Multiple-Breath Washout as a Marker of Lung Disease in Preschool Children with Cystic Fibrosis

Abstract

Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

“…13 15 By contrast, the proportion of children with cystic fibrosis with abnormal FEFV parameters during the first 2 years of life was much higher in both this and previous studies 6 11 43 than observed in such children during the preschool years. 1 This increased sensitivity of the RVRTC during early life could reflect differences in technique, associated for example with the application of highly standardised lung inflations and external thoraco-abdominal compressions to force expiration, but 1 The dashed vertical line represents the lower 95% limit of normality (ie, only 2.5% of healthy controls have Z scores below this level) for FEV 0.5 , FVC and FEF . Any results to the left of this line are unusually low.…”

“…Although it has been suggested that there may be a slight negative age dependency of LCI in healthy infants during the first months of life, 33 34 most of the infants in this study were over 6 months of age when these effects were less marked, and all but one of the healthy controls had results that fell within the normal range established for preschool children, ie ,7.8. 1 Although it can be argued that a higher upper limit for LCI of 8 should be applied to infants under 6 months of age, 35 only one infant with cystic fibrosis would have been re-classified as having an LCI in the normal range had we used this approach.…”

“…[1][2][3][4][5][6] Parameters derived from forced expiratory manoeuvres have traditionally been used to monitor lung function in older patients with cystic fibrosis and forced expiratory volume in 1 second (FEV 1 ) is still considered to be a predictor of prognosis in patients with moderate to severe cystic fibrosis lung disease. 7 8 Although infants cannot perform such manoeuvres, forced expiratory flow-volume (FEFV) loops can be obtained by substituting voluntary effort with application of an external pressure to the chest and abdomen to force expiration.…”

Chest health surveillance utility in the early detection of bronchiolitis obliterans syndrome in children after allo-SCT

“…Our results suggest that only PFTs are reliable to diagnose BOS early and may identify potential asymptomatic patients, and that in those who cannot undergo PFT, especially young children, novel alternative techniques such as multiple-breath washout testing needs to be explored. 15,16 As our understanding about the pathophysiology of BOS is improving, and more patients are surviving longer after SCT with GVHD, The National Institutes of Health consensus group recommends consideration of PFTs or spirometry every 3 months during the first year after transplantation in high-risk patients (patients with chronic GVHD). 12 Regular PFTs in the first year after SCT should allow the capture of subtle changes in lung volumes during a period of tapering immunosuppressant agents when most cases of BOS will start to develop and thus allow an opportunity for earlier and most effective intervention.…”

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

“…4,5 The respiratory disease progression in CF is expressed by various pulmonary dysfunctions, [6][7][8][9][10] such as ventilation inhomogeneities, 8,11 pulmonary hyperinflation, 9,12 bronchial obstruction, trapped gas and gas exchange disturbances, 10 most of them occurring early in life, 7,12,13 and progressing even in the absence of clinical signs and symptoms. 11,14,15 Owing to the great phenotypic variability in lung disease even observed among patients carrying the same CFTR genotype, several association studies have been conducted to find modifying genetic factors and to study their influence on CF disease outcome. 16 So far, five genes showed an association in at least two independent populations with more than 500 participants in total, namely MBL2, IFRD1, IL8 and TGFB1 that are involved in the immune response and EDNRA that might influence CF lung disease by altering smooth muscle tone in the airways and/or vasculature.…”