Chronic Obstructive Pulmonary Disease (COPD) Biomarker Identification Study

Completed

Conditions: COPD

Registration Number: NCT01780298

Lead Sponsor: Philip Morris Products S.A.

Brief Summary: Chronic obstructive pulmonary disease (COPD) is a common inflammatory disease of the airway affecting approximately 10% of individuals aged 40 years or more with a smoking history. The disease is characterized by an increase in numbers of airway white blood cells (neutrophils, lymphocytes and monocytes). Stimulation of white blood cells results in the release of different agents of inflammation. Some of these agents give an indication of the presence or severity of a disease when measured.

This case control study will be conducted at The Heart Lung Centre, London, UK. The study aims to determine biomarkers for the differentiation of subjects with COPD (GOLD Stage 1-2 and who are current smokers with a ≥ 10 pack year smoking history) and three matched control groups: one of non-smoking subjects (never smoked), one of ex-smokers and one of current smokers. COPD subjects will be matched to the non-COPD subjects by gender, age and ethnicity.

The study will include a range of physiological measurements including lung function, computerized tomography scans (CT scans), cardio pulmonary exercise test and computerized multichannel lung sounds analysis (Stethographics). In addition, lung inflammation will be assessed by cellular and molecular biomarkers using e.g. transcriptomics and proteomics technologies.

Detailed Description: At the screening visit, subject consent will be obtained prior to conducting any study related procedures. Informed consent may be obtained on registration/review visit at the Centre where it is conducted and thus prior to visit 1.

The screening visit will involve obtaining demographic data and medical history information as well as performing safety assessments such as vital sign measurements, electrocardiogram (ECG), and clinical laboratory tests. An induced sputum sample will be obtained to ensure that subjects can produce an adequate sputum sample. Smokers will receive information on smoking cessation at the screening visit and follow-up telephone call.

Subjects will come back to the center on up to four further occasions if they meet the inclusion/exclusion criteria at screening:

* visit 2: 4 to 21 days after screening,

* visit 3: 3-14 days post visit 2, and

* visit 4: 3-14 days post visit 3.

A follow-up telephone call will be conducted 3-10 days post visit 4.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 252

Inclusion Criteria

Not provided

Exclusion Criteria

Current evidence or recent history of any clinically significant disease or abnormality (other than COPD in the subjects with COPD group), which in the opinion of the Investigator, would put the subject at risk, or which would compromise the quality of the study data, including but not limited, to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities.
Females with a positive pregnancy test at visit 1 or 3.
Females currently breastfeeding.
Involvement in the planning and conduct of the study.
Surgery or significant trauma within 3 months of visit 1.
History of tuberculosis or other non-specific pulmonary diseases such as asthma.
Symptoms, signs or laboratory findings suggestive of an ongoing infective illness as judged by the Investigator at visit 1 or 2.
Participation in any clinical study with an investigational drug in the 4 months prior to visit 1, or participation in a study with a new formulation of a marketed drug in the 3 months prior to visit 1, or participation in a methodology study in the month prior to visit 1.
Symptoms of any clinically significant illness within 2 weeks prior to visit 1.
A significant history of alcohol abuse or consumption of more than the recommended units of alcohol per week (28 units for males and 21 units for females).
A significant history of drug abuse (including benzodiazepines) or a positive test of drug abuse test at visit 1.
Subjects, who in the opinion of the Investigator should not, for safety or compliance reasons, participate in the study.
Use of prohibited medications.
Subjects who have a first degree relative (parents, sibling or child) already enrolled in the study.

Additional Exclusion Criteria - subjects with COPD

Recent history of hospitalization due to an exacerbation of airway disease within 3 months of the screening visit or subjects with need for increased treatments for COPD within 6 weeks prior to the screening visit.
Prior lung volume reduction surgery or history of chest/lung irradiation.
Regular use of daily oxygen therapy.
Long standing history and primary diagnosis of asthma.
Use of systemic steroids within 3 months prior to the screening visit.
Respiratory tract infection within 6 weeks prior to the screening visit.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred)	Up to 59 days
Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred)	Up to 59 days
Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred)	Up to 59 days
Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred)	Up to 59 days
Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres)	Up to 59 days
Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS)	Up to 59 days	Stethographics analysis was performed using the 16-channel lung sound analyzer system STG1602 (Stethographics, Boston, MA, USA) following the supplier's recommendations. Lung sound data are obtained from an intermediate deeper-than-normal breath (pattern 2; P2). Each breath pattern is recorded for a minimum of 30 seconds allowing 3 to 6 breaths to be taken, with measurements completed over 3 to 4 minutes. Each of the 16 parameters derived from one measurement are evaluated and a score from 0 to 10 is assigned based on the value of the individual parameter. The total standard Acoustic COPD Score (ACOPDS) is calculated as the sum of the individual score for each parameter, which permits a maximum score of 160. Although this stethographics analysis system was considered experimental, a higher score was associated with poor health outcomes and a lower score with a better health state.
Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale	Up to 59 days	The MMRC scale uses a simple grading system to assess a subject's level of dyspnea (shortness of breath). Subjects were asked to grade the degree of breathlessness related to activities by choosing 1 of the following answers: * 0: Not troubles by breathlessness except on strenuous exercise * 1: Short of breath when hurrying or walking up a slight hill * 2: Walks slower than contemporaries on the level because of breathlessness, or has to stop for breath when walking at own pace * 3: Stops for breath after about 100 meters or after a few minutes on the level * 4: Too breathless to leave the house, or breathless when dressing or undressing.
Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE)	Up to 59 days	The BODE Index is a 10-point scale to assess prognostic factors in COPD patients. Body mass index ("B"), airway obstruction ("O"), dyspnea ("D"), and exercise tolerance ("E") are each graded on a 4 point scale (0 to 3), except body mass index (0 or 1) . The final BODE Index value is the sum of the scores for each prognostic factor, where a higher BODE score indicates a higher risk of death. The modified BODE (mBODE) index as defined by Lopez-Campos (2010) was used in this study, and is composed of the following factors: * Body mass index: (0 or 1) * Degree of airflow obstruction (FEV1% Pred): (0 to 3) * Functional dyspnea (MMRC Dyspnoea Scale): (0 to 3) * Exercise capacity (VO2max): (0 to 3) Lopez-Campos, José Luis, et al. "Modified BODE indexes: Agreement between multidimensional prognostic systems based on oxygen uptake." International Journal of Chronic Obstructive Pulmonary Disease (2010): 133-140.
High-Resolution Computerised Tomography (HRCT) of the Chest	Up to 59 days	CT scans were assessed by two radiologists. A scoring system from 0 to 4 was applied, depending upon the component: 1. Extent of disease (emphysema): 0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe 2. Severity of bronchial dilatation: 0=none; 1=mild (1.5x to 2.5x diameter of pulmonary artery); 2=severe (\>2.5x diameter of pulmonary artery) 3. Traction bronchiectasis: 0=none; 1=mild (1.5x to 2.5x diameter); 2=severe (\>2.5x diameter). 4. Total bronchiectasis score derived by adding the bronchial dilatation and traction bronchiectasis scores 5. Bronchial wall thickening: 0=none; 1=0.5x; 2=0.5-1x; 3= \>1x the diameter of the adjacent pulmonary artery 6. Small airways disease: 0=absent, 1=mild, 2=moderate, 3=severe and 4=very severe The total score (higher score indicated a poor outcome) was derived from the mean of all scores. This is described in Chaudhary, Nveed, et al. "Physiological and biological characterization of smokers with and without COPD." F1000Research 6 (2017).