Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS)

Abstract

Background: COPD is characterised by reduced airway lumen dimensions and fewer peripheral airways. Most studies of airway properties sample airways based upon lumen dimension or at random, which may bias comparisons given reduced airway lumen dimensions and number in COPD. We sought to compare central airway wall dimensions on CT in COPD and controls using spatially matched airways, thereby avoiding selection bias of airways in the lung.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) recruited smokers with COPD and controls aged 50-79 years and 40-80 years, respectively. COPD was defined by current guidelines. Using CT image data, airway dimensions were measured for all central airway segments (generations 0-6) following 5 standardised paths into the lungs. Case-control airway comparisons were spatially matched by generation and adjusted for demographics, body size, smoking, CT dose, per cent emphysema, airway length and lung volume.

Results: Among 311 MESA COPD participants, airway wall areas at generations 3-6 were smaller in COPD compared with controls (all p<0.001). Among 1248 SPIROMICS participants, airway wall areas at generations 1-6 were smaller (all p<0.001), and this reduction was monotonic with increasing COPD severity (p<0.001). In both studies, sampling airways by lumen diameter or randomly resulted in a comparison of more proximal airways in COPD to more peripheral airways in controls (p<0.001) resulting in the appearance of thicker walls in COPD (p<0.02).

Conclusions: Airway walls are thinner in COPD when comparing spatially matched central airways. Other approaches to airway sampling result in comparisons of more proximal to more distal airways and potentially biased assessment of airway properties in COPD.

Keywords: COPD epidemiology; Imaging/CT MRI etc.

Figure 1. Airway Wall Area According to COPD Status Stratified by Generation Number in the MESA COPD Study

*p<0.05 for within-generation comparison of mean wall area between participants with no COPD to those with COPD. Mean values and differences adjusted for age, gender, height, race-ethnicity, smoking status, airway length, percent emphysema_−950HU, BMI-determined CT dose, and lung volume at CT. Abbreviations: COPD denotes chronic obstructive pulmonary disease, MESA Multi-Ethnic Study of Atherosclerosis, CI confidence interval, HU Hounsfield units, BMI body mass index, and CT computed tomography.

Figure 2. Airway Wall Areas According to COPD Severity Stratified by Generation Number in SPIROMICS

*p<0.05 for within-generation comparison of airway wall area between participants with no COPD to those with the COPD severity indicated. Mean values and differences adjusted for age, gender, height, race-ethnicity, smoking status, airway length, percent emphysema_−950HU, BMI-determined CT dose, and lung volume at CT. Abbreviations: COPD denotes chronic obstructive pulmonary disease, SPIROMICS Subpopulations and Intermediate Outcome Measures in COPD Study, HU Hounsfield units, BMI body mass index, and CT computed tomography.

Figure 3. Pi10 According to COPD Status in SPIROMICS

*p<0.05 for comparison of mean Pi10 between participants with no COPD to those with COPD. Calculation of Pi10 required 5 or more airways per participant; therefore, Pi10 was not computed for generations 0 to 2. Mean values and differences adjusted for age, gender, height, race-ethnicity, smoking status, airway length, percent emphysema_−950HU, BMI-determined CT dose, and lung volume at CT. Abbreviations: COPD denotes chronic obstructive pulmonary disease, SPIROMICS Subpopulations and Intermediate Outcome Measures in COPD Study, CI confidence interval, HU Hounsfield units, BMI body mass index, and CT computed tomography.