Discussion
Our study conducted in schooler asthmatic children found significantly
lower lung function at baseline in patients compared to healthy
controls, either “usual” spirometric parameters or shape indexes, and
higher BD reversibility. Shape indexes were found to be slightly more
sensitive in identifying asthmatic children at baseline than zFEV1 with
the same specificity while their BD reversibility showed high
sensitivity and low specificity compared to Δ%FEV1. Conversely,
specificity was higher for Δ%FEV1.
Qualitative and quantitative assessment of the descending limb of the
FVL and its variability with airway obstruction have already been
addressed in past studies, by visual examination or objective measures13,14,23,24. β-angle, constructed to transcribe the
curvature of the FVL into a single numerical value 16,
is the angle between the first and second half of the FVL at the point
of maximum flow point at mid pulmonary volume. β-angle and its
simplified estimate, FEF50/PEF, in absolute values or z-scores, were
significantly lower at baseline in our school-aged asthmatic children
compared to healthy subjects, in keeping with previous reports
demonstrating more concave FVL configuration measured by smaller β-angle
in asthmatic preschoolers 17 or schoolers18,19,25.
When testing the diagnostic value to separate asthmatics from controls
in our population, AUC’s were similar for zβ-angle or zFEF50/PEF and
“usual” spirometric parameters, with relatively lower AUC for zFEV1
(figure 2 and table 3 ). zβ-angle and zFEF50/PEF showed
slightly higher sensitivity than zFEV1 suggesting that the presence of
an early airway obstruction is rather detected by indexes describing FVL
curvature than by zFEV1. The specificity was the same for zβ-angle and
zFEF50/PEF or zFEV1 (table 3 ). A recent report in schooler
asthmatics found large AUC and sensitivity for β-angle and, in contrast
to our study, FEV1 sensitivity was also high while β-angle and FEV1’s
specificities were very low 18. The different patterns
of sensitivity – specificity at baseline indicate that a significant
proportion of false diagnosis of asthma would result if solely shape
indexes would be taken in consideration to identify airway obstruction.
FEV1, the gold standard parameter for diagnosing an airway obstruction,
is obtained in the first second of the forced expiration, situated on
the effort-dependent part of FVL. Thus, FEV1 would theoretically be more
affected by subject’s effort than distal flows (i.e. FEF50
reported here) located on the second part of forced expiration,
considered effort-independent once airway dynamic compression has
occurred. Nevertheless, FVL shape is highly conditioned by child’s
cooperation and comprehension to perform an optimal, sustained
expiratory effort, to obtain a reproducible PEF and a complete
expiration to attain the residual volume. This maneuver is easily
acquired with appropriate guidance and encouragement from experienced
technicians in a pediatric lung function testing lab, but caution must
be taken when interpreting a pediatric FVL.
To improve the diagnostic ability of spirometric parameters to detect
asthma in children, we investigated whether the combination of shape
indexes with “usual” spirometric parameters will improve their
discriminating power. AUC’s improved and the best sensitivity was
obtained when shape indexes were associated with zFEV1 and the best
specificity when they were associated with zFEV1/FVC (table 3 ),
in agreement with recent reports demonstrating that the association of
quantitative and qualitative parameters may enhance the diagnosis
accuracy 18,25.
Our study confirms and extends these observations by testing the BD
reversibility of shape indexes and “usual” spirometric parameters and
shows larger BD responses for shape indexes in asthmatics than controls,
with no difference for Δ%FEV1 (table 1 ). Furthermore, Δ%β-angle
and Δ%FEF50/PEF were significantly higher in symptomatic than in
asymptomatic asthmatic children (table 2 ), but not BD response of
the other spirometric parameters. Δ%β-angle exhibited high sensitivity
and low specificity contrary to Δ%FEV1 showing low sensitivity and high
specificity (table 3 ). A significant decrease in the upward
concavity of the FVL after short-acting BD inhalation have previously
shown for other shape indexes in asthmatic children aged 5 to 12y15 and adults 24 or after 8 weeks of
inhaled corticosteroids in young adults 14.
The effect of short acting BD in asthma is dependent on complex
interactions between airway caliber, ventilation and lung perfusion
distribution, ventilation-to-perfusion ratio, and cardiac output26. Short acting BD may have contradictory effects
related to its action on distribution of ventilation – perfusion
inequalities that may improve, worsen or not change27. BD might act on peripheral airway obstruction with
improvement of gas mixing and, consequently, of FVL shape. Contrarily,
BD may also worsen gas mixing as partially opens up previously full
closed airways, that will become inhomogenously ventilated regions with
slow emptying during expiration 26, resulting in no
change in FVL curvature.
The aim of our study was to investigate the BD reversibility of shape
indexes in the context of a lung function testing lab, procedure
routinely used in the diagnosis and follow-up of asthmatic children. Our
studied children had less severe asthma with normal baseline lung
function in the majority (zFEV1/FVC <-1.64 in less than a
fifth) and anti-asthmatic treatment in more than half that might partly
underestimate the BD change. Nevertheless, our data suggest a positive
effect of BD inhalation on FVL shape, especially in symptomatic
asthmatics, with high sensitivity for Δ%β-angle and high specificity
for Δ%FEV1 to separate asthmatics from healthy children. Accordingly,
considering exclusively Δ%FEV1 as optimal diagnostic tool for
reversibility assessment as stated in a number of international
guidelines 3,28,29, would result in a large number of
false negatives.
In conclusion, our study confirms previous reports that the shape of FVL
should be taken in consideration when interpreting a forced spirometry
in children. Shape indexes and FEV1 at baseline and their BD
reversibility had about the same diagnostic value in detecting airway
obstruction but with a different pattern of sensitivity – specificity,
being complementary. Quantitative and qualitative assessment of FVL may
improve the ability to detect airway obstruction, FEV1 reflecting more
proximal while shape indexes peripheral, distal bronchial obstruction.
Future perspectives will imply to assess more frequently in practice the
association of different lung function parameters by establishing a
spirometry score based on shape indexes and “usual” spirometric
values, easy to compute and to integrate into spirometers’ software, in
order to improve asthma diagnostic or to assess the long-term benefit of
anti-asthmatic therapies in pediatric population.