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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 173-176

Nebulized budesonide in the patients with acute asthma exacerbation: A randomized clinical trial


1 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Interventional Pulmonology, Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission05-Feb-2020
Date of Acceptance25-Feb-2020
Date of Web Publication17-Jun-2020

Correspondence Address:
Dr. Atefeh Abedini
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_9_20

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  Abstract 


Background: The management of asthma currently focuses on the Global Initiative for Asthma (GINA) guideline. This randomized clinical trial aimed to find whether the addition of nebulized budesonide to basic treatment would further improve the peak expiratory flow (PEF) rates and decrease the hospitalization days in patients through asthma exacerbation. Methods: Eligible patients with a definitive diagnosis of asthma exacerbation in the emergency department of Masih Daneshvari hospital were entered into this study. Patients were divided into the intervention and the control groups based on random numbers. To follow the GINA guidelines, both the groups received hydrocortisone (3 mg/kg slow IV stat) at the arrival, oxygen and nebulizer containing salbutamol and ipratropium bromide three times every 30 min and then every 8 h during the first 24 h. Nebulized budesonide (0.5 mg/2 ml) was added to the regimen of the intervention group and nebulized saline as the placebo in the control group. PEF of all eligible cases was measured on arrival and then at 1, 6, and 24 h after the ending of the first session of inhalation. Results: Hospitalization days decreased significantly in the intervention group (P ≤ 0.001). There was no median ± standard deviation of PEF in the intervention group after 1 h (P = 0.019) and stayed higher than the control group on 6 and 24 h, respectively (P = 0.015 and P = 0.050). Conclusion: Adding nebulized budesonide to the main treatment regimen of an acute asthma attack helps the patients gaining better respiratory flow and reduces the hospitalization time.

Keywords: Asthma (D001249), nebulizer (D009330), peak expiratory flow


How to cite this article:
Kiani A, Razavi F, Farahani M, Valizadeh J, Bandegani N, Emami H, Abedini A. Nebulized budesonide in the patients with acute asthma exacerbation: A randomized clinical trial. Biomed Biotechnol Res J 2020;4:173-6

How to cite this URL:
Kiani A, Razavi F, Farahani M, Valizadeh J, Bandegani N, Emami H, Abedini A. Nebulized budesonide in the patients with acute asthma exacerbation: A randomized clinical trial. Biomed Biotechnol Res J [serial online] 2020 [cited 2020 Jul 7];4:173-6. Available from: http://www.bmbtrj.org/text.asp?2020/4/2/173/286851




  Introduction Top


Asthma is a chronic airway inflammation characterized by airway hyperresponsiveness, reversible airflow obstruction, and variable respiratory symptoms that if not controlled, may extremely cripple the patient's life and eventually lead to death.[1],[2] Asthma exacerbations which contribute heavily to morbidity and mortality of the patients can happen even in mild asthma; therefore, a suitable strategy to manage is necessary.[3] The management of asthma currently focuses on the Global Initiative for Asthma (GINA) guideline which has recommended the administration of oxygen, short-acting beta-agonists (SABA), ipratropium, and systemic corticosteroids such as hydrocortisone.[4]

The first serious discussions and analyses of that efficiency of budesonide in asthma emerged during the 19th century by the Massachusetts Medical Society.[5] Budesonide is one of the most potent local anti-inflammatory agents from the corticosteroid group.[6] Budesonide inhalers are now well established in the management of adult and childhood asthma.[7] Budesonide as a form of inhaled corticosteroid (ICS) acts by decreasing inflammation in the airways, facilitating easier breathing.[8] ICSs are available in the form of nebulizer as well.

Current evidence strongly suggests the benefits of augmenting budesonide current therapeutic strategies in maintenance therapy and asthma control. Prior studies that have noted the importance of budesonide in controlling asthma were mostly focused on maintenance and reliever therapy.[9],[10] So far, however, there has been little discussion about nebulized budesonide on adults' asthma exacerbation.

In the current double-masked, placebo-controlled study, we aimed to find whether the addition of nebulized ICS to the main treatment of asthma attacks in the emergency department would further improve the peak expiratory flow (PEF) rates and decrease the hospitalization days in patients through asthma exacerbation.[4]


  Methods Top


Patients

Cases with more than 18 years of age with a definitive diagnosis of asthma exacerbation based on the American Thoracic Society criteria referred to the emergency department of Masih Daneshvari hospital from March 2019 to September 2019 were enrolled in this study.[11] Exclusion criteria were as following: flu, being under treatment with other forms of medication, pregnancy, confirmed pulmonary infection in chest X-ray, and accompanying disease of the heart, kidney, and liver.

Setting, design, and treatment protocol

Eligible cases of this two-arm, parallel-group, randomized, blinded trial were randomly assigned to one of the two study groups with the help of a random number table and received the intervention of the group assigned. A statistician classified the patients based on random numbers in either the control group or the intervention group. The statistician was unaware of the type of treatment that they would receive in each group. At the emergency department, a nurse gave the patients' unlabeled medicine based on their code. Patients were informed about two potential types of treatment, but they did not know they would receive which of those.

To follow the GINA guidelines, both the groups received hydrocortisone (3 mg/kg slow IV stat) at the arrival, oxygen and nebulizer containing salbutamol and ipratropium bromide three times every 30 min and then every 8 h during the first 24 h.[4] Nebulized budesonide (0.5 mg/2 ml) was added to the regimen of the intervention group and nebulized distilled water as the placebo in the control group. Normal saline was not chosen as the placebo because it can increase wheezing. Treatment was applied using the nebulizer mask which is attached to central oxygen supply with the flow of 8–9 l/min.

Demographics and clinical measures

PEF, O2 saturation, and Borg Scale of all individuals were assessed on arrival, and then at 1, 6, and 24 h after the completion of the first session of inhalation. Informed written consent was attained by all individuals. Participants were asked about the smoking status. The intervention and control groups were matched in this regard.

Ethical issue

The research had been approved through the Ethics Committee of the National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences. Clinical trial was registered with www.irct.ir: IRCT20170531034256N2.

Discharged criteria

In the case of increasing the PEF up to 60%, improvement of symptoms, and resolution of dyspnea, patients were discharged.

Statistical methods and analysis plans

All data were analyzed using statistical software V. 20 (IBM Corp., Armonk, NY USA). Variables were tested for normality by Kolmogorov–Smirnov test before the analyses. Statistical significance was determined at x ≤ 0.05. The qualitative data were reported as frequency and percentage, and the quantitative variables were reported as mean or median and standard deviation (SD).

Mixed ANOVA for repeated measures was used to compare the PEF levels at different time intervals. Mauchly's sphericity test, along with Greenhouse–Geisser correction, was used to evaluate differences due to time, trial, and their interaction.


  Results Top


A total of 110 individuals referred to the emergency department of XXXX hospital due to an acute exacerbation of asthma were enrolled in the study. Three of 110 patients deteriorated and received epinephrine injection based on GINA. One patient underwent intubation. These four patients were excluded from further analyses.

Among 106 remaining patients enrolled in the study, 16 (30.2%) were female and 37 (69.8%) were male in the intervention group and 11 (20.8) were female and 42 (79.2%) were male in the control group.

There was no difference between the two groups with respect to age (P = 0.52), body mass index (P = 0.35), and PEF-0 (P = 0.55) [Table 1].
Table 1: Clinical and paraclinical characteristics of the study population

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Mixed ANOVA for repeated measures was used to compare the PEF levels at different time intervals. Mauchly's sphericity test, along with Greenhouse–Geisser correction, was used to evaluate differences due to time, trial, and their interaction. Statistical significance was determined at x ≤ 0.05 [Figure 1].
Figure 1: The comparison of peak expiratory flow levels in four points

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As Mauchly's test of sphericity was statistically significant to investigate the effect of time on the dependent variable of PEF, the Greenhouse–Geisser test was applied which showed a significant effect on time (F = 4.79, df = 1.016, P = 0.03). It also revealed that there was no significant interaction effect between time and intervention (F = 0.693, df = 1.016, P = 0.409).

That is while the median ± SD was significantly increased in the intervention group after 1 h (P = 0.019) and stayed higher than the control group on 6 and 24, h respectively (P = 0.015 and P = 0.050). Hospitalization days decreased significantly in the intervention group (P ≤ 0.001). Borg scale, as well as O2 saturation, did not show any difference between intervention and control group.


  Discussion Top


The current double-blind, placebo-controlled study has shown that in the acute phase of asthma exacerbation, applying nebulized budesonide in addition to hydrocortisone, oxygen, nebulized salbutamol, and ipratropium bromide in the emergency department will improve the PEF rates and decrease the hospitalization days.

Since the more prominent pathophysiology of chronic asthma is inflammation and bronchospasm is the main component of asthma exacerbation, ICS is routinely used as the main treatment of chronic asthma and not asthma exacerbation. Although ICS is suggested as the probable treatment of asthma attack in GINA 2019, it is not routinely used due to the high cost of this medicament.[4] In centers with a high overload of patients such as Masih Daneshvari hospital, the availability of hospital beds is an important issue. Furthermore, the cost of lengthy hospitalization for patients and the medical system is significantly higher than medication costs. Therefore, we applied ICS in asthma attacks in the hope of decreasing hospitalization time and increasing PEF. Budesonide was chosen in this regard because it was the only available ICS in the time of conducting this research in Iran. Budesonide was used in the form of nebulizer because it can reach bronchioles and alveoli directly so it may affect rapidly and it does not have systemic side effects; moreover, patients during distress are more comfortable with nebulizer rather than systemic medicine.

In a systematic review published by Edmonds et al., it was concluded that adding ICS to systemic steroids may positively influence the expiratory flows which is in agreement with our results. On the other hand, the evidence was not sufficient enough to come around a conclusion about whether it can reduce the hospital administration period.[12]

Furthermore, Rowe et al. have demonstrated that adding ICSs (budesonide 1600 μg/day) to therapy with oral corticosteroids reduced the number of relapses among patients with acute asthma after discharge from the emergency department.[13]

Busseet al. conducted a meta-analysis on both children and adults regarding the efficiency of ICS in an emergency department. Their research concluded that individuals treated with ICS had fewer admission rates.[14]

Sheikh-Motahar-Vahedi et al. conducted a double-blind randomized placebo-controlled clinical trial for evaluating the effectiveness of nebulized budesonide versus placebo in moderate-to-severe acute asthma attack in an Iranian population. In the control group, nebulized budesonide was prescribed 0.5 mg every ½ h till three doses (1.5 mg total dose), and in the placebo group, the equivalent normal saline was nebulized at the same time. They concluded that nebulized budesonide in adult acute asthma might be effective in reducing patient respiratory distress; in contrast to our results, they expressed that it does not have any significant effect on recovery time or length of hospital stay. Moreover, the choice of saline for placebo may be contributing to the difference between the results.[15]

As the limitations of this study, we can mention the sample size. Future studies with larger sample sizes may contribute to better understanding the benefits of budesonide in asthma exacerbation management.

Another limitation of this study is that we were unable to follow-up on our cases and evaluate the effects of our intervention on the reoccurrence of symptoms and rehospitalization of the patients.


  Conclusion Top


In conclusion, adding nebulized budesonide to the main treatment regimen of acute asthma attack containing oral oxygen, SABA, and systemic corticosteroids may boost the speed of recovery, help the patients gaining better respiratory flow, and reduce the hospitalization time. This is valuable for the patients in their battle against asthma exacerbation and can be beneficial financially both to the patients and the health-care system.

Acknowledgments

This work was supported by NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The authors wish to thank all patients who helped us to conduct this research. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Maslan J, Mims JW. What is asthma? Pathophysiology, demographics, and health care costs. Otolaryngol Clin North Am 2014;47:13-22.  Back to cited text no. 1
    
2.
Marko A, Pace E, Ross KR. Management of Acute, Severe, and Life-Threatening Exacerbations, in Severe Asthma in Children and Adolescents. Cham: Springer; 2020. p. 213-35.  Back to cited text no. 2
    
3.
Sears MR. Can we predict exacerbations of asthma? Am J Respir Crit Care Med 2019;199:399-400.  Back to cited text no. 3
    
4.
2019 GINA Report, Global Strategy for Asthma Management and Prevention; 2019.  Back to cited text no. 4
    
5.
Agertoft L, Pedersen S. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 2000;343:1064-9.  Back to cited text no. 5
    
6.
Brogden RN, McTavish D. Budesonide. An updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis. Drugs 1992;44:375-407.  Back to cited text no. 6
    
7.
Adams NP, Bestall JC, Jones P. Budesonide versus placebo for chronic asthma in children and adults. Cochrane Database Syst Rev 1999;4:276-300.  Back to cited text no. 7
    
8.
Pelaia G, Vatrella A, Busceti MT, Fabiano F, Terracciano R, Matera MG, et al. Molecular and cellular mechanisms underlying the therapeutic effects of budesonide in asthma. Pulm Pharmacol Ther 2016;40:15-21.  Back to cited text no. 8
    
9.
Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev 2013;67:CD007313.  Back to cited text no. 9
    
10.
Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2013;12:CD009019.  Back to cited text no. 10
    
11.
Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement: Asthma control and exacerbations: Standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59-99.  Back to cited text no. 11
    
12.
Edmonds ML, Milan SJ, Camargo CA, Pollack CV Jr., Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 2012;12:Cd002308.  Back to cited text no. 12
    
13.
Rowe BH, Bota GW, Fabris L, Therrien SA, Milner RA, Jacono J. Inhaled budesonide in addition to oral corticosteroids to prevent asthma relapse following discharge from the emergency department: A randomized controlled trial. JAMA 1999;281:2119-26.  Back to cited text no. 13
    
14.
Busse WW, Pedersen S, Pauwels RA, Tan WC, Chen YZ, Lamm CJ, et al. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: Effectiveness of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol 2008;121:1167-74.  Back to cited text no. 14
    
15.
Sheikh-Motahar-Vahedi H, Habibi-Samadi M, Vahidi E, Saeedi M, Momeni M. Nebulized budesonide vs. placebo in adults with asthma attack; a double blind randomized placebo-controlled clinical trial. Adv J Emerg Med 2019;3:e4.  Back to cited text no. 15
    


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