Is there a direct relationship between asthma/wheezing in children in winter and upper respiratory tract infections, what are the current GINA (Global Asthma Initiative) recommendations for the treatment of asthma in children, and how to ensure efficacy and reduce the risk of side effects in the long-term treatment process?...... Recently, the reporter of "Respiratory" invited Hong Jianguo, chief physician and professor of pediatrics of the First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, to give you an authoritative answer, and he also deeply analyzed the status of low-dose hormone combination therapy in the GINA guidelines in combination with clinical practice.
From the perspective of etiology and environmental factors, why children with asthma/wheezing are more likely to be more likely to occur in winter...... Acute onset of illness due to upper respiratory tract infection should not be underestimated
Professor Hung pointed out that autumn and winter are the peak periods for respiratory infections, and some viruses are seasonal, such as respiratory syncytial virus and influenza virus, which are common in children. In the autumn and winter of 2023, we experienced a period of mixed and superimposed infections of multiple pathogens, which further confirmed that the peak season for respiratory infections is autumn and winter, and these are related to asthma and wheezing. The main cause of asthma attacks in children is respiratory tract infections, which are more severe than those in adults, and more than 80% to 90% of acute episodes of asthma or wheezing in children are closely related to respiratory viral infections. In the case of respiratory syncytial virus, for example, when an infant under the age of one is first infected with the virus, it can cause bronchiolitis, which is characterized by wheezing.
Upper respiratory tract infections can cause not only acute exacerbations in people with asthma, but also wheezing in infants and young children with no previous history of asthma. Most wheezing symptoms can persist for a long time, and without early intervention, infection can lead to other conditions, including secondary bacterial infections, not only wheezing. From September and October last year until the Spring Festival, the burden of children was always heavy, mainly due to recurrent upper respiratory tract infections, of which viral infections accounted for a large proportion, as well as Mycoplasma pneumoniae infection. Mycoplasma pneumoniae infection, the pathogen of concern, peaked last year, and the number of cases rose rapidly from the second half of last year to peak. Mycoplasma pneumoniae is different from a virus in that it is an atypical bacterium, and as a superantigen, mycoplasma triggers an immune response that cannot be ignored, and wheezing symptoms are more common in severe or refractory cases of mycoplasma pneumonia. Wheezing symptoms due to mycoplasma infection are markedly different from those caused by bacterial infection alone, and wheezing symptoms are more likely to occur in patients with both viral and mycoplasma infections.
Environmental factors also play an important role in asthma attacks in children. The cold climate in both the north and the south in winter will lead to an increase in the amount of time children spend indoors, which will increase their exposure to indoor environmental pollutants. Pollution here does not necessarily mean poor air quality, for example, children with allergies may be exposed to allergens such as mites, cockroaches, mold and other allergens if they stay indoors for a long time. Excessive exposure to these indoor allergens can exacerbate the development of asthma/wheezing. Therefore, indoor environmental pollution should not be ignored in the process of asthma aggravation in children, and in the northern winter, the degree of external air pollution may be more serious, and exposure to outdoor polluted air is also one of the causes of aggravated asthma/wheezing. Of course, environmental factors also include various factors such as large temperature difference between indoor and outdoor in winter, dry climate, etc., which are not conducive to asthma/wheezing patients.
What are the latest GINA (Global Asthma Initiative) guidelines for the treatment of asthma in children?...... Combined with clinical practice, the status of low-dose corticosteroid combination therapy in the guidelines is interpreted
Professor Hong pointed out that 2023 marks the 30th anniversary of GINA's first edition in 1993, and the initiative has played a huge role in promoting the global asthma response. From the first version of the initiative to the latest version of the 2023 version of the initiative, two points have been emphasized: first, asthma is a chronic disease that can recur, and second, asthma is a heterogeneous disease that manifests differently in different patients and at different time periods. Based on this, GINA has always recommended that we intervene in the whole process of asthma. Asthma is a chronic inflammatory disease with persistent inflammation, so recommended treatments include ongoing therapy (control/maintenance therapy), and palliative therapy, i.e., medications that provide rapid relief of wheezing symptoms during an acute exacerbation, such as bronchodilators.
The preferred strategy for anti-inflammatory therapy is inhaled corticosteroids (ICS), which are easy to implement and effective in reducing the amount of systemic glucocorticoids and minimizing inflammation to prevent recurrent asthma attacks. Other anti-inflammatory drugs include antileukotrienes represented by montelukast sodium. However, there are many types of anti-inflammatory drugs, and clinicians need to consider them holistically when choosing anti-inflammatory drugs. According to mainland clinical statistics, from 2000 to 2010, the proportion of hormones used by children with asthma almost doubled, while the proportion of systemic hormones used decreased by 50%. Hormone is a double-edged sword, and although it has significant efficacy, its side effects cannot be ignored, so we recommend that clinicians avoid the use of systemic hormones in the treatment of childhood asthma and switch to inhaled corticosteroids. Although the dose of inhaled hormone is small, it is an internationally recognized fact that its structure as a chemical is relatively stable and not easy to decompose or convert, and when inhaled hormone enters the lungs, the cells and tissues of the lungs do not have the ability to break down hormones, so inhaled hormones can remain in their original form and enter the body, which is an internationally recognized fact. However, some doctors and patients in mainland China do not have enough awareness of this and believe that inhaled corticosteroids only have a local effect. To be clear, although inhaled hormone doses are small, long-term or high doses may still have some systemic effects.
Clinicians need to make a comprehensive trade-off when determining the dose of inhaled drugs, and use low-dose inhaled corticosteroids as much as possible, as long-term use of inhaled corticosteroids may cause clinical adverse effects. Over the past decade, GINA guidelines have placed more emphasis on minimizing the use of corticosteroids, which is why we are treating patients with the lowest dose of inhaled corticosteroids. In the search for ways to reduce the dose of inhaled hormones and achieve the best therapeutic outcome, the latest GINA makes it clear that this can be achieved through a combination of therapeutic drugs. In adults, the addition of long-acting β agonists to inhaled hormones can be used to reduce the dose of the hormone and improve asthma control, while in children (especially under 6 years of age), combination therapy with other drugs, such as antileukotrienes as anti-inflammatory drugs, is necessary because long-acting β agonists are not yet available clinically. The aim is to reduce the activity of leukotrienes, an inflammatory mediator in asthma, thereby improving the therapeutic effect.
In particular, Professor Hong emphasized that one of the main points of the latest GINA guidelines is the use of inhaled corticosteroids in combination with inhaled bronchodilators, such as beta-2 agonists (SABAs), in the acute phase. At the same time, it is pointed out that the use of combined inhalation therapy should also pay attention to possible adverse reactions, taking β2 receptor agonists as an example, although the specificity of β2 receptors is relatively strong, it may also have an effect on other receptors, so special attention should be paid to avoid overuse, otherwise it will easily cause tachycardia and other phenomena in clinical patients, and it is necessary to be more careful of its serious adverse reactions when used continuously during the acute attack of asthma, such as fatal hypokalemia. If high doses of beta-2 agonists are needed, cardiopulmonary monitoring must be done. Excessive combined use of inhaled corticosteroids may also lead to adverse effects, which is also undesirable. For patients with persistent asthma, we also note that the "black box warning" for montelukast sodium in the United States, for example, is only a reminder to doctors and patients about possible adverse reactions of the drug, and does not mean that it is prohibited, which needs to be clarified.
In the interview, Professor Hong also told us that the current domestic guidelines are being revised, although they have not been officially finalized, but the key content worthy of doctors' attention in addition to the above content, is still the diagnosis and treatment of preschool (less than 6 years old) asthma children, in addition to the application of biological agents, the single use of antileukotrienes or the combination of inhaled hormones in children under the age of 6 anti-inflammatory drugs are recommended, which are still in the range of first-line drugs, such as the domestic "Shunerning" It is a typical anti-leukotriene, which has been on the market for 25 years, its clinical effectiveness is trustworthy, and its safety is also obvious to all.
Expert presentation
Hong Jianguo
Chief physician, professor of pediatrics, and deputy editor-in-chief of the Chinese Journal of Pediatrics. He has long been engaged in clinical and scientific research in the diagnosis and treatment of children's respiratory diseases. He used to be the 3rd and 4th vice chairman of the Allergy Branch of the Chinese Medical Association, the deputy leader of the 13th and 14th Respiratory Group of the Pediatric Branch, the 3rd and 4th chairman of the Allergy Branch of the Shanghai Medical Association, the first vice president of the Allergy Physician Branch of the Chinese Medical Doctor Association, and the first vice president of the Pediatrician Branch of the Shanghai Medical Doctor Association. He presided over the formulation of a number of disease prevention and control guidelines/consensuses such as the Guidelines for the Diagnosis and Prevention of Bronchial Asthma in Children. He has edited 10 academic monographs and published more than 300 academic papers.
* The article is for medical and health practitioners only
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采访撰稿：冬雪凝；责编：Jerry