Seminar: Increased CT Trachea Surface Roughness is Associated with Worse Symptom Burden in COPD

Student: Jason Bartlett

Supervisor: Dr. Miranda Kirby

Abstract

Jason T. Bartlett BSc, James C. Hogg MD, PhD, Jean Bourbeau MD, Wan C. Tan MD and Miranda Kirby PhD

Introduction: Dyspnea, wheeze and cough are hallmark symptoms in patients with chronic obstructive pulmonary disease (COPD) (1), and presence of symptoms is related to more rapid disease progression and increased mortality (2,3). Lower airway remodeling and emphysema on computed tomography (CT) imaging has been associated with both increased dyspnea (4) and chronic cough (4,5), while only airway remodeling is associated with wheeze (4). However, the relationship between structural changes in the trachea and COPD symptoms is not well understood. Histopathological studies have demonstrated that chronic inflammation and remodeling observed in the peripheral airways also occurs in the trachea and main bronchi (6,7). In terms of CT studies, tracheal abnormalities, as measured by the trachea index (TI), have been associated with airflow limitation (8). However, the CT TI measurement uses only a single CT slice representing the narrowest region of the trachea to quantify morphology and provides no information about the overall shape of the trachea surface. Further, investigations focused on trachea topology and its impact on symptom burden in COPD patients has been limited (9).

Objective: The objective of this study was to develop a novel methodology to quantify the entirety of the trachea lumen by measuring surface topology and roughness using fractal analysis (10) in a populationbased study of mainly mild COPD participants (11). We hypothesize that the trachea lumen surface roughness in individuals with COPD will be higher than those without COPD and be significantly associated with airflow limitation. Further, we hypothesize that trachea surface roughness in COPD will be significantly associated with worse symptoms, including dyspnea, wheeze, and cough.

Materials and Methods: Participants from the multi-center prospective CanCOLD study underwent CT imaging and analysis. Established CT measurements included: tracheal index (TI), defined as the smallest ratio of coronal-to-sagittal trachea diameter, low attenuation areas below -950HU (LAA950), and wall thickness for a hypothetical airway of 10-mm lumen perimeter (Pi10). Trachea surface roughness shape (SRS) was calculated as the percent fraction of the measurement box filled by the surface mesh. Multivariable linear/logistic regression models were used to determine association for CT measurements with lung function, CAT≥10, MRC≥3, wheeze, and chronic cough, adjusting for covariates.

Results: A total of 1253 participants were investigated: n=267 never-smokers, n=369 ever-smokers, n=352 mild COPD and n=265 moderate-to-severe COPD. There were no differences between groups for age or race (p<0.05). In models including SRS and TI, SRS was significantly and independently associated with FEV1 (β=-0.11, p<0.001) and FEV1/FVC (β=-0.16, p<0.001), and only SRS was associated with CAT≥10 (OR=1.07, p=0.01), MRC≥3 (OR=1.13, p=0.003) and wheeze (OR=1.05, p=0.01). In models including SRS, LAA950 and Pi10, SRS was significantly and independently associated with FEV1 (β=-0.21, p<0.001), FEV1/FVC β=-0.13, p<0.001), CAT≥10 (OR=1.06, p=0.01), MRC≥3 (OR=1.12, p=0.006), and wheeze (OR=1.05, p=0.01).

Conclusion: SRS measurements were increased in COPD, and associated with worse airflow limitation and COPD symptoms, independent of existing trachea measurements or whole lung emphysema and airway remodeling measures. These findings suggest the CT SRS measurement is an important new biomarker that can help to better understand the impact that trachea abnormities have on airflow limitation and symptom burden in those with COPD.

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