Deep interpretation · New idea of severe asthma ② | What should I do if I can't control severe asthma?New direction of asthma treatment in the future

In 1995, the famous Hong Kong singer Deng Lijun died of asthma, which also gave more people a deeper understanding of the disease of asthma. In China, how many people are being plagued by bronchial asthma (asthma), which is 47.5 million. According to the study of Chinese adult lung health released by "Liu Ye Dao", the prevalence of asthma in the age of 20 and above in China is 4.2%1. The causes of asthma are mostly genetic factors, environmental factors, and drug factors. The pathogenesis of asthma is not completely clear, and it can be summarized as an immune-inflammatory response, neural mechanism and airway high response and its interaction.

The most serious consequences of asthma are death! According to data reported by the Global Cover (GBD) 2015, in 2015, 400,000 people around the world died of asthma. my country's asthma mortality rate is 3.6%2. Is asthma incurable? No, it is a perverted response disease characterized by chronic airway inflammation, which is divided into severity.

Asthma can be divided into mild asthma, moderate asthma, severe asthma. The grades during acute attacks include mild, moderate, severe, and critical weight 3. Patients with mild asthma will experience symptoms such as chest tightness and dyspnea, but the symptoms are relatively mild, and generally have little impact on daily activities. It is only when the amount of activity is large. A little activity will have chest tightness; patients with severe asthma patients have outstanding chest tightness symptoms during the attack, even if they are resting at a static breath; patients with severe severe asthma will have significant chest tightness and dyspnea, and even conscious disorders will occur. The results of blood gas analysis show that carbon dioxide voltage voltage increase significantly.

Most asthma can be controlled by reasonable treatment, but there are always some asthma that can be difficult to achieve good control, that is, severe asthma. Bleak

Severe asthma is an important cause of disability and death

According to GINA 2022, severe asthma refers to asthma that uses large doses of ICS+LABA asthma control, or large -dose ICS+LABA to maintain control. The clinical manifestation is the breathing, anxiety of repeated attacks, with or not with chest tightness and cough, and has a high airway and variable airflow. These will interfere with patients' daily life and sleep. Due to long -term oral glucocorticoids (OCS), the side effects of drugs are particularly obvious, including obesity, diabetes, osteoporosis, cataract, hypertension, etc.; For patients, psychological side effects such as depression and anxiety are particularly worrying. Even using OCS in the short term can cause sleep disorders, increasing the risk of infection, fracture and thrombosis 4.

Severe asthma usually interferes with patients, society, and work life in patients, restrict career choices, and affect patient emotional and mental health. Patients usually have a terrible or unpredictable condition that worsen (acute worsening). Patients with severe asthma often feel lonely and misunderstood because their experience is completely different from most asthma patients. A survey data shows that about 8%of patients with severe asthma try to commit suicide due to the pain caused by disease. This has a great burden on the spiritual and life aspects of severe asthma.

Each eosinophils are important test indicators of asthma

Asthma is a chronic airway inflammatory disease, and inflammatory cells and cytokines play an important role in their development. Compared with patients with mild asthma, inflammatory cells in blood and airway tissue in patients with severe asthma are more obvious, and the level of cytokine expression has also increased significantly.气道炎症判断依据包括血嗜酸粒细胞增高（≥150/μl）、痰嗜酸粒细胞增高（≥2%）、FeNO（呼出气一氧化氮）增高（≥20 ppb）、存在过敏因素、 OCS dependencies and so on. Among them, blood-enchanting cells are very important test indicators for patients with severe asthma. According to the results of China's first adult severe asthma and multi-centered queue (C-BIOPRED research), it is shown that among Chinese adult severe asthma people, they can induce sputum The proportion of eosinophilic granulocytes is a type 2 inflammation symbol, and the proportion of eosinophilic granulocytocycles in the C-BIOPRD queue is 78.6%6-8. Therefore, eosinophils of eosinophils in patients with severe asthma are the most common and especially need to receive attention. "Consensus of Chinese Experts" of "Adding Claims of Pulmonary Diseases of Eliculfoin Cells" also pointed out that eosinophilic granulocytocytic asthma (EA) is the most common asthma phenotype. It can be seen in EOS infiltration 7.

The clinical characteristics of eosinophilic cell -type asthma, in addition to the increased blood/phlegm eosinophils cells, also include frequent acute attacks, oral glucocorticoids (OCS) dependencies, accompanied by complications (such as chronic sinusitis with nose polyps), compared Poor lung function, adult onset, etc. The normally routine eosinophil cell count is a very important testing indicator for patients with asthma. It can be used not only to determine the clinical phenotype of asthma, but also to evaluate whether anti -inflammatory treatment is effective.

It is worth mentioning that severe eosinophilic granulocyte asthma is a common type of severe asthma type 2 inflammatory surface type. Many EPDs were originally manifested as EA, and they need to pay attention to identification. In terms of treatment, according to 2022 Global Prevention and Creation (GINA) ladder treatment plan, severe eosinophilic granulocyte asthma can be treated with type 2 inflammatory pathways. Drugs, anti -IGE and other drugs benefit.

What is the situation of Chinese severe asthma control? According to the 2015 census data, there are about 47.5 million asthma patients across the country, of which about 6%are severe patients. According to the "severe asthma definition, assessment and treatment guidelines" formulated by ERS and ATS in 2014: severe asthma accounts for 5 ~ 10%11 for patients with asthma. Another data shows that the frequency of emergency medical treatment and hospitalization of severe patients with severe patients are 15 times and 20 times 12 times of light medium asthma patients, respectively. Its control is even more worrying. In 2017, a survey of controlling levels of bronchial asthma patients in 30 provinces and cities in my country, a total of 3875 patients were included in 3875 patients. The results showed that the overall control rate of asthma in my country's urban area was only 28.5%13. In the case of such a low overall control rate, the control of patients with severe asthma is even more optimistic.

In addition, the medical cost of severe patients is serious. A British study shows that the medical cost of each severe asthma patients is higher than that of type 2 diabetes, stroke or COPD. In a study in Canada, severe asthma estimates accounting for more than 4%of asthma costs. Patients and family members of severe asthma are also affected by huge economic burdens, not only medical care and drugs, but also losses for income and career choices.

In China, according to the National Asthma Research Cooperation Group, the direct costs of acute hospitalization in patients with asthma patients from 2013-2014 (each time) reached 11,603 yuan. Due to the intensification of asthma diseases, my country's bronchial asthma was listed as one of the key chronic respiratory diseases in 2008, and it was included in the main control of respiratory diseases controlled by healthy China (2019-2030).

Precise targeted biological therapy

Is the important research direction of severe asthma in the future

GINA proposes that the goal of severe asthma treatment is to reduce the acute attack and mortality of the disease, reduce the risk of adverse reactions (OCS), reduce the use of hormones, and achieve good control of asthma symptoms, and maintain normal activity level. According to GINA2022, the treatment of severe asthma in adults is operated according to the fourth and fifth level of step treatment plan. In controlling drugs and the drug path of the preferred link, the fourth level is to keep the ICS-Fumatlo. The fifth level is the reference table type assessment plus LAMA. Considering high-dose ICS-Fumatlo, ± anti-IGE, anti-IL-5/5R, anti-IL-4R, anti-TSLP.

GINA2022 also pointed out that for patients with cymbalous asthma patients with increased levels of blood -intensive granulocytes (≥300/μL), before considering biological therapy, they should first evaluate the cause of asthma, including: category infections (because of class classification (because of class types Roundworm infection is often asymptomatic). For patients with asthma patients who combine eosinophilic granulocytes (≥1500/μL), the possibility of eosinophilic granulitis should be considered, and anti-IL4R drugs should be avoided as much as possible; III Study of IL4R.

It can be seen from the incidence of global severe asthma patients and the burden on the disease that the treatment of severe asthma patients still has large and unsatisfactory needs. Now, the clinical value of biological agents can block the treatment of asthma by blocking the inflammatory factor signal pathway. For great verification, patients with severe asthma are very urgent to quickly relieve the disease. A few days ago, the biological preparations developed on this development have continued to emerge, and severe asthma has entered the era of targeted biological therapy. In the future, precision treatment may be a very promising research direction for severe asthma.

references

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2. Emergency Medicine. People's Health Publishing House, 2015.

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7.Shaw DE, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015; 46(5): 1308- 1321.8.Kupczyk M, Dahlen B, Sterk pj, et al. Stability of Phenotypes defined by Physiology Variables and Biomarkers in Adults with Asthma. Allergy. 2014; 69 (9): 1198-1204.

9. Laviolette, M., Et Al., Effects of Benralizumab on Airways Eosinophils in Asthmatic Patients with Sputum Eosinophilia.

10.Nowak, R.M., et al., A randomized trial of benralizumab, an antiinterleukin 5 Receptor Alpha Monoclonal Antibody, after theACute Asthma. Am J Emerg Med, 2015.33 (1): P. 14-20.

11. The Chinese Medical Association's Respiratory Disease Branch, the asthma group, the Chinese asthma alliance. The severe asthma diagnosis and treatment of the consensus of Chinese experts [J]. Chinese tuberculosis and respiratory magazine. 2017, (11) .813-829.

12. Lin Jiangtao. Strive to improve the prevention and research level of my country's unpleasant asthma J. China combined with breathing magazine, 2010,33 (8): 561-562

13. National Respiratory Medicine Center of the First Affiliated Hospital of Guangzhou Medical University, National Respiratory Diseases Clinical Medicine Research Center. Correction of eosinophilic granulocytes increases related pulmonary disease diagnosis and treatment of Chinese expert consensus. Chinese Medical Journal 2022; 102: 21-35.

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Capture: Wang Lu

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