婴幼儿喘息早期诊断评价及干预性治疗的可行性研究
[Abstract]:Infantile wheezing is a common clinical syndrome in children worldwide. Repeated onset wheezing is associated with acute respiratory virus infection. An individualized treatment strategy based on a wheezing clinical phenotype is the key to optimal clinical control of wheezing / asthma. The first wheezing symptom in most children of asthma occurs in school. At the beginning of the age, about 50% of the wheezing can be completely relieved at the age of 6. It is consistent with the peak age of the respiratory virus infection. The deep understanding of the relationship between the virus infection and the infantile breather helps to understand the inherent immunological mechanism between infection and allergy related inflammation, which can help us to better understand the wheezing and asthma of infants. It has been proved that the most common virus that induces acute asthma attacks in infants is RSV, which is different from the older and adult. The asthma associated with virus infection is becoming more and more important because of its close correlation with bronchial asthma. Repeated attacks of wheezing are the high risk of asthma. The incidence of asthma in infants and young children with repeated wheezing is 5~10 times as high as that of children without wheezing symptoms. Therefore, it is one of the effective measures to reduce the incidence of asthma and improve the health level of children. The problem of birth is the standard for the lack of early diagnosis of infant asthma in clinical, and there is no objective basis for the necessity of early treatment. The root of this problem is the lack of effective clinical judgement on the evaluation of chronic airway inflammation and function in infants.
In recent years, the incidence of asthma is on the rise, which seriously affects the physical and mental health of children. Eosinophil is considered to be the main effect cell of asthma. Eosinophil inflammation is the basic characteristic of asthma. Eosinophil inflammation is a good predictor of asthma aggravation and is considered to be eosinophil. There is no response to viral infection. However, studies have revealed that eosinophils promote the clearance of viruses and enhance the defense ability of the host. It is suggested that eosinophils can stimulate the anti viral defense against the primary host to some extent under the condition of acquired immune response. Many studies have confirmed that children with asthma have been diagnosed with asthma. Phlegm cell typing can objectively reflect the changes in airway inflammation, but unlike adult asthma, children with asthma do not have two specific stable inflammatory phenotypes, eosinophils and non eosinophilic granulocytes. Although the asthma treatment strategy based on these two phenotypes in adults has been successful in clinical work, however, children The diagnosis of asthma is far more complex than that of adults, and the treatment for asthma is very different from that in adults. It is increasingly recognized that a single treatment for asthma children is not likely to be clinically successful because a large group of "child asthma" is not a true sense of asthma, and a part is treated as a respiratory tract. Patients treated with reinfection are highly likely to be neglected asthma. Therefore, the clinical phenotype of asthma and / or asthmatic disease in children can provide potential treatment targets and more individualized treatment for asthma related diseases in children. Therefore, we use liquid based thin layer cell technique to study high-risk groups of asthma, In the case of recurrent wheezing infants with atopic constitution, the sputum induced sputum was collected to detect the phlegm phenotype of phlegm cells, and the results were compared according to the severity of the disease. According to the previous research results, the sputum EOS% > 2.5% was increased in sputum EOS, and the sputum NEU% > 54% was higher in NEU, and the study object was divided into 4 groups. (1) Eosinophil type (EOS% > 2.5%); (2) neutrophils (NEU% > 54%); (3) neutrophils (NEU% < < 54%+EOS% < 2.5%); (EOS% > 2.5%+NEU% > 54%); (EOS% > 2.5%+NEU% > 54%). Serum EDN level of airway inflammation markers in patients with repeated wheezing, and detection of tidal lung function in infants and infants, and compared to montelukast The changes of airway inflammation index and lung function in infants and young children before and after intervention treatment are discussed in order to explore the similarities and differences between infant wheezing and asthma, early diagnosis, rational treatment and improvement of children's health.
This study combined with liquid based thin layer cell production, serum EDN enzyme linked immunosorbent assay and infant tidal lung function testing technology to evaluate the clinical manifestations, airway inflammation phenotypes and airway function of infants and young children with repeated wheezing, in order to confirm that infant wheezing is different from that of typical asthma and is closely related to asthma. The common characteristics are to find out the treatment points of infant wheezing and to explore the importance of early treatment.
The results of the study are as follows:
1 infantile wheezing is closely related to respiratory virus infection. 7 common respiratory virus pathogens screening found that about 76% of the nasopharyngeal aspirates in children with wheezing can detect respiratory virus, of which single infection RSV is the main virus (48%), parainfluenza virus 1,2,3 accounts for 16%, flow virus A, B account for 4.5%, adenovirus 7.5%, mixed infection often 9. %, and three cases of viral infection were found. Only 15% of children did not detect viral pathogens.
In 2890 cases, 867 cases of qualified sputum were collected. At least one inflammatory cell type was found in 504 cases (58.1%), which were neutrophil type (65.2%), eosinophil type (30.6%) and mixed cell type (4.2%). Neutrophil type was the main type of infantile inflammatory cell type, and eosinophil type was more in severe group. The difference was statistically significant compared with the light disease group (P < 0.05). The inflammatory cell count of the sputum specimens induced by the severe group showed a higher count value. Compared with the light disease group, there were significant differences in neutrophils and eosinophils (P < 0.05).
3 the level of serum EDN was different in the different inflammatory cells group, and the eosinophil group was the highest (112.6 + 41.2) mu g/l, followed by mixed cell group (104.8 + 39.4) mu g/l, neutrophils group (88.2 + 36.6) mu g/l and less neutrophil type (60.9 + 34.6) mu g/l, and the difference of serum level between each group was statistically significant (P < 0.05).
4 although there was no significant difference in the eosinophil count of peripheral blood in the inflammatory groups, there was a significant positive correlation between the serum EDN level and the increase of eosinophils in the peripheral blood (gamma =0.781, P < 0.05).
5 tidal pulmonary function indicates that tidal volume decreases in children with recurrent wheezing, and low tidal volume is associated with increased serum EDN level (gamma =0.499, P < 0.05).
6 the respiratory rate in children with wheezing attack was significantly faster than that in the same age control group, and the volume of tidal gas decreased significantly. The index of TPTEF/TE and VPEF/VE reflecting airway obstruction were also lower than those in the control group. The difference was significant (P < 0.05). The respiratory frequency of children in remission stage decreased, VT/kg, TPTEF and VPEF, TPTEF/TE, VPEF/VE all increased significantly, and all the fingers before and after treatment. There was no significant difference in VT/kg between remission group and control group (P > 0.05), but there was significant difference in TPTEF/TE and VPEF/VE between remission group and control group (P < 0.05).
7 the clinical symptoms of 106 patients with montelukast were improved by 42.5% (45/106), 4 weeks after treatment, 12 weeks of asthma, cough, coughing / wheezing (activity), and tidal gas and lung function, compared with the basic values (P < 0.05). Compared with the control group, the number of breathing attacks, the annual average hospitalization days, and the years were compared with the control group. There were statistically significant differences in the use of beta 2AG days and the improvement of lung function (P < 0.05). After 2 years of follow-up, 11 cases (10.4%) were diagnosed as asthma and 19 cases in the control group (39.6%). The two groups were statistically significant (x 2=38.3967, P < 0.05).
8 at the end of the 3 month treatment observation (observation point), the level of serum EDN in the patients with eosinophilic wheezing in the montelukast group was significantly higher than that in the treatment group (P < 0.05), and was significantly higher than the initial level (P < 0.05), while the serum level of EDN in the treatment group was significantly lower than that before the treatment (P < 0.05).
9 the tidal volume of children with wheezing before treatment was significantly reduced, and the index of TPTEF/TE and VPEF/VE of airway obstruction decreased obviously. After 12 weeks of montelukast treatment, PTEF (ml/s), VT/kg, TPTEF and VPEF, TPTEF/TE, VPEF/VE all increased significantly after 12 weeks of treatment (P0.05), and there was a significant difference compared with the control group (P) 0.05), but without treatment, PTEF (ml/s) was also improved after 12 weeks (P0.05), but the difference of TPTEF/TE and VPEF/VE decreased significantly. There was no significant change before and after observation, and there was no significant difference (P0.05).
In this study, the DFA method was used to screen 7 common respiratory viruses for infants and infants, and the liquid based thin layer cell technique was used for the first time to classify the patients, and EDN was used as a marker for airway inflammation. At the same time, the diagnosis and prognosis evaluation of the obstructive airway disease in infants and infants was evaluated by using the tidal lung function. Infant wheezing is different and unstable compared with adult asthma. Eosinophil activation is difficult to detect early. Therefore, the markers of eosinophil activation can be used as a marker for noninvasive airway function evaluation. Dynamic monitoring and assessment of airway function are worth promoting. Montelukast sodium. Blocking eosinophils degranulation is an effective alternative to early intervention in infants with wheezing.
【学位授予单位】:吉林大学
【学位级别】:博士
【学位授予年份】:2013
【分类号】:R725.6
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