Subjects.
Asthmatic and healthy children were prospectively included in this study. Asthma was diagnosed by a pediatric pulmonologist based on Global Initiative for Asthma guidelines and children were referred to the lab for a routine follow-up lung function testing. Long acting BD agents were withdrawn for >12 hours and short acting BD agents for >6 hours before the day of study. The presence of asthma symptoms in the last 3 months and chronic anti-asthmatic therapy as inhaled steroids associated or not with long acting BD agents and leukotriene antagonists were documented. Measurements included subject’s weight, height, transcutaneous oxygen saturation and clinical examination consisted in cardiopulmonary auscultation. Age-matched healthy children were recruited from local primary schools. All children were free of respiratory infection for at least one month before the day of testing. Written informed consent was obtained from the children and their parents at the time of lung function testing. The study was approved by the Ethics Committee (Comité de Protection des Personnes Est III, Centre Hospitalier Universitaire de Nancy, France).
Lung function testing .
Forced spirometry was performed by an experienced technician using electronic flowmeters with computer animation software (Masterscope Erich Jaeger GmbH, Wuertzburg, Germany) according to current recommendations 3,20. The maneuver was explained to the child who was then trained to perform a full inspiration followed by a forced expiration with typical fast rise to PEF and uniform decrease throughout expiration. Usually five maneuvers were necessary until two reproducible FVL’s were achieved. The curve with the best sum between forced vital capacity (FVC) and FEV1 was retained for analysis. Two puffs of salbutamol (Ventoline 100 μg/puff, Glaxo-SmithKline, Marly Le Roi, France) were then administered to the child using an inhalation chamber (Nespacer, Astra France, Monts, France) and forced spirometry repeated after 10 minutes. FVC, FEV1, FEV1/FVC and forced expiratory flow between 25% and 75% of the FVC (FEF25-75%) expressed in absolute values and z-scores 21, at baseline and their response to BD, expressed as z-score and percentage of change reported to baseline (Δ%), were retained for analysis. Part of the spirometric data has already been published 22. For this study, shape indexes, β-angle (figure 1 ) and FEF50/PEF ratio, were computed, as absolute values (β-angle formula being: β = 180 – tan–1[(PEF – FEF50) / (0.5 x FVC)] + tan–1[FEF50 / (0.5 x FVC)]16and z-scores as previously reported 5 and retained for analysis.
Statistical analysis .
The analysis was performed using SAS University Edition statistical software. The qualitative variables were expressed as number (percentage) and the quantitative variables as median [25th; 75th percentiles] as not normally distributed. Mann-Whitney test was used to compare patients and controls. The diagnostic performance was tested for each parameter using Receiver Operating characteristic Curves (ROC) and area under ROC curve (AUC) and its 95% confidence interval (95CI), sensitivity and specificity at the most relevant thresholds, reported. AUC (95CI), sensitivity and specificity were also computed for the combination of spirometric parameters at the respective thresholds. A p value<0.05 was considered statistically significant.