Daily diary cards were used from birth to monitor significant troublesome lung symptoms as previously analysed in detail 12 including components of cough, wheeze, and dyspnoea, and use of β2‐agonists, inhaled corticosteroids, and montelukast. Skin symptoms were monitored as active eczema and use of topical steroids. In addition, the diary cards monitored infections, categorized into common cold, pneumonia, pharyngitis, otitis, fever, gastrointestinal infection, and absence from day care institution because of illness (Figure S1). The diary cards were reviewed with the family by the research MD at each visit to validate symptom definitions. All information were subsequently entered into the online database and double‐checked.
Physical examination was performed by the research MD at all scheduled and acute visits, including lung and heart stethoscopy and examination of skin 13, ear, nose, and throat.
CRP measurement was performed at acute visits or when needed using QuickRead 101 (QuickRead Instrument, Orion Diagnostica, Espoo, Finland).
Tympanometric evaluation of the middle ear pressure was performed at yearly visits or when needed (MT10, Interacoustics, Denmark) on both ears.
Spontaneous physical activity was assessed by age 2 years using an omnidirectional accelerometer worn on the ankle for 2 weeks as previously described 16.
Blood pressure was assessed yearly from age 3 years (Welch Allyn Connex: ProBP 3400).
Lung function by multiple‐breath washout (EcoMedics: Exhalyzer D) was assessed from the age of 3 years.
Airway resistance was measured from 3 years of age by whole‐body plethysmography (Master Screen Body; Erich Jaeger GmbH; Würzburg, Germany) 18.
Airflow was measured by spirometry (Vitalograph: Spirotrac II) before and after inhalation of a standard dose of β2‐agonist from age 5 years.
Fractional nitric oxide (FeNO) was measured using an Aerocrine NO system (CLG77AM chemiluminescence analyzer from Ecophysics AG, Duernten, Switzerland) and assessed from age 5 years.