Infectious Pathogens in Acute Respiratory Illness in Adults and Elderly

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01360398
• Collaborator: (none)
• Enrollment: 127
• Location: 1
• Arm: 1
• Actual Duration (Months): 35.9
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The aim of this study is to generate epidemiological data to further explore determinants of Chronic Obstructive Pulmonary Disease (COPD) and the contribution of bacterial and viral pathogens to Acute Exacerbation of COPD (AECOPD) episodes.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Disorders	Procedure: Blood sample; Procedure: Sputum sample; Procedure: Nasopharyngeal swab; Procedure: Urine sample; Procedure: End tidal breath sample; Other: Data collection; Other: Tests	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 127 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Contribution of Infectious Pathogens to Acute Respiratory Illness in Adults and Elderly
• Actual Study Start Date: Jun 30, 2011
• Actual Primary Completion Date: Jun 27, 2014
• Actual Study Completion Date: Jun 27, 2014

Arms and Interventions

Arm

Intervention/Treatment

Other: Cohort COPD male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices.

Procedure: Blood sample; Blood samples will be collected from all patients at enrolment, at follow-up visits, at exacerbation visits, and during the final visit.; Procedure: Sputum sample; Sputum will be collected from all patients at enrolment, at monthly follow-up visits, at exacerbation visits, and during the final visit. Sputum will be obtained by spontaneous expectoration or induced by stimulation according to standard methods.; Procedure: Nasopharyngeal swab; Nasopharyngeal swabs will be collected from all patients at enrolment and from a subcohort of 30 patients at monthly follow-up visits and at exacerbation visits during the first year.; Procedure: Urine sample; Urine samples will be taken at enrolment and exacerbation visits from all subjects and from the same subcohort of 30 patients providing nasopharyngeal swabs, at monthly follow-up visits during the first year.; Procedure: End tidal breath sample; Breath samples will be collected from all patients at enrolment, at follow-up visits (monthly), at exacerbation visits, and during the final visit.; Other: Data collection; Patient interview, diary cards review and questionnaires completion; Other: Tests; Urine pregnancy test, chest CT-scan, lung function testing and 6-min walk test

Outcome Measures

Primary Outcome Measures

1. Mean Estimated Number of Acute Exacerbation of COPD (AECOPD) [During year 1]

   An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD The Means and Confidence Intervals (CI) were estimated using the Negative Binomial model taking into account time to follow up. Estimated exacerbations were presented as mean number of exacerbations per (/) subject/ year.

2. Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens [During Year 1]

   Bacterial pathogens assessed were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Steptococcus pneumoniae (Sp), Staphylococcus Aureus (Sta), Pseudomonas aeruginosa (Psa), any or other. For each bacteria, the means and CIs were estimated from Negative Binomial model taking into account the follow up time.Estimated exacerbations were presented as mean number of exacerbations/ subject/ year.

3. Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum [During Year 1]

   Bacterial pathogens assessed, by culture, were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Streptococcus pneumoniae (Sp), Staphylococcus aureus (Sta), Pseudomonas aeruginosa (Psa), any bacteria or other bacteria. Overall exacerbation rate is the average number of exacerbations for each subject during their time in the study.

Secondary Outcome Measures

1. Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi [During Year 1]

   Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for any bacteria and Hi.

2. Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp [During Year 1]

   Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Mcat and Sp.

3. Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria [During Year 1]

   Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Sta, Psa and other bacteria.

4. Mean Number of Days Between 2 Consecutive AECOPDs [During Year 1]

   The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.

5. Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit [During Year 1]

   The exacerbations of chronic pulmonary disease tool version 1.0 (EXACT) is a validated self-administered instrument that evaluates the effects of pharmacologic treatment on acute exacerbations of COPD. Analyses of exacerbations in relation to morning or evening EXACT-PRO e-diaries were presented as follows: descriptive statistics on the EXACT daily scores tabulated at enrolment, at any stable and at any, mild, moderate or severe exacerbation visit. EXACT-PRO contains 14 questions with scores ranging from 0 to 4, where 0= best outcome while 4= worse outcome.

6. Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit [During Year 1]

   The COPD assessment test (CAT) is a validated self-administered instrument designed to provide a simple and reliable measure of health status in COPD patients. Its properties have been shown to be similar to the St George's respiratory questionnaire (SGRQ). The CAT comprises 8 items and has a scoring range of 0-40, 0= most positive answer and 40= most negative answer. In this study, the subjects were to complete the CAT questionnaire every 3 months.

7. Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit [During Year 1]

   The NEADL assessed (quarterly in the present study) the ease or difficulty in performing extended activities of daily living. The NEADL scale contains 22 items, each measured on a 4-point Likert scale. There are four dimensions: mobility (6 items); kitchen (5 items); domestic (5 items); leisure (6 items). These are summed producing a total score reflecting general functioning. Each of the 22 individual items had 2 possible scores (0 or 1). Therefore, the range of the NEADL score was 0 to 22. Lower scores indicate greater levels of disability while higher scores indicate greater independence.

8. Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit [During Year 1]

   The EQ-5D is an established measure of generic health outcome that provides a simple descriptive profile and a single index value that can be used in clinical and economic evaluation of healthcare and in population surveys. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 100 (best health state). The negative numbers presented represent a decrease from baseline values and a worsening of health.

9. Number of Subjects Receiving Various Health Care Types During AECOPD [During Year 1]

   AECOPD health care type included: general practitioners (other than the study doctor), pneumologists, other specialists, hospital emergency department, home care nurses, pulmonary rehabilitation programs and/or nutrition advices.

10. Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal [During Year 1]

    Serious adverse events (SAEs) include medical occur-rences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disabil-ity/incapacity.

11. AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay [During Year 1]

    Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.

12. AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [During Year 1]

    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus.

13. Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [During Year 1]

    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Mild exacerbations were defined as worsening symptoms of COPD that were self-managed by the patient.

14. Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [During Year 1]

    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Moderate exacerbations were defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics.

15. Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum [During Year 1]

    Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Severe exacerbations were defined as worsening symptoms of COPD that required treatment with in-patient hospitalisation or home care intervention.

16. AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity [During Year 1]

    An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD. AECOPD severity was assessed as: any, mild, moderate and severe. Any = any COPD symptom regardless of severity. Mild = Worsening symptoms of COPD that are self-managed by the patient. Moderate = Worsening symptoms of COPD that require treatment with oral corticosteroids and/or antibiotics. Severe = Worsening symptoms of COPD that require treatment with in-patient hospitalisation or home care intervention.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who the investigator believes can and will comply with the requirements of the protocol.

• Written informed consent obtained from the subject.

• Male or female subjects between, and including, 40 and 85 years of age, at the time of consent.

• Subjects with confirmed diagnosis of COPD with Forced Expiratory Volume of air expired in 1 second (FEV1) of </=80% of predicted normal and FEV1/Forced expiratory Vital Capacity (FVC)<0.7

• Subjects have moderate, severe, or very severe COPD, according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging.

• Subjects have a current or prior history of >/=10 pack-years of cigarette smoking. Former smokers are defined as those who have stopped smoking for at least 6 months. Number of pack years = (number of cigarettes per day/20) x number of years smoked.

• Subjects present a documented history of >/=1 exacerbation requiring antibiotics and/or oral corticosteroids or hospitalization in the previous 12 months.

Exclusion Criteria:

• Subject also has a confirmed diagnosis of asthma, cystic fibrosis, pneumonia risk factors or other respiratory disorders.

• Subjects having undergone lung surgery.

• Subject has a α-1 antitrypsin deficiency as underlying cause of COPD.

• Subject who experienced a moderate or severe COPD exacerbation not resolved at least 1 month prior to enrolment visit and at least 30 days following the last dose of oral corticosteroids.

• Subject using any antibacterial, antiviral or respiratory investigational drug or relevant vaccine up to 30 days prior to the enrolment visit.

• Subject has other conditions that the principal investigator judges may interfere with the study findings. Women who are pregnant or lactating or are planning on becoming pregnant during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Southampton	Hampshire	United Kingdom	SO16 6YD

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Bourne S, Cohet C, Kim V, Barton A, Tuck A, Aris E, Mesia-Vela S, Devaster JM, Ballou WR, Clarke SC, Wilkinson T. Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study. BMJ Open. 2014 Mar 7;4(3):e004546. doi: 10.1136/bmjopen-2013-004546. Erratum in: BMJ Open. 2015;5(1):e004546corr1. Clarke, Stuart [corrected to Clarke, Stuart C].
• Mayhew D, Devos N, Lambert C, Brown JR, Clarke SC, Kim VL, Magid-Slav M, Miller BE, Ostridge KK, Patel R, Sathe G, Simola DF, Staples KJ, Sung R, Tal-Singer R, Tuck AC, Van Horn S, Weynants V, Williams NP, Devaster JM, Wilkinson TMA; AERIS Study Group. Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations. Thorax. 2018 May;73(5):422-430. doi: 10.1136/thoraxjnl-2017-210408. Epub 2018 Jan 31.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01360398
• Other Study ID Numbers: 114378
• First Posted: May 25, 2011
• Last Update Posted: Feb 15, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: pathogen; Chronic Obstructive Pulmonary Disease; Acute Exacerbations of Chronic Obstructive Pulmonary Disease; COPD; respiratory; AECOPD; exacerbation
• Additional relevant MeSH terms: Respiration Disorders; Respiratory Tract Diseases

Study Results

Participant Flow

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Period Title: Overall Study
STARTED	127
COMPLETED	105
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Overall Participants	127
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.8 (8.6)
Sex: Female, Male (Count of Participants)
Female	59 46.5%
Male	68 53.5%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Mean Estimated Number of Acute Exacerbation of COPD (AECOPD)
Description	An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD The Means and Confidence Intervals (CI) were estimated using the Negative Binomial model taking into account time to follow up. Estimated exacerbations were presented as mean number of exacerbations per (/) subject/ year.
Time Frame	During year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Mean (95% Confidence Interval) [AECOPD/subject/year]	3.04

2. Primary Outcome

Title	Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens
Description	Bacterial pathogens assessed were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Steptococcus pneumoniae (Sp), Staphylococcus Aureus (Sta), Pseudomonas aeruginosa (Psa), any or other. For each bacteria, the means and CIs were estimated from Negative Binomial model taking into account the follow up time.Estimated exacerbations were presented as mean number of exacerbations/ subject/ year.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any	1.59
Hi	1.10
Mcat	0.34
Sp	0.39
Sta	0.16
Psa	0.18
Other	0.01

3. Primary Outcome

Title	Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum
Description	Bacterial pathogens assessed, by culture, were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Streptococcus pneumoniae (Sp), Staphylococcus aureus (Sta), Pseudomonas aeruginosa (Psa), any bacteria or other bacteria. Overall exacerbation rate is the average number of exacerbations for each subject during their time in the study.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Bacteria	1.48
Hi	1.02
Mcat	0.31
Sp	0.37
Sta	0.14
Psa	0.17
Other Bacteria	0.01

4. Secondary Outcome

Title	Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi
Description	Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for any bacteria and Hi.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Bacteria - enrollment	57
Any Bacteria - any stable visit	466
Any Bacteria - any exacerbation visit	188
Any Bacteria - any mild exacerbation visit	17
Any Bacteria - any moderate exacerbation visit	162
Any Bacteria - any severe exacerbation visit	9
Hi - enrollment	32
Hi - any stable visit	287
Hi - any exacerbation visit	129
Hi - any mild exacerbation visit	11
Hi - any moderate exacerbation visit	111
Hi - any severe exacerbation visit	7

5. Secondary Outcome

Title	Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp
Description	Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Mcat and Sp.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Mcat - enrollment	8
Mcat - any stable visit	50
Mcat - any exacerbation visit	40
Mcat - any mild exacerbation visit	1
Mcat - any moderate exacerbation visit	39
Mcat - any severe exacerbation visit	0
Sp - enrollment	19
Sp - any stable visit	177
Sp - any exacerbation visit	47
Sp - any mild exacerbation visit	6
Sp - any moderate exacerbation visit	37
Sp - any severe exacerbation visit	4

6. Secondary Outcome

Title	Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria
Description	Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Sta, Psa and other bacteria.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Sta - enrollment	6
Sta - any stable visit	40
Sta - any exacerbation visit	18
Sta - any mild exacerbation visit	0
Sta - any moderate exacerbation visit	18
Sta - any severe exacerbation visit	0
Psa - enrollment	6
Psa - any stable visit	49
Psa - any exacerbation visit	21
Psa - any mild exacerbation visit	0
Psa - any moderate exacerbation visit	19
Psa - any severe exacerbation visit	2
Other bacteria - enrollment	2
Other bacteria - any stable visit	6
Other bacteria - any exacerbation visit	1
Other bacteria - any moderate exacerbation visit	0
Other bacteria - any mild exacerbation visit	1
Other bacteria - any severe exacerbation visit	0

7. Secondary Outcome

Title	Mean Number of Days Between 2 Consecutive AECOPDs
Description	The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Mean (Standard Deviation) [Days]	55.5 (53.0)

8. Secondary Outcome

Title	Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit
Description	The exacerbations of chronic pulmonary disease tool version 1.0 (EXACT) is a validated self-administered instrument that evaluates the effects of pharmacologic treatment on acute exacerbations of COPD. Analyses of exacerbations in relation to morning or evening EXACT-PRO e-diaries were presented as follows: descriptive statistics on the EXACT daily scores tabulated at enrolment, at any stable and at any, mild, moderate or severe exacerbation visit. EXACT-PRO contains 14 questions with scores ranging from 0 to 4, where 0= best outcome while 4= worse outcome.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Enrollment	0.0 (0.00)
Any stable visit	-3.0 (9.34)
Any onset of exacerbation visit	2.7 (10.24)
Any onset of mild exacerbation visit	0.3 (11.16)
Any onset of moderate exacerbation visit	2.9 (10.30)
Any onset of severe exacerbation visit	2.3 (5.58)

9. Secondary Outcome

Title	Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit
Description	The COPD assessment test (CAT) is a validated self-administered instrument designed to provide a simple and reliable measure of health status in COPD patients. Its properties have been shown to be similar to the St George's respiratory questionnaire (SGRQ). The CAT comprises 8 items and has a scoring range of 0-40, 0= most positive answer and 40= most negative answer. In this study, the subjects were to complete the CAT questionnaire every 3 months.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Enrollment	0.0 (0.00)
Any stable visit	-0.9 (6.04)
Any onset of exacerbation visit	4.1 (7.40)
Any onset of mild exacerbation visit	0.3 (5.17)
Any onset of moderate exacerbation visit	4.3 (7.43)
Any onset of severe exacerbation visit	7.2 (8.14)

10. Secondary Outcome

Title	Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit
Description	The NEADL assessed (quarterly in the present study) the ease or difficulty in performing extended activities of daily living. The NEADL scale contains 22 items, each measured on a 4-point Likert scale. There are four dimensions: mobility (6 items); kitchen (5 items); domestic (5 items); leisure (6 items). These are summed producing a total score reflecting general functioning. Each of the 22 individual items had 2 possible scores (0 or 1). Therefore, the range of the NEADL score was 0 to 22. Lower scores indicate greater levels of disability while higher scores indicate greater independence.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Enrolment	0.0 (0.00)
Any stable visit	6.2 (13.41)
Any onset of exacerbation visit	3.2 (12.78)
Any onset of mild exacerbation visit	3.8 (8.95)
Any onset of moderate exacerbation visit	3.3 (13.18)
Any onset of severe exacerbation visit	0 (11.16)

11. Secondary Outcome

Title	Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit
Description	The EQ-5D is an established measure of generic health outcome that provides a simple descriptive profile and a single index value that can be used in clinical and economic evaluation of healthcare and in population surveys. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 100 (best health state). The negative numbers presented represent a decrease from baseline values and a worsening of health.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Enrolment	0.0 (0.00)
Any stable visit	-1.4 (19.25)
Any onset of exacerbation visit	-14.8 (20.88)
Any onset of mild exacerbation visit	-4.3 (18.78)
Any onset of moderate exacerbation visit	-15.8 (20.44)
Any onset of severe exacerbation visit	-16.9 (28.42)

12. Secondary Outcome

Title	Number of Subjects Receiving Various Health Care Types During AECOPD
Description	AECOPD health care type included: general practitioners (other than the study doctor), pneumologists, other specialists, hospital emergency department, home care nurses, pulmonary rehabilitation programs and/or nutrition advices.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	108
General practitioner - Negative	82 64.6%
General practitioner - Positive	26 20.5%
Pneumologist - Negative	104 81.9%
Pneumologist - Positive	4 3.1%
Other specialist - Negative	103 81.1%
Other specialist - Positive	5 3.9%
Emergency department at the hospital - Negative	96 75.6%
Emergency department at the hospital - Positive	12 9.4%
Nurse home care - Negative	108 85%
Pulmonary rehabilitation program - Negative	98 77.2%
Pulmonary rehabilitation program - Positive	10 7.9%
Nutrition Advice - Negative	107 84.3%
Nutrition Advice - Positive	1 0.8%

13. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal
Description	Serious adverse events (SAEs) include medical occur-rences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disabil-ity/incapacity.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Count of Participants [Participants]	0 0%

14. Secondary Outcome

Title	AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay
Description	Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Bacteria	1.61
Hi	1.30
Mcat	0.47
Sp	0.20
Sta	0.09
Psa	0.14
Spyo	0.00

15. Secondary Outcome

Title	AECOPD Rate With Overall and Specific Viral Pathogens in Sputum
Description	Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any virus	0.99
RSV	0.02
PIV	0.05
ENV	0.63
HMP	0.05
INV	0.06
ADV	0.02
CRV	0.17
HBoV	0.02

16. Secondary Outcome

Title	Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum
Description	Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Mild exacerbations were defined as worsening symptoms of COPD that were self-managed by the patient.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Virus	0.08
RSV	0.00
PIV	0.02
ENV	0.05
HMP	0.00
INV	0.00
ADV	0.00
CRV	0.02
HBoV	0.00

17. Secondary Outcome

Title	Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum
Description	Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Moderate exacerbations were defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Virus	0.85
RSV	0.02
PIV	0.03
ENV	0.54
HMP	0.04
INV	0.06
ADV	0.02
CRV	0.14
HBoV	0.02

18. Secondary Outcome

Title	Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum
Description	Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Severe exacerbations were defined as worsening symptoms of COPD that required treatment with in-patient hospitalisation or home care intervention.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any Virus	0.06
RSV	0.00
PIV	0.00
ENV	0.04
HMP	0.01
INV	0.01
ADV	0.00
CRV	0.01
HBoV	0.00

19. Secondary Outcome

Title	AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity
Description	An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD. AECOPD severity was assessed as: any, mild, moderate and severe. Any = any COPD symptom regardless of severity. Mild = Worsening symptoms of COPD that are self-managed by the patient. Moderate = Worsening symptoms of COPD that require treatment with oral corticosteroids and/or antibiotics. Severe = Worsening symptoms of COPD that require treatment with in-patient hospitalisation or home care intervention.
Time Frame	During Year 1

Outcome Measure Data

Analysis Population Description

The analyses of AECOPD were performed on the Full cohort, which included all subjects eligible for inclusion based on medical history and study specific procedures defined in the protocol and who completed at least the Day 0 visit.

Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
Measure Participants	127
Any AECOPD	1.48
Mild AECOPD	0.13
Moderate AECOPD	1.28
Severe AECOPD	0.07

Adverse Events

Time Frame	SAEs during Year 1 of the study period
Adverse Event Reporting Description	Other (Non-Serious) Adverse Events were not collected as blood sampling was the only invasive procedure performed.
Arm/Group Title	Total Group
Arm/Group Description	Chronic Obstructive Pulmonary Disease [COPD] diagnosed male and female patients between 40 and 85 years of age, recruited among the patients of the Southampton General Hospital and referring practices, enrolled to generate additional data for further exploration of COPD determinants and the contribution of infectious pathogens to Acute Exacerbation of COPD (AECOPD).
All Cause Mortality
	Total Group
	Affected / at Risk (%)	# Events
Total	0/127 (0%)
Serious Adverse Events
	Total Group
	Affected / at Risk (%)	# Events
Total	0/127 (0%)
Other (Not Including Serious) Adverse Events
	Total Group
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.