Please select the eligibility criteria that correspond to the clinical trial below.
Title: Acute and Long-term Effects of Once Daily Oral Inhalation of Tiotropium 18 Mcg Dry Powder Inhalation Capsules in a Placebo Controlled Parallel Group Design Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) of Different Severity
Brief Summary: The primary objective of this study is to investigate the effect of tiotropium vs. placebo on trough FEV1 and FEV1 2 hours post inhalation after 12 weeks of treatment. For both endpoints changes from baseline will be analysed. Three strata of patients will be included (severe COPD, i.e. \<35% of predicted FEV1, moderate COPD, i.e. 35% - \<50% of predicted FEV1, mild COPD, i.e. 50% - 70% of predicted FEV1, according to American Thoracic Society \[ATS\] criteria). The study is conducted in order to find out for which endpoint tiotropium is different from placebo in which stratum.


Options:
A: Inclusion Criteria:

* Adult male and female patients aged 40 with stable moderate to severe COPD (GOLD guidelines).
* Post-salbutamol (FEV1) \< 80% and ≥ 30% of predicted normal value and Post-salbutamol FEV1/FVC \< 70%.
* Current or ex smokers of 10 pack-years.

Exclusion Criteria:

* Patients with no history or current diagnosis of asthma.
* No evidence of an exacerbation within 6 weeks prior to the screening visit.
* No evidence of clinically significant respiratory and/or cardiovascular conditions or laboratory abnormalities.
* No contraindication to use of anticholinergic drugs such as known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma.
B: Inclusion criteria:

* Diagnosis of COPD and diagnosis of asthma before the age of 30
* Current or ex-smokers with a cigarette smoking history of at least 10 pack-years
* Treatment with inhaled steroids at least 1 year before study entry
* FEV1 increase of more than 12% 30 min. after 400 mcg salbutamol or documented reversibility of 12% documented during the past 5 years
* FEV1 increase of more than 200 mL 30 min. after 400 mcg salbutamol or documented increase of 200 mL after reversibility test within the last 5 years
* Post bronchodilator FEV1 less than 80% predicted normal (ECCS) at visit 1
* Post bronchodilator FEV1 less than 70% of FVC at visit 1

Exclusion criteria:

* Respiratory infection or exacerbation 6 weeks prior to Visit 1 or during run-in period.
* Significant diseases other than COPD or asthma
* Myocardial infarction within the last 6 months
* Unstable or life-threatening cardiac arrhythmia requiring intervention or change in therapy in the last year
* Hospitalisation for heart failure (NYHA Class III or IV) within the last year
* History of life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis
* Known active tuberculosis
* History of thoracotomy with pulmonary resection
* History of cancer within the last 5 years (excluding treated basal cell carcinoma)
* Patients requiring oxygen therapy for more than 1 hour per day
* Patients currently in a pulmonary rehabilitation programme or who have completed such a programme within 4 weeks before Visit 1
* Known hypersensitivity to anticholinergic drugs or lactose
C: Inclusion Criteria:

1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

   * Patients must have relatively stable, mild to severe airway obstruction with an FEV1 =\<70% of predicted normal and an FEV1/FVC \< 70 %.
   * Predicted normal values will be taken from the print-outs of the spirometers. Spirometers have to calibrated according to ECCS.
2. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of 10 or more than 10 pack-years. Pack Years = Number of cigarettes/day : 20 x years of smoking (Patients who have never smoked cigarettes must not be included)
4. Patients must be able to perform all study related tests, acceptable pulmonary function tests, including Peak Expiratory Flow Rate (PEFR) measurements, and must be able to maintain diary cards during the study period as required in the protocol.
5. Patients must be able to inhale medication from the HandiHaler.
6. All patients must sign an Informed Consent Form prior to participation in the trial i.e. prior to pre-study washout of their usual pulmonary medications.

Exclusion Criteria:

1. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
2. Patients with a recent history (i.e., one year or less) of myocardial infarction.
3. Patients with any cardiac arrhythmia requiring drug therapy or who have been hospitalised for heart failure within the past three years.
4. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy.
5. Patients with known active tuberculosis.
6. Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed.
7. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
8. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion 1.
9. Patients with any respiratory infection in the past six weeks prior to the Screening Visit (Visit 1) or during the run-in period.
10. Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six week prior to the Screening Visit (Visit 1).
11. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
12. Patients with known symptomatic prostate hypertrophy or bladder neck obstruction.
13. Patients with known narrow-angle glaucoma.
14. Patients using oral corticosteroid medication at unstable doses (i.e., less than four weeks on a stable dose before Visit 1) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
15. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants).
16. Patients with a history of asthma, allergic rhinitis or atopy.
17. Patients with a history of and/or active significant alcohol or drug abuse.
18. Patients who have taken an investigational drug within one month prior to Screening Visit (Visit 1). A log of all subjects screened, and reasons for exclusion for those not randomised will be maintained.
D: Inclusion Criteria:

1. Patients who have signed an written informed consent consistent with ICH GCP guidelines and local legislations prior to participation in the trial.
2. Patients with a diagnosis of COPD. COPD is defined as a disease state characterised by the presence of airflow obstruction often due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyperreactivity, and may be partially reversible.
3. Patients 40 years of age or older without any restriction to sex.
4. Patients who currently smoke or who are ex-smokers with a cigarette smoking history of \>10 pack-years.
5. Patients who have a relatively stable airway obstruction (at least 4 weeks free of COPD exacerbations) with a post bronchodilator FEV1 ? 60% of predicted normal, a post bronchodilation FEV1 \< 70% of FVC, and a MRC symptom score minimum of 2 at Visit 1

Exclusion Criteria:

1. Patients with a history of asthma, allergic rhinitis, atopy, or who have a total (absolute) blood eosinophil count ? 600 per mm3 (= 0.6 \* 109/L) of the first determination at Visit 1
2. Patients with known moderate or severe renal insufficiency.
3. Patients with a recent history (i.e., 6 months or less prior to Visit 1) of myocardial infarction.
4. Patients with any unstable or life threatening cardiac arrhythmia, including patients with a newly diagnosed, clinically relevant arrhythmia on the electrocardiogram (ECG) performed at Visit 1 as well as patients with cardiac arrhythmia requiring an intervention (i.e., hospitalisation, cardioversion, pacemaker placement, and automatic implantable cardiac defibrillator (AICD) placement) or a change in drug therapy during the last year prior to Visit 1.
5. Patients who regularly use oxygen therapy.
6. Patients with known active tuberculosis.
7. Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma are allowed.
8. Patients with a history of life threatening pulmonary obstruction or a history of cystic fibrosis or clinically evident bronchiectasis.
9. Patients who have undergone thoracotomy with pulmonary resection.
10. Patients who are currently in a pulmonary rehabilitation program or who have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
11. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
12. Patients with known symptomatic hyperplasia or bladder neck obstruction. Patients being treated for prostatic hyperplasia and report minimal symptoms may be included and should continue their medications.
13. Patients with known narrow-angle glaucoma.

Answer: C