Discussion
This study demonstrates that most patients with normal pulmonary
function, measured by FEV1, already have significant
lung disease according to physiological (measured by LCI), structural
(HRCT changes) and clinical (chronic PA and PEx) parameters.
Furthermore, having high LCI and/or high CT scores was associated with
chronic PA infection, increased number of major PEx and more days of IV
antibiotic trreatment, all indicators of CF disease activity and
predictors of subsequent FEV1 decline.
It was shown in infants, diagnosed through newborn screening, that early
pulmonary abnormalities can be identified already in the first years of
life18. Furthermore, it has been shown previously that
high LCI levels can be found in asymptomatic infants or small
children19-23. In this study, different from most of
the published studies, the majority of patients were teenagers and
adults, and as it is known, in older patients FEV1 is
considered to best represent disease severity5.
FEV1 in the normal range may be interpreted as ”normal
lungs”, which may lead to an erroneous misinterpretation of the severity
of the disease, and can result in fewer treatments offered by the CF
team, or decreased adherence to treatments by the patients. However, as
shown in the current study, FEV1 in the normal range, is
not sensitive enough to identify early and even significant lung disease
and therefore, it is important to follow specially patients with normal
or slightly decreased FEV1 regularly using other
clinical parameters. Frequent monitoring of lung disease by LCI and
chest CT, repeated sputum cultures with immediate eradication of newly
acquired bacterial infections, and early treatment of PEx may prevent or
at least postpone irreversible lung damage and disease progression.
Frequent monitoring of CF patients using chest CT scans does carry a
potential risk due to radiation exposure and is therefore not always
performed routinely. The new imaging technology with short duration of
radiation exposure and the low radiation CF protocols are associated
with minimal radiation. Furthermore, studies demonstrated that acute
structural changes can be reversible when treated
immediately24-30. The very strong correlation between
LCI and Brody Score suggests that LCI can be used more frequently and as
long as LCI levels remain normal, routine chest CT scans can be
postponed to the time when levels of LCI become abnormal or deteriorate.
It has been shown that in young children, inhalations with hypertonic
saline24 and treatment of pulmonary
exacerbations25 can improve LCI. Furthermore, CFTR
modulator therapy was also shown to improve LCI
levels26, suggesting the interventions at this stage
of lung disease can reverse abnormalities.
An important result of this study is the correlation between the
clinical parameters of CF severity such as PA infection, PEx and days of
IV antibiotic treatment with abnormal LCI and TBS values. Therefore, it
is essential to early identify and treat all changes with the aim to
prevent or reverse disease progression.
In conclusion, the importance of this study lays in the demonstration
that regardless of their age, most CF patients with normal
FEV1 already have evidence of lung disease, as detected
by LCI and chest CT scan, and is associated with increased PEx and more
days of IV treatment. Additional studies are necessary to determine if
early and aggressive treatments will preserve or reverse changes
detected by LCI and CT scans and if early treatment with the current and
future CFTR modulators will avoid or postpone early lung damage.