TY - JOUR
T1 - Comparison of Multiple Breath Washout and Spirometry in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis and Healthy Controls
AU - Kinghorn, Bre Anna
AU - McNamara, Sharon
AU - Genatossio, Alan
AU - Sullivan, Erin
AU - Rosenfeld, Margaret
AU - Siegel, Molly
AU - Bauer, Irma
AU - Pittman, J.
AU - Clem, Charles
AU - Davis, Stephanie D.
AU - Johnson, Robin C.
AU - Davis, Miriam
AU - Davis, Stephanie D.
AU - Leigh, Margaret W.
N1 - Funding Information:
Supported by the Genetic Disorders of Mucociliary Clearance Consortium. The Genetic Disorders of Mucociliary Clearance (U54HL096458) is a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network. The Rare Diseases Clinical Research Network is an initiative of the Office of Rare Diseases Research at the NCATS and is funded through a collaboration between the NCATS and NHLBI. Supported by a Clinical and Translational Science Awards (NIH/NCATS grant UNC ULTR000083), a NIH/NCATS Colorado Clinical and Translational Science Awards (grant UL1 TR001082), and an Intramural Research Program of NIH/National Institute of Allergy and Infectious Diseases. Funding for data analysis and multiple breath washout overreading at Washington University School of Medicine was derived, in part, from the Cystic Fibrosis Foundation Therapeutics Development Network funding for the Center for Infant and Preschool Pulmonary Function Testing (Cystic Fibrosis Foundation DAVIS08Y2).
Publisher Copyright:
© 2020 American Thoracic Society. All rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - Rationale: In cystic fibrosis (CF), the lung clearance index (LCI), derived from multiple breath washout (MBW), is more sensitive in detecting early lung disease than FEV1; MBW has been less thoroughly evaluated in young patients with primary ciliary dyskinesia (PCD). Objectives: Our objectives were 1) to evaluate the sensitivity of MBW and spirometry for the detection of mild lung disease in young children with PCD and CF compared with healthy control (HC) subjects and 2) to compare patterns of airway obstruction between disease populations. Methods: We used a multicenter, single-visit, observational study in children with PCD and CF with a forced expiratory volume in 1 second (FEV1) greater than 60% predicted and HC subjects, ages 3-12 years. Nitrogen MBW and spirometry were performed and overread for acceptability. x2 and Kruskall-Wallis tests compared demographics and lung function measures between groups, linear regression evaluated the effect of disease state, and Spearman's rank correlation coefficient compared the LCI and spirometric measurements. Results: Twenty-five children with PCD, 49 children with CF, and 80 HC children were enrolled, among whom 17 children with PCD (68%), 36 children with CF (73%), and 53 (66%) HC children performed both acceptable spirometry and MBW; these children made up the analytic cohort. The median age was 9.0 years (interquartile range [IQR], 6.8-11.1). The LCI was abnormal (more than 7.8) in 10 of 17 (59%) patients with PCD and 21 of 36 (58%) patients with CF, whereas FEV1 was abnormal in three of 17 (18%) patients with PCD and six of 36 (17%) patients with CF. The LCI was significantly elevated in patients with PCDand CF compared withHC subjects (ratio of geometric mean vs. HC: PCD 1.27; 95% confidence interval [CI], 1.15-1.39; and CF 1.24; 95% CI, 1.15-1.33]). Children with PCD had lower midexpiratory-phase forced expiratory flow % predicted compared with children with CF (62% [IQR, 50-78%] vs. 85% [IQR, 68-99%]; P = 0.05). LCI did not correlate with FEV1. Conclusions: The LCI is more sensitive than FEV1 in detecting lung disease in young patients with PCD, similar to CF. LCI holds promise as a sensitive endpoint for the assessment of early PCD lung disease.
AB - Rationale: In cystic fibrosis (CF), the lung clearance index (LCI), derived from multiple breath washout (MBW), is more sensitive in detecting early lung disease than FEV1; MBW has been less thoroughly evaluated in young patients with primary ciliary dyskinesia (PCD). Objectives: Our objectives were 1) to evaluate the sensitivity of MBW and spirometry for the detection of mild lung disease in young children with PCD and CF compared with healthy control (HC) subjects and 2) to compare patterns of airway obstruction between disease populations. Methods: We used a multicenter, single-visit, observational study in children with PCD and CF with a forced expiratory volume in 1 second (FEV1) greater than 60% predicted and HC subjects, ages 3-12 years. Nitrogen MBW and spirometry were performed and overread for acceptability. x2 and Kruskall-Wallis tests compared demographics and lung function measures between groups, linear regression evaluated the effect of disease state, and Spearman's rank correlation coefficient compared the LCI and spirometric measurements. Results: Twenty-five children with PCD, 49 children with CF, and 80 HC children were enrolled, among whom 17 children with PCD (68%), 36 children with CF (73%), and 53 (66%) HC children performed both acceptable spirometry and MBW; these children made up the analytic cohort. The median age was 9.0 years (interquartile range [IQR], 6.8-11.1). The LCI was abnormal (more than 7.8) in 10 of 17 (59%) patients with PCD and 21 of 36 (58%) patients with CF, whereas FEV1 was abnormal in three of 17 (18%) patients with PCD and six of 36 (17%) patients with CF. The LCI was significantly elevated in patients with PCDand CF compared withHC subjects (ratio of geometric mean vs. HC: PCD 1.27; 95% confidence interval [CI], 1.15-1.39; and CF 1.24; 95% CI, 1.15-1.33]). Children with PCD had lower midexpiratory-phase forced expiratory flow % predicted compared with children with CF (62% [IQR, 50-78%] vs. 85% [IQR, 68-99%]; P = 0.05). LCI did not correlate with FEV1. Conclusions: The LCI is more sensitive than FEV1 in detecting lung disease in young patients with PCD, similar to CF. LCI holds promise as a sensitive endpoint for the assessment of early PCD lung disease.
KW - Cystic fibrosis
KW - Lung clearance index
KW - Lung function
KW - Multiple breath washout
KW - Primary ciliary dyskinesia
UR - http://www.scopus.com/inward/record.url?scp=85090251378&partnerID=8YFLogxK
U2 - 10.1513/AnnalsATS.201905-375OC
DO - 10.1513/AnnalsATS.201905-375OC
M3 - Article
C2 - 32603187
AN - SCOPUS:85090251378
SN - 2329-6933
VL - 17
SP - 1085
EP - 1093
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 9
ER -