Pediatric Year in Review

PEDIATRIC YEAR IN REVIEW 11 UPDATE ON PCD AND NON-CF BRONCHIECTASIS UPDATE ON PCD AND NON-CF BRONCHIECTASIS Adam J. Shapiro, MD Associate Professor, McGill University Health Centre Pediatric Respiratory Medicine Montreal, QC, Canada TREATMENT OF BRONCHIECTASIS EXACERBATIONS Goyal V, Grimwood K, Byrnes CA, Morris PS, Masters IB, Ware RS, McCallum GB, Binks MJ, Marchant JM, van Asperen P, O’Grady KF, Champion A, Buntain HM, Petsky H, Torzillo PJ, Chang AB. Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in chil- dren with bronchiectasis (BEST-2): a multicenter, dou- ble blind, non-inferiority, randomized controlled trial. Lancet. 2018 Oct 6;392(10154):1197-1206. doi: 10.1016/ S0140-6736(18)31723-9. Epub 2018 Sep 18. Summary Antibiotic therapies for acute respiratory exacerbations have not been prospectively studied in children with non-cystic fibrosis (non-CF) bronchiectasis. Despite this, therapeutic guidelines recommend twice daily oral amoxicillin- clavulanate as first line therapy for non-CF bronchiectasis respiratory exacerbations, though compliance may be superior with a once daily medication, such as azithromycin. This prospective, randomized, double blind, placebo controlled trial examines the resolution of acute cough in 179 children with outpatient, non-CF bronchiectasis respiratory exacerbations receiving 21 days of either oral amoxicillin-clavulanate (45 mg/kg/day) or oral azithromycin therapy (5mg/kg/day). Results show azithromycin is non- inferior to amoxicillin-clavulanate for resolution of cough during a non-CF bronchiectasis respiratory exacerbation (77%cough resolution at day 21 with either agent). However, children randomized to oral amoxicillin-clavulanate had a faster resolution of cough versus azithromycin (median 10 versus 14 days). Compliance was excellent and similar in both medication groups. Children taking azithromycin had a greater proportion of azithromycin resistant nasal organisms at the end of therapy versus those taking amoxicillin-clavulanate (80% versus 29%). There are no significant differences in inflammatory markers, time to next exacerbation, pulmonary function, or quality of life markers in children treated with either agent. Sub-group analysis of children on long term antibiotic therapy prior to and during study period did not show significantly different outcomes. Comments 1. Twenty one days of either azithromycin (5mg/kg/day) or amox- icillin-clavulanate (45 mg/kg/day) are equally effective therapies for cough resolution in children with non-CF bronchiectasis, yet higher dose amoxicillin component (80mg/kg/day) and azithromy- cin (up to 10mg/kg/day) may generate different clinical outcomes. 2. Faster resolution of cough with amoxicillin-clavulanate therapy over azithromycin may translate to less missed school/work days and ultimately affect quality of life. 3. Long term effects of increased azithromycin resistant organisms (such as S. aureus) at the end of prolonged azithromycin therapy require further clinical investigation. 4. While compliance with a once daily medication, like azithromycin, seems intuitively superior, this is not the case when studied in a double dummy trial of children with non-CF bronchiectasis, though compliance outside of a clinical trial environment may still be superior with a once daily medication. ADOLESCENT OUTCOMES IN PEDIATRIC BRONCHIECTASIS Kinghorn B, Singleton R, McCallum GB, Bulkow L, Grimwood K, Hermann L, Chang AB, Redding G. Clinical course of chronic suppurative lung disease and bronchiectasis in Alaska Native children. Pediatr Pulmonol. 2018 Dec;53(12):1662-1669. doi: 10.1002/ ppul.24174. Epub 2018 Oct 16. Summary Chronic suppurative lung disease (CSLD) andbronchiectasis are common in indigenous populations, including Alaskan Native (AN) children from the Yukon Kuskokwim Delta region. Older studies report an adolescent “honeymoon period” of decreased respiratory symptoms in children with bronchiectasis, but this trend has not been recently examined. This long-term analysis examines clinical outcomes in 34 AN adolescents (median age 11.8 years) with CSLD or bronchiectasis. At a median follow up of 12 years, CT scans show 14 (41%) with bronchiectasis, 8 (24%) with CSLD lacking bronchiectasis, and 12 (35%) who did not clinically require CT scan. Nearly 80% of children were symptomatic with an abnormal physical examination and/or cough, wheeze, or respiratory exacerbation in the prior 12 months. Half of the subjects had abnormal chest exams, and crackles were more prevalent with confirmed bronchiectasis. Sixty- four percent have obstruction on spirometry, with lower FEV1/FVC values in confirmed bronchiectasis. Despite these findings, there are less episodes of lower respiratory tract infection (LRTI) requiring antibiotics or hospitalization