Effect of Symbicort ® on GR in Sputum in COPD
Condition: Chronic Obstructive Lung Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Symbicort® total dose 400ug/12ug; Symbicort® total dose 800ug/24ug; Formoterol 24ug; BUD total dose 800ug
Intervention description: Symbicort® is combination of formoterol 400ug and budesonide 12ug. Single dose; Symbicort® is combination of formoterol 800ug and budesonide 24ug. Single dose; Turbuhaler; Turbuhaler
Intervention MeSH terms: Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 35 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Chronic Obstructive Lung Disease

Summary:

      The purpose of the research (or "knowledge gap" this research is designed to fill) is to
      understand the science of how the combination therapy of 2 drugs (inhaled longacting
      beta-agonists(LABA) and inhaled corticosteroids (ICS), which are commonly used in chronic
      obstructive pulmonary disease (COPD) patients, is better than each drug alone. ICS and LABA
      both have antiinflammatory properties; that is, they dampen the inflammation in the cells of
      the airways in the lungs. The combination of LABA and ICS has also been shown to improve
      clinical effectiveness in asthma patients. The addition of a LABA to LOW doses of ICS has
      been shown to be more clinically beneficial in asthma than the use of HIGH doses of ICS
      alone. This has allowed a reduction in the total ICS dose and minimised the adverse side
      effects of inhaled corticosteroids. Recent evidence suggests that the use of combination
      therapy of LABA and ICS may also improve clinical effectiveness in COPD patients.

      Investigators will address this hypothesis by examining the inflammation cells of COPD direct
      from the site of disease (the airways) by looking at sputum/mucus. This research will build
      on the existing knowledge of the science of how these drugs work in asthma and COPD and
      allows us to understand the molecular science, which may support new future drug targets for
      patients with COPD, which are greatly needed.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients (n=30) with chronic obstructive pulmonary disease (COPD) with
             mild-to-moderate disease severity (GOLD 1 and 2 guidelines). The post-bronchodilator
             FEV1 will be used in the criteria to define GOLD severity (reference 7/Table 1).

          2. Aged 38-80 years inclusive

          3. FEV1 <15% reversibility (not % predicted) and/or an increase of <200 ml after inhaled
             β2-agonists (400 μg salbutamol)

          4. Patients will be allowed to use their current short-acting β2-agonists (SABA) and
             long-acting β2-agonists (LABA) and short-acting muscarinic-antagonist (SAMA) and
             long-acting muscarinic-antagonists (LAMA). However they should refrain from
             short-acting β2-agonists (SABA) and short-acting muscarinic-antagonist (SAMA) for 6
             hours before the study visit and for long-acting β2-agonists (LABA) and long-acting
             muscarinic-antagonists (LAMA) at least 12 hours before the study visit, unless needed
             by the patient's clinical condition.

          5. Theophylline (an oral tablet bronchodilator) will be required to be stopped at least 3
             days prior to start of Study Visit one, and patients will not be allowed this
             treatment during the study as it may affect the GR response and the bronchodilator
             (lung function, spirometry) responses.

          6. Capable of giving informed consent.

        Exclusion Criteria:

          1. As a result of the medical interview, physical examination or screening
             investigations, the Physician Responsible considers the volunteer unfit for the study.

          2. Patients who have a clinical diagnosis of Asthma, as decided by the Study
             Investigators, as this does not fulfil the diagnosis of chronic obstructive pulmonary
             disease (COPD).

          3. Patients who have had a history of an upper or lower respiratory infection (including
             sinusitis) within 4 weeks prior to study entry, as this can affect the breathing
             response.

          4. Patients who have received oral or parenteral steroids within 4 weeks prior to study
             entry, as this can affect the breathing response and signifies that their condition
             needs to be controlled better.

          5. Patients who have been hospitalised for a COPD exacerbation within 1 month of study
             entry and/or has received antibiotics within 4 weeks of study entry, as this signifies
             that their condition needs to be controlled better.

          6. Patients taking any regular medication that is contraindicated (as indicated in the
             British National Formulary) in those about to receive the study medications listed in
             this protocol; other than the oral contraceptive pill.

          7. Any evidence of a positive pregnancy urine test for female volunteers or females who
             are pregnant or lactating or are likely to become pregnant during the trial. Women of
             child-bearing potential may be included in the study if, in the opinion of the
             investigator, they are taking adequate contraceptive precautions (which will be
             directly enquired at the screening visit).

          8. Patients who have a history of drug allergy which, in the opinion of the Unit
             Physician, contraindicates his/her participation in the study.

          9. Patients with a known or suspected allergy to corticosteroids or any component of the
             formulations and/or suspected hypersensitivity to inhaled corticosteroid (this will be
             asked directly at the screening visit).

         10. Patients who regularly, or on average, drink more than 21 units of alcohol (males) and
             14 units of alcohol (female) per week (this will be asked directly at the screening
             visit).