Predictors of Diffusing Capacity in Children With Sickle Cell Disease: A Longitudinal Study

Area of Science:

• Pediatric Pulmonology
• Hematology
• Cardiopulmonary Medicine

Background:

• Gas exchange abnormalities in pediatric sickle cell disease (SCD) may indicate cardiopulmonary deterioration.
• Identifying predictors of these abnormalities is crucial for understanding disease progression and guiding management in children with SCD (C-SCD).

Purpose of the Study:

• To identify pulmonary function test (PFT) estimates and biomarkers associated with and predictive of abnormal diffusing capacity (DLCO) in C-SCD.
• To evaluate the clinical relevance of measured and estimated DLCO in relation to SCD outcomes.

Main Methods:

• Collected PFT data from 51 C-SCD patients and 22 controls.
• Utilized machine learning (XGBoost) and linear mixed-effects models to identify DLCO predictors.
• Assessed the association between DLCO (measured and estimated) and clinical outcomes like SCD crises and pulmonary hypertension.

Main Results:

• Children with SCD showed diminished hemoglobin-adjusted DLCO and PFT indices compared to controls.
• Forced Vital Capacity (FVC), neutrophils, and FEF25-75 were top DLCO predictors identified by both models.
• Higher estimated DLCO correlated with fewer SCD crises and lower TRJV, but not nocturnal desaturation.

Conclusions:

• DLCO in C-SCD is linked to PFTs reflecting restrictive lung disease, airflow obstruction, and inflammation.
• Predictive models using these indices estimate DLCO and demonstrate significant associations with disease outcomes.
• These findings underscore the clinical utility of DLCO prediction models in managing C-SCD.