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.