COMPARISON OF BRONCHODILATORY EFFECT OF INHALED FORMOTEROL+BUDESONIDE VERSUS INHALED SABUTAMOL+ BUDESONIDE IN MILD ACUTE EXACERBATION OF ASTHMA IN CHILDREN OF 6-12 YEARS -RANDOMISED CONTROLLED TRIAL

Asthma is one of the most prevalent chronic respiratory diseases in children, significantly affecting quality of life and contributing to substantial healthcare utilization worldwide.(1) In children aged 6–12 years,  prevalence of asthma is 5-20% globally and 5–10% in India.(2) Acute exacerbations contribute substantially to morbidity and healthcare utilization in this age group. Early and effective management is essential to prevent functional decline and future severe episodes.

 

Conventional guidelines recommend use of short-acting β₂-agonists (SABA) such as salbutamol for quick relief, which is combined with inhaled corticosteroids (ICS) like budesonide to improve anti-inflammation and prevent lung remodeling. (1)

Formoterol, a long-acting β₂-agonist (LABA) with a rapid onset of action (3–5 minutes), offers the potential to act both as a reliever and controller when combined with ICS. This combination may reduce the frequency of SABA use, improve adherence, and provide prolonged bronchodilation.(3)

 

While studies conducted in adults suggest comparable or superior outcomes with formoterol-budesonide therapy, evidence in children particularly those with mild acute exacerbations is limited.(4) However, children’s airways, drug absorption, and response to treatment differ from adults, making it important to study for age-specific data.(5) Considering the limited amount of data available for children, especially within the Indian context, this study aims to directly compare the effects of inhaled Formoterol+Budesonide and inhaled Salbutamol+Budesonide in children aged 6-12 years experiencing mild asthma attacks. This study aims to address this gap and support more evidence-based decision-making in pediatric asthma care.

A total of 103 children between 6 to 12 years of age, with acute exacerbation of asthma presenting to Pediatric department in MVJMC&RH were enrolled in our study conducted over a period of 2 years from January 2023 to January 2025. Thirteen of them were excluded from the study, as they were unable to do PEFR or had associated pneumonia or congenital heart disease. Ninety children were enrolled in  the study and randomized to 2 groups- 45 to salbutamol+ budesonide group and 45 in formoterol+budesonide group. All children were hemodynamically stable throughout the study period.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure-1 Trial profile Abbreviations – ITT-Intention to Treat

Baseline Characteristics: Comparable in both groups (Table 2).

PARAMETER	SALBUTAMOL + BUDESONIDE N (%) / Mean ± SD	FORMOTEROL + BUDESONIDE N (%) / Mean ± SD	P VALUE
AGE
1.     6–8 years	18 (40.2%)	11 (24.4%)
2.     9–10 years	9 (20%)	9 (20%)
3.     11–12 years	18 (40%)	25 (55.5%)
4.     Mean age	9.2 ± 2.32	10.16 ± 2.17	0.243
SEX
1.     Male	32 (71.1%)	27 (60%)	0.267
2.     Female	13 (28.8%)	18 (40%)
PAST HISTORY
1.     Chronic cough	11 (24.4%)	17 (37.7%)	0.172
2.     Daytime symptoms	5 (11.1%)	5 (11.1%)	1.000
3.     Night-time symptoms	8 (17.7%)	14 (31.1%)	0.141
4.     Exertion-induced symptoms	23 (51%)	29 (64.4%)	0.200
5.     Seasonal variation	42 (93.3%)	41 (91.1%)	0.694
6.     H/O nebulisation	45 (100%)	44 (97.7%)	0.315
7.     Positive response to nebulisation	45 (100%)	42 (93.3%)	0.078
PERSONAL HISTORY
1.     Allergic rhinitis	17 (37.7%)	14 (31.1%)	0.506
2.     Allergic conjunctivitis	3 (6.6%)	4 (8.8%)	0.694
3.     Atopic dermatitis	2 (4.4%)	4 (8.8%)	0.398
FAMILY HISTORY OF ASTHMA/ATOPY	15 (33.3%)	7 (15.5%)	0.050
H/O ASTHMA
1.     Newly diagnosed	6 (14%)	11 (24.4%)	0.204
2.     Known case	39 (86.6%)	34 (75.5%)
Diagnosis based on
1.     Clinical	38 (84.4%)	31 (68.8%)	0.204
2.     Clinical + spirometry	7 (15.5%)	14 (31.1%)
TYPE OF ASTHMA CONTROL
1.     Controlled	7 (15.5%)	7 (15.5%)	0.510
2.     Partially controlled	30 (66.6%)	24 (53.3%)
3.     Poorly controlled	1 (2.2%)	2 (4.4%)
PRIOR LONG-TERM MEDICATION
1.     No treatment	9 (20%)	12 (26.6%)	0.523
2.     ICS (Budesonide)	19 (42.2%)	14 (31.1%)
3.     Formoterol+ICS	17 (37.7%)	19 (42.2%)
AGE OF ONSET OF SYMPTOMS	7.85± 3.09 (mean ± SD)	8.66 ± 3.144 (mean ± SD)	0.224
PRESENT ILLNESS –
1.     SYMPTOMS
a)     Fever	9 (20%)	8 (17.7%)	0.788
b)     Cough	44 (97.7%)	44 (97.7%)	1.000
c)     Running nose	24 (53.3%)	25 (55.5%)	0.832
d)     Wheeze	2 (4.4%)	7 (15.5%)	0.078
e)     Chest tightness	2 (4.4%)	6 (13.3%)	0.138
2.     EXAMINATION FINDINGS
a)     Respiratory rate score 2 (26–30/min)	23 (51%)	21 (46.6%)	0.670
b)     SpO₂ score 2 (<90%)	0	0	0
c)     Retractions	0	0	0
d)     Rhonchi	40 (88.8%)	37 (82.2%)	0.368
e)     Bilateral decreased air entry	0	0	0
3.     Baseline PEFR (L/min)	135.78 ± 51.808	147.78 ± 48.78	0.261
4.     Baseline PASS score	6.09 ± 0.668	6.20 ± 0.726	0.452

Table 2: Baseline variables with present illness and examination

 

Symptomatic Improvement: At 5 minutes, 77.7% in Group A improved vs. 46.6% in Group B (p=0.002). Subsequent intervals showed no difference (Figure 2).

Figure-2: Symptomatic Improvement In The 2 Groups At Different Time Intervals Post Intervention

 

Both the salbutamol+budesonide and formoterol+budesonide groups showed similar improvements in PASS scores over time, with no significant differences between them at any point (Figure 3).              Figure-3: Pass Score In The 2 Groups At Different Time Points Post Intervention

Across all measured time points (baseline, 5, 10, 15, 30, 45, and 60 minutes), there was no statistically significant difference in PEFR scores between the Salbutamol+Budesonide and Formoterol+Budesonide groups. Mean PEFR values were comparable throughout, with both interventions yielding similar improvements over time (all p values > 0.1). (Figure 4)

Figure-4: PEFR In The 2 Groups At Different Time Intervals Post Intervention

 

After 5 minutes, mean percentage improvement in PEFR in Salbutamol+Budesonide group was 28.42% whereas 24.31% improvement was noted in PEFR value in Formoterol+Budesonide group from baseline. At the end of 1 hour, improvement of 26.04% was noted in PEFR value in salbutamol+ budesonide group whereas, 27.4% improvement in PEFR value was noted in Formoterol+Budesonide group, with no statistical significance (Figure 5).

Figure 5: Percentage Improvement In PEFR After The Intervention

A total of 103 children between 6 to 12 years of age, with acute exacerbation of asthma presenting to Pediatric department in MVJMC&RH were enrolled in our study conducted over a period of 2 years from January 2023 to January 2025. Thirteen of them were excluded from the study, as they were unable to do PEFR or had associated pneumonia or congenital heart disease. Ninety children were enrolled in  the study and randomized to 2 groups- 45 to salbutamol+ budesonide group and 45 in formoterol+budesonide group. All children were hemodynamically stable throughout the study period.

 

 

Figure-1 Trial profile Abbreviations – ITT-Intention to Treat

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Baseline Characteristics: Comparable in both groups (Table 2).

PARAMETER	SALBUTAMOL + BUDESONIDE N (%) / Mean ± SD	FORMOTEROL + BUDESONIDE N (%) / Mean ± SD	P VALUE
AGE
5.     6–8 years	18 (40.2%)	11 (24.4%)
6.     9–10 years	9 (20%)	9 (20%)
7.     11–12 years	18 (40%)	25 (55.5%)
8.     Mean age	9.2 ± 2.32	10.16 ± 2.17	0.243
SEX
3.     Male	32 (71.1%)	27 (60%)	0.267
4.     Female	13 (28.8%)	18 (40%)
PAST HISTORY
8.     Chronic cough	11 (24.4%)	17 (37.7%)	0.172
9.     Daytime symptoms	5 (11.1%)	5 (11.1%)	1.000
10.   Night-time symptoms	8 (17.7%)	14 (31.1%)	0.141
11.   Exertion-induced symptoms	23 (51%)	29 (64.4%)	0.200
12.   Seasonal variation	42 (93.3%)	41 (91.1%)	0.694
13.   H/O nebulisation	45 (100%)	44 (97.7%)	0.315
14.   Positive response to nebulisation	45 (100%)	42 (93.3%)	0.078
PERSONAL HISTORY
4.     Allergic rhinitis	17 (37.7%)	14 (31.1%)	0.506
5.     Allergic conjunctivitis	3 (6.6%)	4 (8.8%)	0.694
6.     Atopic dermatitis	2 (4.4%)	4 (8.8%)	0.398
FAMILY HISTORY OF ASTHMA/ATOPY	15 (33.3%)	7 (15.5%)	0.050
H/O ASTHMA
3.     Newly diagnosed	6 (14%)	11 (24.4%)	0.204
4.     Known case	39 (86.6%)	34 (75.5%)
Diagnosis based on
3.     Clinical	38 (84.4%)	31 (68.8%)	0.204
4.     Clinical + spirometry	7 (15.5%)	14 (31.1%)
TYPE OF ASTHMA CONTROL
4.     Controlled	7 (15.5%)	7 (15.5%)	0.510
5.     Partially controlled	30 (66.6%)	24 (53.3%)
6.     Poorly controlled	1 (2.2%)	2 (4.4%)
PRIOR LONG-TERM MEDICATION
4.     No treatment	9 (20%)	12 (26.6%)	0.523
5.     ICS (Budesonide)	19 (42.2%)	14 (31.1%)
6.     Formoterol+ICS	17 (37.7%)	19 (42.2%)
AGE OF ONSET OF SYMPTOMS	7.85± 3.09 (mean ± SD)	8.66 ± 3.144 (mean ± SD)	0.224
PRESENT ILLNESS –
5.     SYMPTOMS
f)      Fever	9 (20%)	8 (17.7%)	0.788
g)     Cough	44 (97.7%)	44 (97.7%)	1.000
h)     Running nose	24 (53.3%)	25 (55.5%)	0.832
i)      Wheeze	2 (4.4%)	7 (15.5%)	0.078
j)      Chest tightness	2 (4.4%)	6 (13.3%)	0.138
6.     EXAMINATION FINDINGS
f)      Respiratory rate score 2 (26–30/min)	23 (51%)	21 (46.6%)	0.670
g)     SpO₂ score 2 (<90%)	0	0	0
h)     Retractions	0	0	0
i)      Rhonchi	40 (88.8%)	37 (82.2%)	0.368
j)      Bilateral decreased air entry	0	0	0
7.     Baseline PEFR (L/min)	135.78 ± 51.808	147.78 ± 48.78	0.261
8.     Baseline PASS score	6.09 ± 0.668	6.20 ± 0.726	0.452

Table 2: Baseline variables with present illness and examination

 

Symptomatic Improvement: At 5 minutes, 77.7% in Group A improved vs. 46.6% in Group B (p=0.002). Subsequent intervals showed no difference (Figure 2).

Figure-2: Symptomatic Improvement In The 2 Groups At Different Time Intervals Post Intervention

 

Both the salbutamol+budesonide and formoterol+budesonide groups showed similar improvements in PASS scores over time, with no significant differences between them at any point (Figure 3).              Figure-3: Pass Score In The 2 Groups At Different Time Points Post Intervention

Across all measured time points (baseline, 5, 10, 15, 30, 45, and 60 minutes), there was no statistically significant difference in PEFR scores between the Salbutamol+Budesonide and Formoterol+Budesonide groups. Mean PEFR values were comparable throughout, with both interventions yielding similar improvements over time (all p values > 0.1). (Figure 4)

                     Figure-4: PEFR In The 2 Groups At Different Time Intervals Post Intervention

 

After 5 minutes, mean percentage improvement in PEFR in Salbutamol+Budesonide group was 28.42% whereas 24.31% improvement was noted in PEFR value in Formoterol+Budesonide group from baseline. At the end of 1 hour, improvement of 26.04% was noted in PEFR value in salbutamol+ budesonide group whereas, 27.4% improvement in PEFR value was noted in Formoterol+Budesonide group, with no statistical significance (Figure 5).

Figure 5: Percentage Improvement In PEFR After The Intervention

 

 

 

 

 

 

 

Table 3: Results

 

 

The only observed side effect was tachycardia. Tachycardia was noted in 20% of children who received salbutamol/budesonide and in 8.8% of children in formoterol/budesonide group (p value 2.25). No child was noted to have either hypertension/ tremor in both the groups.

 

PARAMETER	SALBUTAMOL+BUDESONIDE	FORMOTEROL+ BUDESONIDE	P VALUE
	N (%)	N (%)
TACHYCARDIA	9 (20)	4 (8.8)	2.25
HYPERTENSION	0 (0)	0 (0)	0
TREMORS	0 (0)	0 (0)	0

TABLE 4- ADVERSE EVENTS

 

 

Table 3: Results

 

 

The only observed side effect was tachycardia. Tachycardia was noted in 20% of children who received salbutamol/budesonide and in 8.8% of children in formoterol/budesonide group (p value 2.25). No child was noted to have either hypertension/ tremor in both the groups.

 

PARAMETER	SALBUTAMOL+BUDESONIDE	FORMOTEROL+ BUDESONIDE	P VALUE
	N (%)	N (%)
TACHYCARDIA	9 (20)	4 (8.8)	2.25
HYPERTENSION	0 (0)	0 (0)	0
TREMORS	0 (0)	0 (0)	0

TABLE 4- ADVERSE EVENTS

Asthma is a chronic disease impairing daily life which is characterized by chronic airway inflammation. Management of asthma is continuously evolving for better control and quality of life.

 

According to latest GINA guidelines 2025,(8) inhaled corticosteroid-formoterol can be used as reliever in acute exacerbations of asthma in adults and children more than 12 years, and in children of age 6 to 12 years only when on maintenance Formoterol+ Budesonide combination.

 

In this randomized controlled trial, we investigated and compared the onset and efficacy of formoterol with budesonide versus salbutamol with budesonide in children of 6-12 years of age, experiencing a mild acute asthma exacerbation. Baseline characteristics were similar between both groups: mean ages were 9.2 years (Salbutamol+Budesonide) and 10.16 years (Formoterol+Budesonide), with a male predominance consistent with higher asthma rates among boys as suggested by previous study done by Chowdhury et al.(9) Chronic cough was the most frequent symptom depicting bronchial hyper responsiveness in children with chronic cough during the childhood period is a strong risk factor for the development of asthma. (10) Both daytime and night-time symptoms, exercise-induced triggers, and seasonal variations in severity showed similar distribution across treatment arms. In a similar study done by Koster ES et al in Netherlands in children between 4 to 12 years of age, the prevalence of wheeze ranged from 32% in summer to 56% in autumn.(11)

 

Comorbid allergic conditions such as rhinitis, conjunctivitis, and atopic dermatitis were reported in varying proportions, aligning with existing data on their prevalence and age-related trends as shown in the study done by Soyoung Hong et. al.(12) Asthma control levels (controlled, partially controlled, uncontrolled) and absence of long-term maintenance therapy were also comparable between groups.

 

In our study, symptomatic relief in terms of decrease in cough, wheeze and chest tightness at 5 minutes post intervention was significantly more in the Salbutamol + Budesonide group (77.7%) compared to the Formoterol + Budesonide group (46.6%, p = 0.002). However, both groups showed equal improvement by 10 minutes and subsequently. 

 

PASS scores and percentage change in PEFR improved similarly in both groups, with no statistically significant differences at any time point. After 10 minutes, the pattern of improvement was same in both the groups.

 

The pharmacodynamics of both medications reveal they are β2-adrenergic agonists, but while salbutamol acts quickly and briefly for acute relief, formoterol has a similarly rapid onset but with prolonged action, making it suitable for both maintenance and rescue therapy. (13)

 

These findings are consistent with a  double blinded randomized control trial done by Jenish et.al.(14) They compared the bronchodilatory effects of inhaled formoterol+ budesonide (dose: 200μg and 12μg respectively) combination with salbutamol (200μg)+ budesonide (200μg) administered by metered dose inhaler and spacer in children of 5-15 years with mild acute exacerbation of asthma with Modified Pulmonary Index Score (MPIS) between 6-8. The Modified Pulmonary Index Score (MPIS) is a clinical scoring system (range 0–12) that assesses acute asthma severity based on respiratory rate, oxygen saturation, accessory muscle use, wheeze, inspiratory–expiratory ratio, and heart rate. FEV₁ (% predicted) and Modified Pulmonary Index Score (MPIS) improved significantly from baseline in both groups as early as 1 minute post-administration, with no significant differences observed between the two treatments at any time point.

 

Findings from adult studies by Chew et al.(15) comparing inhaled budesonide/ formoterol with inhaled budesonide showed comparable improvements in oxygen saturation, PEFR (p value 0.4) in both the groups at 1 minute. Another study done by Lai et al.(16) comparing inhaled budesonide/formoterol with salbutamol showed similar improvement in post treatment outcomes (in terms of respiratory rate, oxygen saturation and PEFR) in both the groups except that tachycardia was noted in salbutamol group (p value- 0.001).

 

Study done by David S Pearlman et al.(17) showed that in children aged 6 to <12 years with asthma who remained symptomatic on ICS monotherapy, the combination of formoterol and budesonide (pMDI 9/160 μg) produced significant and clinical improvements in lung function compared to budesonide alone (p value <0.015). This supports the efficacy of adding a long-acting β2-agonist to ICS in achieving better symptom control and lung function in pediatric patients not adequately controlled on monotherapy.

 

Adverse events were infrequent and mild, with tachycardia occurring slightly more often in the salbutamol + budesonide group, though not statistically significant, and no cases of hypertension or tremors were reported. These findings align with Jenish et al.,(17) who observed tremors in two children receiving salbutamol and one receiving formoterol, highlighting the favorable safety profile of both regimens in acute asthma.

 

The findings from our study, supported by evidence from previous research, indicate that formoterol Budesonide combinations exhibit a rapid bronchodilatory effect which is comparable to that of short-acting β₂-agonists such as salbutamol Budesonide combination.  This suggests its potential utility as a rescue medication during acute exacerbations in children. The rationale for ICS/formoterol therapy is based on concerns about the risks of SABA reliever therapy, and the potential benefit of titrating additional ICS through the same vehicle of bronchodilator reliever use.

 

The study's findings are limited by its small sample size, single-centre study, short observation period, focused on children with mild asthma, and the use of PEFR instead of spirometry for assessing airway function.

 

Inhaled Formoterol+Budesonide combination has rapid onset of action within 5 mins and similar efficacy as bronchodilator as inhaled Salbutamol+Budesonide combination, traditionally used as reliever in children 6-12 years of age. Inhaled formoterol+ budesonide combination also found to be safe and can be used as reliever in acute asthma exacerbation in children of age 6 -12 years of age, taking into consideration long term risks associated with repeated use of SABA. Further large-scale, longitudinal studies are warranted to assess the sustained efficacy and long-term safety profiles of these therapeutic combinations.

             

Acknowledgements

We thank all participating patients, their families, and the staff of the Department of Pediatrics, M.V.J. Medical College & Research Hospital, for their contributions to this study.

 

Conflict of Interest

The authors declare no conflicts of interest.

 

Funding

No specific funding was received for this study.

 

Ethical Approval

Approved by the Institutional Ethics Committee of M.V.J. Medical College & Research Hospital. Written informed consent obtained from guardians.

 

1.           Bateman Ed, Hurd Ss, Barnes Pj, Bousquet J, Drazen Jm, Jm F, et al. Global strategy for asthma management and prevention: GINA executive summary. PubMed [Internet]. 2025 Mar 26 [cited 2025 Mar 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/18166595/

2.           Lai Ck, Beasley R, Crane J, Foliaki S, Shah J, Weiland S. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). PubMed [Internet]. 2025 Mar 26 [cited 2025 Mar 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/19237391/

3.           Castro-Rodriguez Ja, Rodrigo Gj. A systematic review of long-acting β2-agonists versus higher doses of inhaled corticosteroids in asthma. PubMed [Internet]. 2025 Mar 26 [cited 2025 Mar 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/22926172/

4.           Mansur Ah, Kaiser K. Long-term safety and efficacy of fluticasone/formoterol combination therapy in asthma. PubMed [Internet]. 2025 Mar 26 [cited 2025 Mar 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/23098325/

5.           Global Initiative for Asthma - GINA [Internet]. 2025 [cited 2025 Apr 1]. 2022 GINA Main Report. Available from: https://ginasthma.org/gina-reports/

6.           Bahadori K, Doyle-Waters Mm, Marra C, Lynd L, Alasaly K, Swiston J, et al. Economic burden of asthma: a systematic review. PubMed [Internet]. 2009 [cited 2025 Mar 26]; Available from: https://pubmed.ncbi.nlm.nih.gov/19454036/

7.           Maue DK, Krupp N, Rowan CM. Pediatric asthma severity score is associated with critical care interventions. World J Clin Pediatr [Internet]. 2017 Feb 8 [cited 2025 Nov 30];6(1):34–9. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5296627/

8.           2025 GINA Severe Asthma Guide [Internet]. Global Initiative for Asthma - GINA. [cited 2025 Nov 30]. Available from: https://ginasthma.org/2025-gina-severe-asthma-guide/

9.           Chowdhury NU, Guntur VP, Newcomb DC, Wechsler ME. Sex and gender in asthma. European Respiratory Review [Internet]. 2021 Nov 17 [cited 2025 May 1];30(162). Available from: https://publications.ersnet.org/content/errev/30/162/210067

10.         Nishimura H, Mochizuki H, Tokuyama K, Morikawa A. Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic cough. Pediatric Pulmonology [Internet]. 2001 [cited 2025 May 1];31(6):412–8. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.1068

11.         Koster ES, Raaijmakers ,Jan A. M., Vijverberg ,Susanne J. H., van der Ent ,Cornelis K., and Maitland-van der Zee AH. Asthma Symptoms in Pediatric Patients: Differences throughout the Seasons. Journal of Asthma [Internet]. 2011 Sept 1 [cited 2025 Apr 29];48(7):694–700. Available from: https://doi.org/10.3109/02770903.2011.601780

12.         Hong S, Son DK, Lim WR, Kim SH, Kim H, Yum HY, et al. The prevalence of atopic dermatitis, asthma, and allergic rhinitis and the comorbidity of allergic diseases in children. Environ Health Toxicol. 2012;27:e2012006.

13.         Chew KS, Kamarudin H, Hashim CW. A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks. Int J Emerg Med. 2012 Apr 13;5:16.

14.         Jenish J Arun, Rakesh Lodha, Sushil K Kabra. Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol in acute asthma: a double-blind, randomized controlled trial. BMC Pediatr. 2012 Mar 7;12:21.

15.         Chew KS, Kamarudin H, Hashim CW. A randomized open-label trial on the use of budesonide/formoterol (Symbicort®) as an alternative reliever medication for mild to moderate asthmatic attacks. Int J Emerg Med [Internet]. 2012 Apr 13 [cited 2025 May 6];5:16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352303/

16.         Koh HP, Lai ,Sin Nan, Chong ,Woon Wee, and Mohd Pauzi Z. Budesonide/formoterol turbuhaler vs pMDI salbutamol for acute asthma in outpatient emergency department: a prospective, randomized, open-label study. Journal of Asthma [Internet]. 2025 Apr 3 [cited 2025 May 6];62(4):694–704. Available from: https://doi.org/10.1080/02770903.2024.2438094

17.         Pearlman DS, Eckerwall G, McLaren J, Lamarca R, Puu M, Gilbert I, et al. Efficacy and safety of budesonide/formoterol pMDI vs budesonide pMDI in asthmatic children (6–<12 years). Annals of Allergy, Asthma & Immunology [Internet]. 2017 Apr 1 [cited 2025 May 6];118(4):489-499.e1. Available from: https://www.sciencedirect.com/science/article/pii/S1081120617300558

18.         Jenish J Arun, Rakesh Lodha, Sushil K Kabra. Bronchodilatory effect of inhaled budesonide/formoterol and budesonide/salbutamol in acute asthma: a double-blind, randomized controlled trial. BMC Pediatr [Internet]. 2012 Mar 7 [cited 2025 Mar 26];12:21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324377/