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

BACKGROUND: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease. METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario). RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences. CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.

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

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

Towards developing a valid scoring tool for bronchitis during flexible bronchoscopy.

BACKGROUND: A valid bronchoscopic scoring tool for bronchitis would be useful for clinical and research purposes as currently there are none in children. From 100 digitally recorded flexible bronchoscopies (FB), we related the various macroscopic features to airway neutrophil % to develop a FB-derived bronchitis score (BScoreexp ). We aimed to develop a FB-derived bronchitis tool. METHODS: FB recordings for six visualised features: secretions (amount and color) and mucosal appearance (erythema, pallor, ridging, oedema) based on pre-determined criteria on a pictorial chart were assessed by two physicians independently, blinded to the clinical history. These features were used to obtain various models of BScoreexp that were plotted against bronchoalveolar lavage (BAL) neutrophil % using a receiver operating characteristic (ROC) curve. Inter- and intra-rater agreement (weighted-kappa, K) were assessed from 30 FBs. RESULTS: Using BAL neutrophilia of 20% to define inflammation, the highest area under ROC (aROC) of 0.71, 95%CI 0.61-0.82 was obtained by the giving three times weightage to secretion amount and color and adding it to erythema and oedema. Inter-rater K values for secretion amount (K = 0.87, 95%CI 0.73-1.0) and color (K = 0.86, 95%CI 0.69-1.0) were excellent. Respective intra-rater K were 0.95 (0.87-1.0) and 0.68 (0.47-0.89). Other inter-rater K ranged from 0.4 (erythema) to 0.64 (pallor). CONCLUSION: A repeatable FB-defined bronchitis scoring tool can be derived. However, a prospective study needs to be performed with larger numbers to further evaluate and validate these results.