Lung function testing
Comprehensive lung function testing was done at 12 years of age. Flow volume spirometry was performed to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), mean forced expiratory flow between 25% and 75% of FVC (FEF25-75), and slow vital capacity (VC). FEV1/FVC was calculated as a measure of expiratory flow limitation. Dysanapsis ratio, an index of discrepancy in size between the airway and the lung, was calculated as FEF25-75/FVC divided by an estimate of static recoil pressure at 50% of FVC based on child age(17). Body plethysmography was used to measure static lung volumes, i.e. total lung capacity (TLC) and residual volume (RV), and the ratio RV/TLC was calculated as a measure of air trapping. Diffusion capacity of the lung for CO (DLCO) was measured with single breath technique, being the product of the rate constant for uptake of CO (KCO) and alveolar volume. Impulse oscillometry (IOS) provides information about the mechanical properties of large as well as small airways. Resistance was estimated at 5 Hz (R5, reflecting total resistance) and at 20 Hz (R20, reflecting central resistance), while R5-R20 reflects peripheral resistance. During small airway obstruction, reactance (elastance) of the lung (X) decreases at 5 Hz (giving a more negative value of X5), while the resonant frequency (Fres) increases together with the area under the reactance curve (AX), which is a measured from X at 5 Hz to Fres. During multiple breath washout (MBW) of N2, the number of lung volume turnovers required to lower the end-tidal N2-concentration to 5% and 2.5% of the initial concentration are termed lung clearance index (LCI5.0 and LCI2.5 respectively) and is a measure of overall ventilation inhomogeneity. Analysis of the N2 concentration during each breath provides more detailed information of whether the inhomogeneity arises from conductive (Scond) or acinar (Sacin) airways. Higher values of LCI, Scond and Sacinindicate more ventilation inhomogeneity. See supplement for detailed description.
To investigate reversibility, in most subjects, all pulmonary function measurements were performed before and 15 minutes after inhalation of 200 µg salbutamol.
Data is presented as medians with interquartile range (IQR) of absolute values or % of predicted values, proportion below lower limit of normal or above upper limit of normal, and as proportion below the 5th or above the 95th centile in the group of the term born controls. For more detailed information, see supplement.