How much do you know about inhaled corticosteroids, one of the important drugs for treating COPD?

Chronic obstructive pulmonary disease (COPD) is a common chronic airway disease. The prevalence of COPD in people aged 20 and above in my country is 8.6%, and the prevalence in people aged 40 and above is 13.7%. Based on this, it is estimated that the number of people suffering from COPD in my country is close to 100 million. As a key disease in the "Healthy China 2030" action plan, the prevention and control of COPD is extremely severe.

Glucocorticoids are currently widely used and effective anti-inflammatory preparations in clinical practice, including inhaled corticosteroids (ICS) and systemic glucocorticoids, which play an important role in the maintenance treatment of patients with stable COPD and the treatment of acute exacerbations.

ICS can not only reduce the infiltration of various inflammatory cells and the expression of inflammatory factors, but also inhibit airway mucus hypersecretion, enhance mucus clearance, increase the expression of β receptors, reduce airway hyperresponsiveness, and relieve airway spasm. It is widely used in the treatment of COPD due to its high local concentration and few systemic adverse reactions.

1. ICS inhalation device selection

The selection of inhalation device needs to be based on its characteristics and combined with a comprehensive assessment of the patient's age and condition. The inhalation flow rate and inhalation device are the basis of inhalation therapy.

Dry powder inhalers are highly dependent on the patient's inspiratory flow rate and inhalation technique, and require patients to carefully choose them based on their characteristics and their personal inspiratory flow rate. Pressurized metered-dose inhalers (pMDIs) and soft mist inhalers have low internal resistance and relatively low requirements for the patient's inspiratory flow rate.

In particular, the co-suspension pMDI uses co-suspension technology to adsorb drug crystals onto porous phospholipid sphere carriers (particle size is about 3.0 μm) according to the prescribed ratio and then loads them into a container together with the propellant. When used, it releases an aerosol with a constant dose and ratio.

The proportion of microparticles in the drug output by co-suspension pMDI is 61%~69%, and the lung deposition rate can reach up to 48%. Compared with traditional pMDI, the dose and proportion of various drugs in the aerosol delivered by co-suspension pMDI are not affected by the number, time and intensity of the device shaking before use and the inspiratory flow rate, and the drugs are output in equal proportion. At the same time, for patients with poor hand-mouth coordination and poor use of traditional pMDI, the combination of pMDI + spacer can reduce the deposition of drugs in the throat, increase the deposition rate of drugs in the lungs, and reduce the cooling sensation of the spray at the same time, reduce airway irritation, thereby improving the safety and efficacy of medication, and solving the coordination problem of inhalation.

2. Precautions for the 7 major ICS applications

1. Patients with a COPD Assessment Test (CAT) score of ≥10 and a modified British Medical Research Council (mMRC) scale of ≥2 at the time of initial treatment should be given adequate bronchodilator treatment. If symptoms are still poorly controlled, it is necessary to evaluate whether combined ICS treatment is needed.

2. For patients at high risk of acute exacerbation, the need for combined ICS treatment should be fully evaluated.

3. For patients with COPD and asthma, ICS treatment is recommended in combination with one or two long-acting bronchodilators. ICS treatment should be used with caution in patients with COPD and bronchiectasis (symptoms) with recurrent infections and COPD and active tuberculosis.

4. (1) For patients with peripheral blood eosinophils (EOS) ≥300 cells/μl, combined ICS treatment is recommended based on symptoms and risk of acute exacerbation. (2) Combined ICS treatment should be considered when peripheral blood EOS is 100-300 cells/μl. (3) ICS treatment is not recommended when peripheral blood EOS is <100 cells/μl or there is a risk of infection.

5. (1) For COPD patients with peripheral blood EOS < 300 cells/μl and no frequent acute exacerbations, ICS can be discontinued. Before discontinuing ICS, the risks and benefits of ICS use should be reassessed, and follow-up and evaluation should be strengthened. (2) For patients with peripheral blood EOS ≥ 300 cells/μl, regardless of whether they have a history of frequent acute exacerbations, ICS discontinuation is not recommended. (3) After ICS discontinuation, the use of one or two long-acting bronchodilators is recommended.

6. During the acute exacerbation of COPD, individualized short-term systemic corticosteroids are recommended based on the severity.

7. During the acute exacerbation of COPD, nebulized ICS is recommended to replace or partially replace systemic hormones.

III. Five high-risk factors for ICS that increase the risk of pneumonia and adverse reactions

1. High-risk factors: smoking, age ≥55 years, history of acute exacerbation or pneumonia, body mass index <25 kg/m2, mMRC>2 points, or severe airflow limitation.

2. Other common adverse reactions: oral candidiasis, throat irritation, cough, hoarseness and skin contusion.

3. Rare adverse reactions: allergic reactions such as rash, urticaria, angioedema and bronchospasm.

4. Very rare events include cataracts, hyperglycemia, mycobacterial infection (including Mycobacterium tuberculosis), Cushing's syndrome, dyspepsia and arthralgia.

In summary, ICS is one of the important drugs for the treatment of COPD. It has both advantages and disadvantages when used. Medical personnel are required to implement individualized treatment clinical practices based on the evidence-based Chinese COPD guidelines and clinical experience.

References:

[1] Liang Zhenyu, Wang Fengyan, Chen Rongchang. Important updates and prospects of the guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease (2021 revised version)[J]. International Journal of Respiratory Diseases, 2021, 41(19): 1457-1461.

【2】Chen Yahong. Background and thoughts on writing the "Expert consensus on standardized management of glucocorticoids in chronic obstructive pulmonary disease"[J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2021, 44(12): 1034-1036.