Deterioration of lung diffusion capacity during childhood in sickle cell diseaseWord count: 1500To the Editor,The American Society of Hematology guidelines, 2019, recommended obtaining pulmonary function tests (PFTs) in patients with sickle cell disease (SCD) with various respiratory symptoms even if they are at their steady state.1 These guidelines acknowledged that the usefulness of routine PFT is unknown because of the lack of research. However, this society further suggested that if the PFTs are obtained, it should be a comprehensive study including lung volumes and lung-diffusing capacity for carbon monoxyde (DLCO), in addition to spirometry.1 A large study in adult patients (n=310) with SCD showed that pulmonary function is abnormal in 90% of adult patients with Hb-SS.2 Common abnormalities included restrictive physiology and decreased DLCO. In this study, decreased DLCO indicated more severe sickle vasculopathy characterized by impaired hepatic and renal function, and a negative linear correlation existed between DLCO and age, suggesting that in adults with Hb-SS, disruption of alveolar–capillary gas exchange progressively deteriorated with time.2 Two recent cross-sectional studies of children with SCD showed that pulmonary function, including DLCO, worsened with age and showed correlations with biological markers of inflammation (induced sputum IL‐6 levels or blood neutrophilia).3,4Overall, these studies highlight the potential interest of DLCO measurement in SCD. The DLCO is the product of KCO (carbon monoxide coefficient of transfer) and alveolar volume (VA) and these two latter indices need to be interpreted separately since the decrease in DLCO is often mitigated by a preserved KCO or even increased KCO in SCD. It has been demonstrated that when corrected for hemoglobin levels, the children with SCD compared to controls of similar age had elevated KCOcorrected. The determination of alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity for carbon monoxide (DLCO) or for nitric oxide (DLNO) has been done in SCD since the seventies, demonstrating an increase in Vc in SCD. KCO is mathematically linked to both Dm and Vc (1/KCO = VA/Dm + VA/θVc); thus, the increase in KCO is related to Vc increase, but since DLCO has been shown to worsen with age, the changes of DLCO, VA and KCO over time in children with SCD deserve to be studied.The objectives of our study were to describe the evolution of DLCO and its determinants, KCO and VA, and to further assess the initial risk factors of the decrease in DLCO in children/adolescents with SCD. To this end, we retrospectively recorded the routine follow-up PFTs of children with SCD who were included in a prospective cross-sectional study that included the measurement of both DLCO and DLNO with the calculation of Dm and Vc.5