Study on asthma control status in children with bronchial asthma and allergic rhinitis

had a clear reduction in FEV1. The group with FEV1 < 80% had a higher need for ICS than the other two groups, and after 6 months of treatment, this group had an average number of requests for SABA reliever medication of 1.0 ± 1.4 times, higher than the groups with mild and normal FEV1. In addition, the respiratory function and good asthma control rate according to CARATkids of the group with clearly reduced FEV1 were lower than those of the other two groups.

Stout conducted a study on a group of asthmatic children aged 8-11 years living in the city in two periods from 1992-1994 (Cohort 1) and from 1998-2001 (Cohort 2). For children diagnosed with mild intermittent asthma based on clinical symptoms, after measuring spirometry to classify the severity of asthma, 22.8% of children in cohort 1 and 27.7% of children in cohort 2 were diagnosed with moderate and severe asthma 149 . Thus, spirometry plays a role in classifying the severity of asthma in children over 5 years old more accurately and objectively than asking about the patient and clinical examination. Based on spirometry, we can distinguish the severity of asthma and classify asthma phenotypes. The concomitant decrease in FEV1 values with FeNO concentrations may suggest that clinicians can classify a group of asthmatic children with a non-allergic asthma phenotype who have reduced respiratory function, poor response to ICS treatment, or who have been diagnosed with asthma but have missed prophylaxis or used medication irregularly.

Nowadays, scientists use a new approach to determine the pathophysiological phenotype of asthma (endotype). The phenotype is determined through genetic markers on the airway, which in HPQ is often the type 2 asthma endotype. In this phenotype, Th2 cell-dependent inflammatory markers are measured by non-invasive methods through sputum samples, exhaled air, nasal lavage fluid, bronchial lavage fluid, urine, serum and blood 150 . The combination of clinical phenotype and pathophysiological phenotype helps clinicians to orient treatment drugs during the process of monitoring asthma control,

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especially in severe asthma cases, treatment with biological products is required. According to Agache et al., classifying immune responses into two main types: type 2 immune responses and non-type 2 immune responses, identifying inflammatory markers that increase at each time point and in different allergic diseases, thereby helping clinicians choose targeted drugs according to the correct pathophysiological mechanism. Increased blood eosinophil counts predict treatment response to anti-IL4/IL5 antibodies, IL-13, anti-IgE antibodies as well as CRTH2 antagonists 151 .

CONCLUDE

Through research and longitudinal monitoring of 124 children with bronchial asthma with VMDƯ from 6 to 15 years old at the Department of Immunology - Allergy - Rheumatology, National Children's Hospital from October 1, 2016 to December 31, 2019, we drew the following conclusions:

1. Nasal nitric oxide thresholds in asthmatic children with allergic rhinitis.

- The nNO concentration in children with asthma was higher than in children with asthma without asthma and healthy children. The cut-off point of nNO for diagnosing allergic rhinitis in children with asthma was 605 ppb, with a sensitivity of 85.5% and a specificity of 66.7%, the area under the curve was 0.81 with p<0.001.

- The nNO concentration was highest in the severe intermittent asthma group and lowest in the mild intermittent asthma group. The more severe the asthma and the more reduced the respiratory function, the lower the nNO concentration.

- nNO concentration is closely positively correlated with FeNO and allergic factors such as eosinophils in peripheral blood.

2. Asthma control status in children with asthma and allergic rhinitis

- After 6 months of preventive treatment, the rate of complete asthma control in children with HPQ and VMDƯ was lowest according to GINA 2016 standards at 67.5%, and highest according to ACT standards at 96.1%.

- The CARATkids score is capable of distinguishing well the levels of asthma control. With the CARATkids threshold = 4.5, the area under the ROC curve is 0.957; the sensitivity is 100%, the specificity is 79.8% to distinguish the level of asthma control with VMDƯ in children.

- The asthma control rate according to CARATkids is equivalent to the asthma control rate according to FeNO.

- Airway FeNO and nNO concentrations decreased after preventive treatment of asthma and VMDƯ.

3. Asthma phenotype in children with bronchial asthma and allergic rhinitis

- Children with moderate to severe asthma had the highest rate (62.1%) with high FeNO and nNO concentrations, poor asthma control rate and higher ICS dose requirement than the HPQ group with mild asthma.

- Children with HPQ and VMDƯ with nNO level < 605ppb had lower FeNO, IgE concentration, eosinophil count in peripheral blood and respiratory function after 6 months of treatment than the group with nNO level ≥ 605ppb.

- Children with COPD with low FEV1 have a high need for ICS. After 6 months of treatment, this group has a low rate of complete asthma control and a high need for SABA reliever medication.

- Blood eosinophil parameters, blood IgE, FeNO, nNO are inflammatory markers that help in the process of classifying asthma phenotypes, predicting the severity of asthma and predicting the ability to respond to corticosteroid treatment.

SOME LIMITATIONS OF THE STUDY

- Because the HPQ characteristics of children are mainly allergic asthma, the group of bronchial asthma without allergic rhinitis is often small. The limited sample size of the asthma group without allergic rhinitis and healthy children makes it difficult to detect differences in inflammatory factors during the research process as well as treatment prognosis.

- Due to limitations in the study design, we have not been able to design a longitudinal follow-up of the asthma group without VMDƯ in children.

- Assessment of inflammation in bronchial asthma requires assessment of the airways, however, due to technical problems, we used indirect indicators such as eosinophils in peripheral blood. At the same time, in this study, only total IgE testing was performed, not specific IgE testing, which is an important characteristic factor in bronchial asthma.

- nNO concentration is a factor affected by many factors and has a wide range of fluctuations, so the nNO concentration results in this study are different from many other studies. In fact, the world has not yet reached a consensus on the nNO threshold in the diagnosis and monitoring of VMDƯ treatment.

PROPOSAL

Measurement of exhaled nitric oxide concentration (FeNO, nNO) is a non-invasive, easy-to-perform method that objectively assesses inflammation in both the upper and lower airways in older children with asthma and allergic rhinitis. Medical facilities specializing in the field of allergy immunology should be equipped with exhaled nitric oxide concentration measuring machines to diagnose and monitor the treatment of HPQ patients.

In clinical practice, it is necessary to combine medical history, clinical examination with specific tests such as skin prick test with respiratory allergens, respiratory function test and measurement of nitric oxide concentration in the airway to help diagnose and classify asthma phenotypes, thereby choosing the appropriate treatment and dose for each asthma patient. It is necessary to individualize the treatment of bronchial asthma.

Assessment of asthma control and comorbidities should be combined with appropriate toolkits such as CARATkids during disease control monitoring, especially for children with asthma and comorbidities.

LIST OF PUBLISHED WORKS RESEARCH RESULTS OF THE THESIS TOPIC

1. Nguyen Tran Ngoc Hieu, Nguyen Thi Dieu Thuy, Luong Cao Dong (2020). Application of CARATkids questionnaire in asthma control in children with bronchial asthma and allergic rhinitis. Journal of Clinical Medicine and Pharmacy 108, 15(3), 63-67.

2. Nguyen Tran Ngoc Hieu, Luong Cao Dong and Nguyen Thi Dieu Thuy (2020). The role of airway Nitric Oxide in controlling asthma with allergic rhinitis in children. Journal of Medical Research, Hanoi Medical University, 131 (7),141 - 147.

3. H. Nguyen - Tran - Ngoc, Th. Nguyen - Thi - Dieu, D. Luong - Cao et al (2021). Study of control status in children with bronchial asthma and allergic rhinitis. J Func Vent Pulm, 37(12).13-19.

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