Infectious Pathogens in Acute Respiratory Illness in Adults and Elderly

Contribution of Infectious Pathogens to Acute Respiratory Illness in Adults and Elderly

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Disorders
• Intervention / Treatment: Procedure: Blood sample; Procedure: Sputum sample; Procedure: Nasopharyngeal swab; Procedure: Urine sample; Procedure: End tidal breath sample; Other: Data collection; Other: Tests

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Estimated Number of Acute Exacerbation of COPD (AECOPD)	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.	During year 1
Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens	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.	During Year 1
Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum	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.	During Year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi	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.	During Year 1
Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp	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.	During Year 1
Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria	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.	During Year 1
Mean Number of Days Between 2 Consecutive AECOPDs	The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.	During Year 1
Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit	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.	During Year 1
Number of Subjects Receiving Various Health Care Types During AECOPD	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.	During Year 1
Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal	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.	During Year 1
AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay	Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.	During Year 1
AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum	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.	During Year 1
AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity	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.	During Year 1

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General 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.
• Wilkinson TMA, Van den Steen P, Cheuvart B, Baudson N, Dodet M, Turriani E, Harrington L, Meyer N, Rondini S, Taddei L, Mukherjee P. Seroprevalence of Bordetella pertussis Infection in Patients With Chronic Obstructive Pulmonary Disease in England: Analysis of the AERIS Cohort. COPD. 2021 Jun;18(3):341-348. doi: 10.1080/15412555.2021.1920904. Epub 2021 May 6.
• Malvisi L, Taddei L, Yarraguntla A, Wilkinson TMA, Arora AK; AERIS Study Group. Sputum sample positivity for Haemophilus influenzae or Moraxella catarrhalis in acute exacerbations of chronic obstructive pulmonary disease: evaluation of association with positivity at earlier stable disease timepoints. Respir Res. 2021 Feb 24;22(1):67. doi: 10.1186/s12931-021-01653-8.
• Germovsek E, Ambery C, Yang S, Beerahee M, Karlsson MO, Plan EL. A Novel Method for Analysing Frequent Observations from Questionnaires in Order to Model Patient-Reported Outcomes: Application to EXACT(R) Daily Diary Data from COPD Patients. AAPS J. 2019 Apr 26;21(4):60. doi: 10.1208/s12248-019-0319-9.
• Wilkinson TMA, Aris E, Bourne SC, Clarke SC, Peeters M, Pascal TG, Taddei L, Tuck AC, Kim VL, Ostridge KK, Staples KJ, Williams NP, Williams AP, Wootton SA, Devaster JM. Drivers of year-to-year variation in exacerbation frequency of COPD: analysis of the AERIS cohort. ERJ Open Res. 2019 Feb 25;5(1):00248-2018. doi: 10.1183/23120541.00248-2018. eCollection 2019 Feb. Erratum In: ERJ Open Res. 2019 Jul 29;5(3):
• Williams NP, Ostridge K, Devaster JM, Kim V, Coombs NA, Bourne S, Clarke SC, Harden S, Abbas A, Aris E, Lambert C, Tuck A, Williams A, Wootton S, Staples KJ, Wilkinson TMA; AERIS Study Group. Impact of radiologically stratified exacerbations: insights into pneumonia aetiology in COPD. Respir Res. 2018 Jul 28;19(1):143. doi: 10.1186/s12931-018-0842-8.
• Wilkinson TMA, Aris E, Bourne S, Clarke SC, Peeters M, Pascal TG, Schoonbroodt S, Tuck AC, Kim V, Ostridge K, Staples KJ, Williams N, Williams A, Wootton S, Devaster JM; AERIS Study Group. A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD. Thorax. 2017 Oct;72(10):919-927. doi: 10.1136/thoraxjnl-2016-209023. Epub 2017 Apr 21.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2011
• Primary Completion (Actual): June 27, 2014
• Study Completion (Actual): June 27, 2014

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: COPD; exacerbation; AECOPD; Chronic Obstructive Pulmonary Disease; respiratory; pathogen; Acute Exacerbations of Chronic Obstructive Pulmonary Disease
• Additional Relevant MeSH Terms: Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: 114378

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 114378
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register