Asthma is a chronic respiratory condition affecting millions of children worldwide, necessitating effective management strategies to ensure well-controlled symptoms and improved quality of life. In this groundbreaking study, researchers investigate the comparative effectiveness of two different administration regimens of inhaled budesonide, a common corticosteroid used in asthma treatment, on mild and moderate well-controlled childhood asthma. The study, titled "Once-Daily vs. Twice-Daily Administration of Inhaled Budesonide for Mild and Moderate Well-Controlled Childhood Asthma: A Randomized Controlled Trial," aims to provide valuable insights into the optimal dosing frequency of budesonide to achieve and maintain asthma control in pediatric patients. This randomized controlled trial represents a pivotal advancement in pediatric asthma management research. By comparing once-daily and twice-daily inhalation regimens of budesonide, the study seeks to address several critical questions: Effectiveness: Does once-daily administration of budesonide provide comparable asthma control as the conventional twice-daily regimen in children with mild to moderate well-controlled asthma? Safety: What are the safety profiles of these two dosing regimens? Are there any notable differences in side effects or adverse events? Patient Compliance: How does the dosing frequency affect patient adherence and satisfaction? Can a once-daily regimen lead to improved adherence among children with asthma? Cost-Efficiency: Are there cost-saving implications associated with once-daily dosing that may make it a more viable option for long-term asthma management? The research team will conduct a rigorous, double-blind, and randomized controlled trial, enrolling a diverse group of pediatric participants with mild to moderate well-controlled asthma. They will monitor key asthma control indicators, such as lung function, symptom frequency, rescue medication use, and overall quality of life, to assess the impact of once-daily vs. twice-daily budesonide administration. By shedding light on the comparative effectiveness and safety of these dosing strategies, this study holds the potential to revolutionize the way we manage childhood asthma. Ultimately, the findings from this trial may lead to personalized treatment recommendations, allowing healthcare providers to tailor asthma management plans to each child's unique needs, thereby improving overall asthma control and enhancing the well-being of young patients and their families. This research is a critical step toward achieving more precise and patient-centric asthma care.

1. Once-Daily vs. Twice-Daily Administration of Inhaled
Budesonide for Mild and Moderate Well-Controlled
Childhood Asthma:
A Randomized Controlled Trial

2. Introduction
• Asthma is a chronic inflammatory condition of the lung airways
resulting in recurrent and episodic variable respiratory symptoms.
• It is a common chronic disease of childhood, causing significant
morbidity.
• Inhaled corticosteroids (ICS) are the most effective controller
medications and are standard of care.
• Controller medication are adjusted up or down in a stepwise
approach to achieve good symptom control.

3. Asthma Definition (GINA)
• History of respiratory symptoms (more than one): wheeze, cough,
shortness of breath, chest tightness that
oVary over time and in intensity
oOccur or are worse at night/on waking
oTriggered by exercise, allergens, laughter, cold air
oOccur or worsen with viral infections
• Variable expiratory airflow limitation:
oFEV1/FVC below lower limit of normal
oSignificant bronchodilator reversibility (FEV1 > 12% of pre-bronchodilator
value)
oFEV1 > 12% after 4 weeks of anti-inflammatory treatment

4. Classification of severity
• Mild asthma: that can be controlled with Step 1 or 2 (as-needed ICS-
formoterol or with low dose ICS)
• Moderate asthma: that can be controlled with Step 3 (low dose ICS-
LABA)
• Severe asthma: that requires Step 4 or 5 (high dose ICS-LABA) to
prevent it from becoming uncontrolled or that remains uncontrolled
despite treatment

6. • Present evidence as to whether equivalent dosages of ICS given once-
daily or divided twice-daily are equally effective, is conflicting.
• Various studies have been conducted but most of these studies are
from developed countries rather than developing countries like India
where compliance is an important issue.
• By simplifying the dosing regimen, compliance can be improved and
asthma-related morbidity can be reduced since these patients usually
require long-duration treatment.
Rationale of study

7. Aims and objectives
• To compare median change in morning peak expiratory flow rate
(PEFR) and clinical asthma control in children receiving total daily
dosage of inhaled budesonide administered either as once-daily or
divided twice-daily dose.

8. Materials and methods
• Study design: Open label randomized control trial
• Study area: Tertiary care hospital in Northern India
• Study period: December 2017 to February 2019
• Inclusion criteria: Children 5 - 12 years of age with mild or moderate
well-controlled asthma (as per GINA 2017 guidelines) who were on
regular follow-up

9. GINA 2017 GINA 2022
Definition Asthma is a heterogeneous disease, usually
characterized by chronic airway
inflammation
Asthma is a chronic inflammatory disease of the
airways that is characterized by variable and
recurring symptoms, airflow limitation, and airway
hyperresponsiveness
Classification Classified asthma severity as mild, moderate,
and severe based on symptoms and lung
function
Classified asthma severity as mild, moderate, or
severe based on symptoms, lung function and risk
factors
Management Recommended a stepwise approach to
asthma treatment based on symptoms and
lung function
Recommended a personalized stepwise approach to
asthma treatment based on symptoms, risk factors,
biomarkers, and patient preferences
Medications Recommended the use of inhaled
corticosteroids (ICS) as first-line therapy for
persistent asthma, with the addition of long-
acting beta2-agonists (LABA) or leukotriene
receptor antagonists (LTRA) as needed
Emphasized the importance of ICS as the cornerstone
of asthma therapy, and recommended the use of
add-on therapies such as LABA, LTRA, or biologics
(Omalizumab – Anti IgE, Mepolizumab – Anti IL5,
Dupilumab – Anti IL4R)
Patient education Encouraged healthcare providers to provide
education on asthma self-management,
including the use of peak flow meters and
action plans
Expanded the focus on patient education to include
shared decision-making, inhaler technique, and
environmental control measures

10. Exclusion criteria:
• Treatment naïve children diagnosed to have asthma
• Children with history of severe asthma in the preceding 6 months
• Children with any other underlying chronic lung conditions
• Children having received systemic corticosteroids (oral or
intravenous) in the preceding 4 weeks
• Children who have had respiratory tract infection or emergency room
treatment in the preceding 4 weeks

11. Methodology
• Children and their parents were taught how to measure PEFR and
were asked to record their morning and evening PEFR daily for 2
weeks to get their personal best or baseline morning PEFR, evening
PEFR, and diurnal variation.
• PEF was measured using peak flow meter of same company for all
patients and the best of 3 measurements was recorded.
• After 2 weeks, baseline spirometric parameters (FEV1, FVC, FEV1/FVC
ratio, PEFR), GINA 2017 symptom control, Asthma Control
Questionnaire (ACQ) score were recorded.

12. GINA symptom
control
questionnaire:
Asthma Control
Questionnaire
(ACQ):

13. • Subjects then entered the open label treatment phase where they
were randomized into two groups (OD and BD treatment).
• Simple randomization of subjects were done using a computer
programme and allocation concealment was ensured with the help of
a statistician not directly involved in the analysis of the study results,
using sequentially numbered, opaque sealed envelopes.

14. • Budesonide was given through metered dose inhaler (MDI) along with
spacer in all patients:
oMild asthma: 200 mcg single evening dose or 100 mcg twice a day
o Moderate asthma: 400 mcg single evening dose or 200 mcg twice a day
• Patients were provided with MDI Salbutamol 100 mcg (SABA) for
symptom relief, as required, throughout the study.

15. • Primary outcome of the study was median change in morning PEFR in
children taking once- and twice-daily ICS.
• Secondary outcomes included were:
omedian change in evening PEFR
omedian change in diurnal variation in PEFR
oasthma symptom control as per GINA 2017
omean change in ACQ score
olung function measurements taken at the clinic (PEFR, FEV1, FVC, FEV1/FVC).

16. • At home, subjects recorded their morning and evening PEFR daily and
ACQ weekly.
• Follow-up was done at 4 weeks, 8 weeks and 12 weeks.
• At every follow-up visit, patients were asked to bring all the recorded
data. Spirometric parameters and asthma symptom control as per
GINA 2017 guidelines were assessed.
• Step up of treatment was done at follow-up according to GINA 2017
assessment of asthma control by increasing the dose of inhaled
corticosteroids or addition of long-acting beta-agonist (LABA).

17. The patients were withdrawn from the study if:
• They needed any new asthma medications -
oany other inhaled corticosteroids
osystemic corticosteroids
oLABA
oantileukotriene inhibitors
otheophylline
osodium cromoglycate
• They did not adhere to the prescribed treatment during the study
period.
• They had any acute exacerbations.

19. Statistical analysis
• Data were collected using a pretested data collection sheet and data
were managed using Microsoft Excel. Analysis was conducted using
IBM SPSS STATISTICS (version 22.0) on an intent-to-treat basis.
• For skewed data, comparisons for two groups were made by Mann–
Whitney test.
• For normally distributed, Student t-test was applied to compare two
groups.
• Group comparisons were done using chi square or Fisher exact test
whichever applicable. Changes were calculated by subtracting values
at different weeks from baseline.

20. Results
Baseline
characteristics:
No significant
differences
between the
groups

21. The median
decrease in
evening PEFR was
significantly higher
in the OD group
(9.00 L/min; IQR:
−12.00–31.00
L/min) compared
to the BD group
(1.00 L/min; IQR:
−16.00–21.50
L/min; p = 0.001).

23. Discussion
• The primary outcome was median change in morning PEFR which was
not statistically significant (p value 0.222) between the two groups.
• The rest of the spirometric parameters and symptom control related
variables were also not significant.
• Only median change in evening PEFR was in favor of twice daily
regimen.

24. • The results of this study are consistent with those of a Swedish study
conducted by Möller et al. involving 206 children with stable asthma
(age 5–15 y) who received budesonide by dry-powder inhaler (DPI). In
this study, there was no significant difference in morning PEFR.
• The results are also similar to a study done in the UK by Woodcock et
al. using fluticasone furoate in moderate asthma patients, which
showed non-inferiority of once-daily regimen.

25. • The results of the present study differ from a Canadian study by
Boulet et al. of patients aged 12 y or more with mild or moderate
asthma, which revealed results in support of BD regimen.
• In this study the once-daily dose was administered in the morning.
• Difference in efficacy between the two dosing regimens may have
been reduced if the once-daily dose had been given at the end of the
day, as given in the present study.

26. Conclusion
• To conclude, once-daily administration of inhaled budesonide is not
inferior to twice-daily administration of equivalent daily dosage of
inhaled budesonide.
• Asthma control can be maintained with once-daily administration in
most patients with mild to moderate asthma.

27. Limitations
• Open label design of study
• Adherence was not measured objectively in the present study, so it
cannot be commented whether the results of the study are
confounded by adherence or not, as there were studies which
showed improved adherence with once-daily regimen.
• Results are applicable for MDI with spacer only, not other modes like
DPI
• Results applicable only for inhaled Budesonide, not other ICS
• Did not study severe asthma

33. Thank you