[The relevance of leukotriene D4 synthase gene A(-444)C polymorphism to clinical responsiveness of leukotriene receptor antagonist in patients with allergic rhinitis].

OBJECTIVE: To investigate the leukotriene D4 synthase gene A (LTD4S A)-444 C polymorphism in persistent allergic rhinitis (AR) of Chinese Han nationality and to evaluate its relevance to clinical responsiveness of leukotriene receptor antagonist. METHOD: There were 150 patients [87 males, 63 females, average age (38 +/- 14)] diagnosed with persistent AR in Allergy clinic in our hospital from March 2010 to March 2012; 146 healthy controls (78 males, 68 females, mean age (39 +/- 12)). We detected LT D4SA-444C polymorphism and allele frequencies with Polymerase Chain Reaction (PCR) and-Restriction Fragment Length polymorphism (RELP). The treatment group received monotherapy leukotriene receptor antagonist (montelukast) for 4 weeks. Urinary leukotriene D4 (LTD4) levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment, respectively. We evaluated anti-leukotriene treatment response according to the changement of symptoms, signs PTS and urinary LTD4. We tested correlation between LT D4S gene-444C allele frequency and the treatment response by multivariate analysis of variance. RESULT: (1) LTD4S gene-444 genotype AA/CC, AC/CC frequency is 70.7% (106/150) and 29.3% (44/150), allele A, C frequencies is 67.3% (101/150) and 32.7% (49/150) in AR group, and LTD4S gene-444 genotype AA/CC, AC/CC frequency is 76.7% (112/146) and 23.3% (34/ 146), allele A, C frequencies is 74.0% (108/146) and 26.0% (38/146) in healthy control group, there is not statistically significant difference between two groups. (2) Among 150 AR patients, compared to patients with AA/CC genotype, the genotype AC/CC patients are younger [average age (35 +/- 9), and (50 +/- 18) respectively, F = 5.891, P < 0.05], with earlier age of onset [(31 +/- 4), and (46 +/- 6) respectively, F = 6.985, P < 0.05], longer course of disease [(8.7 +/- 2.1), and (3.1 +/- 2.0) respectively, F = 11.43, P < 0.05], higher symptom scores (8.2 +/- 0.2; 4.8 +/- 0.3), higher signs score (7.3 +/- 3.3; 3.4 +/- 5.1), and the difference was statistically significant. (3) After 4 weeks of montelukast treatment in AR patients, treatment response of anti-leukotriene in genotype AC/ CC patients is better than those in AA/CC genotype patients (F = 11.01, P < 0.05), the differences of treatment response between two groups were correlated with LTD4 levels in vivo, clinical symptoms and signs of patients. CONCLUSION: In a Chinese Han population the LTD4SA-444B polymorphism might be one of the factors in the clinical response to leukotriene receptor antagonists in persistent AR patients.

Clinical value of the high expression of corticosteroid receptor-beta mRNA in the nasal mucosa of steroid-resistant patients with allergic rhinitis.

PURPOSE: This study investigated clinical values of corticosteroid (CS) receptor α and ß in the nasal mucosa of patients with allergic rhinitis (AR) by determining CS receptor α and ß mRNA expression following steroid treatment. PROCEDURES: Among 120 outpatients, 65 had persistent AR, including 36 being sensitive to steroid treatment (steroid-sensitive group) and 29 being resistant to steroid treatment (steroid-resistant group). In addition, 30 patients with deflection of the nasal septum alone, which was corrected by surgery, were recruited as controls. Fluorescent quantitative reverse transcription-PCR was used to quantify CS receptor α and ß mRNA expression in the nasal mucosa of patients. RESULTS: Results showed that CS receptor ß mRNA expression in the nasal mucosa was significantly higher in the steroid-resistant group [(5.62 ± 1.28) × 102 copies/µg] compared with the steroid-sensitive [(4.62 ± 0.48) × 102 copies/µg, t = -6.67, p < 0.01] and control [(5.32 ± 0.55) × 102 copies/µg, t = -8.29, p < 0.01] groups. There were significant differences in the mRNA expression ratio of CS receptor α to ß between the steroid-sensitive (658.32 ± 65.16) and steroid-resistant (525.70 ± 68.10) groups (t = 10.16, p < 0.01). CONCLUSION: A high level of CS receptor ß mRNA but a low level of CS receptor α mRNA expression in patients with steroid-resistant AR indicates steroid resistance. CS receptor ß plays a role in evaluating the effects of steroid therapy for AR.

[Study of three-grade preventive health education and lifestyle intervention in the treatment of allergic rhinitis].

OBJECTIVE: Investigate the effect of three-grade preventive health education and lifestyle intervention in the treatment of allergic rhinitis (AR). METHOD: Two hundred and ten selected cases needed for triple prevention were randomly divided into three groups, each group included 70 cases were undertaken for a three-year randomized controlled study. Group A, treated with Budesonide nasal spray. Group B, combined Budesonide nasal spray with Hydrochloric acid left Kabbah Sting nasal spray. Group C, taking health education management and lifestyle intervention on the basis of group B's therapy. A health lecture or health problems counseling and the dissemination of health education information were undertaken, quarterly. It was mainly for health knowledge awareness, and healthy behaviors formation rate guidance. Lifestyle intervention included a balanced diet, avoiding the allergens of living environment and aerobic exercise (daily 0.5-1.0 h). The score of the signs and symptoms in each group were obtained respectively at the beginning of study, 1 year after intervention and 3 years after intervention, as well as the comparison of patient compliance of follow-up. RESULT: The improved score of the signs and symptoms, endoscopy and radiological results were used to evaluate the treatment effect. There was no significant difference among the score of signs and symptoms in three groups. Comparing in group, before intervention,1 year after intervention and 3 years after intervention, the signs and symptoms of patients in three groups had improvement at different degree. The score of four symptoms (rhinobyon, rhinorrhoea, rhinocnesmus, sneezing) and signs were significant lower than before the intervention, there were a significant difference (P < 0.05). There were 8 patients in group A (11.43%), 6 patients in group 13 (8.57%) and 1 patient in group C (1.43%) lost to follow-up at 3 years after the intervention. The patient compliance of group C was significantly higher than groups A and B. CONCLUSION: Triple prevention health education for AR can significantly improve the treatment compliance of AR patients for treatment, while ensuring clinical efficacy.

[Relationship between eosinophils in nasal discharge and responses to treatment of inhaled glucocorticosteroid in patients with persistent allergic rhinitis].

OBJECTIVE: To evaluate the treatment responses of persistent allergic rhinitis with and without eosinophils (EOS) in nasal discharge to inhaled glucocorticosteroid (CS), and therefore to verify whether low eosinophil level in nasal discharge can predict poor response to treatment with CS. METHOD: Forty-two symptomatic allergic rhinitis patients, who had not received CS therapy in three months preceding the study, were examined before and 2 month, 4 months and 6 months after treatment with CS. At each visit, all patients underwent symptom scoring and physical sign scoring. The level of eosinophil cationic protein (ECP) in the nasal discharge supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to nasal discharge EOS percentages, an EOS group (EOS > or = 3%) and a non-EOS group (EOS < 3%). The response to CS therapy (as measured by symptom and physical sign scores) and the changes of nasal discharge measurements were compared between the 2 groups. RESULT: In the EOS group, the baseline EOS [0.086 (0.065; 0.176)] and ECP level [(326 +/- 145) microg/L] were significantly higher than EOS [0.016 (0.005; 0.022)] and ECP level [(154 +/- 58) microg/L] of the non-EOS group, t = 4.40, 3.32, respectively, all P < 0.01. After 2 months and 6 months of CS therapy, the nasal discharge EOS, ECP level were 0.038 (0.006; 0.070), 0.019 (0.010; 0.060), (175 +/- 122) microg/L, (175 +/- 153) microg/L, respectively in the EOS group,which were significantly different as compared to baseline values (F = 6.73, 7.38, respectively all P < 0.05). But in the non-EOS group, the nasal discharge EOS and ECP level were 0.014 (0.004; 0.032), 0.015 (0.010; 0.026), (118 +/- 60) microg/L, (112 +/- 60) microg/L, respectively at 2 and 6 months, which showed that the nasal discharge EOS level and the symptom and physical sign scores did not improve significantly (F = 0.82, P > 0.05), but the ECP level did improve (F = 3.78, P < 0.05). The average daily dose of CS was not different between the two groups at any visits. CONCLUSION: In persistent allergic rhinitis with low EOS in nasal discharge, CS therapy for 6 months failed to improve symptoms and physical signs.

[Changes of leukotriene D4 in nasal discharge and plasma of patients with persistent allergic rhinitis and the effects of antihistamine].

OBJECTIVE: To investigate the changes of leukotriene D4 (LTD4) in nasal discharge and plasma of patients with persistent allergic rhinitis (AR) and the effects of antihistamine. METHOD: The investigation was a prospective, randomized controlled trial. Forty AR patients (group C) were divided randomly into two subgroup. One group received oral antihistamine 10 mg everyday for one week (group CA) and another group received no loratadine tablets 10 mg everyday for one week (group CB). Fifteen age matched healthy (group D) people were enrolled as control. The level of LTD4 and interleukin-5 (IL-5) in both nasal discharge and plasma by using enzyme linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), cell counts and cell differentials in nasal discharge, were measured before and after three month. The clinical symptom and life quality scores of group C were also investigated. RESULT: The concentrations of LTD4 in nasal discharge [(794 +/- 305) pg] and plasma [(5219 +/- those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P 1185) ng/L] in group C were significantly higher than those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P < 0.05]. The level of LTD4 in nasal discharge was positively correlated with the percentage of neutrophil (r = 0.453, P < 0.05) and IL-5 (r = 0.364, P < 0.05). The pre- and post-therapy concentrations of nasal discharge and plasma in group CA were (812 +/- 1592) pg, (657 +/- 495) pg and (5422 +/- 935) ng/L, (4589 +/- 1057) ng/L respectively; While in group CB the concentrations were (776 +/- 227) pg, (860 +/- 194) pg and (5074 +/- 1850) ng/L, (6063 +/- 450) ng/L, respectively. There were no significant difference either in the level of LTD4 in nasal discharge or in plasma in both groups (all P > 0.05). CONCLUSION: The results suggested that LTD4 was involved in airway inflammation in AR. Antihistamine was not effective enough in decreasing the levels of LTD4 in both nasal discharge and plasma of AR patients.

[Relationship between nasal discharge eosinophils and responses to treatment of inhaled glucocorticosteroid in patients with allergic rhinitis].

OBJECTIVE: To evaluate the treatment responses of persistent allergic rhinitis with and without nasal discharge eosinophilia (EOS) to inhaled glucocorticosteroid (CS), and therefore to verify whether low nasal discharge eosinophils predict poor response to treatment with CS. METHODS: Forty-two symptomatic allergic rhinitis patients, who had not received CS therapy in three months preceding the study, were examined before and 2 month,4 months and 6 months after treatment with CS. At each visit, all patients underwent symptom scoring and physical sign scoring. The level of eosinophil cationic protein (ECP) in the nasal discharge supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to nasal discharge EOS percentages, an EOS group (group A, EOS > or = 0.03) and a non-EOS group (group B, EOS < 0.03). The response to CS therapy (as measured by symptom and physical sign scores) and the changes of nasal discharge measurements were compared between the 2 groups. RESULTS: In the group A, the baseline EOS [0.086 (0.065; 0.176)] and ECP level [(326 +/- 145) microg/L] were significantly higher than those of the group B [0.016 (0.005; 0.022)] and ECP level (154 +/- 58) microg/L], respectively, t = 4.40, 3.33, both, all P < 0.01. After 2 month and 6 months CS therapy, the nasal discharge EOS, ECP pred were 0.038 (0.006; 0.070), 0.019 (0.010; 0.060), (175 +/- 122) microg/L, (175 +/- 153) microg/L, respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 7.38, respectively, all P < 0.05). But in the non-EOS group, the nasal discharge EOS ECP pred were 0.014 (0.004; 0.032), 0.015 (0.000; 0.026), (118 +/- 60) microg/L, (112 +/- 60) microg/L, respectively at 2 and 6 months, which showed that the the nasal discharge EOS pred and the symptom and physical sign scores improved did not change (F = 0.82, P > 0.05), but the ECP level improved (F = 3.78, P < 0.05). and the average daily dose of CS wear not different between the two groups at any visits. CONCLUSIONS: In persistent allergic rhinitis with low nasal discharge EOS, CS therapy for 6 months failed to improve symptom and physical sign.

[Clinical research of Ibudilast on treating the steroid resistant allergic rhinitis].

OBJECTIVE: To compare the efficacy and safety of histamine H1 receptor antagonist loratadine with Leukotriene receptor antagonist Ibudilast in steroid resistant allergic rhinitis in a randomized controlled clinical trial. METHOD: Thirty-five cases were treated by Ibudilast, and 34 cases by loratadine. Score system was used to compare the therapeutic effect of these two drugs on clinical symptoms and signs. RESULT: Ibudilast shows a better curative effect than loratadine in the improvement of the total scores on clinical symptom and signs(P<0.05). Scores of symptoms and signs in Ibudilast group after 3, 7, 14 days decreased significantly by means of square analysis of single factor (P<0.01). No complication was observed. CONCLUSION: Ibudilast can effectively alleviate the clinical symptoms and signs of steroid resistant allergic rhinitis with confirmed efficacy and safety, thus is recommended in steroid resistant allergic rhinitis. Increased doses or prolonged treatment of steroid is inappropriate.

[Effects of long term use of beclomethasone dipropionate nasal spray on bone density with perennial allergic rhinitis].

OBJECTIVE: To study the effects of long term use of beclomethasone dipropionate (BDP) nasal spray on bone density with perennial allergic rhinitis (AR) in adults. METHOD: A 5-year randomized study was conducted on the effects of BDP nasal spray on serum calcium, phosphorus, alkaline phosphatase, and bone density determined before and after the treatment in 36 adult patients with perennial AR. 20-45 years of age, were randomly divided into 3 groups. That is group A (nasal spray 1 - <3 year), group B (nasal spray BDP 3 - <5 year) and group C (nasal spray BDP > or =5 year). The data were analyzed by paired t test. RESULT: The perennial AR were followed up for more than > or =1 year, > or =3 year and > or =5 year to observe the influences of nasal spray BDP. There were no significant difference between the data examined before and after the treatment (P > 0.05). Bone development is not influenced by nasal spray BDP < or =400 microg/d within 5 years. CONCLUSION: Long term use of BDP nasal spray in adult patients does not lead to osteoporosis if the lowest effective steroid dose is given.

[Relationship between alpha- and beta-isoform of corticosteroid receptors and corticosteroid resistant allergic rhinitis].

OBJECTIVE: To clarify the relationship between the expression of alpha- and beta-isoform of corticosteroid receptors (CS) in peripheral blood mononuclear cell (PBMC) and response to corticosteroid in patients with allergic rhinitis (AR). METHODS: Semi-quantitative RT-PCR was used to detect the expression of CS-alpha, beta in PBMC in patients with AR and to observe the different responses to corticosteroid in controls. Immunocytochemical assay was used to detect the expression of protein of CS-alpha and CS-beta. RESULTS: 1) The expression of CS-alpha mRNA was detected in the sensitive group and the resistant group of patients with AR and the controls with CS-alpha/GAPDH mRNA (x +/- s) 1.15 +/- 0.75, 1.63 +/- 0.78, 1.27 +/- 0.51 respectively. 2) The expression of CS-beta mRNA in PBMC in the resistant group of patients with AR was significantly higher than that in the sensitive group and the controls (P < 0.05), with CS-beta/GAPDH mRNA 1.42 +/- 0.73, 0.82 +/- 0.59, 0.80 +/- 0.68 respectively. 3) The number of CS-beta-positive PBMC in the resistant group was significantly higher than that in the sensitive group and the controls (P < 0.01), with the number of CS-beta-positive PBMC 28.8% +/- 9. 9%, 5.9% +/- 3.2%, 5.5% +/- 6.8% respectively. CONCLUSIONS: It is shown that the excessive expression of CS-beta may serve as a novel predictor of corticosteroid resistance in patients with AR.