Nghiên cứu hiệu quả điểu trị bệnh viêm mũi dị ứng do dị nguyên bụi bông bằng phương pháp giải mẫn cảm đặc hiệu đường dưới lưỡi TT TIENG ANH

MINISTRY OF EDUCATION AND TRAINING Ministry of Defense VIETNAM MILITARY MEDICAL UNIVERSITY QUẢN THÀNH NAM STUDY ON THE TREATMENT EFFECTIVENESS OF ALLERGIC RHINITIS CAUSED BY COTTON DUST ALLERGEN BY THE SPECIFIC SUBLINGUAL IMMUNOTHERAPY METHOD Specialty: Biomedical science Code: 72 01 01 SUMMARY OF DOCTORAL THESIS Hanoi - 2021 WORKS IS COMPLETED AT THE VIETNAM MILITARY MEDICAL UNIVERSITY Supervisors: Assoc Prof Dr Nghiêm Đức Thuận Prof DSC Vũ Minh Thục Reviewer 1:Assoc Prof Dr Tran Cong Hoa Reviewer 2: Assoc Prof Dr Pham Dang Khoa Reviewer 3: Assoc Prof Dr Nguyen Văn Doan The doctoral thesis will be presented in front of The Thesis Evaluation Council at: day month year Thesis can be found at: National Library Military Medical University ………………………… BACKGROUND Allergic rhinitis is one of the common diseases that can affect all subjects Up to now, there have been few large-scale, standardized studies on the prevalence of allergic rhinitis; According to a study, the prevalence of allergic rhinitis in geographical regions: Asia, Europe, America, and Africa has been reported to be 15%-25% Among the causes of allergic rhinitis, cotton dust and wool dust have long been identified with allergen properties and are the main cause of occupational allergic rhinitis in many countries around the world Currently, in the treatment of allergic rhinitis, the specific immunotherapy treatment is the method of treatment according to the disease mechanism with higher efficiency than other treatment methods: better clinical progress, especially reducing costs in treatment In Vietnam, specific sublingual immunotherapy treatment for allergic rhinitis has been applied to different allergens However, there is no comprehensive study on the effectiveness of sublingual-specific immunotherapy for allergic rhinitis caused by cotton dust allergen Because of the above reasons, we conducted this study with the following objectives: Describe clinical and subclinical characteristics of allergic rhinitis caused by cotton dust allergen Evaluation of clinical changes and some immunoassays in patients with allergic rhinitis caused by cotton dust allergens receiving the specific sublingual immunotherapy treatment method The contributions of the thesis This is the first study using cotton dust allergen made in Vietnam to treat by the sublingual immunotherapy method for allergic rhinitis caused by cotton dust allergen Along with clinical symptom remission, the study also showed the role of the immune response before and after specific sublingual immunotherapy treatment of Th2, Th1, and Th17 cells in allergic rhinitis Total IgE concentration decreased, IgG (especially IgG4) increased, IL-17 decreased, IFN-ϒ increased, indicating that there is immunomodulation of the method as well as confirming the quality of cotton dust allergen The study also showed the safety of cotton dust allergen and the 3-year treatment period for better results The structure of the thesis The thesis consists of 131 pages: Introduction (2 pages); Literature review (32 pages); Research objects and methods (21 pages); Research results (36 pages); Discussion (36 pages); Conclusion (3 pages); Recommendation (1 page) The thesis includes 50 tables, 23 charts, figures, 163 references (23 documents in Vietnamese, 140 documents in English; 67 documents in the last years); Appendix and list of subjects participating in the study CHAPTER OVERVIEW 1.1 Definition and classification of allergic rhinitis 1.1 Definition Allergic rhinitis is an inflammation of the nasal mucosa with the role of IgE antibodies, this disease usually occurs due to exposure to respiratory allergens, with pathological manifestations characterized by symptoms: itchy nose, sneezing, runny nose, and blocked or stuffy nose Allergic rhinitis is often accompanied by allergic conjunctivitis Occupational allergic rhinitis is an inflammatory disease of the nose, characterized by the persistent or persistent presence of symptoms (such as nasal congestion, sneezing, runny nose, itchy nose) and/or limited nasal ventilation and/or excessive secretions the cause of which is related to the work environment 1.2 Classification of allergic rhinitis Classification according to Allergic Rhinitis and its Impact on Asthma (2008) - “intermittent allergic rhinitis” < days/week < weeks - “persistent allergic rhinitis” > days/week and lasting> weeks 1.2 Situation of allergic rhinitis 1.2.1 In the world Chaari N et al (2009), conducted a study on 600 apprentices in the textile industry in Monastir, France in 2009 and showed that 120 apprentices (20%) had allergic reactions when exposed to cotton during the apprenticeship In 2013, Dantas P et al published a study on the prevalence of rhinitis symptoms in factory workers at Nova Esperanỗa, Sao Paulo, Brazil exposed to cotton dust, the results after evaluating a total of 124 workers with 63.7% complained of nasal obstruction; 57.2% had the itchy nose; runny nose 46.7% and 66.1% of study subjects appeared sneezing Tarbox J (2017), studied the role of cotton dust in respiratory symptoms in the western Texas fall, cotton harvest season This study shows that cotton dust is the main cause of nasal and lung manifestations; In addition, cotton dust is also a common cause of rhinitis in textile factory workers A study by Maoua M et al in 2018 on occupational rhinitis and asthma in the textile industry in the central region of Tunisi showed that the prevalence of occupational allergic rhinitis was up to 34.10% 1.2.2 Vietnam In 2002, Vu Van San studied the clinical characteristics of occupational allergic rhinitis caused by cotton-wool dust in Hai Phong carpet weaving company, showing that the rate of occupational rhinitis was 32.5% After months of specific immunotherapy by subcutaneous injection for 62 patients with allergic rhinitis caused by cotton dust allergen, there was a marked improvement in functional symptoms and a statistically significant change with the skin prick test and immunoassays Nguyen Trong Tai (2013) studied the effectiveness of injectionspecific immunotherapy in 43 patients with allergic rhinitis caused by cotton dust allergen for a period of years by invitro test and showed that: total and specific IgE decreased, IgG increased compared to before treatment was statistically significant The author confirmed that injection-specific immunity to cotton dust allergen changes the pathogenesis of allergic rhinitis caused by cotton dust allergen Research by Nguyen Giang Long (2018) on 1082 workers at Nam Dinh yarn factory and Song Hong garment joint-stock company showed that 502 workers had symptoms of allergic rhinitis in which the skin prick test was positive for dust allergen cotton is 236 workers (47%) 1.3 Mechanism of allergic rhinitis caused by cotton dust allergen - Sensitization phase: The allergen first enters the body, is presented to T lymphocytes by antigen-presenting cells There are no symptoms at this stage - Immediate phase: occurs in 10-15 minutes when the body is reexposed to the sensitized allergen Symptoms such as asthma, stuffy nose are the result of binding between IgE-specific allergens and allergens that activate mast cells in the nasal mucosa - Late-stage: occurs from to 48 hours The cellular response predominates due to cell-to-cell interactions under the influence of cytokines The mechanism of allergic rhinitis has well described the role of Th2 However, recently there is much new evidence for the role of Th17 cells in the mechanism of allergic rhinitis, Th17 induces IL-17A, IL17F, IL-22, TNF-α, and IL-21 Studies seem to suggest that Th17 cells may be involved in the neutrophil infiltration that occurs during the acute phase of an allergic reaction IL-17 is thought to be involved in allergen-specific Th2 cell activation, eosinophil accumulation, and serum IgE production, thus suggesting a regulatory role for IL-17A on Th2-type allergic immune response 1.4 Diagnosis of allergic rhinitis Diagnosis of allergic rhinitis is based on: - Take allergy history - Clinical symptoms: functional symptoms include nasal itching, sneezing, runny nose, and stuffy nose; Physical symptoms include pale nasal mucosa, edema, discharge, swollen nose, overgrowth…depending on the degree - Subclinical: based on skin prick test, total and specific IgE 1.5 Allergic Rhinitis Treatment Methods 1.5.1 Non-drug treatment: Allergen prevention, lifestyle education, 1.5.2 Non-specific treatment: antihistamines, anti-leukotrienes, anti-IgE, anti-congestive, mast cell stabilizers 1.5.3 Specific treatment This is a method of immune tolerance to allergens, also known as desensitization or hyposensitization, by subcutaneous immunotherapy (SCIT) Sublingual immunotherapy (SLIT) or local nasal immunotherapy (LNIT) suitable allergens for a period of time relieve symptoms of allergic rhinitis, asthma, insect allergies, or allergies food response Currently, LNIT is not widely used * Subcutaneous immunotherapy SCIT is usually started empirically at a low dose, increased slowly, and a safe but sufficient maintenance dose is achieved The main mechanism by which allergen-specific IgG is increased, especially IgG4, increases the production of IgA antibodies, which block the IgE effector mechanisms and stimulate IL-10-producing monocytes These humoral responses reflect allergen-specific modulation of T-cell responses The main risk of SCIT is a systemic allergic reaction: the rate of systemic side effects is high, even causing anaphylaxis, which requires medical facility treatment, which can lead to patient abandonment of treatment * Sublingual immunotherapy The mechanisms of action of SLIT are not the same as those of SCIT Although both drug pathways produce similar effects on allergic inflammation in target organs, the “tissue” where the immunotherapy interacts with the immune system is different The oral mucosa is characterized by antigen-presenting cells (APCs) which are dendritic cells (DCs) Therefore, the immunostimulatory capacity and immune tolerance are also different With a higher than normal concentration of allergen, instead of a Th2-directed immune response, with the production of IL-4, IL-5, IL13, IL-17 SLIT alters the immune response in the Th1 direction: related to IL-2 and IFN- γ production, in the regulatory cell (Treg) direction: related to the production of IL-10, TGF-β This change in response pattern explains the decrease in IgE synthesis, decrease in inflammatory cells and increase the synthesis of IgG antibodies, called “blocking antibodies”, especially IgG4 which plays a blocking role in allergen binds to specific IgE 1.6 Safety of SLIT In a large trial of 1500 children and adults treated with grass allergen SLIT for seasonal allergic rhinitis, Maloney et al found most adverse events to be local reactions such as irritation throat, itchy or swollen mouth, and itchy ears Symptoms were usually transient and resolved spontaneously, and there were no cases of severe treatment-related reactions in this study Novembre (2004) documented 11 reported cases of anaphylaxis out of a total of billion doses of SLIT administered since 2000 CHAPTER SUBJECTS AND RESEARCH METHODS 2.1 Research subjects 2.1.1 Research subjects in phase 1: Workers at garment factory Z176-General Department of Military Industries and Manufacture, and garment factory X20-General Department of Logistics, Ministry of Defense * Selection criteria: - As a worker, an employee working at Z176, X20, who has been exposed to cotton dust allergen - Minimum working time of 12 months by the time of enrollment of subjects into the study - Healthy enough to participate in the study - Agree to participate in the study * Exclusion criteria: - Do not consent to participate in the study - Absence at the time of the study - Working time is less than 12 months - Insufficient health, lucidity, ability to participate in research 2.1.2 Research subjects in phase 1: workers had been screened to meet the study criteria * Selection criteria: - Workers diagnosed with allergic rhinitis caused by cotton dust allergen - Agree to participate in the study - Eligible for outpatient treatment with a minimum period of years - Complete research records - In the case of allergic rhinitis patients who are suffering from acute bacterial infection in the nose and sinuses, if they meet the above selection criteria, the research team will treat all the superinfections and then continue to be included in the study - For patients being treated with drugs: antihistamines, corticosteroids (local or systemic), after stopping treatment for weeks, they will be selected for the study if they meet the selection criteria * Exclusion criteria: - The patient is or is planning to become pregnant during the course of treatment - Patients with allergic rhinitis not caused by cotton dust allergen - Patients with medical diseases: cardiovascular, liver and kidney diseases, chronic respiratory diseases, mental diseases, autoimmune diseases - Do not consent to participate in the study - Incomplete research record 2.2 Research methods 2.2.1 Research design Multi-phase study design: Cross-sectional descriptive study, clinical trial study * Sample size for cross-sectional descriptive study Apply the formula to estimate sample size for a cross-sectional descriptive study to determine a population proportion: Specifically: Z1-α/2: is the confidence limit coefficient In this study chose α = 0.05, then Z1-α/2 = 1.96 p: is the rate of allergic rhinitis caused by cotton dust allergen, according to the research of author Nguyen Giang Long, the rate of allergic rhinitis caused by cotton dust allergen at Nam Dinh textile company is 0.143 d: is the absolute error In this study chose d = 0,02 The minimum study sample size is 1177 people In fact, the total number of study subjects of phase was: n = 1812 people * Sample size for clinical trials Specifically: n: Minimum study sample size p1: the percentage of patients with allergic rhinitis caused by cotton dust allergen with a positive skin prick test before treatment, the investigation results in the descriptive study was 100% p2: percentage of patients with allergic rhinitis caused by cotton dust allergen with positive skin prick test after treatment According to research by Huynh Quang Thuan, the rate of patients with positive skin prick test after sublingual immunotherapy treatment was 75.56% Take p2 = 0.76 = 0,12 α: probability of type I error In this study chose α = 0,05, then Z1- α/2 =1,96, β: probability of type II error In this study chose β = 0,2, then Z1- β = 0,842 According to the above formula, n = 27 patients can be calculated Adjusted for dropout, with a predicted dropout rate of 25%, the minimum number of patients to be included in the intervention study was 36 In fact, 52 patients met the study criteria 16 - The difference was not statistically significant with p > 0.05 in terms of inferior turbinate hypertrophy between the occupational age groups 3.1.4 Subclinical features Table 3.4 Results of skin prick test with cotton dust allergen (n=195) Factory Z176 Enterprise Total X20 Skin prick test results n (%) n (%) n (%) Negative 0 0 0 (+) 16 15.1 22 24.7 38 19.5 (+) 51 48.1 37 41.6 88 45.1 Positive (+) 35 33.0 29 32.6 64 32.8 (+) 3.8 1.1 2.6 Total 106 100 89 100 195 100 - No patient had a negative skin prick test result - The proportion of patients with positive skin prick test results 2(+) and 3(+) accounted for the majority, 45.1% and 32.8%, respectively; 19.5% of patients had a positive skin prick test of 1(+) and patients (2.6%) had a positive skin prick test of 4(+) Table 3.5 Serum globulins level (n=52) Immunoglobulins Min - Max Median IgA (mg/dL) 26.773 – 211.826 61.509 IgE (UI/mL) 575.424 – 38008.333 1227.756 IgM (mg/dL) 53.192 – 651.331 217.362 IgG1 (mg/dL) 190.237 – 1039.985 563.025 IgG2 (mg/dL) 129.365 – 716.437 255.103 IgG3 (mg/dL) 23.587 – 341.660 78.012 IgG4 (mg/dL) 4.823 – 362.322 45.937 - Serum IgA level in patients was from 26,773 to 211,826 (mg/dL), median: 61,509 (mg/dL) 17 - The serum IgE level in patients was from 575,424 to 38008,333 (UI/mL), median: 1227,756 (UI/mL) - Serum IgM level in patients from 53,192 to 651,331 (mg/dL), median: 217,362 (mg/dL) - Serum IgG4 level in patients from 4.823 to 362.322 (mg/dL), median: 45,937 (mg/dL) 3.2 Effectiveness of treatment by sublingual specific desensizitation 3.2.1 Change in clinical symptoms Table 3.6 Change the degree of nasal itching before and after treatment (n=52) Degree Initial After years n (%) n (%) Severe 13 25.0 0.0 Moderate 16 30.8 0.0 Mild 23 44.2 1.9 Normal 0.0 51 98.1 p 0.05 Serum IL-12, IL-6 levels after treatment increased more than before treatment The difference was statistically significant with p < 0.05 The change in mean serum IL-17 levels at the time before and after years of treatment was statistically significant with p < 0.001 Chart 3.3 Change in quality of life score over time of treatment Quality of life score improved gradually over time of treatment From the time before treatment to years after treatment, the quality of life score decreased by 2.17 points Quality of life scores tend to decline rapidly in the 12 months after treatment CHAPTER DISCUSSION 4.1 Clinical and subclinical features of allergic rhinitis caused by cotton dust allergens 4.1.1 The percentage of allergic rhinitis caused by cotton dust allergen The study results showed that the percentage of allergic rhinitis 23 caused by cotton dust allergen in the two locations was 10.76% This rate is lower than other studies on textile workers 4.1.2 Functional symptoms According to the results of table 3.1, 98.5% of the study subjects had itchy nose, 99.5% had sneezing, 96.9% had runny nose and 97.2% had stuffy nose However, the symptoms are mainly mild and moderate Thus, allergic rhinitis caused by cotton dust allergen has all the symptoms of rhinitis in general 4.1.3 Physical symptoms Nasal mucosa The results of the study showed that: All patients had the injury to the nasal mucosa to varying degrees The difference in the degree of injury to the nasal mucosa between the group with working time of fewer than 10 years and from 10 years or more did not have a statistically significant difference with p > 0.05 Inferior turbinate condition The results of table 3.3 showed that mild hypertrophy in the inferior turbinate accounted for the majority with 51.3%; no patient had severe hypertrophy None of the patients had severe hypertrophy and 27.7% of the patients had normal hypertrophy Comparing with age, we found that there was no difference in the status of hypertrophy in the groups of patients with the working time of fewer than 10 years and from 10 years or more with p > 0.05 The hypertrophy of the inferior turbinate mucosa with a high rate can be explained by the recurrent inflammatory process and the longterm misuse of nasal drops, especially vasoconstrictor, this condition can come on quite soon after several years 4.1.4 Subclinical features Skin prick test Research on skin prick test results shows that 100% of allergic rhinitis patients are sensitive to cotton dust allergen, no patient has 24 negative skin prick test results (Table 3.4) The results of the skin prick test are consistent with the clinical symptoms and show that it is an effective, safe, easy to perform the test in the diagnosis of allergic diseases and the characteristics of the skin prick test results for the patient Allergic rhinitis caused by cotton dust allergen is also quite similar to other allergens Globulins concentrotion The results of table 3.5 showed that the median serum IgE of the patients is: 1227,756 (575,424 - 38008,333) UI/ml This result is much higher than normal adult IgE levels (10 - 150 UI/ml) It can be seen that the level of IgE increase in our study is very high compared to other studies, the high IgE concentration is relatively consistent with the clinical status of 52 treated patients (mainly moderate and high) Many domestic and foreign authors also confirmed that total IgE >450UI/mL indicates an allergic state and if it is very high when the body has more than two different allergic diseases Along with the determination of serum IgE, we also measure the amount of some other Immunoglobulin in the serum IgG is the most abundant antibody in the blood with the main roles of complement activation and opsonization IgG antibodies are considered an alternative protective antibody to IgE allergy antibodies Among IgGs, IgG4 is considered to be a protective antibody in patients with an allergen allergy, which prevents DN from binding to specific IgE before IgE binds to mast cells Table 3.5 showed that IgG4 is 45,937 (4.823 - 362.322) mg/dL, which tends to be lower than normal in patients with allergic rhinitis Meanwhile, IgE was significantly higher than normal people, which is evident in patients with allergic rhinitis in general Immunoglobulin A plays a role in preventing the invasion of allergens We quantified serum IgA and noted: Serum IgA in patients was lower than in normal adults (70 - 400 mg/dL) 25 4.2 Effectiveness of treatment by sublingual specific desensizitation 4.2.1 Change in clinical symptoms * Function symptoms There was a statistically significant difference with p < 0.001 in the degree of nasal itching of patients before and after years of treatment Before treatment, mild and moderate nasal itching were predominant (75.0%) but 25.0% of patients had severe nasal itching After years of treatment, 98.1% of patients no longer had itchy nose (table 3.6) Before treatment, 100% of the patients had some degree of sneezing, most of the patients had severe sneezing (80.8%) After years of treatment, the patients no longer had severe and moderate sneezing; 48.1% of patients no longer sneeze The level of sneezing before treatment and after years of treatment had a statistically significant difference with p < 0.001 (table 3.7) The results of Table 3.8 show that there is a statistically significant difference with p < 0.001 in the degree of the runny nose before and after years of treatment Before treatment, 100% of patients had symptoms of runny nose, mainly moderate and severe (96.1%), of which the severity was 38.4% After years of treatment, 82.7% of patients no longer had a runny nose, the number of patients with severely runny nose was patients.When we performed a case-by-case analysis, the reduction in the runny nose was moderate and there was no increase in the runny nose in any patient The degree of nasal stuffiness had a statistically significant change with p < 0.001 between the initial and years after treatment (Table 3.9) Initially, the proportion of patients with severe and moderate stuffy nose accounted for the majority (98.1%) After years of treatment, patients only had mild stuffy nose (44.2%) or no stuffy nose (55.8%), no more patients with moderate and severe stuffy nose Thus, after treatment, most of the functional symptoms improved positively This result is higher than some studies using other sublingual allergens over a 2-year period 26 * Physical symptoms After treatment, only 26.9% of patients had mild injury to the nasal mucosa with 100% before treatment (50.0% severe, 28.8% moderate; 21.2% mild) The difference between the group of patients in the degree of injury to the nasal mucosa before and after treatment is statistically significant Most of the patieents had a reduction in the condition of the inferior turbinate (78.9) after treatment in which the reduction of ≥2 level accounted for the majority (65.4%) There are still 11 patients (21.1%) with no change in the inferior turbinate This result is also consistent with other authors, who found that the inferior turbinate was less changed after specific immunotherapy than the change in nasal mucosa after treatment For patients with severe inferior turbinate, an inferior turbinate orthopedic approach is required to ensure nasal ventilation 4.2.2 The change in subclinical indicators * Skin prick test Our research results showed that: initially, most patients had positive skin prick test results 2(+), 3(+) with the rate of 90.4%; none of the patients had negative results After years of treatment, the percentage of patients with negative skin prick test was 63.5%; positive 1(+) was 23.1%; 2(+) was 13.4%; No patient had positive skin prick test 3(+), 4(+) There is a statistically significant difference with p < 0.001 in skin prick test results in patients before and after years of treatment (table 3.12) The marked improvement in skin prick test results both in the number of positive cases as well as the positivity levels shows the effectiveness of the treatment and confirms the important role of skin prick testing in diagnosis as well as treatment of allergic rhinitis * Immunoglobulins After 36 months of immunotherapy with cotton dust allergen at the concentration of 300IR/ml, the serum IgE level decreased markedly, the median IgE before treatment was 1227,756 UI/ml, after treatment 27 remaining 676,805 UI/ml (Table 3.13) Although the results of the total IgE concentration after treatment are still high, the clinical symptoms are significantly reduced and the skin prick test is significantly reduced, which is difficult to explain when compared with the total IgE concentration of normal people However, we also found that the results of the total serum IgE content after treatment of other authors were still quite high IgE after treatment decreased significantly, the difference was statistically significant (p < 0.001) In our study, after 36 months of specific immunotherapy treatment with cotton dust allergen at a concentration of 300 IR/ml, the level of IgG in patients increased significantly compared to before treatment (p < 0.001) The level of IgG1 after treatment was 1021,885 (106,287 – 1852,531) (mg/dL) higher than 563,025 (190,237 – 1039,985) mg/dL before treatment, with p < 0.001 The level of IgG4 after treatment was 94,792 (28,472 – 604,536) (mg/dL) higher than 45,937 (4.823 – 362.322) (mg/dl), before treatment (p < 0.001) (Table 3.14, table 3.15) It has been shown that after specific immunotherapy treatment with cotton dust allergen, allergic rhinitis patients have increased the amount of protective antibodies * Cytokines According to the results of Table 3.16, after years of specific immunotherapy treatment, there were also positive changes in some cytokines, especially IL-17 Before treatment, the median IL-17 concentration was 1,752 (0.209 - 15,910) (pg/ml) after treatment, the median concentration was 0.417 (0.209 - 7,970) (pg/ml), the remission was statistically significant This is considered a marker used in the evaluation of specific immunotherapy therapy In this study, we evaluated the change in IFN-, IL-12 levels after years of treatment The study results showed that, the median concentration of IFN-, IL-12 before treatment was 0.886 (0.099 3,606), respectively The increase in serum IL-12 and IFN gamma, together with the improvement in the patient's nasal symptoms after treatment, suggest that this treatment has been effective 28 4.2.3 Change in quality of life After years of immunotherapy, the mean score of quality of life decreased from 2.29 ± 0.63 to 0.12 ± 0.14, a decrease of 2.17 ± 0.53, quality of life is said to have improved if the mean score of quality of life at the later time is lower than this average score at the previous time with 0.5 points or more Thus, after treatment, the patient's quality of life improved very well, which is consistent with the improvement in the patient's symptoms Although the correlation coefficient between symptoms and quality of life was not calculated, these results suggest a linear correlation between the quality of life scores and manifestations of symptoms In summary: Clinical symptoms decreased, skin prick test significantly decreased the positive level and along with the increase of IgG levels, especially IgG4, the decrease of IgE levels and positive changes in cytokines after treatment; along with the improved quality of life of the patients demonstrated the effectiveness of the treatment CONCLUSION Clinical and subclinical features of allergic rhinitis caused by cotton dust allergens -The rate of allergic rhinitis caused by cotton dust allergen is 10.76% - Females with allergic rhinitis accounted for mainly (79.49%) - History of allergies: personal (60.0%), family (51.8%) - The patient has all main symptoms of allergic rhinitis; in which: itchy nose (98.5%), sneezing (99.5%), runny nose (96.9%), stuffy nose (97.4%) Symptoms were mainly moderate and mild - Most of the patients had injury to the nasal mucosa, in which it was severe (48.1%) and moderate (28.8%) - More than 70% of patients had hypertrophy in the inferior turbinate, of which 51.3% were mild and 21.0% were moderate - All patients had positive skin prick tests, mainly grade 2(+) and 3(+) - The serum IgA level in patients was lower than that of normal adults: the lowest was 26,773 mg/dL, the highest was 211.826 mg/dL, the median was 61,509 mg/dL 29 - Total serum IgE content of the patients was elevated: the lowest was 575,424 U/mL, the highest was 38008,333 U/mL and the median was 1227,756 U/mL - The mean serum IgG4 levels of the patients were lower than the upper limit of normal: ranged from 4.823 to 362.322 mg/dL, with a median of 45,937 mg/dL Effectiveness of treatment by sublingual specific desensizitation 2.1 Clinically effective - The majority of patients no longer had any functional symptoms or were still mild - Injury to the nasal mucosa decreased by ≥2 steps (78.8%), followed by a decrease of step (21.2%) ` - Regarding the inferior turbinate, the majority of patients had a good change (65.38%), a fairly good change was 11.54% and 1.93 patients had a moderate change However, the rate of patients with poor change also accounted for - Treatment results had a good effect (98.1%), only 1.9% of patients had a fairly good effect None of the patients had moderate or no effect 2.2 Subclinically effective - The initial skin prick test was 100% positive, after years of treatment, the negative rate was 63.5%, the positive rate was mainly 1(+) with 23.1% and 2(+) with 13.4% - IgE levels in patients after treatment decreased, the median decreased from 1227,756 U/mL to 676,805 UI/mL; serum IgE levels were at a good level (88.46%), there were 5.77% of patients with fairly good changes, 5.77% of patients with moderate changes and no patients with changes in poor level - The IgG content changed at a good level (82.69%); at a fairly good level accounted for (7.69%), a poor level accounted for 3.85% - The level of IgG4 also improved compared to before treatment Increased from 45,937 mg/dL to 94,792 mg/dL - The interleukins were also altered in an allergenic non-responsive pattern Median IL17 decreased from 1.752 mg/dL to 0.417 mg/dL 30 RECOMMENDATIONS It is necessary to research with more patients to evaluate the safety and effectiveness, thereby providing a basis for the widespread use of this allergen to treat patients with allergic rhinitis caused by cotton dust allergen Although evaluation after years of treatment showed the effectiveness of the method and the allergen used for treatment However, whether acquired immunity is sustainable or not requires longer-term studies LIST OF THESIS PUBLICATIONS Quan Thanh Nam, Nghiem Duc Thuan, Vu Minh Thuc (2020) Effectiveness of treatment by sublingual desensitization in patients with allergic rhinitis caused by cotton dust Journal of Military Pharmaco – medicine, 45(7): 224-232 Quan Thanh Nam, Nghiem Duc Thuan (2020) Clinical and subclinical characteristics of allergic rhinitis caused by cotton dust allergens in workers of National Defense garment factories Journal of 108 clinical medicine and pharmacy, 15(7): 54-62 ... of cotton dust in respiratory symptoms in the western Texas fall, cotton harvest season This study shows that cotton dust is the main cause of nasal and lung manifestations; In addition, cotton... divided into levels: normal, mild, moderate, severe - Physical symptoms Các triệu chứng thực thể (niêm mạc mũi, mũi dưới) chia thành mức độ: bình thường, nhẹ, trung bình, nặng The physical symptoms... as well as confirming the quality of cotton dust allergen The study also showed the safety of cotton dust allergen and the 3-year treatment period for better results The structure of the thesis