Discussion
Asthma is generally diagnosed based on the clinical manifestations of recurrent wheezing combined with reversible airflow obstruction. Unlike for adults, there are no objective criteria for the diagnosis of asthma in children under 6 years of age, and especially for those under 3 years of age. At present, the diagnosis and treatment of asthma in this age group is mainly based on the frequency of wheezing attacks and the prediction of high asthma risk based on the mAPI(4, 5). However, the positive rate of asthma prediction based on mAPI is limited (6, 7). Therefore, although atopy is a high-risk factor for asthma, many these children will not develop asthma. There is an urgent need for stable and specific biological indicators to assist in the diagnosis of asthma, and a major focus of research in the field is to find specific biological indicators through the immunological mechanism of asthma(8, 9).
In this study, a small-sample cohort of 43 wheezing children was established. The relationship between the level of circulating CD4+CCR6+CRTh2+memory Th2 cells and a diagnosis of asthma was determined. We found that the level of CD4+CCR6+CRTh2+memory Th2 cells in the asthma group was significantly higher than that in the non-asthma group. Logistic regression analysis further indicated that CD4+CCR6+CRTh2+memory Th2 cells were an independent risk factor for the diagnosis of asthma. In this study, 74.4% of the subjects showed inhaled and/or food allergen sensitization, indicating that most of the included patients had allergic physique. Therefore, we analyzed whether there were differences in CD4+CCR6+CRTh2+memory Th2 cells among other allergic diseases. The increase in CD4+CCR6+CRTh2+memory Th2 cells is specifically related to asthma and is not affected by AR or AD. CD4+CCR6+CRTh2+memory Th2 cells have certain tissue specificity and reflect allergic airway inflammation. This result can be further demonstrated by the fact that higher level of CD4+CCR6+CRTh2+memory Th2 cells in asthmatic children than non-asthmatic children in atopic population.
CD4+CCR6+CRTh2+memory Th2 cell is a type of pathogenic memory-type Th2 cell. Pathogenic memory-type Th2 cells are mainly distributed in local tissues for long periods of time and play key roles in the maintenance of chronic allergic inflammation(10-12). CD4+CRTH2+CCR6+cells are memory Th2 cells that produce IL-17, which is mainly found in the airway. CD4+CRTH2+CCR6+cells secrete IL-17, IL-4, and IL-13, leading to the infiltration neutrophils and eosinophils, which is responsible for chronic inflammation associated with asthma. This course of events reflects the immune memory of allergic airway inflammation in the lung tissue. A small number of pathogenic memory-type Th2 cells can enter the circulation(10, 11). Therefore, the detection of circulating CD4+CRTH2+CCR6+memory Th2 cells producing IL-17 is an indicator of previous and chronic airway allergic inflammation, an important immunological feature of asthma.
In conclusion, despite of small sample, our exploratory study found that because CD4+CCR6+CRTh2+memory Th2 cells have certain lung tissue specificity and an increase in circulating memory Th2 cells reflects previous and present allergic chronic inflammation, these cells can be used as a potential biological indicator for diagnosis of asthma in preschool children, especially in atopic children. We will further expand the sample size and prolong the follow-up time to validate the current results.