|Year : 2021 | Volume
| Issue : 1 | Page : 12-16
Effect of leukotriene receptor antagonist therapy in bronchial asthma – A prospective, preliminary, hospital-based, randomized study in rural Konaseema, Andhra Pradesh
Bhargav Prasad Bathula1, Pandit Vinodh Bandela2, Pentakota Ravikumar3, Bhima Sankar Duvvuri3, Subba Rao Polimati3
1 Department of Pulmonary Medicine, NRIIMS, Visakhpatnam, Andhra Pradesh, India
2 Department of Biochemistry, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India
3 Department of Pulmonary Medicine, KIMS And RF, Amalapuram, Andhra Pradesh, India
|Date of Submission||14-Jul-2020|
|Date of Acceptance||13-Oct-2020|
|Date of Web Publication||07-Dec-2021|
Dr. Bhargav Prasad Bathula
Flat No.104, C Block, Doctor's Quarters, Medical Campus of Anil Neerukonda Hospital, Sangivalasa,Visakhapatnam-531162 Andhra Pradesh
Source of Support: None, Conflict of Interest: None
BACKGROUND: The role of leukotriene receptor antagonist is well documented in the management of chronic asthma. However, the efficacy in acute asthma is not yet established.
AIM AND OBJECTIVES: This study was designed to evaluate the clinical efficacy of oral montelukast as an add-on drug to the standard therapy of the acute attack of bronchial asthma.
MATERIALS AND METHODS: A prospective, institutional-based, single-blinded, randomized control study was done. A total of 100 (aged between 18 and 60 years) participants diagnosed with acute exacerbations due to bronchial asthma were enrolled in the study. They were divided into study and control groups randomly. The study group patients were treated with 10 mg of montelukast once in a day for 4 weeks as an add-on drug, whereas the control group received only standard medication of acute bronchial asthma (as per Global Initiative for Asthma guidelines). All the participants were monitored at baseline to every week for a month.
RESULTS: All the 100 participants were assessed finally without any dropouts. The baseline characteristics were noted similarly in both groups. The mean age was 35.46 + 13.17 years in the control and 37.86 + 14.43 years in the study group. Majority were males in both the groups. At the end of the 4 weeks of oral montelukast administration, there was improvement in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate at 2 weeks and 1 month. On many occasions, there was a strong improvement in FEV1 and other clinical parameters after continuous treatment with beta-2 agonists and parenteral corticosteroids for patients with acute asthma. Even though there was no improvement in FEV1/forced vital capacity ratio among both the groups at 2 weeks and 4 weeks, statistically significant improvement was seen between 2 weeks to 1 month on baseline parameters.
CONCLUSION: Administration of oral montelukast 10 mg as an add-on drug to standard therapy may help in quick recovery from acute bronchial asthma and relapse.
Keywords: Acute asthma, bronchial asthma, leukotriene receptor antagonist, montelukast
|How to cite this article:|
Bathula BP, Bandela PV, Ravikumar P, Duvvuri BS, Polimati SR. Effect of leukotriene receptor antagonist therapy in bronchial asthma – A prospective, preliminary, hospital-based, randomized study in rural Konaseema, Andhra Pradesh. Indian J Allergy Asthma Immunol 2021;35:12-6
|How to cite this URL:|
Bathula BP, Bandela PV, Ravikumar P, Duvvuri BS, Polimati SR. Effect of leukotriene receptor antagonist therapy in bronchial asthma – A prospective, preliminary, hospital-based, randomized study in rural Konaseema, Andhra Pradesh. Indian J Allergy Asthma Immunol [serial online] 2021 [cited 2022 Jan 18];35:12-6. Available from: https://www.ijaai.in/text.asp?2021/35/1/12/331801
| Introduction|| |
According to the Global Initiative for Asthma (GINA), asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. In India, asthma accounts for 7% of deaths and 3% loss of disability-adjusted life years. Worldwide, it is estimated that approximately 334 million people currently suffer from asthma, and 250,000 deaths are attributed to the disease each year. The prevalence of the disease is continuing to grow and the overall prevalence is estimated to increase by 100 million by 2025. Genetic predisposition is one of the factors in children for the increased prevalence; moreover, urbanization, air pollution, and environmental and tobacco smoke contribute more significantly.
Acute attack of bronchial asthma is the most common reason to visit the emergency department or a general practitioner. Standard treatment for asthma includes parenteral steroids, inhaled beta-2 agonists, oral steroids, anti-cholinergics, intravenous theophyllines, and oxygen therapy. Leukotriene receptor antagonists (LTRAs) are a class of drugs which particularly act on leukotriene receptors. They show good anti-inflammatory ant-asthmatic action over chronic persistent asthma, who were symptomatic despite with inhaled corticosteroids(ICS).
There is very limited literature regarding leukotriene antagonists in acute attack of bronchial asthma. The current study was undertaken to evaluate the clinical efficacy of oral montelukast in acute attack of bronchial asthma.
The study aimed to evaluate the efficacy of oral montelukast 10 mg as an add-on therapy to usual standard therapy for acute attack of bronchial asthma.
| Materials and Methods|| |
The present prospective, institutional-based, single-blinded, randomized controlled trial study was conducted in the Department of Pulmonary Medicine, Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, on bronchial asthma patients during the period of March 2018 to February 2019. The data were collected from patients who were diagnosed with acute attack of bronchial asthma as per GINA guidelines. A total of 100 diagnosed cases of acute attack of bronchial asthma were enrolled in this study. Patients above 18 years of age with acute attack of bronchial asthma were enrolled. Patients who smoke (>10 pack years); those who were already on LTRA/phenytoin/rifampicine/phenobarbitone; those with a history of ischemic heart disease; HIV-positive patients; females who are pregnant; those who are breast feeding; and those who were unable to take adequate contraceptive precautions were not included in this study.
All patients with mild-to-moderate asthmatic exacerbations were randomly divided into two groups. Group 1 (n = 50) patients received standard treatment for management of acute attack of bronchial asthma as per the GINA guidelines (parenteral steroids, short-acting beta-2 agonists with inhaled anticholinergics [Duolin respicules] by nebulization every 4–6 h depending on severity), intravenous theophylline derivatives, oxygen therapy, and other supportive therapy. Lung function tests were repeated with a handheld spirometer (CH8005 (TRUE FLOW Add medzin technik AG, CH8005, Zurich Switzerland) at the time of discharge. All the patients were then followed up later at outpatient department level, and assessment with spirometer was done at the end of 2 weeks. All the patients were followed up to 4 weeks after initiation of therapy and this was the end point of the study. After the end of the study, a detailed clinical evaluation was carried out with spirometric evaluation with the handheld spirometer. Any adverse effects due to the drug and number of exacerbations were noted for all the patients. Thus, the global assessment was done for all the patients at the end of 4 weeks of therapy.
Comparison of demographic characteristics such as age, duration of the illness, and pulmonary function tests between the groups was done using Student's unpaired t-test. P < 0.05 was considered statistically significant.
| Results|| |
The mean age of the participants in the study and control groups was 35.46 + 13.17 and 37.86 + 14.43 years, respectively (t = 0.8685, P = 0.3813). The distribution of participants is shown in [Table 1].
|Table 1: Gender distribution of the patients in the study and control groups|
Click here to view
The mean duration of the illness was higher in the study group compared to the control group (6.02 + 1.67; 5.38 + 1.90), although it was not statistically significant (t = 1.7856; P = 0.0773). Dyspnea and cough were the most common presenting symptoms in patients presenting with acute attack of bronchial asthma. [Graph 1] shows symptoms at the time of admission in the study and control groups.
We have observed that almost half of the patients had moderate severity of acute attacks of bronchial asthma, while the remaining half had mild severity of acute attacks. Nearly 43 out of 100 had at least one admission in the previous 1 year. Many patients had >1 admission in the previous year.
Data analysis in [Table 2] shows that forced vital capacity (FVC) had improved in the study group only, whereas forced expiratory volume in 1 s (FEV1)/FVC ratio had significantly improved in both groups. However, from admission to discharge time, improvement was 13% in the study group, whereas it was 5% only in the control group. However, a statistically significant improvement was observed at the end of 2 weeks and at 1 month in the study group.
|Table 2: Comparison of forced expiratory volume in 1 s (1 s), forced vital capacity, forced expiratory volume in 1 s/forced vital capacity, and peak expiratory flow rate among the groups at different intervals|
Click here to view
FEV1 on admission (OA) and on discharge was almost similar in both the groups (study and control groups, 1.178 ± 0.28 and 1.66 ± 0.33 vs. 1.216 ± 0.29 and 1.5 ± 0.3, respectively). However, at 2nd week and after completion of 1st month of oral montelukast therapy, there was a statistically significant improvement [Table 3].
|Table 3: Mean difference in forced expiratory volume in 1 s values among the study and control groups|
Click here to view
[Table 2] shows that no statistically significant improvement was noted in FVC of the study group participants. Even though FEV1/FVC had improved among both the groups at the 2nd and 4th weeks, a statistically significant improvement was noted by 1 month after admission only. However, a statistically significant improvement in peak expiratory flow rate (PEFR) was noted in the study group from baseline to 1 month gradually.
We have also observed that during 1 month of follow-up period, there were exacerbations in two participants in the study group, whereas in the control group it was in ten participants.
| Discussion|| |
Most of the participants were between the age group of 18 and 22 years; 44% (n = 22) of the study group and 36% (n = 18) of the control group individuals belong to this age group. A total of 43 participants had a previous history (1 year prior to admission) of hospitalization, which was slightly higher in the study group (n = 23) when compared to the control group (n = 20). Silverman et al. observed 24% of hospitalizations in the previous year due to the acute attack. It gives an impression that nearly one third of the patients with bronchial asthma are having repeated exacerbations, which may be due to poor control of asthma in these patients. The mean duration of the illness due to bronchial asthma (in days) was higher in the study group (6.02 ± 1.67 days) compared to the control group (5.38 ± 1.90 days), which was found to be statistically insignificant (P = 0.0773). Cameron et al. reported that the mean duration of bronchial asthma illness was almost 20.4 ± 12.7 days in the study group and 19.8 ± 4.0 days in the placebo group.
The most common presenting symptoms were dyspnea (95%) and cough (74%); the results were in accordance to the findings of Manfreda et al. In our study, almost half (24 cases out of 50) of the patients had moderate bronchial asthma, whereas the remaining (26 cases) had mild severity of acute attacks. Ramsay et al. observed moderate exacerbations in 17.8%, severe exacerbations in 39.7%, and life-threatening exacerbations in 41.1% of cases. Severe exacerbations were not included in the present study. It may be the reason why the number of mild and moderate exacerbations was higher in our study when compared to that of other studies.
FEV1 had gradually improved in the study group from baseline to the end point of the therapy. The mean improvement was observed to be 32.6% higher in participants who were treated with montelukast (study group) compared to control. Camargo et al. observed 14.8% improvement in FEV1 at 2 h from baseline after intravenous montelukast compared with 3.6% for placebo among patients with acute bronchial asthma with a initial FEV1 of just under 50% predicted. Rmsay et al. also observed that montelukast has given 15.7% higher improvement in FEV1 compared with 7.0% with placebo and 20.7% for the intravenous form.
In our study, we observed no statistically significant improvement in FVC among the study patients taking oral montelukast in comparison with the control group. FVC at the end of 1 month was 2.93 ± 0.26 in the study group and 3 ± 0.24 in the control group. Statistical significance could not be established (P = 0.2369. The results were in accordance with the findings of Silverman et al. and Nelson et al.,
However, FEV1/FVC ratio improved significantly at the end of 1 month in the study group by 26.07% as compared to the control group where improvement was 13.7% (P < 0.0001). FEV1/FVC ratio OA in the study group was 60.22 ± 7.76 and in the control group, it was 61.44 ± 8.22 (P = 0.4463 not significant).
At the end of 1 month, the corresponding readings improved to 86.29 ± 7.24 and 75.2 ± 8.6, respectively (P = 0.0001).
There was a significant improvement in PEFR at the time of discharge, 2 weeks, and 1 month in the study group taking oral montelukast. The mean improvement was 41% at the end of 1 month in the montelukast group as compared to the placebo group. Rmsay et al., in a randomized double-blind placebo-controlled study, observed that patients who received montelukast had a significantly higher PEFR than those who received placebo in the morning after admission with a difference of 57.4l/min (P < 0.04). Zubairi et al. and Ferreira et al., noted no significant difference in PEFR. Most of the participants in our study were with mild exacerbations and they could perform the PEFR maneuver correctly. This could be the reason for more positive improvement in PEFR in our study compared to others.
In our study, there were no serious adverse effects noted. In the literature, headache (18.4%), flu (4.2%), abdominal pain (2.9%), cough (2.9%), and heart burn (2.1%) have been reported as the common side effects with montelukast in adults.
We noted 14 exacerbations (28%) in the control group during the therapy, which is higher when compared to that of the study group 10 (20%). Emerman et al. reported a relapse rate of 17% after treatment of acute attack of bronchial asthma over 2-weeks period. Rowe et al. reported a relapse rate of 14.5% after discharge from acute attack of bronchial asthma.
| Conclusion|| |
The present study showed that in acute asthma exacerbations, additional administration of oral montelukast resulted in improvement in FEV1 and PEFR at 2 weeks and 1 month as compared to standard treatment alone. It gives an impression that montelukast can help decrease the relapse rate by more intensive and comprehensive management among patients at high risk.
The sample size of this study was small and we have not included patients with severe exacerbation. We have not included biological marker such as cysteinyl leukotriene for better evaluation. Further studies are needed to draw proper conclusions and for generalization.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
GINA-2019 Global Strategy for Asthma Management and Prevention. Available from: http://www.ginasthma.org
. [Last accessed on 2020 Apr 12].
Aggarwal AN, Chaudhry K, Chhabra SK, D'Souza GA, Gupta D, Jindal SK, et al
. Prevalence and risk factors for bronchial asthma in Indian adults: a multicentre study. Indian J Chest Dis Allied Sci 2006;48:13-22.
Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004;59:469-78
American Thoracic Society. What constitutes an adverse health effect of air pollution? Official statement of the American Thoracic Society. Am J Respir Crit Care Med 2000;161:665-73.
Balzano G, Fuschillo S, Gaudiosi C. Leukotriene receptor antagonists in the treatment of asthma: an update. Allergy 2002;57 Suppl 72:16-9.
Robinson DS, Campbell D, Barnes PJ. Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial. Lancet 2001;357:2007-11.
Silverman RA, Nowak RM, Korenblat PE, Skobeloff E, Chen Y, Bonuccelli CM, et al
. Zafirlukast treatment for acute asthma: Evaluation in a randomized, double-blind, multicenter trial. Chest 2004;126:1480-9.
Camargo CA Jr., Smithline HA, Malice MP, Green SA, Reiss TF. A randomized controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med 2003;167:528-33.
Manfreda J, Becklake MR, Sears MR, Chan-Yeung M, Dimich-Ward H, Siersted HC, et al
. Prevalence of asthma symptoms among adults aged 20-44 years in Canada. CMAJ 2001;164:995-1001.
Ramsay CF, Pearson D, Mildenhall S, Wilson AM. Oral Montelukast in acute asthma exacerbations: A randomized, double blind, placebocontrolled trial. Thorax 2011;66:7-11.
Nelson KA, Smith SR, Trinkaus K, Jaffe DM. Pilot study of oral montelukast added to standard therapy for acute asthma exacerbations in children aged 6 to 14 years. Pediatr Emerg Care 2008;24:21-7.
Zubairi AB, Salahuddin N, Khawaja A, Awan S, Shah AA, Haque AS, et al
. A randomized, double-blind, placebo-controlled trial of oral montelukast in acute asthma exacerbation. BMC Pulm Med 2013;13:20.
Ferreira MB, Santos AS, Pregal AL, Michelena T, Alonso E, de Sousa AV, et al
. Leukotriene receptor antagonists (Montelukast) in the treatment of asthma crisis: Preliminary results of a double-blind placebo controlled randomized study. Allerg Immunol (Paris) 2001;33:315-8.
Emerman CL, Woodruff PG, Cydulka RK, Gibbs MA, Pollack CV Jr., Camargo CA Jr. Prospective multicenter study of relapse following treatment for acute asthma among adults presenting to the emergency department. MARC investigators. Multicenter Asthma Research Collaboration. Chest 1999;115:919-27.
Rowe BH, Spooner CH, Ducharme FM, Bretzlaf JA, Bota GW. Corticosteroid following acute exacerbations of asthma,Cochrane DatabaseSyst Rev 2001.
[Table 1], [Table 2], [Table 3]