Data collection, management and analyses

Through an interview with the child and parent(s) data on baseline health including, data on former episode(s) with asthma-like symptoms, current and former asthma medication, atopic status and data on environment and sociodemographic will be collected and directly entered in the REDCap trial database (see table 2 for details recorded). Moreover, we will extract data on prescribed medication and information from the child’s medical records from birth and 4 years ahead from date of inclusion. We will monitor asthma-like symptoms, defined as wheeze or whistling sounds, breathlessness or troublesome cough severely affecting the well-being of the child, via diary data registered online via the REDCap system. The parents will report daily for 21 days their child’s asthma-like symptoms, use of medication, possible AEs and sick leave. A link for this registration is sent once daily via REDCap. If the child also participates in the vitamin D study arm, the parents continue to fill out the diary once weekly for 1 year. The participants included in the azithromycin study will deliver a blood sample at baseline, measuring C reactive protein and white blood cell count. Faecal samples will be collected at baseline, 3 weeks, 3 months and 1 year after inclusion. Both studies include biosamples for measuring airway microbiota, pathogenic bacteria, vira and the airway immune profile. The vitamin D study arm also includes samples from the nose for gene expression of the upper airway. Further, in the vitamin D study arm at inclusion and after 3 months (ie, at their local hospital) a blood sample and a urine sample will be taken for measuring 25(OH)D, Ca, Ph, ALP, PTH and urine Calcium:Creatinine ratio, which will be evaluated by an independent paediatrician for signs of vitamin D intoxication and vitamin D insufficiency.

Overview of data we will access at the time of inclusion and over study procedures

If the child is participating in both study arms the overlapping procedures will only be taken once.

*As in the Azithromycin study arm.

AEs, adverse events; ALP, alkaline phosphatase; BMI, body mass index; Ca, calcium; ICS, inhaled corticosteroids; IgE, immunoglobulin E; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroids; 25(OH)D, 25-hydroxyvitamin D; Ph, phosphorus; PTH, parathormone; REDCap, Research Electronic Data Capture; SABA, short-acting beta-agonists.

Further, they will attend a clinical follow-up visit at the COPSAC research clinic 1 year after enrolment for collection of a variety of bio samples, screening for AEs and interviewing the parent(s) regarding the recent years’ exacerbations, medication use and step-up/step-down in preventive asthma medication.

The planned study procedures are listed in table 2. Further, a more in-depth description of the methods for sampling and assessments of the biosamples is given in online supplemental material.

bmjopen-2021-054762supp001.pdf

An intention-to-treat analysis will be carried out with all randomised children by treatment group.