Analysis of adverse reactions induced by subcutaneous immunotherapy against dust mite allergy in 234 cases with allergic rhinitis and asthma / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the incidence of local reactions (LRs) and systemic reactions (SRs) of subcutaneous immunotherapy (SCIT) and to analyze the potential risk factors of such reactions in Chinese population.</p><p><b>METHOD</b>This is a retrospective study on 234 dust mite sensitized patients with allergic rhinitis and asthma who received allergen immunotherapy in our hospital from 2003 to 2010. Chart review was conducted to capture clinical data of reactions to immunotherapy. Parameters included signs and symptoms, the onset of reaction, and interventions in treating such reactions, particularly, the administration of epinephrine (EPI) and adjustment of vaccine dosage due to LRs and SRs.</p><p><b>RESULT</b>The 234 patients received a total of 7679 injections. Among them, 4973 LRs (64.8%) and 235 SRs (3.1%) were observed in 67 patients (28.6% of all patients). SRs included respiratory symptoms (205 events, 88.4%) and cutaneous symptoms (31.5%). Of the total of 235 SR events, 212 (90.2%) were presented as mild SRs and 23 (9.8%) were in severe SR category (grade III and grade IV, EAACI grading system). Overall, severe SRs accounted for 0.3% of total injections. Seventeen of the 23 SR events required epinephrine treatment (0.2% of total injections). Of the 67 patients, 61 completed the course of treatment after dose adjustment; 36 patients had their doses decreased prior to further advancing to target dose. Nineteen subjects tolerated splitting two injections at 30 minutes interval. Six patients advanced the dose based on protocol and another 6 had to stop immunotherapy. Most of the SRs (77.4%) occurred during the maintenance phase of immunotherapy. The levels of TIgE, SIgE D1 and SIgE D2 were found to be significantly higher in patients with SRs comparing to patients without SRs (P < 0.05). SRs more commonly occurred in patients with age less than 14 years than their older counterparts (95.5% vs. 85.6%, OR = 3.58, 95%CI = 1.040 - 12.322, P < 0.01). The incidence of SRs were significantly higher in asthma patients who received SCIT than non-asthma patients (OR = 2, 95%CI = 1.136 - 4.624).</p><p><b>CONCLUSION</b>Our study suggests that risk factors of SRs include maintenance phase (higher allergen vaccine doses), patients with asthma, age of less than 14 years, higher levels of TIgE, and SIgE D1 and SIgE D2. Effective management includes proper dose adjustment, splitting doses into 2 injections at 30 min apart, and strictly following immunotherapy indications.</p>

Clinical efficacy of a standardized specific immunotherapy against house dust mite in 85 asthmatic children / 中华儿科杂志

<p><b>OBJECTIVE</b>The scientific basis and the clinical effectiveness of allergen specific immunotherapy (SIT) administered by subcutaneous injection are well established. This study aimed to observe the changes in amount of inhaled corticosteroids, total IgE, specific IgE, peak expiratory flow rate (PEF), etc. during a standardized SIT against house dust mite in allergic asthmatic children.</p><p><b>METHOD</b>Children (5 - 13 years old) with mild to moderate allergic asthma seen from February 2005 to June 2008 were enrolled into this study. A non- randomized retrospective study was performed. All children were diagnosed sensitive to dust mites, the treatment group accepted standardized dust mite allergen specific immunotherapy. Each fourth injections were defined as observation points, the study took 3.4 years. The investigators recorded the treatment, the cumulative allergen extract, changes of daily doses of inhaled corticosteroid, peak expiratory flow (PEF), total IgE (TIgE), specific IgE (SIgE). The control group only received inhaled corticosteroids. The daily doses of inhaled corticosteroid and the number of asthma attacks, and the control rate were compared between the 2 groups.</p><p><b>RESULT</b>Totally 85 children were treated with SIT [(7.6 ± 1.4) years], 45 males and 40 females; 50 children received only drug treatment [(7.7 ± 1.5) years], 28 males and 22 females. The cumulative dose of allergen was up to (69.7 ± 4.8) µg after the 20 times injection, the dose of inhaled corticosteroids was significantly less than that in the control group (t = 2.359, P < 0.05). PEF was significantly higher than that of pre-treatment level (F = 7.874, P < 0.05). TIgE and SIgE had no significant change (t = 0.313, P > 0.05, t(Derp) = 0.517, t(Derf) = 0.717, P > 0.05). After the treatment, the control rate of the SIT group was 85.5%, that of the control group was 62.0% (χ(2) = 10.150, P < 0.01).</p><p><b>CONCLUSION</b>The standardized SIT against house dust mite could reduce steroid use in mild to moderate allergic asthmatic children. After (38.7 ± 2.3) weeks, the cumulative dose of allergen was up to (69.7 ± 4.8) µg, inhaled corticosteroid was significantly reduced. At the end of SIT, 85% of patients obtained complete control of asthma. Total IgE and mite-specific IgE had no significant changes.</p>

Results of skin prick test in 908 children with asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To report the results of skin prick test in 908 children with asthma in order to provide references for treatment of asthma.</p><p><b>METHODS</b>Skin prick test was performed using ALK-Abell's inhaled prick reagents and the German Merck company's food prick reagents. Histamine was used for positive control, and normal saline, for negative control.</p><p><b>RESULTS</b>Skin prick test showed positive in 703 cases (77.4%). The positive rates of inhaled and food allergens were 76.9% and 37.1%, respectively. Dermatophagoides culinae and house dust mite were two common inhaled allergens (72.4% and 74.7% respectively). Shrimp was the most common food allergen (22.9%), followed by tuna (7.3%) and mussels (6.7%). The strongest response of skin prick test was usually caused by dermatophagoides culinae (64.0%) and house dust mite (66.4%), followed by mould 1 (7.1%). The positive rate of inhaled and food allergens increased with increasing age (p<0.05).</p><p><b>CONCLUSIONS</b>The positive rate of skin prick test in the 908 children with asthma was higher. These results of this study may be useful in an epidemiological survey and specific immunotherapy of asthma.</p>

Role of c-Jun N-terminal kinase signal transduction pathway in the course of airway remodeling of asthma rat / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the course of asthma airway remodeling, to explore whether IL-1beta participates in asthma airway remodeling mediated by JNK signal transduction pathway.</p><p><b>METHODS</b>Totally 72 male Sprague-Dawlay rats (6 - 8 weeks old, weighing about 120 g) were randomly divided into control groups (36 rats) and asthma groups (36 rats). The rats were sensitized for inducing asthma by intraperitoneal injection of ovalbumin and AL(OH)3 and were repeatedly exposed to aerosolized ovalbumin for 4, 8, 12 weeks (A4, A8, or A12 group), each had 12 rats, and correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then were repeatedly exposed to 0.9% NaCl for 4, 8, 12 weeks (C4, C8, or C12 group), each had 12 rats. The ultrastructural changes of pulmonary tissues were observed by transmission electron microscope (TEM). The total bronchial wall thickness (Wat) and the airway smooth muscle thickness (Wam) were measured by an image analysis system. The concentrations of IL-1beta in serum and bronchoalveolar lavage fluid (BALF) were tested by a "sandwich" ELISA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Lung tissue extracts were analyzed for phosphorylation of JNK by Western blotting. Linear correlation analysis showed the correlation between Wat and P-JNK protein, Wam and P-JNK protein, levels of IL-1beta in serum and P-JNK protein, levels of IL-1beta in BALF and P-JNK protein.</p><p><b>RESULTS</b>In asthma groups, TEM showed alveolar septal proliferation and alveolus type II epithelial cells swelling. Wat and Wam in all asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, Wat and Wam of group A12 significantly increased (P < 0.01). The concentrations of IL-1beta in serum and BALF of asthma groups were all significantly higher than those of the corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, the concentrations of IL-1beta in BALF of group A12 significantly increased (P < 0.01 or P < 0.05), but the levels of IL-1beta in serum were not significantly different among them (P > 0.05). Mean absorbance values (by immunohistochemistry) of P-JNK and P-c-Jun in asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, those of group A12 significantly increased (P < 0.01 or P < 0.05). The absorbance (by Western Blot) of P-JNK in A4, A8, A12 group was significantly higher than that in C4, C8, C12 groups (P < 0.01, respectively), and compared with group A4, that of P-JNK of A12 significantly increased (P < 0.01), and compared with group A8, there was no significant difference (P > 0.05). Strong positive correlations were found between Wat or Wam and P-JNK (r = 0.823 and r = 0.818, P < 0.01, respectively, n = 68) and between P-JNK and concentration of IL-1beta in serum or BALF (r = 0.717 and r = 0.803, P < 0.01, respectively, n = 68).</p><p><b>CONCLUSIONS</b>The expression of P-JNK and its downstream P-c-Jun in rats of asthma airway remodeling is increased, which implicates that JNK signal transduction pathway plays an important role in the course of asthma airway remodeling. IL-1beta participates in asthma airway remodeling possibly partly through activating JNK signal transduction pathway.</p>

Preparation and evaluation of mouse model of house dust mite-induced asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To prepare a mouse model of asthma by sensitizing and challenging with house dust mite allergen Derp and evaluate its reliability by measuring airway allergy inflammation and airway responsiveness.</p><p><b>METHODS</b>Twelve C57BL/6J mice were randomly divided into two groups: control and asthma model. Mice of the asthma model group were sensitized by intraperitoneal injection of house dust mite allergen Derp on the first and tenth days of the experiment. From the 17th day, the mice were challenged by intranasal Derp, once every other day, seven times. The control group was treated with normal sodium instead of Derp. Twenty-four hours after the last challenge, airway responsiveness was evaluated. Bronchoalveolar lavage and histological examination of the lung were performed.</p><p><b>RESULTS</b>Airway resistance increased and dynamic lung compliance decreased significantly in the asthma model group as compared to the control group (P<0.01). When airway resistance increased by 25% and dynamic lung compliance decreased by 15%, the required metacholine concentration in the asthma model group was significantly lower than that in the control group (P<0.01). In the bronchoalveolar lavage fluid of the asthma model group, the number of total cells, absolute number of eosinophils (EOS) and the percentage of EOS in the total cell were significantly higher than those in the control group (P<0.01). Pulmonary pathological scores in the asthma model group were significantly higher than those in the control group (P<0.01). The asthma model group showed ultrastructural changes of bronchial and pulmonary arterioles. Goblet cells, mastocyte granules, and increased mucus were observed in the lung tissues of the asthma model group.</p><p><b>CONCLUSIONS</b>A mouse model of asthma was prepared by sensitizing and challenging with house dust mite allergen Derp, with the characteristics of airway allergy inflammation and airway hypersensitivity reaction.</p>

Effect of Radix Astragali on signal transducer and activator of transcription activator-4 and its mRNA expression in a rat model of asthma / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the effect of Radix Astragali (RA) on the expression of signal transducer and activator of transcription-4 (STAT4) and its mRNA in the bronchus of a rat model of asthma.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into four groups: the control group, asthma group, high dosage of RA group and low dosage of RA group. In the experiment, the rat model of asthma was established by the ovalbumin (OVA) challenge methods. The lung tissue was gainedfrom the left lung, bronchoalveolar lavage fluid (BALF) was gained from the right lung. The eosinophils (EOS) numbers and differentiated cell numbers in BALF were counted by different counting fluids; the protein expressions of STAT4 were detected by immunohistochemistry; the mRNA expressions of STAT4 were detected by in situ hybridization.</p><p><b>RESULTS</b>(1) In the BALF of the asthma group, the absolute numbers of EOS, the ratios of EOS to the total cell numbers (EOS%) of asthma group [(35.81 +/- 7.30) x 10(7)/L, (8. 20 +/- 1.75)%] were all significantly higher than those of the control group [(1.51 +/- 1.04) x 10(7)/L, (0.70 +/- 0.48)%] (P < 0.01); the total cell numbers in BALF, the absolute numbers of EOS and EOS% of RA groups [(14.89 +/- 2.35) x 10(7)/L, (4.70 +/- 0.82)%; (10.98 +/- 1.81) x 10(7)/L, (3.56 +/- 0.53)%] were all significantly lower than those of asthma group (P < 0.01); (2) The concentration of IL-4 in BALF of asthma group (25.70 +/- 7.36) was significantly higher than that of the control group (8.55 +/- 2.97) (P < 0.01); the concentration of IL-4 of BALF of RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly lower than that of asthma group (P < 0.01); the concentration of IL-12 of BALF of asthma group (16.10 +/- 3.38) was significantly lower than that of the control group (42.33 +/- 9.66) (P < 0.01); the concentration of IL-12 of BALF of the RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly higher than that of the asthma group (P < 0.01); (3) Immunohistochemistry and in situ hybridization showed that the protein content of STAT4 and the STAT4 mRNA expression around the bronchus of asthma group [(0.096 +/- 0.012), (0.098 +/- 0.011)] were lower than those of the control group [(0.216 +/- 0.034), (0.228 +/- 0.032)], while those of RA groups [(0.176 +/- 0.012), (0.185 +/- 0.023); (0.183 +/- 0.011), (0.201 +/- 0.019)] were all significantly higher than that of the asthma group (P < 0.01), the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells were the chief expression cells; (4) the STAT4 and the STAT4mRNA expression around the bronchus had positive correlation with the concentration of IL-12 in BALF while had negative correlation with the concentration of IL-4, absolute numbers of EOS in BALF.</p><p><b>CONCLUSIONS</b>RA has an inhibitory effect on airway inflammation cells infiltration such as EOS, it raises the STAT4 protein and its mRNA expression in the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells, and the key mechanism may be that the IL-12 composition is increased.</p>

Detection of Viral Etiology of Children with Acute Respiratory Infection in Wenzhou Area from 2005 to 2006 / 实用儿科临床杂志

Objective To investigate the 7 kinds of respirovirus etiology of children with acute respiratory infection(ARI) in Wenzhou area from 2005 to 2006.Methods Three thousand nine hundred and seventy children with ARI visited the Yuying children's hospital were chosen,including 308 children with acute upper respiratory infection(URI) and 3 662 children with lower respiratory infection(LRI).Direct immunofluorescence(DIF) was used to detect the respiratory syncytial virus(RSV),adenovirus(ADV),influenza virus(IV) A and B,parainf-luenza virus(PIV) type 1,2,3 from nasopharyngeal secretions(NPS) collected from these patients.Results Among the 3 970 samples,1 773(44.7%) positive results were determined and the positive rate of RSV(36.2%) was the highest.The isolating rate of respirovirus were all conspicuous difference in sex(?2=9.2 P

Effect of macrophage inflammatory protein-1alpha and its mRNA on airway inflammation of mouse asthma model / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the effect of macrophage inflammatory protein-1alpha(MIP-1alpha) and its mRNA on airway inflammation of mouse with induced asthma.</p><p><b>METHODS</b>Seventy male BALB/C mice were randomly divided into the control group and asthma group (including 7 subgroups, 10 mice each). The control group included group A(24) (the lavaging subgroup was sacrificed 24 h after the last challenge) and group A(0) (the non-lavaging subgroup was sacrificed from 18 h to 24 h after the last challenge); asthma group included group B(3) (the lavaging subgroup was sacrificed 3 h after the last challenge), group B(8) (the lavaging subgroup was sacrificed 8 h after the last challenge), group B(24) (the lavaging subgroup was sacrificed 24 h after the last challenge), group B(36) (the lavaging subgroup was sacrificed 36 h after the last challenge) and group B(0) (the non-lavaging subgroup was sacrificed from 18 h to 24 h after the last challenge). In the experiment, the mice model of asthma was established by the ovalbumin (OVA) challenge methods. Eosinophils (EOS) numbers and differentiated cell numbers in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of MIP-1alpha in serum and BALF were measured by sandwich enzyme-linked immunosorbent assay (sandwich ELISA); the protein expressions of MIP-1alpha were detected by immunohistochemical techniques; the mRNA expressions of MIP-1alpha were determined by in situ hybridization technique.</p><p><b>RESULTS</b>(1) The concentrations of MIP-1alpha in BALF and serum of group B(3) [(30.2 +/- 4.2) pg/ml, (30.8 +/- 4.6) pg/ml], group B(8) [(35.3 +/- 4.9) pg/ml, (34.9 +/- 5.1) pg/ml], group B(24) [(42.9 +/- 5.8) pg/ml, (41.7 +/- 6.3) pg/ml] and group B(36) [(37.8 +/- 4.7) pg/ml, (35.7 +/- 4.9) pg/ml] were significantly higher than those of group A(24) [(20.9 +/- 3.8) pg/ml, (22.4 +/- 4.3) pg/ml] (P < 0.01); the concentrations of MIP-1alpha in BALF and serum went up at 3 h, reached peak at 24 h, and had descended at 36 h. (2) Immunohistochemistry showed that the protein expressions of MIP-1alpha around the bronchus of group B(0) [(26.4 +/- 6.2)%] were significantly elevated as compared to those of group A(0) [(10.3 +/- 2.5)%] (P < 0.01), the epithelial cell was the chief expression cell. (3) In situ hybridization showed that the mRNA expressions of MIP-1alpha around the bronchus of group B(0) [(23.9 +/- 4.2)%] were significantly increased when compared to those of group A(0) [(8.7 +/- 1.8)%] (P < 0.01), the epithelial cell was the chief expression cell. (4) There was a significant correlation between the concentrations of MIP-1alpha and the numbers of EOS in BALF and between the concentrations of MIP-1alpha and the percentage of EOS numbers in the total cell numbers (EOS%) in BALF.</p><p><b>CONCLUSIONS</b>MIP-1alpha protein and MIP-1alpha mRNA were found strongly expressed in mouse asthma model, the epithelial cell was the chief expression cell; the kinetic characteristic of MIP-1alpha showed that its level increased at 3 h, reached peak at 24 h and declined at 36 h; MIP-1alpha and EOS gathering had a significant correlation.</p>