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Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.
“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”
The researchers observed a significant reduction in the incidence of total asthma exacerbations in the azithromycin-treated group: 1.07/patient-year, compared with 1.86/patient year in the placebo group, which translated into an incidence rate ratio of 0.59 (P less than .0001). Specifically, 127 patients in the placebo group (61%) experienced at least one asthma exacerbation compared with 94 patients in the azithromycin group (44%; P less than .0001). A significant improvement in asthma-related quality of life was also seen among patients in the azithromycin group (adjusted mean difference of 0.36; P = .001).
Though the mechanism of the antiviral effect of macrolides is not yet determined, Dr. Gibson and his associates noted that respiratory viral infection is associated with severe exacerbations in eosinophilic asthma and causes most respiratory infections. “There is a known interaction between eosinophilic airway inflammation, exacerbation rate, and impaired innate antiviral immunity,” they wrote. “Since we observed a benefit of azithromycin on both asthma exacerbations and respiratory infections, we speculate that azithromycin might be acting to prevent viral-induced episodes in asthma.”
“Given the major impact of asthma exacerbations on patients and the community and the ongoing risk posed by these events in patients who remain symptomatic on maintenance therapy, we consider that azithromycin is a valuable addition to existing regimens for treating asthma,” the researchers concluded. “The long-term effects of this therapy on community microbial resistance require further evaluation.”
The overall rates and types of serious adverse events seen in both groups were not significantly different from each other, with serious adverse events having occurred in 16 (8%) patients treated with azithromycin and 26 (13%) patients given the placebo.
The study was funded by the National Health and Medical Research Council of Australia and the John Hunter Hospital Charitable Trust. The authors reported having no financial conflicts directly related to the study.
Since microbial resistance is a well known side effect of antibiotic use, add-on therapy with azithromycin in asthma needs to be restricted to those patients with the highest unmet medical need (for example, frequent exacerbators) and to time periods with the greatest risk of exacerbations (such as winter). Biomarkers that predict the therapeutic response to macrolides might facilitate optimal patient selection. Further research is needed to elucidate the most important mechanism of action of these pleiotropic drugs. Macrolides have anti-inflammatory, antibacterial, and antiviral effects. However, the authors did not observe a reduction in inflammatory cell counts in sputum to support a definite anti-inflammatory effect. Azithromycin also was effective in patients with and without potentially pathogenic microorganisms in sputum cultures at baseline. Since azithromycin reduced both asthma exacerbations and respiratory infections, the benefits of azithromycin might be caused by preventing viral-induced attacks in asthma. Azithromycin stimulates phagocytosis of microbes and dead cells by macrophages (i.e., efferocytosis), an effect that is likely to be independent of the nature of the accompanying neutrophilic or eosinophilic airway inflammation.
Gibson and colleagues have clearly shown that add-on therapy with azithromycin is effective and safe in adult patients with uncontrolled asthma despite treatment with inhaled corticosteroids and long-acting beta-agonists. Azithromycin benefited patients with both eosinophilic and noneosinophilic asthma. However, the effects of long-term therapy with macrolides on community microbial resistance remain a public health concern. Future studies with potentially safer nonantibiotic macrolides in uncontrolled severe asthma are warranted. Since the antimicrobial effects probably contribute to the overall efficacy of macrolides, the beneficial effects of nonantibiotic macrolides might be intermediate between macrolide antibiotics and placebo.
This text is excerpted from a commentary published online July 4 in The Lancet (doi. org/10.1016/S0140-6736[17]31547-7). Guy Brusselle, MD, is with the department of respiratory medicine at Ghent (Belgium) University Hospital and Ian Pavord, MD, is with the University of Oxford’s Nuffield Department of Medicine, England. Both authors disclosed having received honoraria and other financial support from numerous pharmaceutical companies.
Since microbial resistance is a well known side effect of antibiotic use, add-on therapy with azithromycin in asthma needs to be restricted to those patients with the highest unmet medical need (for example, frequent exacerbators) and to time periods with the greatest risk of exacerbations (such as winter). Biomarkers that predict the therapeutic response to macrolides might facilitate optimal patient selection. Further research is needed to elucidate the most important mechanism of action of these pleiotropic drugs. Macrolides have anti-inflammatory, antibacterial, and antiviral effects. However, the authors did not observe a reduction in inflammatory cell counts in sputum to support a definite anti-inflammatory effect. Azithromycin also was effective in patients with and without potentially pathogenic microorganisms in sputum cultures at baseline. Since azithromycin reduced both asthma exacerbations and respiratory infections, the benefits of azithromycin might be caused by preventing viral-induced attacks in asthma. Azithromycin stimulates phagocytosis of microbes and dead cells by macrophages (i.e., efferocytosis), an effect that is likely to be independent of the nature of the accompanying neutrophilic or eosinophilic airway inflammation.
Gibson and colleagues have clearly shown that add-on therapy with azithromycin is effective and safe in adult patients with uncontrolled asthma despite treatment with inhaled corticosteroids and long-acting beta-agonists. Azithromycin benefited patients with both eosinophilic and noneosinophilic asthma. However, the effects of long-term therapy with macrolides on community microbial resistance remain a public health concern. Future studies with potentially safer nonantibiotic macrolides in uncontrolled severe asthma are warranted. Since the antimicrobial effects probably contribute to the overall efficacy of macrolides, the beneficial effects of nonantibiotic macrolides might be intermediate between macrolide antibiotics and placebo.
This text is excerpted from a commentary published online July 4 in The Lancet (doi. org/10.1016/S0140-6736[17]31547-7). Guy Brusselle, MD, is with the department of respiratory medicine at Ghent (Belgium) University Hospital and Ian Pavord, MD, is with the University of Oxford’s Nuffield Department of Medicine, England. Both authors disclosed having received honoraria and other financial support from numerous pharmaceutical companies.
Since microbial resistance is a well known side effect of antibiotic use, add-on therapy with azithromycin in asthma needs to be restricted to those patients with the highest unmet medical need (for example, frequent exacerbators) and to time periods with the greatest risk of exacerbations (such as winter). Biomarkers that predict the therapeutic response to macrolides might facilitate optimal patient selection. Further research is needed to elucidate the most important mechanism of action of these pleiotropic drugs. Macrolides have anti-inflammatory, antibacterial, and antiviral effects. However, the authors did not observe a reduction in inflammatory cell counts in sputum to support a definite anti-inflammatory effect. Azithromycin also was effective in patients with and without potentially pathogenic microorganisms in sputum cultures at baseline. Since azithromycin reduced both asthma exacerbations and respiratory infections, the benefits of azithromycin might be caused by preventing viral-induced attacks in asthma. Azithromycin stimulates phagocytosis of microbes and dead cells by macrophages (i.e., efferocytosis), an effect that is likely to be independent of the nature of the accompanying neutrophilic or eosinophilic airway inflammation.
Gibson and colleagues have clearly shown that add-on therapy with azithromycin is effective and safe in adult patients with uncontrolled asthma despite treatment with inhaled corticosteroids and long-acting beta-agonists. Azithromycin benefited patients with both eosinophilic and noneosinophilic asthma. However, the effects of long-term therapy with macrolides on community microbial resistance remain a public health concern. Future studies with potentially safer nonantibiotic macrolides in uncontrolled severe asthma are warranted. Since the antimicrobial effects probably contribute to the overall efficacy of macrolides, the beneficial effects of nonantibiotic macrolides might be intermediate between macrolide antibiotics and placebo.
This text is excerpted from a commentary published online July 4 in The Lancet (doi. org/10.1016/S0140-6736[17]31547-7). Guy Brusselle, MD, is with the department of respiratory medicine at Ghent (Belgium) University Hospital and Ian Pavord, MD, is with the University of Oxford’s Nuffield Department of Medicine, England. Both authors disclosed having received honoraria and other financial support from numerous pharmaceutical companies.
Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.
“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”
The researchers observed a significant reduction in the incidence of total asthma exacerbations in the azithromycin-treated group: 1.07/patient-year, compared with 1.86/patient year in the placebo group, which translated into an incidence rate ratio of 0.59 (P less than .0001). Specifically, 127 patients in the placebo group (61%) experienced at least one asthma exacerbation compared with 94 patients in the azithromycin group (44%; P less than .0001). A significant improvement in asthma-related quality of life was also seen among patients in the azithromycin group (adjusted mean difference of 0.36; P = .001).
Though the mechanism of the antiviral effect of macrolides is not yet determined, Dr. Gibson and his associates noted that respiratory viral infection is associated with severe exacerbations in eosinophilic asthma and causes most respiratory infections. “There is a known interaction between eosinophilic airway inflammation, exacerbation rate, and impaired innate antiviral immunity,” they wrote. “Since we observed a benefit of azithromycin on both asthma exacerbations and respiratory infections, we speculate that azithromycin might be acting to prevent viral-induced episodes in asthma.”
“Given the major impact of asthma exacerbations on patients and the community and the ongoing risk posed by these events in patients who remain symptomatic on maintenance therapy, we consider that azithromycin is a valuable addition to existing regimens for treating asthma,” the researchers concluded. “The long-term effects of this therapy on community microbial resistance require further evaluation.”
The overall rates and types of serious adverse events seen in both groups were not significantly different from each other, with serious adverse events having occurred in 16 (8%) patients treated with azithromycin and 26 (13%) patients given the placebo.
The study was funded by the National Health and Medical Research Council of Australia and the John Hunter Hospital Charitable Trust. The authors reported having no financial conflicts directly related to the study.
Adults with persistent symptomatic asthma who took azithromycin as an add-on therapy experienced fewer exacerbations and had improved quality of life, compared with their peers who took a placebo, a multicenter, randomized trial demonstrated.
“Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects, and are reported to be beneficial in both eosinophilic and noneosinophilic subtypes,” a group of Australian researchers wrote online July 4 in The Lancet (doi: org/10.1016/S0140-6736[17]31281-3). “Systematic reviews of randomized, controlled trials report benefits of macrolides on asthma symptoms but [we] are unable to draw conclusions about the effects on other endpoints, including exacerbations, due to lack of data, heterogeneity of results, and inadequate study design and sample size.”
The researchers observed a significant reduction in the incidence of total asthma exacerbations in the azithromycin-treated group: 1.07/patient-year, compared with 1.86/patient year in the placebo group, which translated into an incidence rate ratio of 0.59 (P less than .0001). Specifically, 127 patients in the placebo group (61%) experienced at least one asthma exacerbation compared with 94 patients in the azithromycin group (44%; P less than .0001). A significant improvement in asthma-related quality of life was also seen among patients in the azithromycin group (adjusted mean difference of 0.36; P = .001).
Though the mechanism of the antiviral effect of macrolides is not yet determined, Dr. Gibson and his associates noted that respiratory viral infection is associated with severe exacerbations in eosinophilic asthma and causes most respiratory infections. “There is a known interaction between eosinophilic airway inflammation, exacerbation rate, and impaired innate antiviral immunity,” they wrote. “Since we observed a benefit of azithromycin on both asthma exacerbations and respiratory infections, we speculate that azithromycin might be acting to prevent viral-induced episodes in asthma.”
“Given the major impact of asthma exacerbations on patients and the community and the ongoing risk posed by these events in patients who remain symptomatic on maintenance therapy, we consider that azithromycin is a valuable addition to existing regimens for treating asthma,” the researchers concluded. “The long-term effects of this therapy on community microbial resistance require further evaluation.”
The overall rates and types of serious adverse events seen in both groups were not significantly different from each other, with serious adverse events having occurred in 16 (8%) patients treated with azithromycin and 26 (13%) patients given the placebo.
The study was funded by the National Health and Medical Research Council of Australia and the John Hunter Hospital Charitable Trust. The authors reported having no financial conflicts directly related to the study.
FROM THE LANCET
Key clinical point:
Major finding: Azithromycin reduced the incidence of total asthma exacerbations, compared with placebo (1.07/patient-year vs. 1.86/patient-year, respectively, for an incidence rate ratio of 0.59; P less than .0001).
Data source: A randomized, placebo-controlled, multicenter trial of 420 adults with persistent, uncontrolled asthma.
Disclosures: The study was funded by the National Health and Medical Research Council of Australia and the John Hunter Hospital Charitable Trust. The authors reported having no financial conflicts directly related to the study.