May 30, 2024

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2021 GINA guide: Can Azithromycin Cure Asthma?

2021 GINA guide: Can Azithromycin Cure Asthma?


2021 GINA guide: Can Azithromycin Cure Asthma?  Can Azithromycin Cure Asthma? Check out what the latest GINA guide says!


Due to the high drug resistance rate of azithromycin, the treatment of adult community-acquired pneumonia (CAP) has begun to reduce its use. The treatment of Mycoplasma pneumoniae pneumonia is no longer the first choice [1], but azithromycin is “odd”-there are effects other than antibiotics: unique Immunomodulatory effect.

Low-dose azithromycin long-term maintenance treatment can be used to prevent or reduce the acute exacerbation of a variety of chronic respiratory diseases, such as asthma, COPD, bronchiectasis, etc. Many related guidelines, such as GINA 2020 [2], GOLD 2021 [3], ERS branch Expansion of management guidelines [4], etc., are still recommended for selective patients, azithromycin has a broad application space, so azithromycin has embarked on a new altar.


What is the status of Azithromycin in the latest GINA 2021?

Addition of azithromycin therapy in adults:

medium and high-dose ICS/LABA treatment of eosinophilic and non-eosinophilic asthma in adults with persistent symptoms, supplemented with azithromycin (3 times a week) treatment can reduce acute exacerbations (level B evidence) .

In GINA 2021, azithromycin is the first to “board” the five-step diagram of asthma, and azithromycin is included in the other control options for the fifth level of treatment (Figure 1).

2021 GINA guide: Can Azithromycin Cure Asthma?
Figure 1 Individualized management of adult and adolescent asthma to control symptoms and minimize future risks

The drugs used to treat asthma can be divided into control drugs (controller) and relief drugs (reliever), as well as additional treatment drugs for severe asthma. In layman’s terms, control medications are long-term maintenance medications, while relief medications are emergency medications.

Additional therapeutic drugs for severe asthma:

mainly bio-targeted drugs, such as anti-IgE monoclonal antibodies, anti-IL‑5/IL‑5 receptor monoclonal antibodies and anti-IL‑4 receptor monoclonal antibodies, and others as well as azithromycin Etc. [5].

Management of severe asthma Add-on treatments for severe asthma include: long-acting cholinergic drugs (LAMA), leukotriene receptor antagonists (LTRA), low-dose azithromycin (adults) and biologically targeted drugs for Severe allergies or type 2 asthma. If there are other options, long-term oral steroids (OCS) should be avoided as maintenance therapy because of the many side effects.



Evidence grounds

It is not recommended for no reason. The recommendation evidence for Azithromycin in GINA 2021 mainly comes from two clinical trials and one meta-analysis.

AZISAST research

The enrolled subjects were non-smokers with severe asthma (defined as GINA grade 4~5), after high-dose inhaled hormone (ICS) and long-acting β2 receptor agonist (LABA), there were still at least 2 acute episodes in the past 6 months For exacerbated patients, the experimental group (n = 55) added 250 mg azithromycin 3 times a week to the ICS/LABA treatment. The primary efficacy endpoint was the severe acute exacerbation rate during the 26 weeks of antibiotic treatment, and the secondary efficacy endpoint Including lung function, Asthma Control Rating Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ).

The results showed that there was no significant difference in the rate of severe acute exacerbation within 26 weeks between the azithromycin group and the placebo group (p = 0.682), but the subgroup analysis found that for the non-eosinophilic severe asthma subgroup (defined as peripheral blood eosinophils) ≤ 200 pcs/μl), long-term azithromycin treatment can significantly reduce severe acute exacerbations (p = 0.013). The azithromycin group significantly improved the quality of life score (AQLQ), but there was no significant difference between the lung function and asthma control score (ACQ) between the two groups.


AMAZES research

The enrolled subjects were asthma patients over 18 years of age who were still symptomatic and had no hearing impairment and prolonged QT interval after ICS/LABA treatment. The patient was randomized 1:1 to receive 500 mg azithromycin 3 times a week for 48 weeks.

The primary effective end point was the rate of moderate to severe acute exacerbations of asthma and the asthma-related quality of life within 48 weeks. There were 213 patients in the azithromycin treatment group and 207 patients in the placebo group.

The results showed that azithromycin can reduce acute exacerbations (1.07 times/patient-year) vs placebo group (1.86 times/patient-year), incidence rate ratio (IRR) 0.59 (P <0.0001), azithromycin group ≥ 1 acute exacerbation Significantly reduced (P <0.0001). Azithromycin significantly improved asthma-related quality of life (P = 0.001).



Oral treatment of azithromycin in adults with persistent symptoms for 48 weeks can reduce acute exacerbations and improve quality of life.



In 2019, a meta-analysis found that azithromycin maintenance treatment for severe asthma, eosinophilic or non-eosinophilic asthma can reduce acute exacerbations (Figure 2).

2021 GINA guide: Can Azithromycin Cure Asthma?
Figure 2 The incidence rate (IRR) and 95% confidence interval (95% CI) of acute exacerbation between azithromycin and placebo groups



1. GINA 2021 indications:

After standard treatment, patients with severe asthma who still have persistent symptoms and require medium and high doses of ICS/LABA are recommended to receive long-term maintenance treatment with azithromycin after evaluation by a specialist;

2. Adverse drug reactions:

long-term oral azithromycin diarrhea is more common [7], macrolides can cause prolonged QT interval (sudden death in severe cases), hearing loss, etc.;

3. Drug resistance:

After long-term treatment with azithromycin, the resistance rate of oropharyngeal streptococcus macrolides increases, which can increase the drug resistance levels of individuals and groups, but its clinical characteristics are currently unclear;

4. Course of treatment:

No benefit was seen in the 3-month clinical trial. The current clinical trials are limited to less than 1 year. The benefits and risks of longer treatment are not yet clear;

5. Off-label medication:

The long-term maintenance treatment of azithromycin is off-label medication. The risk should be informed and the relevant procedures should be improved.


Sum up

1. Asthma is a heterogeneous disease with different clinical phenotypes. If severe asthma is still poorly controlled after standardized treatment, additional treatment drugs can be selected based on the clinical phenotypic assessment of asthma;

2. In adult patients with asthma after standardized treatment of medium and high doses of ICS/LABA treatment, if there are still persistent symptoms, supplemented with azithromycin (500 mg 3 times a week) treatment can reduce the acute exacerbation and improve the patient’s quality of life;

3. Long-term azithromycin treatment is an add-on treatment, not a first-line and second-line medication for asthma. It is an unconventional medication. The indications and contraindications should be strictly grasped, and the pros and cons should be weighed and adverse reactions should be monitored during use to avoid abuse;

4. Following the GINA guidelines, individualized repeated assessment of the condition, monitoring of treatment response and adjustment of treatment plan, to find the lowest effective treatment level to maintain asthma control, and achieve the best control of asthma.




(source:internet, reference only)

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