To evaluate the results of asthma control by ICS and LABA according to GINA at the Center of Allergy and Clinical Immunology, Bachmai Hospital for 3 months.
Journal of military pharmaco-medicine no8-2019 EVALUATE THE RESULTS OF ASTHMA CONTROL BY ICS AND LABA ACCORDING TO GINA Nguyen Giang Nam1; Ta Ba Thang2; Nguyen Van Doan3 SUMMARY Objectives: To evaluate the results of asthma control by ICS and LABA according to GINA at the Center of Allergy and Clinical Immunology, Bachmai Hospital for months Subjects and methods: 66 patients diagnosed with bronchial asthma and managed at the asthma counseling unit at the Center of Allergology and Clinical Immunology, Bachmai Hospital from August 2012 to August 2015 The patients were controlled by ICS and LABA according to GINA 2012 Patients were examined clinic and tested paraclinics (lung function, serum level of interleukine 4, 5, 13, TNF-α) at the times of study: pre-treatment and after 1, and months of asthma control Evaluate the result of asthma control according to GINA guideline (2012) Results and conclusion: The rates of controlled patients significantly increased with 30.3%, 80.3% and 80.3%, respectively The rates of partly controlled and uncontroled patients decreased significantly after months of control The rate of obese patients with uncontrolled was higher than that in normal patients (75.7% vs 14.3%) (p < 0.01) VC, FVC, FEV1 increased significantly in controlled group (p < 0.05) The median values of IL-4, IL-5, IL-13 change with no diference between control level, TNF-α concentrations differed according to the control level * Keywords: Asthma; Asthma control; ICS; LABA; Global initiative for asthma INTRODUCTION Bronchial asthma (BA) is a common disease in the world and tends to increase over the world [2, 7] According to statistics of the World Health Organization, every 10 years, the prevalence of the asthma had increased by 20 - 50%, especially in the past 20 years [8] An inflammatory response is an important pathogenesis mechanism in BA The characteristics of the asthma are heterogeneous and clinical manifestations by the exacerbations of asthma Asthma control is the primary treatment for patients [2] Use of an inhaled corticosteroid (ICS) and a long acting β2 adrenergic agonist (LABA) has been proven to be effective in asthma control: reducing the incidence and severity of asthma, improving clinical symptoms, respiratory function and quality of life for patients [10] In the global initiative for asthma (GINA), ICS has been used to treat BA from stage II However, the results of asthma control by ICS and LABA differ in different patients [0] The aims of this research: Evaluate of the results of asthma control by ICS and LABA according to GINA at the Center of Allergology and Clinical Immunology, Bachmai Hospital for months Thainguyen Medical College 103 Military Hospital Bachmai Hospital Corresponding author: Ta Ba Thang (tabathang@yahoo.com) Date received: 21/08/2019 Date accepted: 18/10/2019 166 Journal of military pharmaco-medicine no8-2019 SUBJECTS AND METHODS Subjects The study was carried out on 66 patients diagnosed with BA and managed at the asthma counseling unit at the Center of Allergology and Clinical Immunology, Bachmai Hospital from August 2012 to August 2015 * Selection criteria: Diagnosis of asthma according to the GINA guideline (2012), without acute exacerbations, adherence to treatment, asthma controlled by ICS and LABA with dosages corresponding to the degrees of disease (based on the asthma degrees) according to GINA guideline, acceptance of monthly examination and testing indicated by doctors * Exclusion criteria: Acute exacerbation, acute bacterial rhinosinusitis, other respiratory diseases, non-compliance with ICS and LABA and no acceptance of research Methods A descriptive, prospective and longitudinal study Patients were examined clinically and tested for lung function, serum level of IL-4; IL-5; IL-13, TNF-α at the times of study: pre-treatment and after 1, and months of asthma control Serum levels of IL-4, IL-5, IL-13, TNF-α were measuted by immunofluorescence method on IMMULITE 1000 system at the Department of Immunology (Military Medical University) Doses of asthma control with ICS and LABA were in accordance with to GINA guideline (2011) and adjusted monthly to asthma stages When patient with acute exacerbations should be used ventolin inhaler 300 µg/time and to repeat every 15 - 20 minutes, if symptoms are not relieved, they will be taken to hospital for treatment Classification of asthma degrees according to GINA guideline (2012): I, II, III, IV levels from each time of evaluation: pre-treatment of control and after 1, and months of control Evaluate the result of asthma control according to GINA guideline (2011) Data were analyzed by using SPSS 12.0 RESULTS AND DISCUSSION General characteristics of the patients Table 1: Age and gender Gender Age Male Female Total n % n % n % < 20 1.5 1.5 3.0 20 - 29 4.5 12.1 11 16.7 30 - 39 13.6 13.6 18 27.3 40 - 49 1.5 7.6 9.1 167 Journal of military pharmaco-medicine no8-2019 50 - 59 3.0 13 19.7 15 22.7 ≥ 60 9.1 12.1 14 21.2 Total 22 33.3 44 66.7 66 100 45.3 ± 16.82 X ± SD The average age of study patients was 45.3 ± 16.82 years, of which the incidence of asthma among the age groups 30 - 39 and 50 - 59 accounted for the highest proportion, respectively (27.3% and 22.7%) and the age group < 20 had the lowest rate (3.0%) Previous studies showed that BA was common in young people: Nguyen Van Doan et al (2011) showed that asthma in patients aged 21 - 40 was 26% [1] Chi C.H et al (2016) showed that asthma occured mainly in patients aged 24 58 years [5] In our research, there were 67.9% of female and 32.1% of male Le Thi Tuyet Lan and Huynh Anh Kiet (2013) had studied 108 asthma patients at the respiratory clinic at Hochiminh City University of Medicine and Pharmacy showed that the prevalence of asthma was 65.74% of women and 34.26% of men Table 2: The characteristics of patients before the asthma control Number of patients Characteristics n = 66 % 8.44 ± 6.52 Duration of disease ( X ± SD) (year) Onset of disease: Early 14 21.2 Late 52 78.8 Level I 10.6 Level II 26 39.4 Level III 14 21.2 Level IV 19 28.8 Severity of asthma: Mean time of disease in patients was 8.44 ± 6.52 years Late onset was predominant (80.3%) The rate of patients at level II was the highest (39.4%) and level I was the lowest (10.6%) Chu Thi Cuc Huong (2008) showed that it was mainly asthma level III and IV (41.5% and 30.9%, respectively) Le Thi Tuyet Lan et al (2013) showed that 43.52% of patients with level I [2] Reed C.E (1999) showed that the patients with level III and IV were higher than patients with level I, II 168 Journal of military pharmaco-medicine no8-2019 Results of control Table 3: Results of asthma control after 1, and months (n = 66) Time Level of control After month (1) After months (2) After months (3) p* n % n % n % Controlled asthma 20 30.3 53 80.3 53 80.3 < 0,05 Partly controlled asthma 32 48.5 11 16.7 9.1 < 0,05 Uncontrolled asthma 14 21.2 3.0 10.6 < 0,05 (*: Chi-squared test) The rate of controlled asthma increased gradually after and months of control accounting for 30.3%, 80.3% and 80.3%, respectively (p < 0.05) The number of patients with partly and uncontrolled asthma reduced significantly after months of treatment: there were 10.6% of patients with uncontrolled asthma after months According to Vu Thi Hong (2015), after - months of control with ICS and LABA, controlled and partly controlled patients increased gradually: the rate of uncontrolled patient decreased compared to pre-treatment (p < 0.05) Nguyen Hoang Phuong (2018) showed that at 3th, 6th and 12th month after asthma control, the rates of controlled patients by ICS and LABA increased gradually (10%, 33.33% and 85%, respectively) compared to pre-treatment [3] O’Byrne et al (2005) revealed that asthma control was significantly improved after combining ICS and LABA Ross K.R et al (2015) showed that LABA combined with low dose of ICS helped to enhance control more effectively than increased in doubled ICS dose [11] Table 4: The relationship between level of asthma control and clinical characteristics after months of control (n = 66) Control level Controled Partly controlled Uncontroled (n = 53) (1) (n = 6) (2) (n = 7) (3) n % n % n % Thin 7.7 0 0 Normal 40 75.5 83.33 14.3 Obesity 17.0 16.67 75.7 Median (min - max) 20.8 (15.6 - 28.4) 22.0 (18.6 - 25.7) 25.2 (18.8 - 27.7) Early 13 24.5 16.66 0.0 Late 40 75.5 83.34 100 Clinical characteristics BMI Onset p* 0.002 < 0.05 > 0.05 169 Journal of military pharmaco-medicine no8-2019 Asthma level I 53 100 50.0 0.0 II 0,0 50.0 0.0 III 0.0 0,0 42.85 IV 0.0 0,0 57.15 In the group of uncontrolled asthma, the rate of obese patients was higher than that in normal group (75.7% vs 14.3%) (p < 0.01) with the highest median (25.2) (p < 0.05) The onset of the disease had not been different according to the levels of control According to Shannon Novosad et al (2013), leptin increase and adiponectin decrease in obese patients that was more difficult to asthma control According to GINA (2016), late-onset asthma is more likely to be non-allergic and requires higher-dose ICS or no response to < 0.001 corticosteroids that make asthma to be more difficult controlled [8] The onset of the disease has not been different according to the levels of control After months of control, 42.85 - 57.15% of patients with level III and IV were not controlled Gupta PR et al (2015) studied 447 asthma patients after months of control with fluticasone propionate and salmeterol, the patients treated by fluticasone propionate and salmeterol were better controlled, the severity of asthma was (2%) lower than that of group treated with fluticasone propionate and montelukast (6%) [11] Table 5: The change of VC, FVC, FEV1 according to asthma control levels after months of control (n = 66) Control level Controled (n = 53) (1) % change compare pre-control Partly controlled (n = 6) (2) Uncontroled (n = 7) (3) n % n % n % < 12% 21 39.62 66.66 71.42 ≥ 12% 32 60.38 33.34 28.58 < 12% 17 32.07 66.66 85.71 ≥ 12% 36 67.93 33.34 14.29 < 12% 11.32 16.66 57.14 ≥ 12% 47 88.68 83.34 42.86 VC FVC FEV1 After months of control, VC, FVC, FEV1 increased significantly in controlled group (p < 0.05) Chi C.H et al (2016) showed that there was a correlation between decreased lung function with level of asthma control (p < 0.001) [5] 170 Journal of military pharmaco-medicine no8-2019 Table 6: The change of serum cytokines according to control levels after months of control (n = 66) Control level Median (min - max) Uncontroled Cytokine (n = 7) IL-4 Partly controlled (n = 6) Controled (n = 53) 5.52 5.52 5.52 (4.46 - 7.64) (4.46 - 6.58) (2.26 - 12.58) IL-5 0.075 0.075 0.075 (0.075 - 117.45) (0.075 - 16.65) (0.075 - 1.82) IL-13 2.26 1.93 1.6 (1.6 - 53.22) (1.6 - 2.26) (1.6 - 53.22) TNF-α 0,1 0,1 (0.1 - 32.31) (0.1 - 4.65) (0.1 - 1.62) p* 0.661 0.150 0.366 0.005 (*: Kruskal Wallis test) After months of control, median values of IL-4, IL-5, IL-13 changed with no difference between the control levels (p > 0.05), TNF-α concentrations differed according to the control level (p = 0.005) Lee Y.C (2001) revealed that there was a relation between serum IL-4 level of acute asthma patients and partly controlled and controled asthma (p < 0.001) Brown K.R et al (2017) showed that there was a significant difference in IL-4 level between controlled and uncontrolled asthma (p = 0.03) [4] According to Brown K.R et al (2017), there was a significant difference in IL-13 levels between controlled and uncontrolled asthma (p = 0.03) [4] Janeva E.J et al (2015) showed that IL-13 level after months of control by ICS and LABA improved clinical symptoms and gained a controlled level for patients [7] Joseph J (2004) revealed that median serum level of IL-13 in patients regularly using ICS was significantly higher than controlled asthma (p < 0.003) CONCLUSION Research results of control with ICS and LABA for asthma patients after months, we showed the following remarks: - In asthma patients controlled by ICS and LABA, the rate of asthma controlled patients significantly increased after 1, and months of control with rates 30.3%, 80.3% and 80.3%, respectively - The rate of obese patients with uncontrolled was higher than that in normal patients (75.7% vs 14.3%) (p < 0.01) VC, FVC, FEV1 increased significantly in controlled group (p < 0.05) The median values of IL-4, IL-5, IL-13 changed with no difference between the control levels (p > 0.05) TNF-α concentrations differed according to the control level (p = 0.005) 171 Journal of military pharmaco-medicine no8-2019 REFERENCES Nguyen Van Doan et al Study on the status of bronchial asthma in Vietnam 2009 2011 Scientific and Technological Project of Ministerial Level Hanoi 2011 Le Thi Tuyet Lan, Huynh Anh Kiet The correlation between bronchial asthma control level according to ACT and the health-related quality of life according to AQLQ (S) Hochiminh City Medicine Topics of Internal Medicine 2013, Vol 1, No 17, Supplement No 1, pp.137-141 Nguyen Hoang Phuong Treatment of allergic asthma caused by dermatophagoides pteronyssinus allergens with specific immunotherapy by sublingual route The Docteral Thesis in Medicine Hanoi Medical University 2018 Brown K.R, Krouse R.Z, Calatroni A, Visness C.M, Sivaprasad U, Kercsmar C.M et al Endotypes of difficult-to-control asthma in inner-city African American Children 2017, 12 (7) Chi C.H, Liao J.P, Zhao Y.N et al Effect of inhaled budesonide on interleukine-4 and interleukine-6 in exhaled breath condensate of asthmatic patients Chinese Medical Journal 2016, pp.819-823 172 Bhat A.C Is there a relation between gender and age of onset of asthma with severity of asthma: A study of 181 cases 2016, ISSN - 2249-555X, Value: 79.96 Janeva E.J, Goseva Z et al The effect of combined therapy ICS/LABA and ICS/LABA plus montelukast in patients with uncontrolled severe persistent asthma based on the serum IL-13 and FEV1 Open Access Macedonian Journal of Medical Sciences 2015, (2), pp.268-272 Global strategy for asthma management and prevention 2018 update Holguin F, Bleecker A.R, Buss W.W et al Obesity and asthma: An association modified by age of asthma onset J Allergy Clin Immunol 2011, June, 127 (6), pp.1486-1493 10 Sobande P.O, Kercsmar C.M Inhaled corticosteroids in asthma management Respir 2008, 53 (5), pp.652-633 11 Gupta P.R Addition of LABA to low dose ICS in asthma: Is it justified Journal of Respiratory Medicine Research and Treatment DOI: 2015, 10.5171 12 Ross K.R, Hart M.A Assessing the relationship between obesity and asthma in adolescent patients: A review Adolescent Health, Medicine and Therapeutics 2013, pp.39-49 ... time of evaluation: pre-treatment of control and after 1, and months of control Evaluate the result of asthma control according to GINA guideline (2011) Data were analyzed by using SPSS 12.0 RESULTS. .. adherence to treatment, asthma controlled by ICS and LABA with dosages corresponding to the degrees of disease (based on the asthma degrees) according to GINA guideline, acceptance of monthly... of treatment: there were 10.6% of patients with uncontrolled asthma after months According to Vu Thi Hong (2015), after - months of control with ICS and LABA, controlled and partly controlled patients