Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test.

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21 years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

Ventilation Inhomogeneity and Bronchial Basement Membrane Changes in Chronic Neutrophilic Airway Inflammation.

BACKGROUND: Bronchial epithelial reticular basement membrane (RBM) thickening occurs in diseases with both eosinophilic (allergic bronchial asthma [BA]) and neutrophilic (cystic fibrosis [CF] and primary ciliary dyskinesia [PCD]) chronic airway inflammation; however, the lung function and airway remodeling relation remains unclear. The aim of this study was to test whether ventilation inhomogeneity is related to RBM thickening. METHODS: Multiple breath washout test, endobronchial biopsy, and BAL were performed in 24 children with CF, 11 with PCD, 15 with BA, and in 19 control subjects. Lung clearance index at 2.5% (1/40th) of starting nitrogen concentration (LCI2.5), RBM thickness, and lavage fluid cytology were quantified; their mutual associations were studied by using Spearman rank correlations (r). RESULTS: In asthma, ventilation inhomogeneity (mean ± SD) was mild (LCI2.5, 9.3 ± 1.4 vs 7.9 ± 0.9 in control subjects; P = .0391), and the RBM thickened (5.26 ± 0.98 µm vs 3.12 ± 0.62 µm in control subjects; P < .0001). No relation between RBM thickness and ventilation inhomogeneity or lavage cytology was found. In CF and PCD, RBM thickness was similar to that in asthma (4.54 ± 0.66 µm and 5.27 ± 1.11 µm, respectively), but ventilation inhomogeneity was significantly higher (LCI2.5, 12.5 ± 2.4 and 11.8 ± 2.5). Both in CF and PCD, RBM thickness correlated with LCI2.5 (r = 0.594, P = .015; r = 0.821, P = .023). In PCD only, RBM thickness was also related to the number of neutrophils in lavage fluid (r = 0.821; P = .023). CONCLUSIONS: Lung function impairment in relation to RBM thickness was milder in BA than in CF and PCD. In asthma, ventilation inhomogeneity did not correlate with RBM thickness, whereas it did in CF and PCD. This outcome suggests a different structure-function relation in these diseases.

Treatment response of airway clearance assessed by single-breath washout in children with cystic fibrosis.

BACKGROUND: We studied the ability of 4 single-breath gas washout (SBW) tests to measure immediate effects of airway clearance in children with CF. METHODS: 25 children aged 4-16 years with CF performed pulmonary function tests to assess short-term variability at baseline and response to routine airway clearance. Tidal helium and sulfur hexafluoride (double-tracer gas: DTG) SBW, tidal capnography, tidal and vital capacity nitrogen (N2) SBW and spirometry were applied. We analyzed the gasses' phase III slope (SnIII--normalized for tidal volume) and FEV1 from spirometry. RESULTS: SnIII from tidal DTG-SBW, SnIII from vital capacity N2-SBW, and FEV1 improved significantly after airway clearance. From these tests, individual change of SnIII from tidal DTG-SBW and FEV1 exceeded short-term variability in 10 and 6 children. CONCLUSIONS: With the tidal DTG-SBW, an easy and promising test for peripheral gas mixing efficiency, immediate pulmonary function response to airway clearance can be assessed in CF children.