Causes, Characteristics and Mechanisms of Infective Exacerbations in Subjects With Asthma and Chronic Obstructive Pulmonary Disease (COPD)
Condition: Asthma; COPD
MeSH terms: Asthma
Study type: Observational

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. 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,

        1. To what extent viral or bacterial bronchitis can be diagnosed from tests of
           inflammation?

        2. How clearing of infection relates to clearing of inflammation?

        3. What are the changes in the body's defense mechanisms that make a patient more prone to
           frequent infective bronchitis?

        4. How do the measurements in sputum, exhaled breath, blood and urine relate to viral and
           bacterial bronchitis?

        5. 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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Asthmatics with 1 or more exacerbation in last calendar year.
      
Keywords: airway inflammation; susceptibility to infections; inflammatory response in blood and urine; infective exacerbations; asthma; COPD