Pediatric Year in Review

PEDIATRIC YEAR IN REVIEW 3 UPDATE IN CYSTIC FIBROSIS MANAGEMENT with early Pseudomonas aeruginosa would decrease the risk of pulmonary exacerbations and prolong the time to pseudomonas recurrence. This multicenter double-blind randomized placebo-controlled study followed subjects for 18 months. Participants who were between the ages of 6 months and 18 years were given azithromycin or placebo three times a week in addition to their standard inhaled tobramycin. The study found that there was a marked decrease in pulmonary exacerbations in the group treated with azithromycin (>40%), and weight increased by > 1 kg when on azithromycin. However there was no significant change observed in microbiology. Comments 1. There were no safety concerns when taking azithromycin. 2. Subjects had fewer pulmonary exacerbations when on Azithromycin then when on inhaled tobramycin alone. 3. Subjects had increased weight gain on Azithromycin compared to inhaled tobramycin alone. 4. There was no added benefit when compared to inhaled tobramy- cin alone with regard to microbiology. CYSTIC FIBROSIS RELATED DIABETES Kelly A, De Leon DD, Sheikh S, Camburn D, Kubrak C, Peleckis AJ, Stefanovski D, Hadjiliadis D, Rickels MR, Rubenstein RC. Islet Hormone and Incretin Secretion in Cystic Fibrosis after Four Months of Ivacaftor Therapy. Am J Respir Crit Care Med. 2019 Feb 1;199(3):342-351. PMID:30130412 Summary This study examines the effects of prolonged ivacaftor therapy on glucose tolerance and insulin and incretin secretion in a small cohort of patients. A number of parameters were examined before and after starting ivacaftor. Spirometry, oral glucose tolerance test, mixed meal tolerance tests glucose potentiated arginine tests and plasma insulin, C peptide, glucagon-like peptide-1, and total glucose dependent insulinotropic polypeptide were measured. The investigators found that there was improved insulin secretion and glucagon secretion suggesting improved beta cell function. AIRWAY EPITHELIAL HIERARCHY Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, Rogel N, Burgin G, Tsankov AM, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Tata PR, Mou H, Shivaraju M, Bihler H, Mense M, Tearney GJ, Rowe SM, Engelhardt JF, Regev A, Rajagopal J. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018 Aug;560(7718):319-324. PMID:30069044 Summary Investigators study the cellular composition and hierarchy of the mouse trachea using state of the art single cell RNA sequencing methods and in vivo lineage tracing and describe a unique cell type that expresses extremely high amounts of CFTR. This very unique cell is referred to as the airway ionocyte. The ionocyte is also present in human airways. This cell type is very rare comprising less than 1% of the total cells in the airway. The investigators go on to describe the lineage of multiple other airway cell types including club cells tuft cells ciliated cells and goblet cells. These approaches provide the community with cell-type specific expression programs that will highlight key disease genes and provide insight into the origins of airway disease. OTHER ARTICLES OF INTEREST Donaldson SH, Laube BL, Corcoran TE, Bhambhvani P, Zeman K, Ceppe A, Zeitlin PL, Mogayzel PJ Jr, Boyle M, Locke LW, Myerburg MM, Pilewski JM, Flanagan B, Rowe SM, Bennett WD. Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR. JCI Insight. 2018 Dec 20;3(24). PMID:30568035 Ratjen F, Klingel M, Black P, Powers MR, Grasemann H, Solomon M, Sagel SD, Donaldson SH, Rowe SM, Rosenfeld M. Changes in Lung Clearance Index in Preschool-aged Patients with Cystic Fibrosis Treated with Ivacaftor (GOAL): A Clinical Trial. Am J Respir Crit Care Med. 2018 Aug 15;198(4):526-528. PMID: 29614238 DonaldsonSH, Pilewski JM, GrieseM, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT; VX11- 661-101 Study Group. Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. PMID: 28930490 Abou Alaiwa MH, Launspach JL, Grogan B, Carter S, Zabner J, Stoltz DA, Singh PK, McKone EF, Welsh MJ. Ivacaftor-induced sweat chloride reductions correlate with increases in airway surface liquid pH in cystic fibrosis. JCI Insight. 2018 Aug 9;3(15). PMID:30089726