longitudinal follow up to assess biomarkers predictive of emphysema progression in patients with copd (chronic obstructive pulmonary disease)

Conditions: Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema

Summary: 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