Discussion
Our original finding is to show that DLCO indices deteriorate but from
elevated values to normal values during childhood in SCD. The elevated
values of DLCO in childhood are related to a frank increase in KCO due
to the increase in Vc. This increase in Vc is at least partly related to
the increase in cardiac output due to anemia, thus related to
vasodilation that is further limited on exercise. The decrease in KCO
that is observed with age is probably related to a decrease in
vasodilation or even related to pulmonary vascular bed remodeling.
The increase in Vc and KCO change correlated since the more the KCO was
elevated at baseline (visit 1) and the more was its subsequent decrease.
Thus, the deterioration that was evidenced is related to the loss of an
adaptive process. Persistent intravascular hemolysis over decades leads
to chronic vasculopathy, with ∼10% of patients developing pulmonary
hypertension. Thus, follow-up of DLCO may help to detect at risk
patients, which warrants further studies. Moreover, DLCO has been
correlated with both exertional dyspnea and performance (6 minute walked
distance) in adult SCD further emphasizing its
usefulness.6
A frank deterioration of DLCOcorrected and
KCOcorrected % predicted was observed only 2-3 years
apart. Nevertheless, at a median fifteen years of age, the KCO predicted
values were still into the normal range (z-scores -1.645 to +1.645) for
almost all participants. This result is consistent with the finding of
only slightly reduced KCO values (~80% predicted) of
young adult patients (~30 years) with
SCD.6 The more severe deterioration of
KCOcorrected in men could be consistent with the fact
that NO bioavailability and NO responsiveness are greater in women than
in men with SCD, allowing the preservation of capillary vascular bed in
women.
Elevated level of serum LDH is a marker of nonspecific tissue damage and
its negative correlation with subsequent decrease in
DLCOcorrected may seem counterintuitive. Nevertheless,
those patients who had the lesser degree of DLCO decrease over time and
the higher levels of LDH were those with normal baseline DLCO, which may
traduce the lack of compensatory vasodilation already present in the
patients with more severe disease.
Our study has inherent limitations related to its design. Seventeen
(28%) participants had no follow-up PFTs; logically they were older
explaining their loss of follow-up in a pediatric center. Finally, DLCO
measurement was made with two different breath-hold durations between
visit 1 (4 seconds) and visit 2 (10 seconds). The reduced breath-hold
time of the first measurement could have lowered the baseline alveolar
volume; nevertheless, a significant decrease was subsequently observed,
as expected from the decrease in FVC, which argues against a bias.
In conclusion, our retrospective study shows that DLCO indices
significantly decrease in adolescents with SCD from elevated values to
normal values and that the decrease in KCO was proportional to the
baseline increase in capillary blood volume, while the decrease in DLCO
was inversely proportional to baseline LDH concentration.