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EDITORIAL
Year : 2020  |  Volume : 15  |  Issue : 2  |  Page : 47-48
Role of long-term azithromycin therapy for severe bronchial asthma


1 Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE
2 Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

Date of Submission01-Feb-2020
Date of Acceptance07-Feb-2020
Date of Web Publication03-Apr-2020

Correspondence Address:
Prof. Mohamed S Al-Hajjaj
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah
UAE
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DOI: 10.4103/atm.ATM_38_20

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How to cite this article:
Al-Hajjaj MS, Al Moamary MS. Role of long-term azithromycin therapy for severe bronchial asthma. Ann Thorac Med 2020;15:47-8

How to cite this URL:
Al-Hajjaj MS, Al Moamary MS. Role of long-term azithromycin therapy for severe bronchial asthma. Ann Thorac Med [serial online] 2020 [cited 2020 Aug 11];15:47-8. Available from: http://www.thoracicmedicine.org/text.asp?2020/15/2/47/281870




Macrolides, including erythromycin, clarithromycin, and azithromycin, are one of the most widely used antibiotics.[1] They are commonly prescribed for acute respiratory infections.[2] The efficacy of the long-term use of macrolides has been documented for other chronic respiratory infections, i.e., chronic obstructive pulmonary disease and bronchiectasis.[3],[4] In view of the well-known antibacterial, immunomodulatory, and potential antiviral properties of macrolides, they are likely to have a beneficial effect on chronic asthma and asthma exacerbations.[5]

Epidemiology studies have shown that Mycoplasma pneumoniae infection may worsen asthma symptoms and can produce wheezing in individuals who do not have asthma.[6] Among 51 children with a first asthmatic attack, acute M. pneumoniae infection was found in 50%. At follow-up, the patients infected with M. pneumoniae were more likely to have recurrent asthma than those without these infections. Among infected patients, recurrences tended to be rapid if the patient was not treated with a macrolide.[7]

The global initiative for asthma guidelines suggested to add macrolides as add-on treatment in patients who are nonallergic asthmatics (low type II inflammation).[8] The Saudi initiative for asthma guidelines has advocated the use of long-term macrolides in steroid-resistant asthmatics or those who are not eligible or able to use biological agents.[9]

Reiter et al. published a meta-analysis in 2013 on macrolides for the long-term management of asthma.[10] They concluded that there is a significant improvement in the peak expiratory flow, symptoms, quality of life, and airway hyperreactivity but not forced expiratory volume in one second. However, in this study, an exacerbation was not included.

In 2015, a Cochrane systematic review was done on the use of long-term macrolides in bronchial asthma.[11] Authors found 23 studies that had been published for the past similar review in 2007. They reported that 1513 participants received either macrolide or placebo. There were major concerns about the difference between methods and results among different studies which were reflected on the quality and reliability of the outcomes. However, the authors showed that macrolides were not better than placebo for most of the important outcomes they looked at such as exacerbations requiring hospital admission or treatment with oral steroids. However, they may have some benefits on symptom scale and lung functions. There were no reports of serious side effects of macrolides, but 16 studies did not say whether any occurred.

Brusselle et al. published a multicenter randomized, double-blind, placebo-controlled trial on the use of azithromycin for the prevention of exacerbations in severe asthma known as AZISAST.[12] Over 26 weeks and using azithromycin at a dose of 250 mg twice weekly on 109 patients, they noted a significant improvement in the Asthma Quality of Life Questionnaire score. There was no significant difference between the control and treated group for the primary endpoints (rate of severe exacerbations and lower respiratory tract infections). However, when they considered only patients with noneosinophilic asthma, there were less exacerbations in this group.

More recently, Gibson et al. have published another randomized, double-blind, placebo-controlled trial on the effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma known as AMAZES study.[13] Over 48 weeks and using 500 mg twice a week for 420 patients, authors found that compared to placebo, the treated group have shown a significant reduction in the number of exacerbation rate, annual asthma exacerbations rate, and the percentage of exacerbation free days that is better in eosinophilic patients. They also showed improved asthma-related quality of life. The study excluded patients with hearing impairment or the QT interval prolongation. Diarrhea was the most common side effect reported (34% in the treatment group vs. 19% in the placebo group).

In our view, azithromycin is effective in preventing asthma exacerbations when inhaled corticosteroids and long-acting beta 2-agonists are not enough, and the use of biologic drugs is not feasible or ineffective. Benefits include the reduction of reported symptoms, improved quality of life scores, and reduction of exacerbations as well as improved pulmonary function tests. These benefits are likely to be mediated by preventing respiratory infections, enhancing viral inactivation, and anti-inflammatory effects of macrolides. Long-term azithromycin therapy is to be reserved for patients at highest risk for exacerbations and preferably restricted to months of autumn and winter when most respiratory viral infections occur. It is best used for patients with frequent exacerbations who are not candidates for biologics therapy; for example, neutrophilic asthma, and in situ ations where biologic drugs are not available or unaffordable.

The long-term antibiotics resistance is a concern and needs to be addressed in future studies.[14] Azithromycin is a safe drug with diarrhea as the most frequently reported side effect. Before the initiation of the drug, a precautionary measure is to exclude patients with prolongation of QT interval and/or hearing impairment. The ideal dose is 500 mg three times per week for 48 weeks.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Hara K, Suyama N, Yamaguchi K, Kohno S, Saito A. Activity of macrolides against organisms responsible for respiratory infection with emphasis on Mycoplasma and Legionella. J Antimicrob Chemother 1987;20 Suppl B:75-80.  Back to cited text no. 1
    
2.
Guzik J, Patel G, Kothari P, Sharp M, Ostrowsky B, UHF Outpatient ASP Collaborative Team. Antibiotic prescribing for acute respiratory infections in New York City: A model for collaboration. Infect Control Hosp Epidemiol 2018;39:1360-6.  Back to cited text no. 2
    
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Sun XJ, He ZY. Macrolides for treatment of chronic obstructive pulmonary disease. Chin Med J (Engl) 2019;132:1261-3.  Back to cited text no. 3
    
4.
Laska IF, Chalmers JD. Treatment to prevent exacerbations in bronchiectasis: macrolides as first line?. Eur Respir J 2019;54:1901213.  Back to cited text no. 4
    
5.
Luisi F, Gandolfi TD, Daudt AD, Sanvitto JP, Pitrez PM, Pinto LA. Anti-inflammatory effects of macrolides in childhood lung diseases. J Bras Pneumol 2012;38:786-96.  Back to cited text no. 5
    
6.
Lei WT, Lin HH, Tsai MC, Hung HH, Cheng YJ, Liu SJ, et al. The effects of macrolides in children with reactive airway disease: A systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther 2018;12:3825-45.  Back to cited text no. 6
    
7.
Mauricio AP, Bacharier LB, Castro-Rodriguez JA. Efficacy of Macrolides on Acute Asthma or Wheezing Exacerbations in Children with Recurrent Wheezing: A Systematic Review and Meta-analysis. Pediatric Drugs 2020. p. 1-12.  Back to cited text no. 7
    
8.
Reddel HK. The Impact of the Global Initiative for Asthma (GINA): Compass, Concepts, Controversies and Challenges. BRN Rev 2019;5:4-18.  Back to cited text no. 8
    
9.
Al-Moamary MS, Alhaider SA, Alangari AA, Al Ghobain MO, Zeitouni MO, Idrees MM, et al. The Saudi initiative for asthma – 2019 update: Guidelines for the diagnosis and management of asthma in adults and children. Ann Thorac Med 2019;14:3-48.  Back to cited text no. 9
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10.
Wang X, Luo J, Wang D, Liu B, Liu C. The efficacy and safety of long-term add-on treatment of azithromycin in asthma: A systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e17190.  Back to cited text no. 10
    
11.
Kew KM, Undela K, Kotortsi I, Ferrara, G. Macrolides for chronic asthma. Cochrane Database Syst Rev 2015;9:CD002997.  Back to cited text no. 11
    
12.
Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): A multicentre randomised double-blind placebo-controlled trial. Thora×2013;68:322-9.  Back to cited text no. 12
    
13.
Gibson PG, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res 2019;5. pii: 00056-2019.  Back to cited text no. 13
    
14.
Edelstein PH. Azithromycin phenotypic versus clinical resistance. Antimicrob Agents Chemother 2019;64. pii: E01986-19.  Back to cited text no. 14
    




 

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