults and children with bronchiectasis between January 1, 2001, and October 10, 2022. We used a narrative synthesis approach and estimated aggregate costs for several countries. RESULTS: We identified 53 publications reporting on the economic burden and/or health care utilization of people with bronchiectasis. Total annual health care costs per adult patient ranged from 2021 $3,579 to $82,545 USD and were predominantly driven by hospitalization costs. Annual indirect costs including lost income because of illness (reported in only five studies) ranged from $1,311 to $2,898 USD. Total health care costs in children with bronchiectasis were $23,687 USD annually in the one study that estimated them. Additionally, one publication found that children with bronchiectasis missed 12 school days per year. We estimated aggregate annual health care costs for nine countries, ranging from $101.6 million per year in Singapore to $14.68 billion per year in the United States. We also estimated the aggregate cost of bronchiectasis in Australian children to be $17.77 million per year. INTERPRETATION: This review highlights the substantial economic burden of bronchiectasis for patients and health systems. To our knowledge, it is the first systematic review to include the costs for children with bronchiectasis and their families. Future research to examine the economic impact of bronchiectasis in children and economically disadvantaged communities, and to further understand the indirect burden of bronchiectasis on individuals and the community, is needed.

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.

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.

Assessment of future water demand and supply using WEAP model in Dhasan River Basin, Madhya Pradesh, India.

Understanding the available resources and the needs of those who use them is necessary for the evaluation and allocation of water resources. The main sectors utilizing the basin water resources are agriculture, drinking water, animal husbandry, and industries, and the efficient and rational management of water resources to be distributed among those different sectors of activity is vital. This study attempts to develop an integrated water resource management system for the Dhasan River Basin (DRB) by employing a scenario analysis approach in conjunction with Water Evaluation and Planning Model (WEAP) to analyze trends in water use and anticipated demand between 2015 and 2050, simulating five possible scenarios (I, II, III, IV, and V) as for external driving factors. For the WEAP modeling framework, 2015 was chosen as a current (base) year for which all available information and input data were given to the model and the future demand situation was analyzed for the period 2016-2050 (forecasting period). From the findings, it was observed that for the forecasting period, total water demand, unmet demand, and streamflow were 185.29 Bm3, 117.35 Bm3, and 58.26 Bm3, respectively, in the case of scenario I; 232.34 Bm3, 162.17 Bm3, and 59.87 Bm3 in case of scenario II; 139.40 Bm3, 84.37 Bm3, and 58.15 Bm3 in case of scenario III; 186.15 Bm3, 118.76 Bm3, and 56.98 Bm3 in case of scenario IV; and 181.89 Bm3, 96.87 Bm3, and 53.11 Bm3 in case of scenario V. Results of the study indicated that by 2050, increasing population growth, industrial development, and an increase in the agricultural area will rise the water demand dramatically, posing threats to the environment and humans. Therefore, implementing improved irrigation technologies, advancing agricultural practices on farms, and constructing water conservation and retaining structures could significantly reduce the unmet demands and shortfalls in DRB. Overall findings reveal that the pressure on the Dhasan water resources would increase in the future, and thus several suggestions have been provided to assist decision-makers in sustainable planning and management of water resources to meet future demands.

Multifocal Extramedullary Relapse With Neuroleukemiosis in a Case of Early T-Cell Precursor ALL: 18F-FDG PET/CT Findings.

ABSTRACT: Early T-cell precursor ALL (acute lymphoblastic leukemia) is a rare type of childhood and adult T-cell ALL. Disease recurrence is common within 2 years from the time of initial diagnosis. Outcomes of relapse have been characterized through risk stratification schemes, and one of the major determinants of overall survival is the overall tumor burden and sites of relapse. Although testicular recurrence is common; Peripheral nerve as a site of recurrence is relatively rare. We present a case of early T-cell ALL on maintenance therapy with multifocal relapse on FDG PET/CT in the cervical lymph nodes, the testis, and the left sciatic nerve. Bone marrow and flow cytometry confirmed the relapse.

Allergic bronchopulmonary aspergillosis in association with rheumatic heart disease: report of three cases.

Allergic bronchopulmonary aspergillosis is usually seen in patients with asthma or cystic fibrosis. Its association with rheumatic heart disease has not been adequately reported in literature. We report our experience of three cases who were diagnosed cases of rheumatic heart disease. Their symptomatology and clinical findings required further evaluation and investigations, which were suggestive of allergic bronchopulmonary aspergillosis. The patients were treated with steroids and/or antifungals before proceeding with the valve replacement.

Barriers and facilitators of physical activity in children with bronchiectasis: Perspectives from children and parents.

Background: Current 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 methods: This 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. Results: From 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. Conclusion: Programs 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.

Early and midterm patency of arteriovenous fistula for hemodialysis access using different techniques and their advantages and disadvantages.

This descriptive retrospective study was done to observe the different techniques of arteriovenous fistula creation for advantages and disadvantages, complications, and early and midterm patency. Fifty-three arteriovenous fistulas were created from September 2018 to August 2020 using four different techniques. Radio-cephalic arteriovenous fistula was usually the first option. Other techniques like brachio-cephalic arteriovenous fistula, radio-basilic arteriovenous fistula, and brachio-basilic arteriovenous fistula were used when the radio-cephalic fistula had thrombosed or could not be constructed due to small-sized cephalic vein in the forearm. The majority of patients (41 (77.35%)) underwent radio-cephalic fistula creation. Early patency was 38 (92.7%) in the radio-cephalic technique whereas it was 12 (100%) in the radio-basilic, brachio-cephalic, and brachio-basilic techniques combined. The midterm patency was 32 (78%) in the radio-cephalic technique, 5 (83%) in the brachio-cephalic technique, 3 (75%) in the radio-basilic technique, and 1 (50%) in the brachio-basilic technique. Radio-basilic and brachio-cephalic are alternative techniques for fistula creation after radio-cephalic depending upon the size of the basilic vein in the forearm or cephalic vein in the cubital fossa or arm. The radio-basilic technique may have advantages over the brachio-cephalic technique which need to be further evaluated. Proximal fistulas like brachio-basilic and brachio-cephalic are more commonly associated with limb edema.

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.

Bronchiectasis - Exercise as Therapy (BREATH): rationale and study protocol for a multi-center randomized controlled trial.

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.