Longitudinal Follow up to Assess Biomarkers Predictive of Emphysema Progression in Patients With COPD (Chronic Obstructive Pulmonary Disease)

Inclusion Criteria:

General Inclusion Criteria

- Male or female healthy subjects or COPD (GOLD I to III) outpatients with or without
A1AT deficiency

- Ex-smokers for at least 9 months with a smoking history of >=20 pack years

- Signed informed consent consistent with ICH-GCP (International Conference on
Harmonisation - Good Clinical Practice) guidelines prior to participation in the
study, which includes the application of study restrictions

- Age >= 40 and <=70 years

- Body mass index (BMI) of >= 18 and <= 35 kg/m2 (<= 30 kg/m2 in the MRI subset)

- Ability to perform all study related procedures including technically acceptable
pulmonary function tests, body plethysmography, DLCO ( Diffusing Capacity of the lungs
for Carbon Monoxide) , sputum induction (if applicable), chest CT (Computed
Tomography) and MRI (if applicable)

Inclusion Criteria Specific for Patients with COPD - Patients must have a current diagnosis
of COPD made by a physician prior to or during Visit 1 and a mMRC (Modified Medical
Research Council Dyspnea Scale) score of 1 or more. The diagnosis of COPD must be in
accordance with GOLD Guidelines and must be documented by the following criteria: Known
relatively stable airway obstruction with a post-bronchodilator FEV1 (Forced Expiratory
Volume in first second)/FVC (Forced Vital Capacity) < 70 %

- The current COPD must be mild, moderate or severe based on lung functions and symptoms
and the clinical situation must have stabilized for at least 4 weeks prior to Visit 1.
The following definitions adapted from the GOLD Guidelines apply:

1. mild: post-broncho-dilator FEV1 >=80% of predicted normal (GLI 2012 and JRS 2014)
at Visit 1

2. moderate: 50%<= post-broncho-dilator FEV1 < 80% of predicted normal (GLI 2012 and
JRS 2014) without chronic respiratory failure at Visit 1

3. severe: 30%<= post-bronchodilator FEV1 <50% of predicted normal (GLI 2012 and JRS
2014) without chronic respiratory failure at Visit 1

- Patients must be on stable therapy (not limited to respiratory medication) for the
last 4 weeks prior to Visit 1

Inclusion Criteria Specific Patients with COPD and A1AT Deficiency

- Documented A1AT deficiency of ZZ genotype

Inclusion Criteria Specific Healthy Subjects

- Normal lung function values at Visit 1 with a documented post-bronchodilator FEV1
>=80% of predicted normal (GLI 2012 and JRS 2014) and a post-bronchodilator FEV1/FVC
>= lower limit of normal

- Mean post DLCO over all acceptable measurements at Visit 1 of >= 70% of predicted
normal

- Further inclusion criteria apply

Exclusion Criteria:

General Exclusion Criteria

- Previous participation in this study or participation in another trial with an
investigational drug within 6 weeks prior to Visit 1 or during the study

- Significant pulmonary disease or other significant medical conditions* (as determined
by medical history, examination and clinical investigations at screening) that may in
the opinion of the investigator result in any of the following:

1. Put the subject at risk because of participation in the study

2. Cause concern regarding the subject's ability to participate in this study *e.g.
rheumatoid arthritis, inflammatory bowel disease, severe liver disease,
psoriasis, hematological, infectious and psychiatric diseases

- Documented history of asthma. For allergic rhinitis or atopy, source documentation to
verify that the subject does not have asthma

- Planned surgery during the study expected to interfere with study procedures and
outcome

- Blood withdrawal of more than 100 mL within the past 6 weeks prior to Visit 1 and
between Visit 1 and 2

- Significant alcohol or drug abuse within past 2 years prior to Visit 1

- Women who are pregnant, nursing or plan to become pregnant while in the study

- Place of permanent residence of less than 3 months prior to Visit 1

- For the MRI subset: subject who do not meet the following criteria for the MRI
assessment at Visit 2: systolic blood pressure between 90 and 180 mmHg (SBP),
diastolic blood pressure between 50 and 110 mmHg (DBP), pulse rate between 40 and 110
bpm, ear temperature between 35 - 37.5 C, and a glomerular filtration rate (GFR) >= 30
mL/min (GFR must not be older than 14 days from the MRI assessment)

Exclusion Criteria Specific for Patients with COPD

- Respiratory tract infection or COPD exacerbation in the 4 weeks prior to Visit 1 or
during the screening period prior to Visit 2, if rescheduling rules cannot be met

Exclusion Criteria Specific Patients with COPD and A1AT Deficiency

- Newly added anti-inflammatory treatment within 4 weeks prior to Visit 1

- Patients on treatment with PDE (Phosphodiesterase)-5 inhibitors (e.g. Roflumilast) and
maintenance treatment Methylxanthines (e.g. Theophylline)

- Hospitalisation for respiratory failure during the year prior to Visit 1

- A history of cystic fibrosis

- Clinical diagnosis of bronchiectasis requiring specific treatment

- Clinically relevant abnormal baseline hematology and blood chemistry

- Known active tuberculosis

- Patients with change in any therapy within 4 weeks prior to Visit 1

- Current and planned A1AT augmentation therapy

- A malignancy for which the patient has undergone resection, radiation or chemotherapy
within past 5 years. Patients with treated basal cell carcinoma or fully cured
squamous cell carcinoma are allowed

- Inability to comply with restrictions regarding diet, life style and medication

- Further exclusion criteria apply