Multiple breath washout: A noninvasive tool for identifying lung disease in symptomatic military deployers

Abstract

Rationale: Military deployments to austere environments since November 9, 2001 may put "deployers" at risk for respiratory disease. Sensitive, noninvasive tools for detecting large and small airways injury are needed to identify early disease and help inform management for this at-risk population.

Objectives: We examined multiple breath washout (MBW) as a tool for identifying deployment-related airways disease and assessed host and exposure risk factors compared to healthy controls.

Methods: Between March 2015 and March 2020, 103 healthy controls and 71 symptomatic deployers with asthma and/or distal lung disease completed a questionnaire, spirometry and MBW testing. SAS v. 9.4 was used to compare MBW parameters between deployers and controls via univariate analyses and adjusted for demographic factors using multiple linear regression.

Measurements and main results: Deployers were significantly more likely than controls to have an abnormal lung clearance index (LCI) score indicating global ventilation inhomogeneity. Adjusting for sex, smoking status, smoking pack-years and body mass index, LCI scores were significantly more abnormal among those with deployment-related asthma and distal lung disease compared to controls. The unadjusted variable Sacin (a marker of ventilation inhomogeneity in the acinar airways) was higher and thus more abnormal in those with both proximal and distal airways disease. Deployers who reported more frequent exposure to explosive blasts had significantly higher LCI scores.

Conclusions: This study demonstrates the utility of MBW in evaluating exposure-related airways disease in symptomatic military personnel following deployment to austere environments, and is the first to link exposure to explosive blasts to measurable small airways injury.

Keywords: Lung clearance index; Military deployment; Multiple breath washout; Occupational exposure.

Figure 1.

Transition between conducting and acinar airways: H&E high-power view shows the transition or respiratory zone between conducting and acinar airways. Terminal bronchioles are the last segment of the conducting portion of the respiratory tract and are lined with ciliated columnar epithelium. They divide to form the respiratory bronchioles (RB) which marks the beginning of the acinus. The respiratory bronchioles (lined with more cuboidal epithelium that may or may not have cilia) communicate with the alveolar ducts leading to multiple alveolar spaces, where gas exchange in the lung occurs. The Scond parameter, determined from multiple breath washout of nitrogen or an inert gas, is a measurement of ventilation heterogeneity in the conducting airways while the Sacin measurement indicates ventilation heterogeneity in the acinar region of the lung.

Figure 2.

Distribution of multiple breath washout parameters by diagnostic groups. A. LCI score was significantly higher in both the DDLD only and DDLD and DRA groups compared to controls in unadjusted analyses and the combined group remained significant in adjusted analyses. B. The group with DDLD and DRA had a significantly higher Sacin*VT compared to controls in unadjusted analyses. C. There was no significant difference in Scond*VT between the deployment lung disease groups and controls. Dark gray shaded groups were significantly different (p<0.05) from the control group using Tukey pairwise comparisons if the overall ANOVA test was statistically significant.