Table 2.

Summary of biomarker assessments

Variables	Biomarker assessment
Pre-specified soluble biomarkers
Blood	Total and differential cell counts. DNA analyses (to determine A1AT genotype).
Induced sputum*	Neutrophil elastase activity. Proteinase 3 activity. Cat G activity.
Serum/plasma	Tissue turnover biomarkers (including neutrophil elastase-specific elastin fragment). Other protease-generated neoepitopes (including Cat S cleaved decorin). Soluble form of receptor for advanced glycation end products. Surfactant protein D. Lysyl oxidase-like 2. Biomarkers of systemic inflammation (including IL-6, high-sensitivity C reactive protein, white cell count and fibrinogen).
Imaging biomarkers
CT scanning	Airway morphology Mean lumen diameter. % wall area. Mean segmental and subsegmental airway wall thickness. Square root of wall area of bronchus with internal perimeter of 10 mm (pi10). Emphysema (on inspiratory CT) PD15 of the CT histogram. PD15 adjusted for inspired lung volume. % lung voxels with attenuation ≤–950 HU (LAA-950). Air trapping (on expiratory CT) % lung voxels with attenuation ≤–856 HU (LAA-856). Registration-based parenchyma measurements % normal lung, % emphysema and % small airway disease.
MRI	Conducted at 1.5 Tesla in a subset of subjects without airflow limitation and in patients with COPD and without A1ATD to assess functional lung parameters, including pulmonary blood flow.
Clinical parameters/assessments	Spirometry to assess FEV1 and FVC. DLCO and DLCO per unit of alveolar volume. Body plethysmography (functional residual capacity, total lung capacity, inspiratory capacity, inspiratory vital capacity, residual volume and expiratory reserve volume). Pulse oximetry. Symptom questionnaires (modified Medical Research Council dyspnoea scale, COPD Assessment Test, St. George’s Respiratory Questionnaire). 6-min walk test. Body mass index and BODE index. Adverse events and MESI.

*Collected at selected sites.

A1AT, alpha1-antitrypsin; A1ATD, alpha1-antitrypsin deficiency; BODE, Body mass index, airway Obstruction, Dyspnea, and Exercise; Cat, cathepsin; COPD, chronic obstructive pulmonary disease; DL_CO, diffusing capacity of the lungs for carbon monoxide; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; HU, Hounsfield Units; IL-6, interleukin-6; LAA, low attenuation areas; MESI, medical events of special interest; PD15, lung density at the 15th percentile point of the CT histogram.