1. DL Hahn, MB Plane, OS Mahdi, GI Byrne NAPCRG October 2006
Secondary outcomes of a pilot randomized trial of azithromycin treatment for asthma
DL Hahn, MB Plane, OS Mahdi, GI Byrne
NAPCRG October 2006

2. Significance Asthma currently viewed as noninfectious
Treatment palliative, not curative
Asthma research is biased
Inadequate contribution from primary care

3. Chlamydia pneumoniae Obligate intracellular organism Endemic worldwide
Acute bronchitis (5%)
Pneumonia (10%)
Under Recognized

4. Chlamydia pneumoniae (Cpn)
Reinfection and chronic infection
Causes chronic inflammatory damage
Examples: trachoma, tubal infertility
Is asthma a chlamydial disease?

5. Cpn associated with asthma
Organism detection
Seroepidemiology
Prospective clinical studies
Treatment observations

6. Clinical trial: ASTHMA Pilot (Antibiotic Study To Help Manage Asthma)
Design: RCT (6 wks treatment, 3 mos follow up)
Setting: Community practices
Participants: Adults with stable persistent asthma
Intervention: Azithromycin or placebo & UC
Outcomes: Juniper AQLQ, symptom & medication changes; Cpn antibodies at baseline and follow up

7. Aims Feasibility* Effectiveness** Microbiologic correlates**
*JABFP 2004
**PLoS Clinical Trials 2006

8. Results - Feasibility favorable
10 practices in US/Canada
45 subjects
80-87% follow up
Demographics broadly representative

9. Results - Effectiveness
Juniper AQLQ improved: 0.25 (-0.3, 0.8)
Symptoms improved: 0.68 (0.1, 1.3)
Medication decreased: 0.59 (-0.5, 1.6)
Baseline IgA antibodies predicted worse symptoms at 6 months (P=0.04)
Symptom improvement 28% in high IgA vs. 12% in low IgA (P=0.27)

11. Apparent bimodel response
Binary outcome:
AQLQ improvement ≥1 unit and/or
≥50% decrease in rescue BD use
Azithromycin: 9/17 (53%)
Placebo: 2/15 (13%)
P=0.03

12. Limitations
Pilot
Small
Limited outcome measures
Short duration

13. Strengths Effectiveness RCT design Representative population
Objective evidence for RAO
Validated serologic technique
Patient-oriented outcomes

14. Conclusion
Results support performance of further effectiveness studies to investigate whether asthma is treatable with antibiotics

15. Strength of Recommendation Taxonomy (SORT) - A method for grading evidence*
Clinical trials
Level 1
Generalizable
Internally valid
Patient-oriented outcomes
Level 2 otherwise
*JFP, JABFP, AFP

16. Your tax dollars at work
AZMATICS
MIA
No. subjects
600
144
Duration
1 year
6 months
Description
Effectiveness
Mechanistic
SORT
Level 1
Level 2
Cost
$3.5M
$7.5M
Approved?
Yes