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

The study will include 60 healthy subjects (ex-smoker without any airflow limitation), 125 COPD GOLD (global initiative for chronic obstructive lung disease) I , 125 COPD GOLD II, 125 COPD GOLD III and up to 20 patients with COPD and A1AT (Alpha1-Antitrypsin) deficiency (ZZ genotype). Soluble and imaging biomarkers will be investigated addressing different aspects of disease pathways postulated to be relevant for COPD progression.


Eligibility Criteria:
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