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.