Background
CF is the most common life-limiting autosomal recessive disease in
Caucasian population, and is a complex multisystemic disorder caused by
mutations in the gene encoding the cystic fibrosis transmembrane
conductance regulator (CFTR), an ion channel which primarily regulates
anion transport through cell surface. To date, more than 2000 mutations
have been identified 1. Functional failure of CFTR
leads to multisystemic dysfunction, involving lungs, gastrointestinal
tract, liver and pancreatic gland. Impaired mucociliary clearance and
dense secretions primarily result in chronic pulmonary inflammation and
infections, irreversible lung architecture modification, respiratory
failure and death 2.
In the last decade, LCI started to be used in CF management as an
efficacy endpoint in interventional trials thanks to its ability to
effectively assess small airways disease both in preschool and
middle-age children, when forced expiratory volume in 1 second (FEV1) is
generally within normal range and CF lung disease still mild3-5.
LCI is the most commonly reported MBW index in the pediatric literature
and it is defined as the number of functional residual capacity lung
turnovers required to reduce the alveolar concentration of a tracer-gas
to a given fraction of its starting value, historically 1/40 (2.5%). A
particular advantage of LCI in pediatric population is feasibility by
passive cooperation and minimal coordination across all the pediatric
age ranges 6.
Horsley et al. described Lung clearance index as a sensitive, repeatable
and practical measure of airways disease also in adults with cystic
fibrosis
Despite being the gold standard for the assessment of pulmonary function
in CF lung disease, FEV1 measurement through spirometry has been shown
to be less sensitive than LCI in detecting early abnormalities and
peripheral airways disease in CF 8. LCI is an early
marker of ventilation inhomogeneity, reflecting initial airways
dysfunction in CF population with normal pulmonary function tests9-10 and is being recognized as a useful surrogate
pulmonary outcome measure, especially in the new era of CFTR modulators,
where new disease trajectories will require adequate clinical markers to
characterize clinical phenotypes and monitor the efficacy of treatments11-14.
LCI is a sensitive and feasible measures index (LCI) with strong
intra-test and iter-test repeatability 15.
In CF, pulmonary exacerbations are crucial events which progressively
determine a loss of respiratory function, worsening of the quality of
life and negatively impact overall survival. According to studies, lung
function fails to return to baseline value in up to 25% of CF pulmonary
exacerbations, despite a prompt antibiotic treatment16-17. In contrast to studies in which FEV1 was used
as primary outcome, consistently showing a positive treatment effect18-21, studies addressing LCI as outcome measure
obtained heterogeneous results 22-24. LCI
significantly increases in patients with a pulmonary exacerbation, but
LCI response to therapy for pulmonary exacerbations is heterogeneous and
not completely clear in literature .
Our primary aim was to evaluate LCI index short-term variability in
pulmonary exacerbation after antibiotic intravenous therapy. We also
aimed to analyze the possible correlations between spirometry and LCI
values post therapy course to support treatment variability.