Discussion
According to our results, LCI values appear to significantly vary during
the course of a pulmonary exacerbation in people with CF as an important
tool to monitor response to antibiotic therapy. In particular, we
demonstrate a significant correlation between the gold standard CF lung
function parameter FEV1% and a small airways inhomogeneity index such
as LCI 2.5.
Hatziagorou et al. investigated the use of LCI to assess intravenous
antibiotic treatment response in pulmonary exacerbation with a
significant improvement in most lung function parameters: LCI
(p=0.0001), FEV1% (p=0.05), FEV1 z-score (p=0.033) and FEF25-75
(p=0.046). LCI decreased by a mean of 1.77 lung turnovers with an
average decrease in LCI of 26% (p=0.001) and average increase in FEV1%
of 10.36% (p=0.05)29. These data are more encouraging
than ours but the caseload is much smaller (13 patients).
Our data are more in line with Robinson et al. that reported a LCI2.5
mean decrement of 0.48 lung turnovers with a 3.8% change and with Eef
Vanderhelst that had described a significant decrease of 4.5% among CF
adult patients 23.
We might hypothesize that in the pre-school population there is a
greater variation in LCI post antibiotic treatment, with an average
treatment effect of −15.5% (95% CI −25.4 to −5.6). Interestingly, in
that population no distinction was made between PE requiring oral or IV
therapy 30. In fact, also in our population we notice
a better increase of LCI 2.5 in < 18 years patients, perhaps
mirroring a less pronounced structural and functional lung damage.
As reported in literature, under clinical stability conditions, the
inter-individual variability of LCI was of 16%. Our data suggest the
hypothesis that this variability during PE is reduced for the presence
of inflammation, mucus and increased broncostriction31.
Sacin and Scond are two values that are becoming more studied in
literature, especially Sacin that reflects alveolar functionality,
starting point of lung damage in CF disease. In contrast to Vanderhelst,
our data demonstrate that LCI 2.5 correlates with both Sacin and Scond
emphasizing how much in CF-PE both proximal and distal airways are
affected 23.
In our setting, LCI2.5 and FEV1 are concordant in showing a
statistically significant amelioration of lung function after an IV
antibiotic therapy. Despite its limits, we suggest that LCI may be
adopted as an additional biomarker to assess lung function response to
antibiotic therapy, during a pulmonary exacerbation.
According our experience, we focuse attention on 4 patients who showed a
greater drop in LCI 2.5 (> 15%) and analyzing their
clinical conditions we try to explain this anomalous trend. One of these
patients had Allergic Bronchopulmonary Aspergillosis, spirometric
indexes improved but LCI value did not respond; one pediatric patient
did not respond probably for her severe anatomic compromission, with TC
confirming severe atelectasis in upper lobe of the right lung. Two adult
women patients from starting to the end of hospitalization preserved
more or less the same spirometric values, including FEF 25-75% for
small airways, despite primary value of LCI 2.5 and secondary
inhomogeneity parameters had a severe worsening.
A major limitation to our study is the lack of a baseline LCI 2.5
assessment due to SARS-CoV-2 pandemic and the routine availability of
Exhalyzer –D in our center only after March, 2020. Among limitations
were the lack of knowledge about aerosol therapy treatment (Dornase
alfa, hypertonic solution, bronchodilators) performed during the
hospitalization for IV antibiotic treatment, and the typology of chest
physiotherapy administered by respiratory therapists.
Sovrainfections could represent another possible bias factor that
prevented improvements of LCI 2.5 values. Even it was possible that
patients had allergies to intravenous antibiotics and this clinical
aspect could influence value at the end of IV antibiotic treatment.
The variability of LCI response for each patient could be explained by
the different clusters of bronchopulmonary flare-ups in CF adult
patients, as recently reported in the literature, but further studies
are needed to prove this hypothesis 32.
In conclusion, our study shows that LCI is a valid tool to monitor
antibiotic responses in PE in CF in the same way as the FEV1%, with the
advantages of being easy to perform especially in pediatric population.
We can assume that LCI will be used in conjunction with the clinic, to
be evaluated halfway through the antibiotic cycle to make any treatment
implementations or total changes.
Future long-term studies are needed to confirm these findings.