Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency

Abstract

Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.

Agreement between multiple-breath nitrogen washout systems in children and adults

“…Our LCI data are well within the range of previous studies [33][34][35]. For example, a recent study using NDD reported a mean LCI of 6.3 in 33 controls (8 to 60 years) whereas it was 6.6 in 101 controls (5 to 65 years) in our study [35].…”

“…For example, a recent study using NDD reported a mean LCI of 6.3 in 33 controls (8 to 60 years) whereas it was 6.6 in 101 controls (5 to 65 years) in our study [35]. These data are also reassuring that relevant lung disease was clearly absent in our control population though we did not assess spirometry in the latter.…”

Functional lung MRI for regional monitoring of patients with cystic fibrosis

“…Spirometry was performed with the Power-Cube Body+ instrument (Ganshorn Deutschland GmbH, Neuenkirchen, Germany). MBW tests were performed by ultrasonic technology using the EasyOne Pro LAB™ (ndd medical technologies AG, Zurich, Switzerland) following the protocol described by Fuchs et al[ 28 ].…”

Training in multiple breath washout testing for respiratory physiotherapists

“…It has been shown to detect early lung disease in children and adults and is more sensitive than measures of spirometry (FEV1) in both CF and bronchiectasis (2,5,11). Indices from the MBW test have also been shown to be sensitive to lung disease in asthma (13), COPD (14) and alpha-1-antitrypsin deficiency (20).…”