Trial Outcomes & Findings for Occurrence of Potential Bacterial and Viral Pathogens in Stable Chronic Obstructive Pulmonary Disease and During Acute Exacerbations of the Disease, in Asia Pacific (NCT NCT03151395)

Last Updated: 2021-06-14

Results Overview

The proportion of sputum samples obtained at each visit (confirmed stable or AECOPD visits) and positive for specific bacterial pathogens by bacteriological methods (overall and by bacterial species). Numerator is the number of sputum samples positive for a given pathogen and denominator is the number of visits with a sputum sample tested for a given pathogen. Proportion is computed with 95% confidence intervals. A confirmed stable visit is defined as a scheduled study visit for which the investigator confirms that the subject is stable/ has recovered from a previous exacerbation. Bacterial pathogens include Haemophilus influenzae (Hi), Non-typeable Haemophilus influenzae (NTHi), non-Haemophilus influenzae (Non-Hi), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pseumoniae), Acinetobacter baumannii (A. baumannii).

Recruitment status

COMPLETED

Study phase

Target enrollment

197 participants

Primary outcome timeframe

Over the course of one year from the study start (Month 0 to Month 12)

Results posted on

2021-06-14

Participant Flow

Participant milestones

Participant milestones
Measure	Total Group Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Overall Study STARTED	197
Overall Study COMPLETED	182
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Total Group Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Overall Study Adverse Event	2
Overall Study CONSENT WITHDRAWAL NOT DUE TO ADV. EVENT	6
Overall Study Subjects could not perform last visit before study completion date due to local COVID19 restrictions	3
Overall Study Unspecified reason	4

Baseline Characteristics

Occurrence of Potential Bacterial and Viral Pathogens in Stable Chronic Obstructive Pulmonary Disease and During Acute Exacerbations of the Disease, in Asia Pacific

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Age, Continuous	68.5 Years STANDARD_DEVIATION 7.3 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	187 Participants n=5 Participants
Race/Ethnicity, Customized ASIAN - EAST ASIAN HERITAGE	126 Participants n=5 Participants
Race/Ethnicity, Customized ASIAN - SOUTH EAST ASIAN HERITAGE	71 Participants n=5 Participants

PRIMARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Outcome measures

Outcome measures
Measure	Total Group n=196 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Any, Any stable visit	74.2 Percentage of sputum samples Interval 70.4 to 77.7
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Any, Any AECOPD visit	78 Percentage of sputum samples Interval 72.1 to 83.2
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Hi, Any stable visit	94.6 Percentage of sputum samples Interval 84.2 to 99.1
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Hi, Any AECOPD visit	94.1 Percentage of sputum samples Interval 76.6 to 99.7
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs NTHi, Any stable visit	94.6 Percentage of sputum samples Interval 84.2 to 99.1
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs NTHi, Any AECOPD visit	94.1 Percentage of sputum samples Interval 76.6 to 99.7
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Non-Hi, Any stable visit	5.4 Percentage of sputum samples Interval 0.9 to 15.8
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Non-Hi, Any AECOPD visit	5.9 Percentage of sputum samples Interval 0.3 to 23.4
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs M. catarrhalis, Any stable visit	0.9 Percentage of sputum samples Interval 0.3 to 1.9
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs M. catarrhalis, Any AECOPD visit	3.3 Percentage of sputum samples Interval 1.5 to 6.4
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs S. pneumoniae, Any stable visit	2.5 Percentage of sputum samples Interval 1.4 to 4.1
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs S. pneumoniae, Any AECOPD visit	2.4 Percentage of sputum samples Interval 0.9 to 5.1
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs S. aureus, Any stable visit	3.1 Percentage of sputum samples Interval 1.8 to 4.7
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs S. aureus, Any AECOPD visit	3.3 Percentage of sputum samples Interval 1.5 to 6.4
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs P. aeruginosa, Any stable visit	8.5 Percentage of sputum samples Interval 6.4 to 11.0
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs P. aeruginosa, Any AECOPD visit	14.4 Percentage of sputum samples Interval 10.0 to 19.5
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs K. pneumoniae, Any stable visit	26.4 Percentage of sputum samples Interval 22.8 to 30.1
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs K. pneumoniae, Any AECOPD visit	24.9 Percentage of sputum samples Interval 19.3 to 31.0
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs A. baumannii, Any stable visit	2.2 Percentage of sputum samples Interval 1.2 to 3.6
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs A. baumannii, Any AECOPD visit	4.3 Percentage of sputum samples Interval 2.1 to 7.6
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Other bacteria, Any stable visit	47.7 Percentage of sputum samples Interval 43.5 to 51.8
Percentage of Sputum Samples Positive for Bacterial Pathogens as Identified by Bacteriological Methods, in Any Stable COPD Patients and During AECOPDs Other bacteria, Any AECOPD visit	45 Percentage of sputum samples Interval 38.3 to 51.8

PRIMARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The proportion of sputum samples obtained at each visit (confirmed stable visits and AECOPD visits) and positive for specific viral pathogens by PCR (overall and by viral species). The numerator is the number of sputum samples positive for a given pathogen and the denominator is the number of visits with a sputum sample tested for a given pathogen. The proportion is calculated with 95% confidence intervals. Viral pathogens, as identified by PCR, include respiratory syncytial virus (RSV), parainfluenza virus, enterovirus, human rhinovirus (HRV), metapneumovirus, influenza virus, adenovirus, bocavirus and coronavirus.

Outcome measures

Outcome measures
Measure	Total Group n=195 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Any, Any stable visit	15 Percentage of sputum samples Interval 12.2 to 18.2
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Any, Any AECOPD visit	35.6 Percentage of sputum samples Interval 29.1 to 42.5
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs RSV, Any stable visit	0.9 Percentage of sputum samples Interval 0.3 to 2.0
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs RSV, Any AECOPD visit	1 Percentage of sputum samples Interval 0.2 to 3.1
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Parainfluenza virus, Any stable visit	0.7 Percentage of sputum samples Interval 0.2 to 1.7
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Parainfluenza virus, Any AECOPD visit	4.7 Percentage of sputum samples Interval 2.3 to 8.2
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Enterovirus, Any stable visit	0.6 Percentage of sputum samples Interval 0.1 to 1.4
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Enterovirus, Any AECOPD visit	0 Percentage of sputum samples Interval 0.0 to 1.9
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs HRV, Any stable visit	8.1 Percentage of sputum samples Interval 6.0 to 10.6
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs HRV, Any AECOPD visit	16.6 Percentage of sputum samples Interval 11.8 to 22.3
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Metapneumovirus, Any stable visit	0 Percentage of sputum samples Interval 0.0 to 0.7
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Metapneumovirus, Any AECOPD visit	0 Percentage of sputum samples Interval 0.0 to 1.9
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Influenza virus, Any stable visit	0.7 Percentage of sputum samples Interval 0.2 to 1.7
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Influenza virus, Any AECOPD visit	8.2 Percentage of sputum samples Interval 4.9 to 12.7
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Adenovirus, Any stable visit	2 Percentage of sputum samples Interval 1.1 to 3.4
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Adenovirus, Any AECOPD visit	4.1 Percentage of sputum samples Interval 1.9 to 7.6
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Bocavirus, Any stable visit	0.2 Percentage of sputum samples Interval 0.0 to 0.8
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Bocavirus, Any AECOPD visit	0 Percentage of sputum samples Interval 0.0 to 1.9
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Coronavirus, Any stable visit	2.6 Percentage of sputum samples Interval 1.5 to 4.1
Percentage of Sputum Samples Positive for Viral Pathogens as Identified by Polymerase Chain Reaction (PCR) in Stable COPD Patients and During AECOPDs Coronavirus, Any AECOPD visit	5.7 Percentage of sputum samples Interval 3.0 to 9.5

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The proportion of sputum samples obtained at each confirmed stable/AECOPD visit and positive for specific bacterial pathogens as measured by real-time qualitative PCR/quantitative PCR, (overall and by bacterial species,) are computed with 95% confidence intervals. The numerator is the number of sputum samples positive for a given pathogen and the denominator is the number of visits with a sputum sample tested for a given pathogen. The bacterial pathogens include H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, P. aeruginosa and S. pyogenes. A confirmed stable visit is defined as a scheduled study visit for which the investigator confirms that the subject is stable / has recovered from a previous exacerbation.

Outcome measures

Outcome measures
Measure	Total Group n=195 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR Any, Any stable visit	67 Percentage of sputum samples Interval 63.0 to 70.9
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR Any, Any AECOPD visit	74.7 Percentage of sputum samples Interval 68.3 to 80.5
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR H. influenzae, Any stable visit	42.9 Percentage of sputum samples Interval 38.7 to 47.0
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR H. influenzae, Any AECOPD visit	39.7 Percentage of sputum samples Interval 33.0 to 46.7
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR M. catarrhalis, Any stable visit	13.7 Percentage of sputum samples Interval 11.0 to 16.8
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR M. catarrhalis, Any AECOPD visit	26.8 Percentage of sputum samples Interval 20.9 to 33.3
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. pneumoniae, Any stable visit	16.8 Percentage of sputum samples Interval 13.9 to 20.1
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. pneumoniae, Any AECOPD visit	19.1 Percentage of sputum samples Interval 14.0 to 25.0
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. aureus, Any stable visit	10.6 Percentage of sputum samples Interval 8.2 to 13.4
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. aureus, Any AECOPD visit	9.3 Percentage of sputum samples Interval 5.7 to 13.9
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR P. aeruginosa, Any stable visit	16.3 Percentage of sputum samples Interval 13.4 to 19.6
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR P. aeruginosa, Any AECOPD visit	16.5 Percentage of sputum samples Interval 11.7 to 22.1
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. pyogenes, Any stable visit	0.4 Percentage of sputum samples Interval 0.1 to 1.1
Percentage of Sputum Samples Positive for Bacterial Pathogens in Stable COPD Patients and During AECOPDs, as Identified by PCR S. pyogenes, Any AECOPD visit	1 Percentage of sputum samples Interval 0.2 to 3.1

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the sputum samples taken from Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Concordance between bacteriological methods (culture) and PCR sputum results are described for all the combinations of bacterial presence by both measures. Each category name includes the following parameters: Bacteria species-Culture (yes/no)- PCR (yes/no). Concordance is expressed as the number of sputum samples in a given category among the total number of sputum samples assessed for the presence of bacterial pathogens by both culture and PCR

Outcome measures

Outcome measures
Measure	Total Group n=740 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit H. influenzae, Culture No, PCR No	425 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit H. influenzae, Culture No, PCR Yes	260 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit H. influenzae, Culture Yes, PCR No	4 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit H. influenzae, Culture Yes, PCR Yes	51 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit M. catarrhalis, Culture No, PCR No	613 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit M. catarrhalis, Culture No, PCR Yes	115 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit M. catarrhalis, Culture Yes, PCR No	0 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit M. catarrhalis, Culture Yes, PCR Yes	12 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. pneumoniae, Culture No, PCR No	610 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. pneumoniae, Culture No, PCR Yes	111 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. pneumoniae, Culture Yes, PCR No	1 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. pneumoniae, Culture Yes, PCR Yes	18 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. aureus, Culture No, PCR No	655 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. aureus, Culture No, PCR Yes	62 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. aureus, Culture Yes, PCR No	9 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit S. aureus, Culture Yes, PCR Yes	14 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit P. aeruginosa, Culture No, PCR No	599 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit P. aeruginosa, Culture No, PCR Yes	67 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit P. aeruginosa, Culture Yes, PCR No	20 Sputum samples
Number of Sputum Samples in a Given Category Relative to All Combinations for Each Bacterial Pathogen, When Identified by Bacteriological Methods or PCR, at Any Visit P. aeruginosa, Culture Yes, PCR Yes	54 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each confirmed stable visit, and positive for bacterial pathogens by bacteriological methods (overall and by bacterial species). The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator forced expiratory volume in 1 second (FEV1) and can be divided into four GOLD grades \[GOLD, 2013\]: GOLD 1 (MILD): FEV1 ≥ 80% predicted; GOLD 2 (Moderate)= 50% ≤ FEV1 \< 80% predicted; GOLD 3 (Severe) = 30% ≤ FEV1 \< 50% predicted; GOLD 4 (Very Severe) = FEV1 \< 30% predicted.

Outcome measures

Outcome measures
Measure	Total Group n=280 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Any, GOLD 2	150 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Any, GOLD 3	217 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Any, GOLD 4	44 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Hi, GOLD 2	12 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Hi, GOLD 3	20 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Hi, GOLD 4	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade NTHi, GOLD 2	12 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade NTHi, GOLD 3	20 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade NTHi, GOLD 4	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Non-Hi, GOLD 2	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Non-Hi, GOLD 3	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Non-Hi, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. pneumoniae, GOLD 2	4 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade M. catarrhalis, GOLD 2	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade M. catarrhalis, GOLD 3	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade M. catarrhalis, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. pneumoniae, GOLD 3	10 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. pneumoniae, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. aureus, GOLD 2	7 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. aureus, GOLD 3	6 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade S. aureus, GOLD 4	4 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade P. aeruginosa, GOLD 2	14 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade P. aeruginosa, GOLD 3	24 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade P. aeruginosa, GOLD 4	9 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade K. pneumoniae, GOLD 2	70 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade K. pneumoniae, GOLD 3	60 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade K. pneumoniae, GOLD 4	16 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade A. baumannii, GOLD 2	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade A. baumannii, GOLD 3	9 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade A. baumannii, GOLD 4	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Other bacteria, GOLD 2	87 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Other bacteria, GOLD 3	149 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by Bacteriological Methods, and Classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade Other bacteria, GOLD 4	28 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each confirmed stable visit, and positive for bacterial pathogens by PCR (overall and by bacterial species). The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator forced expiratory volume in 1 second (FEV1) and can be divided into four GOLD grades \[GOLD, 2013\]: GOLD 1 (MILD): FEV1 ≥ 80% predicted; GOLD 2 (Moderate)= 50% ≤ FEV1 \< 80% predicted; GOLD 3 (Severe) = 30% ≤ FEV1 \< 50% predicted; GOLD 4 (Very Severe) = FEV1 \< 30% predicted.

Outcome measures

Outcome measures
Measure	Total Group n=277 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 2	146 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 3	184 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 4	36 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade H. influenzae, GOLD 2	95 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade H. influenzae, GOLD 3	120 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade H. influenzae, GOLD 4	19 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade M. catarrhalis, GOLD 2	30 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade M. catarrhalis, GOLD 3	42 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade M. catarrhalis, GOLD 4	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pneumoniae, GOLD 2	39 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pneumoniae, GOLD 3	47 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pneumoniae, GOLD 4	6 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. aureus, GOLD 2	33 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. aureus, GOLD 3	20 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. aureus, GOLD 4	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade P. aeruginosa, GOLD 2	33 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade P. aeruginosa, GOLD 3	44 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade P. aeruginosa, GOLD 4	12 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pyogenes, GOLD 2	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pyogenes, GOLD 3	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade S. pyogenes, GOLD 4	0 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each confirmed stable visit, and positive for virus pathogens by PCR (overall and by viral species). The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator forced expiratory volume in 1 second (FEV1) and can be divided into four GOLD grades \[GOLD, 2013\]: GOLD 1 (MILD): FEV1 ≥ 80% predicted; GOLD 2 (Moderate)= 50% ≤ FEV1 \< 80% predicted; GOLD 3 (Severe) = 30% ≤ FEV1 \< 50% predicted; GOLD 4 (Very Severe) = FEV1 \< 30% predicted.

Outcome measures

Outcome measures
Measure	Total Group n=277 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 2	25 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 3	52 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Any, GOLD 4	5 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade RSV, GOLD 2	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade RSV, GOLD 3	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade RSV, GOLD 4	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Parainfluenza virus, GOLD 2	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Parainfluenza virus, GOLD 3	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Parainfluenza virus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Enterovirus, GOLD 2	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Enterovirus, GOLD 3	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Enterovirus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade HRV, GOLD 2	14 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade HRV, GOLD 3	27 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade HRV, GOLD 4	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Metapneumovirus, GOLD 2	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Metapneumovirus, GOLD 3	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Metapneumovirus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Influenza virus, GOLD 2	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Influenza virus, GOLD 3	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Influenza virus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Adenovirus, GOLD 2	6 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Adenovirus, GOLD 3	5 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Adenovirus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Bocavirus, GOLD 2	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Bocavirus, GOLD 3	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Bocavirus, GOLD 4	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Coronavirus, GOLD 2	2 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Coronavirus, GOLD 3	11 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in Stable COPD Patients, as Identified by PCR, and Classified by GOLD Grade Coronavirus, GOLD 4	1 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each AECOPD visit, and positive for bacterial pathogens by bacteriological methods (overall and by bacterial species). Classification of severity of AECOPD as follows: Mild = controlled with an increase in dosage of regular medications; Moderate = requires treatment with systemic corticosteroids and/or antibiotics; Severe = requires hospitalization.

Outcome measures

Outcome measures
Measure	Total Group n=209 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD M. catarrhalis, Moderate AECOPD	6 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Any, Mild AECOPD	9 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Any, Moderate AECOPD	138 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Any, Severe AECOPD	16 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Hi, Mild AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Hi, Moderate AECOPD	11 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Hi, Severe AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD NTHi, Mild AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD NTHi, Moderate AECOPD	11 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD NTHi, Severe AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Non-Hi, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Non-Hi, Moderate AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Non-Hi, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD M. catarrhalis, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD M. catarrhalis, Severe AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. pneumoniae, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. pneumoniae, Moderate AECOPD	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. pneumoniae, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. aureus, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. aureus, Moderate AECOPD	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD S. aureus, Severe AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD P. aeruginosa, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD P. aeruginosa, Moderate AECOPD	26 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD P. aeruginosa, Severe AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD K. pneumoniae, Mild AECOPD	4 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD K. pneumoniae, Moderate AECOPD	43 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD K. pneumoniae, Severe AECOPD	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD A. baumannii, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD A. baumannii, Moderate AECOPD	8 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD A. baumannii, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Other bacteria, Mild AECOPD	4 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Other bacteria, Moderate AECOPD	84 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by Bacteriological Methods and Classified by Severity of AECOPD Other bacteria, Severe AECOPD	6 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each AECOPD visit, and positive for bacterial pathogens by PCR (overall and by bacterial species). Classification of severity of AECOPD is as follows: Mild = controlled with an increase in dosage of regular medications; Moderate = requires treatment with systemic corticosteroids and/or antibiotics; Severe = requires hospitalization.

Outcome measures

Outcome measures
Measure	Total Group n=194 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pyogenes, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Mild AECOPD	13 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Moderate AECOPD	117 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Severe AECOPD	15 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD H. influenzae, Mild AECOPD	10 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD H. influenzae, Moderate AECOPD	62 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD H. influenzae, Severe AECOPD	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD M. catarrhalis, Mild AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD M. catarrhalis, Moderate AECOPD	44 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD M. catarrhalis, Severe AECOPD	5 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pneumoniae, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pneumoniae, Moderate AECOPD	32 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pneumoniae, Severe AECOPD	4 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. aureus, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. aureus, Moderate AECOPD	15 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. aureus, Severe AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD P. aeruginosa, Mild AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD P. aeruginosa, Moderate AECOPD	24 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD P. aeruginosa, Severe AECOPD	6 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pyogenes, Moderate AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Bacterial Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD S. pyogenes, Severe AECOPD	0 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Number of sputum samples obtained at each AECOPD visit, and positive for viral pathogens by PCR (overall and by viral species). Classification of severity of AECOPD is as follows: Mild = controlled with an increase in dosage of regular medications; Moderate = requires treatment with systemic corticosteroids and/or antibiotics; Severe = requires hospitalization.

Outcome measures

Outcome measures
Measure	Total Group n=194 Sputum samples Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Enterovirus, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Enterovirus, Moderate AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Enterovirus, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD HRV, Mild AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD HRV, Moderate AECOPD	26 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Mild AECOPD	6 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Moderate AECOPD	56 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Any, Severe AECOPD	7 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD RSV, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD RSV, Moderate AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD RSV, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Parainfluenza virus, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Parainfluenza virus, Moderate AECOPD	6 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Parainfluenza virus, Severe AECOPD	2 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD HRV, Severe AECOPD	3 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Metapneumovirus, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Metapneumovirus, Moderate AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Metapneumovirus, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Influenza virus, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Influenza virus, Moderate AECOPD	14 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Influenza virus, Severe AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Adenovirus, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Adenovirus, Moderate AECOPD	7 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Adenovirus, Severe AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Bocavirus, Mild AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Bocavirus, Moderate AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Bocavirus, Severe AECOPD	0 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Coronavirus, Mild AECOPD	1 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Coronavirus, Moderate AECOPD	9 Sputum samples
Number of Sputum Samples Positive for Viral Pathogens (Overall and by Species) in AECOPD Patients, as Identified by PCR, and Classified by Severity of AECOPD Coronavirus, Severe AECOPD	1 Sputum samples

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Incidence rate is estimated by the mean number of exacerbations per subject and per year from Negative Binomial model (or Poisson model in case of under dispersion) without covariates and computed with 95% confidence intervals (CI). Confirmed AECOPDs include AECOPD events plus missed AECOPD events (i.e.: all morning alerts confirmed by phone call (as well as cases with no morning alert) for which there has been no site visit but for which AECOPD medical records are available). Potential AECOPDs include all morning alert confirmed by phone call for which there has been no site visit and for which no medical records are available.

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade Total, Confirmed AECOPDs	1.27 AECOPDs per person-year Interval 1.04 to 1.54
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 2, Confirmed AECOPDs	0.78 AECOPDs per person-year Interval 0.54 to 1.14
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 3, Confirmed AECOPDs	1.51 AECOPDs per person-year Interval 1.17 to 1.94
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 4, Confirmed AECOPDs	1.99 AECOPDs per person-year Interval 1.37 to 2.89
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade Total, Confirmed AECOPDs plus potential AECOPDs	1.3 AECOPDs per person-year Interval 1.07 to 1.58
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 2, Confirmed AECOPDs plus potential AECOPDs	0.81 AECOPDs per person-year Interval 0.56 to 1.16
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 3, Confirmed AECOPDs plus potential AECOPDs	1.56 AECOPDs per person-year Interval 1.2 to 2.01
Incidence Rate (Per Subject Per Year) of Confirmed and Confirmed Plus Potential AECOPDs, Overall and by GOLD Grade GOLD 4, Confirmed AECOPDs plus potential AECOPDs	1.99 AECOPDs per person-year Interval 1.37 to 2.89

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Classification of severity of AECOPD is as follows: Mild- Controlled AECOPD with an increase in dosage of regular medications; Moderate- Requires treatment with systemic corticosteroids and/ or antibiotics; Severe- Requires hospitalisation.

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, 0	181 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, 0	115 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, 0	168 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, 1	12 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, 1	38 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, 1	21 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, 2	3 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, 2	15 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, 2	7 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, 3	1 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, 3	11 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, 3	0 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, 4	0 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, 4	7 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, 4	1 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Mild AECOPD, >4	0 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Moderate AECOPD, >4	11 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by Severity of AECOPD Severe AECOPD, >4	0 Participants

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator forced expiratory volume in 1 second (FEV1) and can be divided into four GOLD grades \[GOLD, 2013\]: GOLD 1 (MILD): FEV1 ≥ 80% predicted; GOLD 2 (Moderate)= 50% ≤ FEV1 \< 80% predicted; GOLD 3 (Severe) = 30% ≤ FEV1 \< 50% predicted; GOLD 4 (Very Severe) = FEV1 \< 30% predicted.

Outcome measures

Outcome measures
Measure	Total Group n=99 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, 0	48 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, 1	17 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, 2	6 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, 3	4 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, 4	1 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 2, >4	3 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, 0	42 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, 1	15 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, 2	21 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, 3	5 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, 4	7 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 3, >4	9 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, 0	3 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, 1	6 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, 2	5 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, 3	0 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, 4	4 Participants
Number of Subjects With AECOPDs, Classified by Number of Exacerbations and by GOLD Grade GOLD 4, >4	1 Participants

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Descriptive statistics (mean, standard deviation) on the number of days of AECOPD episodes are presented, overall and by AECOPD severity.

Outcome measures

Outcome measures
Measure	Total Group n=227 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Days of AECOPD Episodes, Overall and by AECOPD Severity Any Severity	14.3 Days Standard Deviation 9.0
Number of Days of AECOPD Episodes, Overall and by AECOPD Severity Mild	20.3 Days Standard Deviation 11.1
Number of Days of AECOPD Episodes, Overall and by AECOPD Severity Moderate	12.6 Days Standard Deviation 6.3
Number of Days of AECOPD Episodes, Overall and by AECOPD Severity Severe	21.5 Days Standard Deviation 16.5

SECONDARY outcome

Timeframe: At Month 0, Month 6 and Month 12

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The CAT is a patient-completed instrument to assess the heath-related quality of life (HRQOL) and symptom burden in patients with COPD. Descriptive statistics (mean, standard deviation) on the CAT scores are tabulated at each stable visit. The CAT index is derived as the sum of the ratings recorded for each of the eight individual items. Each of these items has 6 possible scores (0, 1, 2, 3, 4 or 5), leading to a range of 0 (best score) to 40 (worst score) for CAT score.

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
COPD Assessment Test (CAT) Score in Stable COPD Patients Month 0	11.78 Units on the CAT scale Standard Deviation 5.56
COPD Assessment Test (CAT) Score in Stable COPD Patients Month 6	12.56 Units on the CAT scale Standard Deviation 6.08
COPD Assessment Test (CAT) Score in Stable COPD Patients Month 12	13.71 Units on the CAT scale Standard Deviation 6.53

SECONDARY outcome

Timeframe: Over the course of one year from the study start: (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The CAT is a patient-completed instrument to assess the HRQOL and symptom burden in patients with COPD. Descriptive statistics (mean, standard deviation) on the CAT scores are tabulated by frequency of exacerbations). The CAT index is derived as the sum of the ratings recorded for each of the eight individual items. Each of these items has 6 possible scores (0, 1, 2, 3, 4 or 5), leading to a range of 0 (best score) to 40 (worst score) for CAT score.

Outcome measures

Outcome measures
Measure	Total Group n=41 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
CAT Score by Frequency of Exacerbations 1 exacerbation	2.05 Units on the CAT scale Standard Deviation 5.62
CAT Score by Frequency of Exacerbations 2 or 3 exacerbations	3.08 Units on the CAT scale Standard Deviation 5.01
CAT Score by Frequency of Exacerbations >3 exacerbations	3.79 Units on the CAT scale Standard Deviation 4.84

SECONDARY outcome

Timeframe: At Month 0, Month 6 and Month 12

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

The SGRQ-C is designed to assess HRQOL and current health of the patients. Descriptive statistics (mean, standard deviation) on the SGRQ-C scores are tabulated at each stable visit. The SGRQ-C total score is derived as the weighted sum of the forty individual items leading to a range of 0 (best score) to 100 (worst score) as detailed in the reference manual \[St George's Respiratory Questionnaire for COPD patients, version 1.3, 2016\].

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score in Stable COPD Patients Month 0	35.22 Units on the SGRQ-C scale Standard Deviation 17.21
St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score in Stable COPD Patients Month 6	34.38 Units on the SGRQ-C scale Standard Deviation 16.52
St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score in Stable COPD Patients Month 12	35.1 Units on the SGRQ-C scale Standard Deviation 17.86

SECONDARY outcome

Timeframe: At Pre-Month 0 (screening visit) and Month 12.

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Summary statistics (mean, standard deviation) on post bronchodilator FEV1% of predicted normal value is tabulated at enrolment and final visit.

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Post-bronchodilator FEV1 Percentage of Predicted Normal Value in Stable COPD Patients Pre-Month 0	47.83 Percentage of FEV1 Standard Deviation 13.94
Post-bronchodilator FEV1 Percentage of Predicted Normal Value in Stable COPD Patients Month 12	46.93 Percentage of FEV1 Standard Deviation 14.93

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Healthcare utilization includes all unscheduled visits to a physician office, visits to urgent care, visits to emergency department, and hospitalizations. The impact of AECOPD on healthcare utilization is assessed during the stable periods. Hospitalizations that were associated with the disease being studied were not collected as Adverse Events (AEs) or as serious AEs (SAEs) as per protocol.

Outcome measures

Outcome measures
Measure	Total Group n=197 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Patients With Healthcare Utilisation During Stable Periods Physician's office consultations	135 Participants
Number of Patients With Healthcare Utilisation During Stable Periods Urgent care	4 Participants
Number of Patients With Healthcare Utilisation During Stable Periods Emergency department	20 Participants
Number of Patients With Healthcare Utilisation During Stable Periods Hospitalization	26 Participants

SECONDARY outcome

Timeframe: Over the course of one year from the study start (Month 0 to Month 12)

Population: Analysis was performed on the Full Analysis Set which included all screened subjects who were enrolled except for those subjects who discontinued the study at Month 0 visit.

Healthcare utilization includes all unscheduled visits to a physician office, visits to urgent care, visits to emergency department, and hospitalizations. The impact of AECOPD on healthcare utilization is assessed during exacerbation periods. Hospitalizations that were associated with the disease being studied were not collected as AEs or as SAEs as per protocol.

Outcome measures

Outcome measures
Measure	Total Group n=104 Participants Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Number of Patients With Healthcare Utilisation During Exacerbation Periods Physician's office consultations	48 Participants
Number of Patients With Healthcare Utilisation During Exacerbation Periods Urgent care	2 Participants
Number of Patients With Healthcare Utilisation During Exacerbation Periods Emergency department	13 Participants
Number of Patients With Healthcare Utilisation During Exacerbation Periods Hospitalization	20 Participants

Adverse Events

Total Group

Serious events: 1 serious events

Other events: 1 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Total Group n=197 participants at risk Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Infections and infestations Pneumonia necrotizing	0.51% 1/197 • Number of events 1 • Unsolicited adverse events and serious adverse events (SAE) related to study procedures have been collected during the whole study period (from Month 0 to Month 12. In the Participant flow section, there are 2 participants reported with "adverse event" reason for not completed: 1 was for SAE described in the Serious Adverse Events section below, and the other one was for a SAE not related to study procedure, and hence, no information (System Organ Class \& Preferred Term) was collected, as per protocol, for this SAE. Hospitalizations that were associated with the disease being studied were not collected as AEs or as SAEs as per protocol.

Other adverse events

Other adverse events
Measure	Total Group n=197 participants at risk Moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) patients with at least 1 documented moderate or severe Acute exacerbation of COPD (AECOPD) in the year before enrolment and for whom sputum and blood samples are collected during specified visits.
Respiratory, thoracic and mediastinal disorders Cough	0.51% 1/197 • Number of events 1 • Unsolicited adverse events and serious adverse events (SAE) related to study procedures have been collected during the whole study period (from Month 0 to Month 12. In the Participant flow section, there are 2 participants reported with "adverse event" reason for not completed: 1 was for SAE described in the Serious Adverse Events section below, and the other one was for a SAE not related to study procedure, and hence, no information (System Organ Class \& Preferred Term) was collected, as per protocol, for this SAE. Hospitalizations that were associated with the disease being studied were not collected as AEs or as SAEs as per protocol.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER