Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (Drs. Parth M. Rali and Gupta); Family Medicine, Northwell Health, NY (Dr. Baffour-Awuah); Children’s Hospital of Philadelphia, PA (Dr. Grishma Rali); Department of Family Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (Dr. Mayur Rali) mrali@northwell.edu
The authors reported no potential conflict of interest relevant to this article.
Macrolides have immunomodulatory and anti-inflammatory effects in addition to their antibacterial effects. Maintenance treatment with macrolides such as azithromycin has been proven to be effective in chronic neutrophilic airway diseases (FIGURE). There have been attempts to assess whether this therapy can be useful in asthma management, as well. Some randomized controlled trials and meta-analyses have shown conflicting results, and early studies were limited by lack of data, heterogeneous results, and inadequate study designs.
The AZithromycin Against pLacebo in Exacerbations of Asthma (AZALEA) study was a randomized, multicenter, double-blind, placebo-controlled clinical trial in the United Kingdom among patients requiring emergency care for acute asthma exacerbations. Azithromycin added to standard care for asthma attacks did not result in clinical benefit.57 While azithromycin in acute exacerbation is not currently recommended, recent trials in outpatient settings have shown promise.
The AZIthromycin in Severe ASThma study (AZISAST) was a randomized, double-blind, placebo-controlled trial in subjects with exacerbation-prone severe asthma in Belgium. Low-dose azithromycin (250 mg 3 times a week) as an add-on treatment to combination ICS-LABA therapy for 6 months did not reduce the rate of severe asthma exacerbations or lower respiratory tract infection (LRTI). However, subjects with a non-eosinophilic variant (neutrophilic phenotype) experienced significant reduction in the rate of exacerbation and LRTI.58
Chronic azithromycin might prove to be a useful agent in the long-term management of asthma patients whose disease is not well controlled on inhaled therapy
The recently published Asthma and Macrolides: the AZithromycin Efficacy and Safety Study (AMAZES) shows promise for chronic azithromycin therapy as an add-on to medium-to-high-dose inhaled steroids and a long-acting bronchodilator in adults with uncontrolled persistent asthma. This was a large multicenter, randomized, double-blind, placebo-controlled, parallel group trial in New Zealand and Australia. Patients were excluded if they had hearing impairment or abnormally prolonged QTc. Azithromycin at a dose of 500 mg 3 times a week for 48 months reduced asthma exacerbations and improved QoL compared to placebo. The effect was sustained between subgroups based on phenotypes (eosinophilic vs noneosinophilic; frequent exacerbators vs nonfrequent exacerbators) and even among those with symptom differences at baseline (eg, cough or sputum positivity). The rate of antibiotic courses for respiratory infectious episodes was significantly reduced in the azithromycin-treated group.59
The take-away: Chronic azithromycin might prove to be a useful agent in the long-term management of asthma patients whose disease is not well controlled on inhaled therapy. Further studies on mechanism and effects of prolonged antibiotic use will shed more light. For more information, see When guideline treatment of asthma fails, consider a macrolide antibiotic; http://bit.ly/2vDAWc6.
