AsthmaNCT00512954
Causes, Characteristics and Mechanisms of Infective Exacerbations in Subjects With Asthma and Chronic Obstructive Pulmonary Disease (COPD)
An observational study of Asthma and COPD, run by McMaster University at 1 site in Canada.
Trial summary
Diseases of the airways (bronchi) of the lungs include asthma and chronic obstructive pulmonary disease (COPD), which are leading causes of reduced quality of life, loss of work, hospital admissions and deaths and result in a major economic burden to the patient and society. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2007to Jul 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Asthmatics with 1 or more exacerbation in last calendar year.
Who may be able to join
- Male or female (medically or surgically postmenopausal or practicing an accepted form of barrier or hormonal contraception) subjects between 18 - 80 years.
- Any severity of exacerbation of obstructive airway disease attending the outpatient clinic.
- History of at least two exacerbations in the past 12 months prior to recruitment that required a course of prednisone or antibiotic or long acting bronchodilator or inhaled corticosteroid, in addition to the daily maintenance therapy.
- Signed written informed consent to participate in the protocol and ability to return to the outpatient clinic for repeated clinic visits.
Who cannot join
- If the exacerbation is severe enough to warrant hospitalization.
- Active malignancy.
- Significant gastrointestinal, hematological, cardiovascular or cerebrovascular disorder that would affect compliance with follow up visits.
- Recent (within the past 2 months) or planned (within the study period) lung surgery.
- Psychosis, alcoholism, active substance abuse or any personality disorder that would make compliance with the follow up visits problematic.
- Pregnant or nursing females, as this could affect the compliance during the trial.
- Any other medical or social condition, which in the opinion of the investigator could confound the interpretation of the data derived from this study.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Firestone Institute for Respiratory Health, St. Joseph's Healthcare
Hamilton, Ontario, L8N 4A6
About this study
Official title: A Prospective One Year Study of the Causes, Characteristics, Mechanisms and Kinetics of Exacerbations in Subjects With Asthma
Diseases of the airways (bronchi) of the lungs include asthma and chronic obstructive pulmonary disease (COPD), which are leading causes of reduced quality of life, loss of work, hospital admissions and deaths and result in a major economic burden to the patient and society. Worsening (exacerbation) of these conditions is common and is frequently due to viral or bacterial infection, which causes inflammation in the bronchi, i.e. bronchitis. Ways to objectively measure the inflammation are needed to improve diagnosis, cause and severity and to guide treatment. The investigators also need to understand changes in the body's defense (immune) mechanisms that make some patients have more frequent infective bronchitis.
At present, sputum cell counts are able to identify different types of bronchitis, their severity and may be able to differentiate viral from bacterial infection. Other measurements in sputum, exhaled breath, blood and urine are also available to measure this inflammation. Measurement of immune cells in the blood gives us an idea about the working capacity of the immune system of the body.
Read more
The investigators plan to study patients with asthma or COPD at the time of worsening of their condition to identify,
- To what extent viral or bacterial bronchitis can be diagnosed from tests of inflammation?
- How clearing of infection relates to clearing of inflammation?
- What are the changes in the body's defense mechanisms that make a patient more prone to frequent infective bronchitis?
- How do the measurements in sputum, exhaled breath, blood and urine relate to viral and bacterial bronchitis?
- What are the differences in the measurements in sputum, exhaled breath, blood and urine in asthma and COPD?
Read the detailed description
Exacerbations of asthma and COPD are a major cause of morbidity, mortality and economic burden to the patient and society. Exacerbations are usually associated with worsening of airway inflammation which, as identified by quantitative sputum cell counts, can be neutrophilic, eosinophilic, combined eosinophilic and neutrophilic or neither, a result of different causes. The commonest cause of exacerbations is infection. Neutrophilic exacerbations are common and are usually associated with bacterial and non-bacterial infections but eosinophilic exacerbations might also predict viral infections. However the investigators are still unsure whether aspects of neutrophilic inflammation can differentiate viral from bacterial infections. Also the exact relationship between etiology, mechanisms of susceptibility to infection, inflammation and airway responsiveness during an exacerbation is poorly understood. As a result, the physician assumes that clinical improvement from an exacerbation corresponds to resolution of infection and underlying inflammation of airways at the same time. However, inflammation of the airways may persist beyond the resolution of infection, which may contribute to the morbidity and mortality of the disease.
The primary objective of this study is to better understand the correlation between the different types of inflammation and infection of the airways during exacerbations. Secondary objectives are to understand the susceptibility to infections and methods to assess the inflammatory response and airway responsiveness during infections. To attain these objectives we will compare the total cells, percentage of neutrophils, percentage of eosinophils in sputum and nasal secretions, sputum fibrinogen, sputum total lactate dehydrogenase, microbial load in sputum and nasal secretions, exhaled nitric oxide, p H of exhaled breath condensate, serum procalcitonin, intensity of urinary 3-bromotyrosine, 3-chlorotyrosine, 3, 5- dibromotyrosine and dityrosine, symptom score, FEV1 and Mannitol PD15 at different time points during an exacerbation, compare the activity of toll like receptors (2,4,7,9) and natural killer T cells during the stable phase of disease with the number of infective exacerbations during the course of one year and test the feasibility of mannitol challenge testing as a method to induce sputum and measure airway hyperresponsiveness. Our approach will be to identify 100 patients with variable (asthma) or chronic airflow limitation (COPD), reporting within 2 to 5 days of the onset of an exacerbation during the course of one year. The clinical, physiological, inflammatory, microbiological and immunological parameters will be assessed on the day of presentation (day 0), day 7, 14 and at 6 to 8 weeks. The information collected at 6 to 8 weeks will serve as baseline data, if the patient is clinically stable at this point in time. If the patient has a next exacerbation during the course of the trial, then the same procedure will be followed.
This work will enhance the knowledge of issues needed to improve diagnosis of exacerbations of airways disease, their causes, the mechanisms involved and the most appropriate treatment. The results may lead to future randomized controlled trials, in which treatment of exacerbations will be based on the most appropriate measurements that will eventually lead to better management of airway diseases, reduce the overall cost of therapy and improve the quality of life of these patients.
- Keywords
- airway inflammation, susceptibility to infections, inflammatory response in blood and urine, infective exacerbations, asthma, COPD
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2007 (estimated)
- Study startApr 2007
- Primary completionDec 2009
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, St. Joseph's Healthcare Hamilton
- Investigators
- Parameswaran K Nair, MD, PhD, Principal investigator, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, OntarioFrederick E Hargreave, MD, Principal investigator, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512954
- Sponsor's protocol ID
- 06-2671
- Status last verified
- Jul 2009
- First submitted
- 7 Aug 2007
- Last updated
- 19 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Jayaram L, Pizzichini MM, Cook RJ, Boulet LP, Lemiere C, Pizzichini E, Cartier A, Hussack P, Goldsmith CH, Laviolette M, Parameswaran K, Hargreave FE. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006 Mar;27(3):483-94. doi: 10.1183/09031936.06.00137704.
PubMed 16507847Johnston SL. Overview of virus-induced airway disease. Proc Am Thorac Soc. 2005;2(2):150-6. doi: 10.1513/pats.200502-018AW.
PubMed 16113484Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006 May 15;173(10):1114-21. doi: 10.1164/rccm.200506-859OC. Epub 2006 Feb 16.
PubMed 16484677Chaudhuri N, Dower SK, Whyte MK, Sabroe I. Toll-like receptors and chronic lung disease. Clin Sci (Lond). 2005 Aug;109(2):125-33. doi: 10.1042/CS20050044.
PubMed 16033327Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, DeKruyff RH, Umetsu DT. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med. 2006 Mar 16;354(11):1117-29. doi: 10.1056/NEJMoa053614.
PubMed 16540612Silkoff PE, Carlson M, Bourke T, Katial R, Ogren E, Szefler SJ. The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma. J Allergy Clin Immunol. 2004 Nov;114(5):1241-56. doi: 10.1016/j.jaci.2004.08.042.
PubMed 15536442Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004 Jul 15;39(2):206-17. doi: 10.1086/421997. Epub 2004 Jul 2.
PubMed 15307030Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, Koskela H, Brannan JD, Freed R, Andersson M, Chan HK, Woolcock AJ. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med. 2001 Feb;163(2):406-12. doi: 10.1164/ajrccm.163.2.9912091.
PubMed 11179114Kharitonov SA, Barnes PJ. Exhaled biomarkers. Chest. 2006 Nov;130(5):1541-6. doi: 10.1378/chest.130.5.1541.
PubMed 17099035
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective One Year Study of the Causes, Characteristics, Mechanisms and Kinetics of Exacerbations in Subjects With Asthma
- ClinicalTrials.gov ID
- NCT00512954
- Acronym / sponsor ID
- 06-2671
- Keywords
- airway inflammation, susceptibility to infections, inflammatory response in blood and urine, infective exacerbations, asthma, COPD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, St. Joseph's Healthcare Hamilton
- Study start
- Apr 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 8 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diseases of the airways (bronchi) of the lungs include asthma and chronic obstructive pulmonary disease (COPD), which are leading causes of reduced quality of life, loss of work, hospital admissions and deaths and result in a major economic burden to the patient and society. Worsening (exacerbation) of these conditions is common and is frequently due to viral or bacterial infection, which causes inflammation in the bronchi, i.e. bronchitis. Ways to objectively measure the inflammation are needed to improve diagnosis, cause and severity and to guide treatment. The investigators also need to understand changes in the body's defense (immune) mechanisms that make some patients have more frequent infective bronchitis.
At present, sputum cell counts are able to identify different types of bronchitis, their severity and may be able to differentiate viral from bacterial infection. Other measurements in sputum, exhaled breath, blood and urine are also available to measure this inflammation. Measurement of immune cells in the blood gives us an idea about the working capacity of the immune system of the body.
The investigators plan to study patients with asthma or COPD at the time of worsening of their condition to identify,
- To what extent viral or bacterial bronchitis can be diagnosed from tests of inflammation?
- How clearing of infection relates to clearing of inflammation?
- What are the changes in the body's defense mechanisms that make a patient more prone to frequent infective bronchitis?
- How do the measurements in sputum, exhaled breath, blood and urine relate to viral and bacterial bronchitis?
- What are the differences in the measurements in sputum, exhaled breath, blood and urine in asthma and COPD?
Detailed description
Exacerbations of asthma and COPD are a major cause of morbidity, mortality and economic burden to the patient and society. Exacerbations are usually associated with worsening of airway inflammation which, as identified by quantitative sputum cell counts, can be neutrophilic, eosinophilic, combined eosinophilic and neutrophilic or neither, a result of different causes. The commonest cause of exacerbations is infection. Neutrophilic exacerbations are common and are usually associated with bacterial and non-bacterial infections but eosinophilic exacerbations might also predict viral infections. However the investigators are still unsure whether aspects of neutrophilic inflammation can differentiate viral from bacterial infections. Also the exact relationship between etiology, mechanisms of susceptibility to infection, inflammation and airway responsiveness during an exacerbation is poorly understood. As a result, the physician assumes that clinical improvement from an exacerbation corresponds to resolution of infection and underlying inflammation of airways at the same time. However, inflammation of the airways may persist beyond the resolution of infection, which may contribute to the morbidity and mortality of the disease.
The primary objective of this study is to better understand the correlation between the different types of inflammation and infection of the airways during exacerbations. Secondary objectives are to understand the susceptibility to infections and methods to assess the inflammatory response and airway responsiveness during infections. To attain these objectives we will compare the total cells, percentage of neutrophils, percentage of eosinophils in sputum and nasal secretions, sputum fibrinogen, sputum total lactate dehydrogenase, microbial load in sputum and nasal secretions, exhaled nitric oxide, p H of exhaled breath condensate, serum procalcitonin, intensity of urinary 3-bromotyrosine, 3-chlorotyrosine, 3, 5- dibromotyrosine and dityrosine, symptom score, FEV1 and Mannitol PD15 at different time points during an exacerbation, compare the activity of toll like receptors (2,4,7,9) and natural killer T cells during the stable phase of disease with the number of infective exacerbations during the course of one year and test the feasibility of mannitol challenge testing as a method to induce sputum and measure airway hyperresponsiveness. Our approach will be to identify 100 patients with variable (asthma) or chronic airflow limitation (COPD), reporting within 2 to 5 days of the onset of an exacerbation during the course of one year. The clinical, physiological, inflammatory, microbiological and immunological parameters will be assessed on the day of presentation (day 0), day 7, 14 and at 6 to 8 weeks. The information collected at 6 to 8 weeks will serve as baseline data, if the patient is clinically stable at this point in time. If the patient has a next exacerbation during the course of the trial, then the same procedure will be followed.
This work will enhance the knowledge of issues needed to improve diagnosis of exacerbations of airways disease, their causes, the mechanisms involved and the most appropriate treatment. The results may lead to future randomized controlled trials, in which treatment of exacerbations will be based on the most appropriate measurements that will eventually lead to better management of airway diseases, reduce the overall cost of therapy and improve the quality of life of these patients.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Asthmatics with 1 or more exacerbation in last calendar year.
Key inclusion criteria (4 listed)
- Male or female (medically or surgically postmenopausal or practicing an accepted form of barrier or hormonal contraception) subjects between 18 - 80 years.
- Any severity of exacerbation of obstructive airway disease attending the outpatient clinic.
- History of at least two exacerbations in the past 12 months prior to recruitment that required a course of prednisone or antibiotic or long acting bronchodilator or inhaled corticosteroid, in addition to the daily maintenance therapy.
- Signed written informed consent to participate in the protocol and ability to return to the outpatient clinic for repeated clinic visits.
Key exclusion criteria (7 listed)
- If the exacerbation is severe enough to warrant hospitalization.
- Active malignancy.
- Significant gastrointestinal, hematological, cardiovascular or cerebrovascular disorder that would affect compliance with follow up visits.
- Recent (within the past 2 months) or planned (within the study period) lung surgery.
- Psychosis, alcoholism, active substance abuse or any personality disorder that would make compliance with the follow up visits problematic.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2011.
- Background: PubMed 16507847Jayaram L, Pizzichini MM, Cook RJ, Boulet LP, Lemiere C, Pizzichini E, Cartier A, Hussack P, Goldsmith CH, Laviolette M, Parameswaran K, Hargreave FE. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006 Mar;27(3):483-94. doi: 10.1183/09031936.06.00137704.
- Background: PubMed 16113484Johnston SL. Overview of virus-induced airway disease. Proc Am Thorac Soc. 2005;2(2):150-6. doi: 10.1513/pats.200502-018AW.
- Background: PubMed 16484677Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006 May 15;173(10):1114-21. doi: 10.1164/rccm.200506-859OC. Epub 2006 Feb 16.
- Background: PubMed 16033327Chaudhuri N, Dower SK, Whyte MK, Sabroe I. Toll-like receptors and chronic lung disease. Clin Sci (Lond). 2005 Aug;109(2):125-33. doi: 10.1042/CS20050044.
- Background: PubMed 16540612Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, DeKruyff RH, Umetsu DT. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med. 2006 Mar 16;354(11):1117-29. doi: 10.1056/NEJMoa053614.
- Background: PubMed 15536442Silkoff PE, Carlson M, Bourke T, Katial R, Ogren E, Szefler SJ. The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma. J Allergy Clin Immunol. 2004 Nov;114(5):1241-56. doi: 10.1016/j.jaci.2004.08.042.
- Background: PubMed 15307030Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004 Jul 15;39(2):206-17. doi: 10.1086/421997. Epub 2004 Jul 2.
- Background: PubMed 11179114Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, Koskela H, Brannan JD, Freed R, Andersson M, Chan HK, Woolcock AJ. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med. 2001 Feb;163(2):406-12. doi: 10.1164/ajrccm.163.2.9912091.
- Background: PubMed 17099035Kharitonov SA, Barnes PJ. Exhaled biomarkers. Chest. 2006 Nov;130(5):1541-6. doi: 10.1378/chest.130.5.1541.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parameswaran K Nair, MD, PhD principal investigator
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario
Frederick E Hargreave, MD principal investigator
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and COPD, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00512954, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2011.