Multicentre feasibility of multiple-breath washout in preschool children with cystic fibrosis and other lung diseases

Abstract

Background: Multiple-breath washout (MBW)-derived lung clearance index (LCI) detects early cystic fibrosis (CF) lung disease. LCI was used as an end-point in single- and multicentre settings at highly experienced MBW centres in preschool children. However, multicentre feasibility of MBW in children aged 2-6 years, including centres naïve to this technique, has not been determined systematically.

Methods: Following central training, 91 standardised nitrogen MBW investigations were performed in 74 awake preschool children (15 controls, 46 with CF, and 13 with other lung diseases), mean age 4.6±0.9 years at investigation, using a commercially available device across five centres in Germany (three experienced, two naïve to the performance in awake preschool children) with central data analysis. Each MBW investigation consisted of several measurements.

Results: Overall success rate of MBW investigations was 82.4% ranging from 70.6% to 94.1% across study sites. The number of measurements per investigation was significantly different between sites ranging from 3.7 to 6.2 (p<0.01), while the mean number of successful measurements per investigation was comparable with 2.1 (range, 1.9 to 2.5; p=0.46). In children with CF, the LCI was increased (median 8.2, range, 6.7-15.5) compared to controls (median 7.3, range 6.5-8.3; p<0.01), and comparable to children with other lung diseases (median 7.9, range, 6.6-13.9; p=0.95).

Conclusion: This study demonstrates that multicentre MBW in awake preschool children is feasible, even in centres previously naïve, with central coordination to assure standardised training, quality control and supervision. Our results support the use of LCI as multicentre end-point in clinical trials in awake preschoolers with CF.

FIGURE 1

Success rates of multicentre MBW investigations in awake preschool children without lung disease (control), with CF and with other lung diseases. Summary of success rates for technically acceptable MBW investigations for the total study population and for individual study sites. MBW: multiple-breath washout; CF: cystic fibrosis; ARCN: CF Center at Airway Research Center North; BREATH: CF Center at Biomedical Research in Endstage and Obstructive Lung Disease Hannover; TLRC: CF Center at Translational Lung Research Center Heidelberg; UGMLC: CF Center at Universities of Giessen and Marburg Lung Center; Berlin: CF Center at Charité - Universitätsmedizin Berlin.

FIGURE 2

Multiple-breath washout (MBW) success rates according to age. MBW investigations are grouped according to the age of the children at time of investigation, where “2” stands for the age group of children from 2.0 to 2.9 years of age and so on. The Pearson correlation coefficient r and p-values are provided.

FIGURE 3

Summary of lung clearance index (LCI) in preschool children without lung disease (control), with cystic fibrosis (CF) and with other lung diseases in the multicentre setting. Dotted line represents upper limit of normal of 8.3. Open circles (CF Center at Airway Research Center North), closed circles (CF Center at Biomedical Research in Endstage and Obstructive Lung Disease Hannover), open triangles (CF Center at Translational Lung Research Center Heidelberg), closed triangles (CF Center at Universities of Giessen and Marburg Lung Center) and open squares (CF Center at Charité - Universitätsmedizin Berlin) represent data from individual children from the respective study site. Solid horizontal lines represent median values for each group. **: p<0.01 versus control group.