ASTHMA STUDIES

1. Relationship between gene type and response to Serevent.. ("LARGE")
2. Effectiveness of antibiotics for reducing asthma symptoms. ("MIA")
3. Occurrence of airway infection in non-asthmatics and asthmatics not using inhaled corticosteroids. ("MAMPA")
4. Correlation between blood type and severity of asthma. ("Secretor")
5. Comparison of treatment strategies for asthma that is well controlled on inhaled corticosteroids. ("BASALT")
6. Comparison between tiotropium bromide and increased inhaled corticosteroids as treatment for asthma not well controlled on inhaled corticosteroids alone. ("TALC")

1. Effectiveness of antibiotics for reducing the number and severity of COPD flare-ups. ("MACRO")
2. Pneumococcal Vaccine Response in Chronic Obstructive Pulmonary Disease ("PNEUMO")
3. Anti-leukotriene Therapy for COPD Exacerbations ("LEUKO")

ASTHMA PREVENTION STUDY

If you or your partner have asthma and you're expecting a baby, check out the TIPS asthma prevention study here. Your participation could help us discover how to prevent the development of asthma in children.

Research question: Could regular use of inhaled beta-agonists, the most common treatment for relief of asthma attacks, make asthma worse in some people with the condition?

Background: Studies have shown that some asthmatics respond very well to treatment with long-acting beta agonists (LABA, like Serevent™) while others appear to respond poorly. This difference may be based on differences in genetic makeup. The specific gene that is thought to be responsible is the "B16" gene.
Purpose: To compare the effects of twice daily treatment with Serevent™ or placebo in two groups of asthmatics with different forms of the B16 gene.
Design: This is a 62-week, placebo-controlled clinical trial. Participants must be adults with asthma that requires regular treatment with an inhaled corticosteroid (ICS). Participants first provide a blood sample to test for gene type and perform a series of standard lung function tests. Each person who qualifies for the study is matched with another participant who has similar lung function but the opposite gene type. Matched subjects begin an 8-week run-in period taking only QVAR (an ICS) twice daily and albuterol as needed. They are then randomly assigned to 18 weeks of additional treatment with Serevent™ or placebo. After these 18 weeks, they return to regular use of QVAR and as needed albuterol for an 8-week run-out period. This also serves as the run-in period for the second stage of the study when participants are assigned to the additional treatment with the medication they did NOT use in the first treatment period. At the end of the second treatment period, participants again return to regular use of QVAR and as needed albuterol for a final 10-week run-out period. This trial is now closed to enrollment.
Study significance: This study could help resolve the controversy as to whether regular treatment with a LABA is harmful to a genetically identifiable subgroup of the asthmatic population. If so, it would stimulate development of alternative approaches to treatment for these patients.

Research question: Why does treatment with a common antibiotic (Biaxin™) dramatically improve asthma in some patients?

Background: Some recent research has suggested that one of two bacteria, Mycoplasma or Chlamydia pneumoniae, are found in the airways of approximately 50% of asthmatic patients. These bacteria are common causes of bronchitis and pneumonia but were not previously thought to cause chronic infections or to make asthma worse. Further research has also shown that treatment with a macrolide antibiotic like Biaxin™ can improve asthma, especially in patients with evidence of infection with either Mycoplasma or Chlamydia pneumoniae.
Purpose: To compare the effects of treatment with Biaxin™ versus placebo in two groups of asthmatics, one with evidence of Mycoplasma or Chlamydia pneumoniae and one without.
Study design: This 32-week, placebo-controlled study examines the effect of treatment with Biaxin™ on asthma symptoms in participants whose asthma is not completely controlled when taking a low dose of inhaled corticosteroid (Flovent™). Individuals aged 18-60 years who meet lung function and other eligibility criteria will enter a 4 -week run-in phase of treatment with Flovent™ and "as needed" albuterol. If their asthma is not completely controlled, they will undergo bronchoscopy to obtain samples to examine for the presence of Mycoplasma or Chlamydia pneumoniae in their airways. Participants are then randomly assigned to treatment with Flovent™ twice daily, albuterol as needed, and a pill containing either active Biaxin™ or placebo. Participants visit the clinic every month to perform breathing tests and answer questionnaires, in order to evaluate asthma control. At the end of the treatment period, Biaxin™ or placebo is discontinued, and subjects enter an 8- week washout period. This study is currently enrolling participants.
Study significance: This could lead to a new approach to treatment for a significant portion of people with asthma, and could stimulate the development of new, non-invasive tests for detecting Mycoplasma or Chlamydia infection in the airways.

Research question: Will the application of a recently developed and highly sensitive method of detecting bacteria based on their DNA show that the airways of asthmatics are infected with more or different bacteria than the airways of non-asthmatics?

Background: Until recently, the main method for detecting bacteria was to grow them from a clinical sample in a laboratory. This changed with the development of methods for detecting "signature" sequences of DNA unique to bacteria in clinical samples. Researchers at Lawrence Berkeley National Laboratories have developed the "PhyloChip" to enable rapid detection of bacteria by their DNA. Use of this new gene-based method has shown a much greater number and diversity of bacteria than was previously suspected. Because some patients with asthma have responded well to treatment with antibiotics (see the "MIA" study above), even though they did not appear to have been infected with any known bacteria, we wish to apply these new methods to find out if there are bacteria in the airways of healthy and asthmatic people, and if they differ in number, type or diversity.
Purpose: To compare the number, type and diversity of bacteria revealed by application of the recently developed "PhyloChip" to cell samples obtained by bronchoscopy from healthy and asthmatic adults.
Study design: This study is performed over two visits. During the first, participants undergo a series of breathing tests to determine whether they have asthma. Also during this visit, participants provide blood and sputum samples for analysis. The second visit is for bronchoscopy, a procedure that allows investigators to collect tissue samples from the airways. Using novel array-based methods, investigators will be able to determine if bacteria are present in the airway samples. The results in healthy people, asthmatics not using inhaled corticosteroids and asthmatics using them will be compared.
Study significance: Finding a difference in airway bacteria in people with asthma could stimulate entirely new ways of thinking about the condition and could lead to new approaches to treatment.

Research question: What is the best way to adjust inhaled corticosteroid treatment? Every six weeks on the basis of symptom review and lung function testing, on the basis of the level of exhaled NO, or on the basis of the severity of day-to-day symptoms?

Background: Asthma is a variable disease, so treatment with an inhaled corticosteroid often needs to be adjusted. National guidelines recommend that this adjustment be based on symptoms and lung function test results measured at office visits. A recently proposed alternative is based on the finding that levels of nitric oxide in the air exhaled reflect the intensity of the inflammation of the airways. This suggests that the dose of ICS should be adjusted according to the level of nitric oxide measured. A third approach is to match the use of ICS with the use of albuterol for the relief of symptoms on a day-to-day basis.
Purpose: To compare these three approaches to adjusting ICS dose in order to maintain good asthma control.
Study design: This 44-week study compares the effects of the three approaches. Participants will have three inhalers that are adjusted according to these different strategies. One inhaler will contain active inhaled corticosteroid (QVAR) while the other two will be placebo. Neither the participant nor the study investigator will know which inhaler is active. Asthma control will be assessed by daily symptom records, questionnaires and in-clinic lung function tests.
Study significance: This study could help define the best approach to treating asthma with minimal use of medication and minimal cost to the patient.

1. Effectiveness of antibiotics for reducing the number and severity of COPD flare-ups. ("MACRO")
The prevalence, morbidity, mortality and treatment cost of COPD are high and increasing. A large fraction of the morbidity and cost is attributable to acute exacerbations, and macrolide antibiotics have a variety of antibacterial and anti-inflammatory properties that, in theory, could reduce acute exacerbations. Long-term administration of macrolide antibiotics has resulted in clinically important improvements in patients with other pulmonary disorders. The specific aim of this study is to determine if administration of azithromycin (250 mg per day) for one year will decrease the frequency and/or the severity of COPD exacerbations.