Introduction
Asthma is a common, chronic respiratory disease affecting an estimated 300 million individuals worldwide and all age groups. Global paediatric asthma prevalence has increased strikingly since the 1950s. Asthma is now the most common chronic respiratory condition affecting approximately 5.5 million subjects in the European Union, making it a leading cause of emergency department visits and 1 of the top 3 indications for hospitalization [1-4].
In preschool children, wheezing is one of the most common symptoms in clinical practice. Approximately one in three children has at least one episode of wheeze before their third birthday and a considerable minority of children will continue to experience wheezing in school years and beyond, diagnosed as asthmatic [5-7]. Moreover, preschoolers have the highest rate of unscheduled medical visits and more limitations of everyday activities for wheezing and asthma symptoms, compared with all other age groups [5,8,9]. However, there is considerable uncertainty in the diagnosis of asthma in preschool age, since lung function testing can rarely be performed in children below 3 years. In addition, there is no gold-standard to confirm the diagnosis of asthma and no single abnormal test by itself is sufficient to make the diagnosis [2]. Specifically, a recent European Respiratory Society (ERS) clinical practice guideline recommends using objective tests such as spirometry, bronchodilator reversibility test (BDR) and fractional exhaled nitric oxide (FeNO) as first line tests and bronchial challenge tests as second line tests [2,10].
Spirometry is the most common pulmonary function test, widely used in the non-invasive assessment of lung function to provide objective information for the diagnosis of lung diseases and monitoring lung health. In presence of an experienced operator, spirometry is achievable in the majority of children aged ≥5 years and major asthma guidelines recommend performing it as part of asthma diagnostic work-up [1,2,11-13]. It is important to note that spirometry as a one-off measurement has a low sensitivity and is therefore poor at excluding asthma. Due to the variable nature of the condition, it may result in normal values also in asthmatic patients and serial measurements may be required to confirm the diagnosis. Conversely, abnormal spirometry has good specificity for asthma [2,12].
In contrast with spirometry, which requires the active participation of the patient, the IOS represents an alternative technique to investigate lung function performing an effort-independent analysis of the mechanical properties of the lungs during tidal breathing. Several studies demonstrated that IOS may represent a key tool in studying respiratory function in preschool children (mainly over 3 years old) [14-21]. In this scenario, there is increasing research on IOS that, with or without bronchodilator reversibility, may represent a useful diagnostic tool in patients who cannot perform acceptable and reproducible spirometry manoeuvres [10,14,15-21]. Different studies have shown that a bronchodilator response (BDR) based on IOS is better than one based on spirometry. In children, several studies showed that a BDR based on IOS discriminates better asthmatic from healthy subjects than one based on spirometry. However, in preschoolers, data are conflicting since in some studies IOS were not able to discriminate wheezy and non-wheezy patients [14,22-25].
Given the diversity of age ranges, equipment and protocols, there is still no consensus in the literature regarding standardization of the cut-off point for the bronchodilator response in preschoolers [14,22]. In past years, several authors suggested different cut-offs between 20-40% [14,23,26,27]. Nevertheless, a recent ERS technical standard suggests that a change of at least -40% in resistance at 5 Hz (R5), +50% in reactance at 5 Hz (X5) and -80% in area of reactance (AX) is required to consider as positive the response in either children or adults [14, 15]. The objective of the present study was to identify the optimal thresholds to define a positive BDR test with IOS in preschoolers with suspected asthma.