Deterioration of lung diffusion capacity during childhood in
sickle cell disease
Word count: 1500
To 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).3,4
Overall, 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