Prevent Wheeze Trial

• Dexamethasone 0.6 mg/kilogram body weight single dose (Drug): Dexamethasone 0.6 mg/kilogram body weight single dose
• Placebo (Drug): Placebo

Primary outcomes

• New episode of wheeze within 12 months from inclusion, yes/no. [12 months]: Whether or not the child had any new wheezing episode within the first 12 months. Wheeze is confirmed by doctor/study nurse or caregiver history supported by viedo. Any episode of wheeze is verified by TAL criteria scoring of 1 or more on the wheeze item (end-expiratory by stethoscope=1, Entire expiration (+/-audible without stethoscope)=2, inspiratory and expiratory (audible without stethoscope)=3). Full TAL scoring is assessed and included in episode evaluation.

Secondary outcomes

• Duration of symptoms for initial episode [6 weeks (4 - 8 weeks)]
• Number of episodes with breathing difficulty within 12 months [12 months]: Episodes of breathing difficulty by 12 months follow-up, including: new breathing difficulty with wheeze (y/n), LRTI without wheeze (y/n), and any hospital admission for breathing difficulties (y/n).
• Time to any episode with breathing difficulties within 12 months after inclusion. [12 months]: Time in number of days.
• Number of episodes with acute breathing difficulty (duration >24 hours) by 12 months. [12 months]
• Total number of days with breathing difficulty within 14 days of intervention. [14 days]
• Total number of days with breathing difficulty within 12 months [12 months]
• Lung function at 6 weeks (4 - 8 weeks) after inclusion [6 weeks]: Tidal breathing flow-volume loop (TBFVL) and oscillometry at scheduled visit 6 (4 - 8) weeks after inclusion.
• Lung function 12 months after inclusion [12 months]: Tidal breathing flow-volume loop (TBFVL) and oscillometry at scheduled visit 12 months after inclusion.
• Quality of Life 6 weeks (4 - 8 weeks) after inclusion. [6 weeks]: Quality of Life assessment in children aged 3 - 24 months in Nepal only. Nepali verison of the Pediatric Quality of Life Inventory Infant Scales (PedsQL).
• Quality of Life 12 months after inclusion [12 months]: Quality of Life assessment in children aged 3 - 24 months in Nepal only. Nepali verison of the Pediatric Quality of Life Inventory Infant Scales (PedsQL).
• Height development within 12 months of study entry [12 months]: Height is measured in centimeters (cm) to the nearest 0.1cm, using a calibrated stadiometer for children >24 months of age. For children <24 months of age, lenght is measured in the recumbent position using an infantometer. Height is measured at inclusion, 6 weeks and 12 months after inclusion.
• Body weight development within 12 months of study entry [12 months]: Body weight in kilograms, 1 decimal. For children >24 months of age, weight will be measured with light clothing using a calibrated electronic scale. For children <24 months, weight will be measured without clothes or with a dry diaper only using a leveled pan scale. Body weight is measured at inclusion, 6 weeks and 12 months after inclusion.
• Time to fulfill criteria for asthma, in accordance with GINA 2025 guidelines, within 12 months. [12 months]: Criteria meeting GINA 2025 definitions for asthma in children <=5 years of age: 1) symptom pattern consistent with asthma and not controlled; >=3 episodes/year or symptoms most days or 2) symptoms occurring more than two days per week with a history of severe wheezing episodes AND: response to trial treatment.

Sex: All, ages: 3 Months to 24 Months

Inclusion criteria:

1. Age 3-24 months
2. LRTI (WHO definition LRTI: Cough or difficulties breathing

   \+ plus either fast breathing ( 2-12 months: > 50 breaths/minute 13-24 months: >40/minute) or: lower chest wall indrawing (retractions/nasal flare/difficulties breathing/wheeze) Acute:<7 days duration of LRTI symptoms
3. No history of previous LRTI/wheeze
4. \+ 1 or more risk factors for recurrent wheeze:

   * Clinical wheeze by presentation (indicated in TAL score>=1 for wheeze item). The scoring matrix is here and in the annex.
   * Indoor pollution exposure: Tobacco smoke exposure a) during pregnancy or b) in house where child lives (regular >= 2week) or polluting cooking facility
   * Atopic/allergic disease in child
   * Atopic/allergic/asthma in sibling, mother or father
   * PT week 34-36 or BW 2000-2500g
   * Eosinophil count >0.30 Informed consent

Exclusion criteria:

* Chronic illness other than atopy (eczema, food allergy),
* Systemic corticosteroid treatment the previous 6 months
* Inhaled corticosteroid treatment, at any time, for >2 weeks
* Clinical suspicion of bacterial pneumonia based upon a temperature ≥39.0°C and at least one of the following: 1. Unilaterally decreased breath sounds or unilateral percussion dullness 2. Pulmonary lobar consolidation and/or radiological high suspicion of empyema on chest x-ray if this is obtained prior to inclusion in the trial. Fills other criteria for high likelihood of bacterial pneumonia (on clinicians' evaluation or CRP>40)
* Evidence of any bacterial infection other than bacterial LRTI, including, but not exclusively: 1. Clinical septicemia 2. Urinary tract infection 3. Meningitis
* participation in another trial
* varicella infection or contact during the last 2-3 weeks
* Fulfill criteria for ICS at time of inclusion, at treating physicians discretion, guided by annex on criteria for unblinding due to medical condition needing open CS treatment (criteria for unbinding Criteria for unblinding.docx)
* Severe wheeze defined by TAL score* >=11 or need for intensive care unit treatment with invasive ventilation at screening.
* Previous admission for a LRTI or physician verified LRTI

• Kari R. Risnes, PhD, Principal investigator, Norwegian University of Science and Technology