Comparison of Pulmonary Index Score after Treatment with Salbutamol Through Nebulisers Vs. Metered–Dose Inhalers with Spacer Device for Treatment of Childhood Wheeze

By Arooj Khan¹, Shaista Azeem Khan¹, Syed Mohsin Ali Shah¹, Faizan Sadiq¹, Abdul Khaliq¹, Shahana Nisar²

Affiliations

1. Department of Child Health, Khyber Teaching Hospital, Peshawar, Pakistan
2. Department of Community Medicine, Bacha Khan Medical College, Mardan, Pakistan

doi: 10.29271/jcpsp.2025.07.932

ABSTRACT
The aim of this study was to compare the mean pulmonary index score after Salbutamol delivery through nebulisers and metered-dose inhalers with spacers for the treatment of wheezing in children aged between 6 and 24 months. This randomised controlled trial was conducted from September 2023 to February 2024. A total of 430 children aged between 6 and 24 months and reported with continuous wheezing were divided into two equal groups. In patients of Group A, medicine was delivered through nebulisation, while in patients of Group B, it was delivered using a metered-dose inhaler with a spacer. The mean ± SD age of the patients was 16.17 ± 4.73 months. The results showed significant improvement in pulmonary index scores of patients in Group B compared to Group A (3.67 ± 1.16 vs. 3.96 ± 0.75, p = 0.002). Salbutamol delivery through metered-dose inhalers with spacers was better than nebulisers for the treatment of childhood wheezing.

Key Words: Childhood wheeze, Metered–dose inhalers, Nebulisers, Pulmonary index score, Salbutamol, Spacer device.

Wheezing is a continuous, melodic sound produced by oscillations in constricted airways that is mostly audible on expiration due to severe airway blockage. Wheezing sounds produced in infants are mostly generated due to nasal blockages with the involvement of many causes, including allergies, infections or anatomical anomalies; the major symptoms of reactive airway disease (RAD) are caused by hyper-responsiveness of the airways.

About 10% visits of infants and young children in the emergency units are due to RAD, causing acute bronchoconstriction. It is mentioned as the primary reason for hospitalisation in 30–50% of cases, standing as a high source of morbidity.¹

β-2 agonist medicines, especially Salbutamol, remain the key component of wheezing management.

Patients are recommended aerosolised medications to alleviate bronchospasms, reduce inflammation of the airways, improve mucus clearance, and either prevent or treat infections.

Inhaled bronchodilator administration is the first line and cornerstone treatment protocol for wheezing. This allows direct delivery of the medicine to the target organ, which permits the use of lower doses to produce equivalent efficacy while lowering adverse events, even after repeated dosing. Nebulisers are the most commonly used devices for the administration of aerosol medicines, followed by metered-dose inhalers (MDI). In a systematic review published in 2020, the response of administering a β2 agonist using a nebuliser was compared with the response of this medicine administered using an MDI plus spacer. The results showed better outcomes with the MDI plus spacer administration compared to the nebuliser.²

Hence, there is a debate on the better method of administration of β2 agonists in children aged between 6 and 24 months. This study was therefore planned to compare the mean pulmonary index score (PIS) after administration of Salbutamol through nebulisers vs. MDI with spacers for treatment of wheezing in children aged between 6 and 24 months, presented in a paediatric emergency unit.

This randomised controlled trial was conducted at the Emergency Paediatrics Department, Khyber Teaching Hospital, Peshawar, Pakistan, from September 2023 to February 2024.

Sample size was estimated considering alpha = 5 (two-sided), power = 80 m1 (PIS, Nebuliser group) = 4.3, m² (PIS, Spacer group) = 3.7, sd1 = 2.6, sd2 = 1.7.³ Estimated sample size was 211.

Table I: Demographics and medical history (n = 430).

Demographics and medical history		Group A (n = 215)	Group B (n = 215)
Age (mean ± SD) months		16.38 ± 4.97	15.96 ± 4.47
Gender
	Males, n (%)	92 (42.79)	123 (47.44)
	Females, n (%)	102 (57.21)	113 (42.56)
Duration of symptoms (mean ± SD) days		3.28 ± 1.26	3.13 ± 1.23

Table II: PIS score at baseline and at the completion of treatments (n = 430).

PIS score		Group A (n = 215)	Group B (n = 215)	p-value
At the time of admission (mean ± SD)		6.53 ± 1.6	6.73 ± 1.47	0.18*
After the completion of treatment (mean ± SD)		3.96 ± 0.75	3.67 ± 1.16	0.00
Level of RAD as assessed by PIS at treatment completion
	Mild (0-3), n (%)	54 (25.12)	106 (49.3)	0.00**
	Moderate (4-7), n (%)	161 (75.88)	109 (50.7)
*Independent t-test, **Chi-square test.

A total of 430 children aged between 6 and 24 months and reported with continuous wheezing were included in this study through consecutive sampling. Exclusion criteria were set as children having a history of chronic lung pathologies (congenital anomalies, bronchopulmonary dysplasia, and cystic fibrosis etc.), children with congenital heart disease, children with a history of ≥1-week intubation during their neonatal period, children with symptoms of croup, and children with PIS ≥12 showing respiratory failure. The protocol of this trial was registered at (httpss:www.clinicaltrials.gov) as NCT06201156.

Patients were randomly divided into two equal groups of 215 patients, each using computer-generated sheet. In Group A, treatment consisted of a standard dose of 0.15 mg/kg of Salbutamol in 3 mL of isotonic sodium chloride solution delivered by a compressed air-driven nebuliser.

For patients in Group B, 3 puffs (90 μg /puff) of Salbutamol using MDI with a spacer were administered, followed by 3 ml of nebulised isotonic sodium chloride solution. For administration of the MDI, the healthcare staff dispensed 1 puff of Salbutamol or placebo into the spacer and then held the mask on the child's face (small or medium mask size as per required) until the child breathed 5 to 6 times through the mask. The whole procedure was repeated for a total of 3 puffs per treatment. All treatments were given at 20-minute intervals between doses.

The PIS was calculated by assessing 4 measures-respiratory rate, wheezing, use of accessory muscles, and inspiratory/expiratory ratio - and scoring each one from 0 to 3, with 0 being normal and 3 being severe. The total PIS score, which ranges from 0 to 12, is then used to categorise the level of respiratory disease as mild (0-3), moderate (4-7), or severe (8-12). Mean post-treatment PIS at the time of admission and at the completion of treatment was compared between the two groups to find the study outcomes.

The study purpose was explained by the trained nursing staff in the presence of at least one of the investigators, and consent was taken from the parents of children participating in the study on written forms.

Data analysis was performed using the SPSS version 26. Mean and standard deviation were calculated for quantitative variables, while the qualitative variables were presented in the shape of frequency and percentage. The findings of the two groups were compared by applying an independent t-test and chi-square test, where p ≤0.05 was considered significant.

The mean ± SD of age in this study was 16.17 ± 4.73 months with an age range of 6 to 24 months. The group-wise demographic details and related medical history is shown in Table I.

The details of the PIS score at the completion of the study showed a significant difference between the PIS scores of patients in Group A compared to Group B. Moreover, no patients in any group had a severe level of PIS score, however, significant number of patients had improved levels of PIS in Group B compared to Group A, as shown in Table II.

Hamza and Harkan conducted a study to evaluate the benefits and utility of MDI with a spacer compared to a nebuliser in preschool children needing mechanical ventilation. The efficacy of these two types of aerosol delivery techniques weas assessed after 10, 20, and 40 minutes of dosing. The results showed that both methods were equally good in the delivery of Salbutamol, however, the patients on MDI with the spacer technique had better FEV1 scores compared to the other group.⁴

Rodriguez-Martinez et al. conducted a meta-analysis on the topic of comparison between MDI and nebulisers for delivery of β-2 agonists in children with AEA or wheezing. This comprehensive review included 15 studies with data of 2,057 children. The analysis reported a significantly better PIS in children where MDI with a spacer was used compared to children where the medicine was delivered through a nebuliser.⁵

The results of the study showed significant improvement in the PIS of patients in Group B compared to patients in Group A (3.67 ± 1.16 vs. 3.96 ± 0.75, p = 0.002). These results of the present study are in line with the studies discussed above,^3-5 and confirm that delivery of Salbutamol using MDI with a spacer is more effective than using a nebuliser in improving the PIS score in children aged between 6 and 24 months, presented at paediatric emergency with wheezing. This method of administration is not only effective but also more affordable and user-friendly as the recently updated Sina-24 guidelines have also emphasised on following a simple multidisciplinary protocol, which is easy to under- stand and can be adopted by all healthcare providers.⁶

The major limitation of the study is that the authors worked on limited parameters for comparing these two aerosol drugs delivery techniques. Future research with additional parameters will enhance these data and will help healthcare providers in improving treatment strategies.

COMPETING  INTEREST:
The authors declared no conflict of interest.

PATIENTS’  CONSENT:
Written consent was obtained from the parents of patients.

AUTHORS’  CONTRIBUTION:
AK: Study concept, planning, manuscript writing, data collection, and interpretation.
SAK: Collection of data, interpretation, and manuscript writing.
SMAS: Collection of data and interpretation.
FS: Literature search, study design, and drafting.
AK: Literature search, critical review, and final checking of the manuscript.
SN: Critical revision of the manuscript.
All authors approved the final version of the manuscript to be published.

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