Primary Outcomes

Description: Hospital admission was defined as the need to stay in the emergency room for more than 4 hours, due to the failure to meet the discharge criteria (PRAM score ≤ 3 and pulse oximetry, ≥ 92%)

Measure: Hospital Admission

Time: Starting at 4 hours post-treatment

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Secondary Outcomes

Description: Change in FEV1 one hour post-treatment in comparison with baseline. Spirometry was performed only in subjects older than 6 years and who could perform the maneuver properly.

Measure: Forced Expiratory Volume in the First Second

Time: One hour post-treatment in comparison with baseline

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Description: Change in the Pediatric Respiratory Assessment Measure (PRAM) score one hour post-treatment in comparison with baseline. The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack. We calculated the difference between the PRAM score measured one hour post treatment and the PRAM score at baseline (PRAM score 1 hour - PRAM score baseline). The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2). minimum value of the difference (Albuterol - Higher Dose, experimental group): -8 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0 minimum value of the difference (Albuterol - Lower Dose, control group): -8 maximum value of the difference (Albuterol - Lower Dose, control group): 0

Measure: Change in PRAM Score After One Hour

Time: One hour post-treatment

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Description: Albuterol determination in the plasma was carried out at at discharge or hospital admission (up to 4 hours post treatment), dosage was accomplished by High Performance Liquid Chromatography.

Measure: Albuterol Determination in the Plasma

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: Changes in glucose serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Glucose Serum Levels

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Electrocardiogram performed at baseline

Measure: Electrocardiogram at Baseline

Time: at baseline

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Description: Change in respiratory rate one hour post-treatment in comparison with baseline.

Measure: Changes in Respiratory Rate After One Hour

Time: One hour post-treatment in comparison with baseline

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Description: The need for additional therapies such as magnesium sulphate or intravenous albuterol were recorded

Measure: Need for Additional Therapies

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: Change in the Pediatric Respiratory Assessment Measure (PRAM) score at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline. The PRAM score is used to assess the severity of asthma attacks, it ranges from 0 to 15, and the higher the score, the greater the severity of the attack. We calculated the difference between the PRAM score measured at discharge or admission and the PRAM score at baseline (PRAM score discharge or admission - PRAM score baseline). The larger the absolute value of the difference, the better the outcome (e.g., a difference of -4 indicates a better outcome that a difference of -2). minimum value of the difference (Albuterol - Higher Dose, experimental group): -9 maximum value of the difference (Albuterol - Higher Dose, experimental group): 0 minimum value of the difference (Albuterol - Lower Dose, control group): -9 maximum value of the difference (Albuterol - Lower Dose, control group): 1

Measure: Changes in PRAM Score at Discharge or Hospital Admission

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Changes in potassium serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Potassium Serum Levels

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Changes in bicarbonate serum levels at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Bicarbonate Serum Levels

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Changes in respiratory rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Respiratory Rate at at Discharge or Hospital Admission.

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Change in pulse oximetry one hour post-treatment in comparison with baseline

Measure: Change in Pulse Oximetry One Hour Post-treatment

Time: One hour post-treatment in comparison with baseline

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Description: Changes in pulse oximetry at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Pulse Oximetry at Discharge or Hospital Admission.

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment) in comparison with baseline.

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Description: Change in heart rate one hour post-treatment in comparison with baseline.

Measure: Changes in Heart Rate After One Hour

Time: One hour post-treatment in comparison with baseline

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Description: Changes in heart rate at discharge or hospital admission (up to 4 hours post treatment) in comparison with baseline.

Measure: Changes in Heart Rate at Discharge or Hospital Admission

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: Electrocardiogram one hour post-treatment to identify possible rhythm disturbances.

Measure: Electrocardiogram One Hour Post-treatment.

Time: One hour post-treatment

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Description: Electrocardiogram at discharge or hospital admission to identify possible rhythm disturbances.

Measure: Electrocardiogram at Discharge or Hospital Admission

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: lengths of stay in the emergency room for discharged patients

Measure: Lengths of Stay in the Emergency Room

Time: one to four hours

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Description: Admission rates in patients with and without any of the following viruses detected by PCR in nasal lavage samples: Adenovirus; Bocavirus; Coronavirus; Enterovirus (Echovirus); Influenza (A H3N2, A H1N1/2009, B and C); Metapneumovirus (subtypes A and B); Parainfluenza 1, 2, 3 and 4 (subtypes A and B); Rhinovirus; Respiratory Syncytial Virus type A and Respiratory Syncytial Virus type B.

Measure: Admission Rates in Patients With and Without Any Virus Detected

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: Admission rates in patients with and without rhinovirus detected by PCR in nasal lavage samples.

Measure: Admission Rates in Patients With and Without Rhinovirus Detect

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Description: Admission rates in patients with the Arg16Gly polymorphisms of the beta-2 adrenergic receptor (Arg16Gly, Arg16Arg and Gly16Gly genotypes).

Measure: Admission Rates in Patients With the Arg16Gly Polymorphisms

Time: at discharge or admission (up to 4 hours post treatment, minimum 1 hour, maximum 4 hours post treatment)

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Primary Outcomes

Measure: Mean Ec50% in response to rising concentration of isoproterenol

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Primary Outcomes

Description: Patients will fill in the (childhood-)Asthma Control Test at baseline, after 3 months [Range score: 0 - 27, 20 or more means asthma under control]

Measure: Asthma control based on (childhood-)Asthma Control Test scores in the first 3 months of the trial

Time: 3 months

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Secondary Outcomes

Description: Patients will fill in the (childhood-)Asthma Control Test at baseline after 6 months [Range score: 0 - 27, 20 or more means asthma under control]

Measure: Change in asthma control at t=6 months (childhood-)Asthma Control Test

Time: 6 months

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Description: Patients will fill in a questionnaire about asthma-related school absences [Minimum score 0 days, maximum score more than 10 days]

Measure: Change in asthma-related school absences

Time: 6 months

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Description: Patients will be questioned what kind of treatment they use at baseline visit, after three months

Measure: Change in therapy in t = 3 months

Time: 3 months

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Description: Patients will fill in the (childhood-)Asthma Control Test at baseline, every month [Range score: 0 - 27, 20 or more means asthma under control]

Measure: Time to reach asthma control (Asthma Control Test score ≥20)

Time: 6 months

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Description: Patients will fill in the Productivity Cost Questionnaire at 0, 3 and 6 months. The IPCQ measures: absenteeism (number of days missed from work in the 4 weeks due to ilness) -- minimum is 0, maximum (in theory) is 28 days Presenteism (productivity lost while at work due to ilness) -- minimum is 0, maximum is 224 hours. In absenteeism, a lower number of days missed from work represent a better outcome; In presenteism, a lower number of hours represent a better outcome For presenteism the number of hours productivity loss is calculated by the following formula using data from the questionnaire. presenteism = number of workingdays affected by illness * (1-efficiencyscore/10)*working hours per working day. This results in a monetary value for productivity loss.

Measure: Cost-effectiveness of ADRB2 genotype guided treatment measured by the Productivity Cost Questionnaire

Time: 3 and 6 months

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Description: Non-response to ICS treatment will be measured by analysing feces samples (microbiome) and nose swabs (epigenome). Nose swabs will be collected after 0, 3 and 6 months and feces after 1 month

Measure: In-depth integrative -omics analysis

Time: 0, 3 and 6 months

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Description: Measured by the Pediatric Asthma-related Quality of Life Questionnaire (PAQLQ). Children are asked to think about how they have been during the previous week and to respond to each of the 32 questions on a 7-point scale (7 = not bothered at all - 1 = extremely bothered). The overall PAQLQ score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains. Subscales are summed.

Measure: Change in quality of life assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) score

Time: 0, 3 and 6 months

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Description: Measured by the PedsQL questionnaire, a 23 item generic score scale consisting of physiological functioning, emotional functioning, social functioning and school functioning questions with multidimensional scales. Subscales are summed. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.

Measure: Change in fatigue scores assessed by the PedsQL questionnaire

Time: 0, 3 and 6 months

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Description: FEV1 will be measured at 0 and 3 months, change in FEV1 will be calculated.

Measure: change in FEV1 at t = 3 months

Time: 0 and 3 months

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Description: FEV1 will be measured at t=0 and 6 months, change in FEV1 will be calculated

Measure: change in FEV1 at t = 6 months

Time: 0, 3 and 6 months

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Description: Exhaled nitric oxide measures will be performed using the Niox Vero at t=0 and 3 months

Measure: change in fraction of exhaled nitric oxide at t=3 months

Time: 0 and 3 months

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Description: Exhaled nitric oxide measures will be performed using the Niox Vero at t=0. 3 and 6 months

Measure: change in fraction of exhaled nitric oxide at t=6 months

Time: 0,3 and 6 months

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