Introduction
Early diagnosis and treatment of asthma, the most frequent chronic
disorder in children, are important to prevent consequences as bronchial
remodeling, infantile morbi-mortality and economic burden1. Asthma phenotypes, guidelines and therapies have
evolved over past years 2, justifying continuous
patient care optimization. Accordingly, lung function testing has a
pivotal role in the initial assessment, follow-up and monitoring the
response to treatment, being an essential contributor to management.
Pediatric spirometry has undergone substantial improvement in
standardization and measurement 3-5. The forced
expiratory flow-volume loop (FVL) is readily obtained by miniaturized,
easy-to-handle electronic flowmeters with numerical transformation of
physiological signals. This test is accessible, not expensive and simple
to use in routine clinical practice. The gold standard outcome, the
forced expiratory volume in 1 s (FEV1), is the most reproducible
spirometric parameter, reflecting bronchial caliber and being correlated
to asthma severity and mortality risk 6,7.
Bronchodilator (BD) reversibility of FEV1 is also fundamental for
initial diagnosis and severity assessment, being a predictor of poor
control in mild to moderate asthma 8 and of response
to inhaled corticosteroids 9. However, FEV1
sensitivity to detect an airway obstruction and /or its BD reversibility
has been disputed in children. This is probably because FEV1 mostly
reflects proximal bronchial obstruction while incipient asthmatic
impairment is primarily located in peripheral airways10. An early sign of peripheral involvement seems to
be the occurrence of ventilation inhomogeneity between different lung
regions, owing to unevenly airway smooth muscle contraction, mucosal
edema and small airway closure 11. This inhomogeneity
was shown to be present even in asthmatic children considered to be
clinically controlled and with respiratory function within normal limits12. During a forced expiration maneuver, the choke
point, where dynamic compression starts, might not be homogeneously
distributed in asthmatic lungs, depending on the parallel peripheral
resistances. Therefore, whereas healthy lungs will empty uniformly
across the forced expired volume, asthmatic lungs will show a successive
inhomogeneous emptying of territories, as expected from a model with
different time constants 13, resulting in an upward
concavity of FVL. Some indexes were previously described to characterize
the shape of FVL 13-15. β-angle, the aperture between
2 lines passing through forced expiratory flow at 50% of the forced
vital capacity (FEF50), one crossing the point at the end of forced
expiration corresponding to residual volume, and the other a point
situated at the height of peak expiratory flow (PEF) on y axis,
indicates an upward convexity or concavity respectively when it is
greater or smaller than 180° 16. β-angle has been
shown to be a robust variable with good reproducibility and feasibility
in adults 16, preschool 17 and
school children 18,19. A simplified approach to
estimate β-angle is to compute FEF50/PEF ratio that presents diagnostic
performances equivalent to β-angle 17.
To overcome the difficulty of interpreting a FVL in children based on a
single parameter, i.e. FEV1 that lacks sensitivity, we
hypothesized that shape indexes, i.e. β-angle and FEF50/PEF,
might be considered in routinely clinical practice to ameliorate
diagnosis capacity of spirometry in identifying the presence of an
airway obstruction and its BD reversibility. The aim of this study was
to determine which parameter at baseline and after BD administration
expressed as percentage of change from baseline (Δ%), has the best
performance in identifying asthmatics from healthy children. The
secondary aim was to assess the diagnosis ability of an association of
shape indexes with “usual” spirometric parameters.