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were withdrawn for 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.