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.