Relationship between ventilation heterogeneity and exercise intolerance in adults with sickle cell anemia

Sickle cell anemia (SCA) causes dysfunction of multiple organs, with pulmonary involvement as a major cause of mortality. Recently, there has been growing interest in the nitrogen single-breath washout (N(2)SBW) test, which is able to detect ventilation heterogeneity and small airway disease when the results of other pulmonary function tests (PFTs) are still normal. Thus, the objectives of the present study were to assess the heterogeneity in the ventilation distribution in adults with SCA and to determine the association between the ventilation distribution and the clinical, cardiovascular, and radiological findings. This cross-sectional study included 38 adults with SCA who underwent PFTs, echocardiography, computed tomography (CT), and 6-min walk test. To evaluate the ventilation heterogeneity, the patients were categorized according to the phase III slope of the N(2)SBW (SIII(N2)). Compared with adults with lower SIII(N2) values, adults with higher SIII(N2) values showed lower hemoglobin levels (P=0.048), a history of acute chest syndrome (P=0.001), an elevated tricuspid regurgitation velocity (P=0.039), predominance of a reticular pattern in the CT (P=0.002), a shorter 6-min walking distance (6MWD) (P=0.002), and lower peripheral oxygen saturation (SpO(2)) after exercise (P=0.03). SIII(N2) values correlated significantly with hemoglobin (r(s)=-0.344; P=0.034), forced vital capacity (r(s)=-0.671; P<0.0001), diffusing capacity for carbon monoxide (r(s)=-0.376; P=0.019), 6MWD (r(s)=-0.554; P=0.0003), and SpO(2) after exercise (P=0.040). Heterogeneity in the ventilation distribution is one of the most common pulmonary dysfunctions in adults with SCA. Moreover, relationships exist between ventilation heterogeneity, worsening of pulmonary structural damage, and reduced tolerance for exercise.