Systemic Endothelial Abnormalities in COPD
Systemic Endothelial Abnormalities in COPD
The purpose of this project is to validate the peripheral arterial pressure waveform
 measurements technique of RAAP (radial artery applanation tonometry), in patients with
 moderate and severe COPD (Chronic Obstructive Pulmonary Disease), and to assess the degree of
 systemic endothelial dysfunction in these patients compared to cigarette smokers with normal
 lung function and non-smokers with normal lung function.
Patients with moderate and severe COPD (GOLD stage II and III) will be studied and their
 results will be compared with age-matched healthy non- smokers and smokers.

 RAAP will be taken every 5 minutes for 15 minutes before salbutamol and every 5 minutes for
 another 15 minutes after salbutamol.

 Several parameters of lipoprotein profiles, anti-oxidant plasma capacity, inflammatory
 cytokines, hormones, growth factors and vascular cell adhesion molecules will be studied in
 blood. In addition, several inflammatory and oxidative markers will be studied in exhaled
 breath condensate. Lung function and impulse oscillometry will be made to investigate airway
 resistance, and exhaled NO (nitric oxide) at different expiratory flows will be measured to
 assess alveolar and bronchial NO. Clinical assessment including dyspnoea and depression
 scores will also be made.
Inclusion Criteria:

 -  • Male subjects with COPD with FEV1/FVC<70%; predicted defined as either stage
 moderate GOLD II (n=15) and severe GOLD III (n=7) diagnosis according to GOLD criteria
 (Global Strategy for the Diagnosis, Management, and Prevention of COPD) or Male
 subjects who are age-matched non-smokers (n=8) and male smokers (n=8) with normal lung
 function (FEV1>80%, FEV1/FVC>70%, n=8)

 -  Smokers:

 An active smoker with a pack history of >10 pack years [number of pack years = (number of
 cigarettes per day / 20) x number of years smoked]. Smokers need to report the time when
 last cigarette was smoked (no less than 6 hours before the study visit).

 -  Patients will be allowed to use their current anticholinergic bronchodilators and
 continue on the dose of inhaled corticosteroids they are currently using. However they
 should refrain from short and long-acting β2-agonists for 6 and 12 hours,
 respectively, before the study visit.

 -  Aged 40 80 years inclusive

 -  Body mass index within the range 19-32kg/m2 inclusive

 -  FEV1 <15% reversibility (not % predicted) and an increase of <200ml after inhaled
 β2-agonists (400μg salbutamol).

 -  Capable of giving informed consent, which includes compliance with the requirements
 and restrictions listed in the consent form.

 -  Subject is available to complete the study.

 Exclusion Criteria:

 -  • As a result of the medical interview, physical examination or screening
 investigations, the Physician Responsible considers the volunteer unfit for the study.

 -  The subject has participated in a study with a new molecular entity during the
 previous 3 months or any other clinical trial during the previous 3 months. In
 case of a non invasive, clinical trial not involving new molecular entities a 2
 week washout will be sufficient

 -  The subject regularly, or on average, drinks more than 21 units of alcohol per
 week.

 -  The subject has received oral steroids within 2 weeks prior to study entry.

 -  The subject has history of an upper respiratory infection (including sinusitis)
 within 2 weeks prior to study entry

 -  The subject has been hospitalised for a COPD exacerbation within 1 month of study
 entry.