COPD
Conditions
Keywords
COPD, Biomarkers, Cigarette Smoke, Lung Inflammation, FEV, Sputum
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.
Interventions
None listed
Sponsors
Philip Morris Products S.A.
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed written informed consent which includes genetic consent. * Ability to comply with study procedures. * Males and females aged 40-70 years inclusive. * Have a body mass index (BMI) between 18 and 35 kg/m2 inclusive and minimum body weights of 50 kg. * Have a normal physical examination, and have normal laboratory values, 12-lead ECG and vital signs (blood pressure, heart rate and respiratory rate), unless the Investigator considers an abnormality as not clinically significant. * Ability to perform reproducible spirometry according to the American Thoracic Society and the European Respiratory Society (ATS/ERS) guidelines (American Thoracic Society, 2005). * Ability to produce a minimum 0.1 gram sputum sample after induction with inhaled hypertonic saline. Additional Inclusion Criteria COPD Group * A clinical diagnosis of COPD according to the GOLD guidelines (stage 1-2). * Current smokers with ≥10 pack-year smoking history. * Demonstrate a post-bronchodilator ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of \<70 % and FEV1 ≥50 % of predicted normal. Additional Inclusion Criteria Non-Smokers Group * Have never smoked tobacco products. * Demonstrate normal lung function by post bronchodilator FEV1 ≥80 % of predicted normal, with no evidence of airway obstruction FEV1/FVC ratio ≥70 %. * Have a sputum eosinophilia \<2 % and a sputum neutrophilia \<80 % from the sample collected at visit 1 (Belda et al., 2000). Additional Inclusion Criteria Smokers Group * Be current smokers with defined smoking history of ≥10 pack years. * Have normal lung function by post bronchodilator FEV1 ≥80 % of predicted normal, with no evidence of airway obstruction FEV1/FVC ratio ≥70 %. Additional Inclusion Criteria Ex-Smokers Group * Be ex-smokers, with defined smoking history of ≥10 pack years and to have quit smoking at least 1 year before entering the study. * Have normal lung function by post bronchodilator FEV1 ≥80 % of predicted normal, with no evidence of airway obstruction FEV1/FVC ratio ≥70 %.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Protein Markers as Determined by Proteomics Analysis of Induced Sputum | Up to 59 days | Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861 |
| Lipid Markers as Determined by Lipidomic Analysis of Blood Samples | Up to 59 days | Reference to be provided upon publication. |
| mRNA and miRNA (Transcriptomics) Derived From Induced Sputum | Up to 59 days | Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861 |
| mRNA and miRNA (Transcriptomics) Derived From Leukocytes Obtained From Blood Samples | Up to 59 days | Results are available at: Martin F, Talikka M, Hoeng J, Peitsch MC. Identification of gene expression signature for cigarette smoke exposure response--from man to mouse. Hum Exp Toxicol. 2015 Dec;34(12):1200-11. doi: 10.1177/0960327115600364 PMID: 26614807 |
| mRNA and miRNA (Transcriptomics) Derived From Nasal Epithelial Cells Obtained by Nasal Scrapes | Up to 59 days | Reference to be provided upon publication. |
| Total Leukocytes and Differential Leukocytes Count in Sputum | Up to 59 days | Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861 |
Countries
United Kingdom
Participant flow
Recruitment details
Study initiated (first subject enrolled): 01 July 2011
Participants by arm
| Arm | Count |
|---|---|
| Group 1: COPD GOLD Stage 1-2 Subjects with a clinical diagnosis of COPD, according to the GOLD guidelines (Stages 1-2), who are current smokers with at least a 10 pack-year smoking history. | 62 |
| Group 2: Current Cigarette Smokers Subjects who are current smokers with at least a 10 pack-year smoking history, and matched to the COPD cases by ethnicity, gender and age (within 5 years). | 65 |
| Group 3: Ex-Smokers Subjects who are ex-smokers with at least a 10 pack-year smoking history who have not smoked for at least one year, and matched to the COPD cases by ethnicity, gender and age (within 5 years). | 64 |
| Group 4: Never Smokers Subjects who have never smoked (non-smokers), and matched to the COPD cases by ethnicity, gender and age (within 5 years). | 61 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Physician Decision | 1 | 5 | 1 | 1 |
| Overall Study | Subject not matched | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Group 4: Never Smokers | Group 3: Ex-Smokers | Group 1: COPD GOLD Stage 1-2 | Group 2: Current Cigarette Smokers |
|---|---|---|---|---|---|
| Age, Continuous | 56.063 years STANDARD_DEVIATION 7.223 | 55.459 years STANDARD_DEVIATION 7.453 | 56.344 years STANDARD_DEVIATION 7.392 | 57.161 years STANDARD_DEVIATION 7.159 | 55.308 years STANDARD_DEVIATION 6.908 |
| Body Mass Index | 26.972 kg/m^2 STANDARD_DEVIATION 3.67 | 26.479 kg/m^2 STANDARD_DEVIATION 3.719 | 27.333 kg/m^2 STANDARD_DEVIATION 3.558 | 26.461 kg/m^2 STANDARD_DEVIATION 3.7 | 27.568 kg/m^2 STANDARD_DEVIATION 3.657 |
| Number of Cigarettes Smoked Per Day | 15.233 Cig/day STANDARD_DEVIATION 11.611 | 0 Cig/day STANDARD_DEVIATION 0 | 22.422 Cig/day STANDARD_DEVIATION 9.135 | 20.611 Cig/day STANDARD_DEVIATION 9.412 | 17.319 Cig/day STANDARD_DEVIATION 7.541 |
| Pack-year | 26.878 Pack-year STANDARD_DEVIATION 21.977 | 0 Pack-year STANDARD_DEVIATION 0 | 28.535 Pack-year STANDARD_DEVIATION 13.33 | 44.770 Pack-year STANDARD_DEVIATION 22.019 | 33.404 Pack-year STANDARD_DEVIATION 14.577 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 247 Participants | 60 Participants | 63 Participants | 60 Participants | 64 Participants |
| Sex: Female, Male Female | 107 Participants | 26 Participants | 27 Participants | 25 Participants | 29 Participants |
| Sex: Female, Male Male | 145 Participants | 35 Participants | 37 Participants | 37 Participants | 36 Participants |
| Weekly Consumption of Alcohol | 6.717 Units of alcohol STANDARD_DEVIATION 6.998 | 5.775 Units of alcohol STANDARD_DEVIATION 6.711 | 8.445 Units of alcohol STANDARD_DEVIATION 7.097 | 6.694 Units of alcohol STANDARD_DEVIATION 7.662 | 5.923 Units of alcohol STANDARD_DEVIATION 6.31 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 62 | 51 / 65 | 35 / 64 | 40 / 61 |
| serious Total, serious adverse events | 0 / 62 | 0 / 65 | 0 / 64 | 0 / 61 |
Outcome results
Primary
Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale
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.
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 completed the study, but 235 were included in the analysis population as data were missing for 5 subjects:~* 3 subjects in the group COPD GOLD stage 1-2~* 1 subject in the group Ex-smokers~* 1 subject in the group Never smokers
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale | 1.053 units on a scale |
| Group 2: Current Cigarette Smokers | Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale | 0.417 units on a scale |
| Group 3: Ex-Smokers | Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale | 0.186 units on a scale |
| Group 4: Never Smokers | Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale | 0.119 units on a scale |
p-value: <0.000195% CI: [0.654, 1.203]t-test, 2 sided
p-value: <0.000195% CI: [0.609, 1.141]t-test, 2 sided
p-value: <0.000195% CI: [0.386, 0.912]t-test, 2 sided
p-value: 0.398595% CI: [-0.093, 0.231]t-test, 2 sided
p-value: 0.026795% CI: [0.026, 0.414]t-test, 2 sided
p-value: 0.003695% CI: [0.104, 0.506]t-test, 2 sided
Primary
Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred)
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred) | 66.158 percent predicted TLCO |
| Group 2: Current Cigarette Smokers | Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred) | 80.264 percent predicted TLCO |
| Group 3: Ex-Smokers | Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred) | 90.710 percent predicted TLCO |
| Group 4: Never Smokers | Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred) | 93.768 percent predicted TLCO |
p-value: <0.000195% CI: [-32.249, -22.973]t-test, 2 sided
p-value: <0.000195% CI: [-29.501, -19.604]t-test, 2 sided
p-value: <0.000195% CI: [-19.043, -9.17]t-test, 2 sided
p-value: 0.098395% CI: [-6.702, 0.585]t-test, 2 sided
p-value: <0.000195% CI: [-13.845, -7.047]t-test, 2 sided
p-value: <0.000195% CI: [-17.302, -9.707]t-test, 2 sided
Primary
High-Resolution Computerised Tomography (HRCT) of the Chest
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).
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | High-Resolution Computerised Tomography (HRCT) of the Chest | 0.939 score on a scale |
| Group 2: Current Cigarette Smokers | High-Resolution Computerised Tomography (HRCT) of the Chest | 0.803 score on a scale |
| Group 3: Ex-Smokers | High-Resolution Computerised Tomography (HRCT) of the Chest | 0.683 score on a scale |
| Group 4: Never Smokers | High-Resolution Computerised Tomography (HRCT) of the Chest | 0.567 score on a scale |
p-value: <0.000195% CI: [0.269, 0.478]t-test, 2 sided
p-value: <0.000195% CI: [0.158, 0.354]t-test, 2 sided
p-value: 0.019995% CI: [0.022, 0.249]t-test, 2 sided
p-value: 0.024795% CI: [0.015, 0.218]t-test, 2 sided
p-value: 0.020495% CI: [0.019, 0.221]t-test, 2 sided
p-value: <0.000195% CI: [0.127, 0.347]t-test, 2 sided
Primary
Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred)
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred) | 130.118 percent predicted R5 |
| Group 2: Current Cigarette Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred) | 109.458 percent predicted R5 |
| Group 3: Ex-Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred) | 103.581 percent predicted R5 |
| Group 4: Never Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred) | 89.671 percent predicted R5 |
p-value: <0.000195% CI: [28.374, 52.521]t-test, 2 sided
p-value: <0.000195% CI: [14.89, 38.185]t-test, 2 sided
p-value: 0.001895% CI: [7.997, 33.324]t-test, 2 sided
p-value: 0.001595% CI: [5.534, 22.286]t-test, 2 sided
p-value: 0.184795% CI: [-2.886, 14.639]t-test, 2 sided
p-value: 0.000395% CI: [9.536, 30.038]t-test, 2 sided
Primary
Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred)
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred) | 2808.259 percent predicted X5 |
| Group 2: Current Cigarette Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred) | 411.670 percent predicted X5 |
| Group 3: Ex-Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred) | 491.128 percent predicted X5 |
| Group 4: Never Smokers | Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred) | 5787.984 percent predicted X5 |
p-value: 0.198195% CI: [-7560.258, 1600.808]t-test, 2 sided
p-value: 0.195695% CI: [-1224.786, 5859.048]t-test, 2 sided
p-value: 0.207795% CI: [-1367.692, 6160.87]t-test, 2 sided
p-value: 0.115495% CI: [-11930.19, 1336.478]t-test, 2 sided
p-value: 0.809595% CI: [-736.151, 577.234]t-test, 2 sided
p-value: 0.111395% CI: [-12030.714, 1278.085]t-test, 2 sided
Primary
Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres)
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres) | 17.816 Hz |
| Group 2: Current Cigarette Smokers | Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres) | 14.362 Hz |
| Group 3: Ex-Smokers | Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres) | 12.971 Hz |
| Group 4: Never Smokers | Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres) | 11.800 Hz |
p-value: <0.000195% CI: [4.51, 7.521]t-test, 2 sided
p-value: <0.000195% CI: [3.379, 6.31]t-test, 2 sided
p-value: <0.000195% CI: [1.923, 4.984]t-test, 2 sided
p-value: 0.041895% CI: [0.045, 2.296]t-test, 2 sided
p-value: 0.035795% CI: [0.096, 2.686]t-test, 2 sided
p-value: 0.000195% CI: [1.303, 3.82]t-test, 2 sided
Primary
Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE)
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.
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 completed the study, but 233 were included in the analysis population as data were missing for 7 subjects:~* 4 subjects in the group COPD GOLD stage 1-2~* 1 subject in the group Current cigarette smokers~* 1 subject in the group Ex-smokers~* 1 subject in the group Never smokers
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE) | 2.357 score on a scale |
| Group 2: Current Cigarette Smokers | Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE) | 1.254 score on a scale |
| Group 3: Ex-Smokers | Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE) | 1.051 score on a scale |
| Group 4: Never Smokers | Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE) | 0.763 score on a scale |
p-value: <0.000195% CI: [1.179, 1.949]t-test, 2 sided
p-value: <0.000195% CI: [0.924, 1.658]t-test, 2 sided
p-value: <0.000195% CI: [0.724, 1.421]t-test, 2 sided
p-value: 0.028295% CI: [0.031, 0.521]t-test, 2 sided
p-value: 0.122395% CI: [-0.057, 0.471]t-test, 2 sided
p-value: <0.000195% CI: [0.273, 0.71]t-test, 2 sided
Primary
Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred)
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred) | 75.572 percent of predicted FEV1 |
| Group 2: Current Cigarette Smokers | Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred) | 100.837 percent of predicted FEV1 |
| Group 3: Ex-Smokers | Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred) | 108.311 percent of predicted FEV1 |
| Group 4: Never Smokers | Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred) | 111.849 percent of predicted FEV1 |
p-value: <0.000195% CI: [-42.203, -30.352]t-test, 2 sided
p-value: <0.000195% CI: [-38.418, -27.06]t-test, 2 sided
p-value: <0.000195% CI: [-31.081, -19.449]t-test, 2 sided
p-value: 0.150495% CI: [-8.398, 1.321]t-test, 2 sided
p-value: 0.000295% CI: [-11.207, -3.741]t-test, 2 sided
p-value: <0.000195% CI: [-15.979, -6.046]t-test, 2 sided
Primary
Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS)
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.
Time frame: Up to 59 days
Population: Of the 252 enrolled subjects, 240 (60 per group) completed the study, and were included in the analysis population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Group 1: COPD GOLD Stage 1-2 | Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS) | 47.983 score on a scale |
| Group 2: Current Cigarette Smokers | Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS) | 18.817 score on a scale |
| Group 3: Ex-Smokers | Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS) | 12.192 score on a scale |
| Group 4: Never Smokers | Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS) | 8.350 score on a scale |
p-value: <0.000195% CI: [33.964, 45.302]t-test, 2 sided
p-value: <0.000195% CI: [29.761, 41.822]t-test, 2 sided
p-value: <0.000195% CI: [23.445, 34.888]t-test, 2 sided
p-value: 0.041895% CI: [0.147, 7.536]t-test, 2 sided
p-value: 0.008495% CI: [1.763, 11.487]t-test, 2 sided
p-value: <0.000195% CI: [5.888, 15.045]t-test, 2 sided
Other Pre-specified
Lipid Markers as Determined by Lipidomic Analysis of Blood Samples
Reference to be provided upon publication.
Time frame: Up to 59 days
Other Pre-specified
mRNA and miRNA (Transcriptomics) Derived From Induced Sputum
Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861
Time frame: Up to 59 days
Other Pre-specified
mRNA and miRNA (Transcriptomics) Derived From Leukocytes Obtained From Blood Samples
Results are available at: Martin F, Talikka M, Hoeng J, Peitsch MC. Identification of gene expression signature for cigarette smoke exposure response--from man to mouse. Hum Exp Toxicol. 2015 Dec;34(12):1200-11. doi: 10.1177/0960327115600364 PMID: 26614807
Time frame: Up to 59 days
Other Pre-specified
mRNA and miRNA (Transcriptomics) Derived From Nasal Epithelial Cells Obtained by Nasal Scrapes
Reference to be provided upon publication.
Time frame: Up to 59 days
Other Pre-specified
Protein Markers as Determined by Proteomics Analysis of Induced Sputum
Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861
Time frame: Up to 59 days
Other Pre-specified
Total Leukocytes and Differential Leukocytes Count in Sputum
Results are available at: Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22. PMID: 26306861
Time frame: Up to 59 days