Greater Benefit With Azithromycin in COPD Patients With H pylori

Azithromycin is more likely to reduce exacerbations of chronic obstructive pulmonary disease (COPD) among patients with antibodies against Helicobacter pylori than among antibody-negative patients, according to a study published in Respiratory Research.¹

Approximately 1 in 5 patients with COPD have persistent systemic inflammation, the cause of which is unclear. H pylori infection, present in nearly 20% of patients with COPD, may contribute to this inflammatory state and was found to correlate with systemic inflammation and decreased lung function.

Azithromycin has antimicrobial properties against H pylori, and its use to prevent COPD exacerbations is becoming increasingly common. However, no data exist on the effectiveness of azithromycin for preventing COPD exacerbations in patients with and without H pylori infection.

Researchers, led by Seung Won Ra, MD, PhD, and Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, Canada, examined the relationship between H pylori infection status and COPD exacerbations.

The current study used data and blood samples from patients in the MACRO Study (Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease study; ClinicalTrials.gov identifier: NCT00325897),² which compared the effect of azithromycin 250 mg daily vs placebo on the time to first COPD exacerbation during a period of 12 months.

Researchers examined data from 1018 patients with COPD; 17.8% were positive for antibodies against H pylori. Almost 3 times as many Caucasians were seropositive as non-Caucasians (37.4% vs 13.6%; P <.001). Study participants were divided into 4 treatment groups: H pylori⁺/azithromycin, H pylori⁻/azithromycin, H pylori⁺/placebo, and H pylori⁻/placebo.

Patients in the H pylori⁺/azithromycin group had the longest time to first exacerbation (11.2 months; 95% CI, 8.4-12.5+ months). Times to first exacerbation became increasingly shorter in the following order: H pylori⁻/azithromycin (8.0 months; 95% CI, 6.7-9.7), H pylori⁺/placebo (7.5 months; 95% CI, 4.9-8.8 months), and H pylori⁻/placebo (5.7 months; 95% CI, 4.5-7.2 months; P =.001 for all comparisons).

The risk for COPD exacerbation was the lowest among patients in the H pylori⁺/azithromycin group (hazard ratio, 0.612; 95% CI, 0.442-0.846; P =.003) after adjusting for confounding factors.

At 3 months of treatment, participants in the H pylori⁺/azithromycin group had reduced levels of soluble tumor necrosis factor receptor-75 (−0.87±0.31 μg/L; P =.002), with levels returning to baseline after discontinuation of azithromycin therapy.

“For patients with COPD who have repeated exacerbations, the daily use of low-dose azithromycin reduces the risk of exacerbation by 25%. However, azithromycin is associated with [reduced] hearing acuity and cardiac arrhythmias,” Dr Sin told Pulmonology Advisor.

“Our study found that we can identify patients who are most likely to benefit from azithromycin by measuring blood antibodies against H pylori. In those who have positive antibodies against H pylori, the use of azithromycin reduces the risk of exacerbation by 39% vs only 21% in those who are antibody negative,” he said.

Dr Sin indicated that checking H pylori infection status as part of COPD management would not be difficult to implement in clinical practice. “Blood measurements for H pylori antibodies are clinically available and relatively inexpensive. This blood test can be used to target azithromycin therapy to patients who will benefit the most from azithromycin,” he said.

The emerging role that H pylori plays in COPD management warrants further investigation, Dr Sin said. “What we don’t know is whether eradication of H pylori with triple therapy (2 antibiotics and proton pump inhibitor) will have an even greater effect than daily azithromycin therapy in reducing the risk of exacerbation. This may be possible because we think the presence of H pylori infection causes systemic inflammation, which in turn worsens lung inflammation.”

Study Limitations

• Researchers do not have data indicating how many patients with H pylori infection developed macrolide resistance after 1 year of exposure to azithromycin.
• Data were not available on presence of gastric disease or other symptoms indicating active H pylori infection
• Detailed information regarding prescription or over-the-counter use of antisecretory drugs, which may be responsible for the prevention or treatment of COPD exacerbations in patients with COPD and gastric symptoms.
• Use of antibiotics or steroids other than azithromycin may affect H pylori titers in study participants.
• The retrospective study design did not focus on potential pathogenic mechanisms underlying the association between H pylori infection and COPD exacerbation.

References

1. Ra SW, Sze MA, Lee EC, et al; on behalf of the Canadian Respiratory Research Network. Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori. Respir Res. 2017;18(1):109. doi: 10.1186/s12931-017-0594-x
2. Albert RK, Connett J, Bailey WC, et al; for the COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698. doi : 10.1056/JENMoa1104623