|Year : 2021 | Volume
| Issue : 4 | Page : 177-181
Comparison of effectiveness of metered dose inhaler with spacer and jet nebulizer in children aged 5–14 years with acute exacerbation of asthma: A pilot randomized controlled trial
Kundan Mittal, Rishabh Batra, Alok Khanna
Department of Pediatrics, PGIMS, Rohtak, Haryana, India
|Date of Submission||01-Apr-2021|
|Date of Decision||17-Jun-2021|
|Date of Acceptance||20-Jun-2021|
|Date of Web Publication||10-Jul-2021|
Dr. Rishabh Batra
S/o K.K. Batra, Moh. Kanoongoyan Amroha, J.P. Nagar - 244 221, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: Asthma is a common and potentially serious chronic disease that imposes a substantial burden on patients, their families, and community. The main treatment of an acute exacerbation includes inhaled short-acting β2-agonists (SABA). The aim of this of study was to compare the effectiveness of metered dose inhaler (MDI) with spacer and jet nebulizer for delivering SABA in children aged 5-14 years presenting to the emergency department with acute asthma.
Subjects and Methods: One hundred subjects were randomly assigned to receive salbutamol by an MDI with spacer or a nebulizer at fixed intervals. The parameters such as respiratory rate, heart rate, use of accessory muscles, auscultatory findings, peak expiratory flow rate (PEFR), development of tremor, pCO2 on venous blood gas, need for hospital admission, and duration of stay in the emergency department were compared between two groups. Statistical tests used were Student's t-test, Chi-square test, and Fisher's exact test.
Results: Clinical improvement in the form reduction of respiratory rate, use of accessary muscles, wheeze, and PEFR was comparable between two groups. Increase in heart rate in children with MDI with spacer group was significantly lower (P < 0.001) than that of nebulizer group at all time intervals during the study period. No significant difference was observed for the need of pediatric intensive care unit admission, duration of stay in emergency department, and adverse events between two groups.
Conclusions: In children aged 5-14 years presenting to the emergency department with acute exacerbation of asthma, the efficacy of MDI with spacer for delivering SABA was comparable with that of nebulizer.
Keywords: Asthma, jet nebulizer, metered dose inhaler, short-acting γ2-agonists, spacer
|How to cite this article:|
Mittal K, Batra R, Khanna A. Comparison of effectiveness of metered dose inhaler with spacer and jet nebulizer in children aged 5–14 years with acute exacerbation of asthma: A pilot randomized controlled trial. J Pediatr Crit Care 2021;8:177-81
|How to cite this URL:|
Mittal K, Batra R, Khanna A. Comparison of effectiveness of metered dose inhaler with spacer and jet nebulizer in children aged 5–14 years with acute exacerbation of asthma: A pilot randomized controlled trial. J Pediatr Crit Care [serial online] 2021 [cited 2021 Sep 19];8:177-81. Available from: http://www.jpcc.org.in/text.asp?2021/8/4/177/321096
| Introduction|| |
Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation. Lung function testing is done to document “variable” expiratory airflow limitation. “Variability” means improvement or deterioration in symptoms and lung function. “Reversibility” refers to rapid improvement in forced expiratory volume in 1 s (FEV1) or peak expiratory flow (PEF) after inhalation of a rapid-acting bronchodilator.
Some patients may remain symptom-free for weeks to months, while some may experience episodic flare-ups (exacerbations) from time to time. In clinical practice, exacerbations are identified as events characterized by a change from the patient's previous status that is sufficient to require a change in treatment. The term “exacerbation” is synonymous with “acute severe asthma” and “flare-up.” The decrease in the lung function can be quantified by measurements such as PEF and FEV1.
The treatment given for the management of an acute exacerbation includes oxygen, inhaled short-acting γ2 agonists (SABA), inhaled corticosteroids, and/or systemic steroids. Apart from these, intravenous magnesium sulfate is likely to be beneficial in patients with more severe acute asthma and mechanical ventilation helps patients with near fatal asthma.
Salbutamol, an SABA, is the most widely used drug for the treatment of acute asthma exacerbation. It has a rapid onset of action with a mean time of 6.5 min for FEV1 to return to 85% of baseline as per Politiek et al. Inhalation route is preferred as the drug that directly reaches the airway, resulting in faster onset of action and fewer side effects. Thus, it can be delivered with the help of an inhaler or a nebulizer. The major issues with the use of pressurized MDI alone are the deposition of aerosolized particles in the oropharyngeal region and upper airways and the in-coordination between the device actuation and inhalation due to lack of patient training, especially in children. This problem can be addressed by using a spacer or valved holding chambers along with it. The problems with jet nebulizers are the requirement of a compressor for aerosol generation, the noise that some of them generate, and the fall in the temperature of the liquid in the nebulizer chamber due to liquid evaporation in the nebulized droplets.
There are various studies comparing the efficacy of these two delivery systems, and even though evidence suggests that both these modes of delivery of drugs by inhalational route are equally effective, there are certain barriers that need to be overcome for the implementation of this evidence-based practice. Thus, this study was planned to address these barriers in the setting of an emergency department of a tertiary care hospital and to re-evaluate if there is any difference in the efficacy of these two delivery systems.
| Materials and Methods|| |
The study was conducted in the emergency department of a tertiary care center in North India over a period of 1 year from 2018 to 2019. The study design was a pilot randomized controlled trial. The study was approved by the institutional ethical committee. Written informed consent was taken from parents before enrollment their children in this study. A child between 5 and 14 years of age, who was already a known case of asthma, who presented to pediatric emergency department with acute exacerbation was taken as the subject. The study flowchart is shown in [Figure 1].
A total of 100 children were enrolled after taking written informed consent from their parents. Children with known asthmatics who were regularly visiting to our hospitals and presenting with acute exacerbation were included in the study. Children who were presenting first time with symptoms of asthma and children with known congenital heart disease and chronic lung diseases were excluded from the study. Basic demographic details and disease history were taken which included the duration, severity of symptoms based on frequency of day and night symptoms, comorbidities, family history, and current treatment being received.
With the help of computer-generated randomization table, the subjects were divided into two groups. The random allocation sequence was implemented using numbered envelopes and thus was concealed until the intervention was assigned. Subjects in Group 1 (MDI with spacer group) received salbutamol with the help of MDI (4 puffs) and spacer (250 ml) thrice at intervals of 20 min, and subjects in Group 2 (nebulizer group) received salbutamol by jet nebulizer thrice at 20 min interval. The puffs were given by the healthcare provider present on duty. The respiratory rate, heart rate, use of accessory muscles, auscultatory findings, and peak expiratory flow rate (PEFR) were recorded first at arrival in the emergency department as baseline parameter before giving any therapy and then every 20 min till 60 min in both groups. PaCO2 on venous blood gas analysis was measured at arrival and after 60 min. The development of tremor as adverse event was recorded during stay at emergency department. The clinical parameters were recorded by senior resident in pediatrics and were confirmed by junior consultant in emergency room. The need for hospital admission and duration of stay in the emergency department were also recorded. Children who had normalized respiratory rate as per their age limit criteria and who had no evidence of use of accessory muscles were further observed continuously in the emergency department. Children who remained tachypneic with respiratory distress were shifted to the pediatric intensive care unit (PICU). The primary outcome was defined improvement in clinical status and duration of stay in emergency room, while the need for admission at PICU was considered as the secondary outcomes.
Statistical testing was conducted with the Statistical Package for the Social Science System version SPSS IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. Continuous variables are presented as mean ± standard deviation, and categorical variables are presented as absolute numbers and percentage. The comparison of normally distributed continuous variables between the groups was performed using Student's t-test. Nominal categorical data between the groups were compared using Chi-square test or Fisher's exact test as appropriate. A P < 0.05 was considered statistically significant.
| Results|| |
Baseline demographic characteristics were comparable in both groups as shown in [Table 1].
The decrease in respiratory rate at 20 min interval was significantly lower in MDI with spacer group, but no significant difference was observed at 40 min and 60 min interval. Increase in heart rate in children with MDI with spacer group was significantly lower (P < 0.001) than that of nebulizer group at 20, 40, and 60 min. The pCO2 change on venous blood gas analysis, decrease in use of accessory muscles of respiration, wheeze, PEFR, and development of adverse event (tremor) were comparable between two groups [Table 2]. No significant differences were observed for the need for PICU admission and duration of stay in the emergency department more than 6 h, in the two groups [Table 3].
|Table 2: Comparison of change of clinical parameters between both groups|
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| Discussion|| |
Asthmatic patient can have “exacerbation” or “flare-up,” which causes worsening of the symptoms. γ2 agonists such as salbutamol which are short acting are given by inhalational route for the management of these exacerbations. The drug can be delivered by inhalers with spacers or nebulizers. The introduction of MDIs with spacers has provided a more efficient, cost-effective, and easier way of delivering SABA to young children. Very limited data are available on this subject, especially from Indian context. In this study, we compared the effectiveness of these two drug delivery systems in 100 subjects randomly divided into two groups.
In our study, the children aged between 5 and 14 years were included. In MDI with spacer group, the mean age of the subjects was 9.64 ± 2.40 years. The mean age of the subjects in nebulizer group was 9.88 ± 2.16 years. A recent cross-sectional study was conducted in Gujarat, India, which showed maximum prevalence in children aged 11 years and that was 36.43%, followed by 1.55%, 15.50%, 16.28%, and 30.23% in age groups of 9, 10, 13–14, and 12 years, respectively.
The decrease in respiratory rate at 20 min interval was significantly lower in MDI with spacer group, but no significant difference was observed at 40 and 60 min interval. Duarte and Camargos conducted the study on 196 subjects comparing salbutamol inhalation given by spacer and oxygen-driven nebulizer. The respiratory rate compared at the end of each of the three cycles showed no significant difference. Jamalvi et al. also compared the pre- and post-inhalation respiratory rates in 150 subjects using MDI with accessory device and small-volume nebulizer and noted no significant difference in the respiratory rate.
Increase in heart rate in children with MDI with spacer group was significantly lower (P < 0.001) than that of nebulizer group at 20, 40, and 60 min. This is in concordance with the results from systemic review by Cates et al., which stated that the pulse rate after treatment (expressed as % change from baseline) was significantly lower when a spacer was used as compared to nebulizer in children (mean difference − 5.41%; 95% confidence interval [CI] −8.34 to − 2.48, I2 = 53%, random-effects). Considering that the mean age of the subjects in both the groups in our study was almost similar, the dependency of heart rate on the age can be excluded as a factor affecting this outcome.
In the current study, use of accessory muscles at baseline in MDI with spacer group and nebulizer group was 56% versus 58%. At 20, 40, and 60 min, the difference between the two groups did not differ significantly. The use of accessory muscles in the two groups was compared by Jamalvi et al., who also concluded that there was no significant difference observed after therapy. The wheeze of some severity (i.e., mild, apparent, marked, or reduced/eliminated) was present in 100% patients in both groups at arrival. However, the comparison of auscultatory findings showed no significant difference in the two groups at any point (P = 0.292, 0.294, and 0.566 at 20, 40, and 60 min, respectively). Yasmin et al. had persistent wheeze in 8% of patients in nebulizer group and 16% of patients in MDI with spacer group. The difference in their study between two groups was also not significant.
The mean change in PEFR at the end of the therapy in the two groups was 52.80 ± 14.29 and 55.8 ± 29.63, which was not significant. Dhuper et al. in a prospective, randomized, double-blinded, placebo-controlled trial with 60 acute asthma adult patients observed the median (interquartile range) improvement in peak flow of 120 (75–180) L/min versus 120 (80–155) L/min in the spacer and nebulizer groups, respectively (P = 0.56). When considering PEFR to compare the effectiveness of the two modalities, it is better to evaluate the outcome based on patient's best or predicted PEFR. This is a limitation of the current study as the patient's best PEFR was not known. No significant difference was observed in the values of pCO2, between two groups after during delivery. Batra et al. compared the arterial blood gas values including pCO2 in their study and no significant difference was observed in their study between the two groups as well. Incidence of adverse events such as tremors was comparable between two study groups, and this observation was consistent with prior studies.,
No significant differences were observed for the need for PICU admission. The calculated risk ratio (RR) for MDI spacer versus nebulizer was 1.07. Cates et al. in their systemic review also concluded that the method of delivery of γ2 agonist did not show a significant difference in hospital admission rates. In adults, the RR of admission for spacer versus nebulizer was 0.94 (95% CI 0.61–1.43). The RR for children was 0.71 (95% CI 0.47–1.08). This review included a total of 1897 children and 729 adults in 39 trials.
Eighteen out of 50 patients (36.0%) in MDI with spacer group and 26 out of 50 patients (52.0%) from nebulizer group required longer stay (>6 h) in the emergency department and the difference was not statistically significant and were treated with repeated nebulization therapy due to incomplete resolution of symptoms. However, the individual duration of stay for each patient was not measured. Staggs et al. in their study compared emergency department length of stay (ED LOS) and associated opportunity cost among children who presented with a mild asthma exacerbation, according to the delivery mode of albuterol: MDI with spacer versus nebulizer. The mean ED LOS for patients in the MDI with spacer group was 170 min compared to 205 min in the nebulizer group.
The strength of this study is as follows: this is a prospective and randomized control design of study, which is done especially in emergency setup of a tertiary care center exclusively in pediatric population. However, there are certain limitations to our study. First, it is pilot study with small number of study subjects. Second, a variable block randomization would have been ideal. Third, universal objective scoring system such as the clinical asthma severity score or pediatric asthma severity score could have been better in describing the outcomes as a single score. Forth, venous blood gas was used instead of arterial as technical difficulty in busy emergency unit. Large multicenter randomized controlled trial on this subject are required to extrapolate results of this study to recommend before promoting routine use of MDI with spacer for delivering SABA for the treatment of acute exacerbation of asthma at pediatric emergency department.
| Conclusions|| |
In children aged 5–14 years presenting to the emergency department with acute exacerbation of asthma, efficacy of MDI with spacer for delivering SABA was comparable with that of nebulizer.
Financial support and sponsorship
The study was supported by the Department of Pediatrics, Pt. B. D. Sharma PGIMS, Rohtak, Haryana.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]