A Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures.

• History of moderate to very severe COPD with a post-bronchodilator forced expiratoryvolume/forced vital capacity (FEV1/FVC) <0.70 and a post-bronchodilator FEV1>20% and ≤80% of predicted normal value at screening.

• Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year= 20cigarettes smoked per day for 1 year).

Exclusion Criteria:

• Clinically important pulmonary disease other than COPD (e.g. active lung infection,clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis,hypoventilation syndrome associated with obesity, and primary ciliary dyskinesia) and/or radiological findings suggestive of a respiratory disease other than COPD that iscontributing to the subject's respiratory symptoms.

• Any disorder, including, but not limited to, cardiovascular, gastrointestinal,hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,haematological, psychiatric, or major physical impairment that is not stable in theopinion of the Investigator and could:

1. Affect the safety of the subject throughout the study

2. Influence the findings of the study or their interpretation

3. Impede the subject's ability to complete the entire duration of study Subjectswho have epilepsy must be on a stable dose of medication for 30 days prior toVisit 4.

• Unstable ischemic heart disease, or uncontrolled arrhythmia, cardiomyopathy, heartfailure, and renal failure, or uncontrolled hypertension as defined by theInvestigator, or any other relevant cardiovascular disorder as judged by theInvestigator

• Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization fora COPD exacerbation within 8 weeks prior to enrolment (Visit 1), based on last dose ofsteroids or last date of hospitalization whatever occurred later.

• Acute upper or lower respiratory infection requiring antibiotics or antiviralmedication within 2 weeks prior to enrolment (Visit 1).

• Pneumonia within 8 weeks prior to enrolment (Visit 1), based on the last day ofantibiotic treatment or hospitalization date, whatever occurred later.

• Pregnant, breastfeeding, or lactating women.

• Any clinically significant abnormal findings in physical examination, vital signs,haematology, clinical chemistry, or urinalysis during screening/run-in period, which,in the opinion of the Investigator, may put the subject at risk because of his/herparticipation in the study, or may influence the results of the study, or thesubject's ability to complete entire duration of the study.

• Use of immunosuppressive medication, including rectal corticosteroids, high potencytopical corticosteroids and systemic steroids within 28 days prior to randomization.

• Receipt of blood products within 30 days prior to enrollment (Visit 1).

• Receipt of any investigational non-biologic product within 30 days or 5 half-livesprior to Visit 1.

• History of alcohol or drug abuse within the past year, which may compromise the studydata interpretation as judged by Investigator or Study Physician.

• Subjects who in the opinion of the investigator or qualified designee have evidence ofactive tuberculosis (TB), either treated or untreated.

• Scheduled in-patient hospitalization or surgical procedure during the course of thestudy.

• Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA, http://www.ginasthma.org/) guidelines or other accepted guidelines. Subjectswith a past medical history of asthma (e.g. childhood or adolescence) may be included.

• The male partner of someone who may become pregnant during the course of the study