Mirjam Stahl1,2,3, Mark O Wielpütz4,3,5, Isabell Ricklefs6,7, Christian Dopfer8,9, Sandra Barth10,11, Anne Schlegtendal12, Simon Y Graeber1,2,3,13,14, Olaf Sommerburg2,3, Gesa Diekmann6,7, Johannes Hüsing15, Cordula Koerner-Rettberg12, Lutz Nährlich10,11, Anna-Maria Dittrich8,9, Matthias V Kopp6,7, Marcus A Mall1,2,3,13,14. 1. 1 Department of Translational Pulmonology. 2. 2 Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, and. 3. 3 Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany. 4. 4 Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany. 5. 5 Department of Radiology, German Cancer Research Center, Heidelberg, Germany. 6. 6 Division of Pediatric Allergology and Pneumology, Department of Pediatrics, Medical University of Lübeck, Lübeck, Germany. 7. 7 Airway Research Center North, German Center for Lung Research, Lübeck, Germany. 8. 8 Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany. 9. 9 Biomedical Research in Endstage and Obstructive Lung Disease, German Center for Lung Research, Hannover, Germany. 10. 10 Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany. 11. 11 Universities Giessen and Marburg Lung Center, German Center for Lung Research, Giessen, Germany. 12. 12 Department of Pediatric Pulmonology, University Children's Hospital of Ruhr University Bochum at St. Josef-Hospital, Bochum, Germany. 13. 13 Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. 14. 14 Berlin Institute of Health, Berlin, Germany; and. 15. 15 Coordination Center for Clinical Trials, Heidelberg University Hospital, Heidelberg, Germany.
Abstract
Rationale: Cystic fibrosis (CF) lung disease starts in early infancy, suggesting that preventive treatment may be most beneficial. Lung clearance index (LCI) and chest magnetic resonance imaging (MRI) have emerged as promising endpoints of early CF lung disease; however, randomized controlled trials testing the safety and efficacy of preventive therapies in infants with CF are lacking. Objectives: To determine the feasibility, safety, and efficacy of preventive inhalation with hypertonic saline (HS) compared with isotonic saline (IS) in infants with CF, including LCI and MRI as outcome measures. Methods: In this randomized, double-blind, controlled trial, 42 infants with CF less than 4 months of age were randomized across five sites to twice-daily inhalation of 6% HS (n = 21) or 0.9% IS (n = 21) for 52 weeks. Measurements and Main Results: Inhalation of HS and IS was generally well tolerated by infants with CF, and the number of adverse events did not differ between groups (P = 0.49). The change in LCI from baseline to Week 52 was larger in infants with CF treated with HS (-0.6) than in those treated with IS (-0.1; P < 0.05). In addition, weight gain was improved in infants with CF treated with HS (P < 0.05), whereas pulmonary exacerbations and chest MRI scores did not differ in the HS group versus the IS group. Conclusions: Preventive inhalation with HS initiated in the first months of life was safe and well tolerated and resulted in improvements in LCI and weight gain in infants with CF. Our results support the feasibility of LCI as an endpoint in randomized controlled trials in infants with CF. Clinical trial registered with www.clinicaltrials.gov (NCT01619657).
RCT Entities:
Rationale: Cystic fibrosis (CF) lung disease starts in early infancy, suggesting that preventive treatment may be most beneficial. Lung clearance index (LCI) and chest magnetic resonance imaging (MRI) have emerged as promising endpoints of early CF lung disease; however, randomized controlled trials testing the safety and efficacy of preventive therapies in infants with CF are lacking. Objectives: To determine the feasibility, safety, and efficacy of preventive inhalation with hypertonic saline (HS) compared with isotonic saline (IS) in infants with CF, including LCI and MRI as outcome measures. Methods: In this randomized, double-blind, controlled trial, 42 infants with CF less than 4 months of age were randomized across five sites to twice-daily inhalation of 6% HS (n = 21) or 0.9% IS (n = 21) for 52 weeks. Measurements and Main Results: Inhalation of HS and IS was generally well tolerated by infants with CF, and the number of adverse events did not differ between groups (P = 0.49). The change in LCI from baseline to Week 52 was larger in infants with CF treated with HS (-0.6) than in those treated with IS (-0.1; P < 0.05). In addition, weight gain was improved in infants with CF treated with HS (P < 0.05), whereas pulmonary exacerbations and chest MRI scores did not differ in the HS group versus the IS group. Conclusions: Preventive inhalation with HS initiated in the first months of life was safe and well tolerated and resulted in improvements in LCI and weight gain in infants with CF. Our results support the feasibility of LCI as an endpoint in randomized controlled trials in infants with CF. Clinical trial registered with www.clinicaltrials.gov (NCT01619657).
Authors: Scott C Bell; Marcus A Mall; Hector Gutierrez; Milan Macek; Susan Madge; Jane C Davies; Pierre-Régis Burgel; Elizabeth Tullis; Claudio Castaños; Carlo Castellani; Catherine A Byrnes; Fiona Cathcart; Sanjay H Chotirmall; Rebecca Cosgriff; Irmgard Eichler; Isabelle Fajac; Christopher H Goss; Pavel Drevinek; Philip M Farrell; Anna M Gravelle; Trudy Havermans; Nicole Mayer-Hamblett; Nataliya Kashirskaya; Eitan Kerem; Joseph L Mathew; Edward F McKone; Lutz Naehrlich; Samya Z Nasr; Gabriela R Oates; Ciaran O'Neill; Ulrike Pypops; Karen S Raraigh; Steven M Rowe; Kevin W Southern; Sheila Sivam; Anne L Stephenson; Marco Zampoli; Felix Ratjen Journal: Lancet Respir Med Date: 2019-09-27 Impact factor: 30.700
Authors: Mario Pieper; Hinnerk Schulz-Hildebrandt; Marcus A Mall; Gereon Hüttmann; Peter König Journal: Am J Physiol Lung Cell Mol Physiol Date: 2020-01-29 Impact factor: 5.464
Authors: Ren-Jay Shei; Kelly A Mackintosh; Jacelyn E Peabody Lever; Melitta A McNarry; Stefanie Krick Journal: Front Physiol Date: 2019-11-05 Impact factor: 4.566