ObjectiveDiagnosis of small airway disease on computed tomography (CT) scans is challenging in patients with a history of chemical warfare exposure. We developed a software package based on different methodologies to identify and quantify small airway disease in CT images. The primary aim was to identify the best automatic methodology for detecting small airway disease in CT scans of Iran-Iraq War victims of chemical warfare.MethodsThis retrospective case–control study enrolled 46 patients with a history of chemical warfare exposure and 27 controls with inspiratory/expiratory (I/E) CT scans and spirometry tests. Image data were automatically segmented, and inspiratory images were registered into the expiratory images' frame using the locally developed software. Parametric response mapping (PRM) and air trapping index (ATI) mapping were performed on the CT images. Conventional QCT methods, including expiratory/inspiratory mean lung attenuation (E/I MLA) ratio, normal density E/I (ND E/I) MLA ratio, attenuation volume Index (AVI), %low attenuation areas (LAA) < -856 in exhale scans, and %LAA < -950 in inhale scans were also computed. QCT measurements were correlated with spirometry results and compared across the two study groups.ResultsThe correlation analysis showed a significant negative relationship between three air trapping (AT) measurements (PRM, ATI, and %LAAExp < -856) and spirometry parameters (Fev1, Fvc, Fev1/Fvc, and MMEF). Moreover, %LAAExp < -856 had the highest significant negative correlation with Fev1/Fvc (r = -0.643, P-value < 0.001). Three AT measurements demonstrated a significant difference between the study groups. The E/I ratio was also significantly different between the two groups (P-value < 0.001). Binary logistic regression models showed PRMFsad, %LAAExp < -856, and ATI as significant and strong predictors of the study outcome. Optimal cut-points for PRMFsad = 19%, %LAAExp < -856 = 23%, and ATI = 27% were identified to classify the participants into two groups with high accuracy.ConclusionQCT methods, including PRM, ATI, and %LAAExp < -856 can greatly advance the identification and quantification of SAD in chemical warfare victims. The results should be verified in well-designed prospective studies involving a large population.