Pulmonary involvement in Gaucher disease patients receiving enzyme replacement therapy: a cross-sectional analysis of radiological and functional lung abnormalities

Pulmonary involvement in Gaucher disease (GD) is underrecognized and may range from asymptomatic radiological abnormalities to respiratory impairment. This study assessed pulmonary involvement and its associations with disease phenotype, genotype, and pulmonary function in patients receiving long-term enzyme replacement therapy (ERT). In this single-center cross-sectional study, 52 genetically confirmed patients with GD receiving ERT underwent clinical assessment and high-resolution computed tomography (HRCT). Spirometry was performed in 34 cooperative patients aged ≥ 6 years. Clinical characteristics, genotype, baseline glucosylsphingosine (lyso-GL1), and disease phenotype were analyzed in relation to pulmonary findings. Respiratory symptoms were present in 19/52 (36.5%) patients. HRCT demonstrated interstitial abnormalities suggestive of interstitial lung disease (ILD) in 24/52 (46.2%), predominantly ground-glass opacities and interstitial thickening. These abnormalities were more frequent in type 3 than type 1 GD (P = 0.001). Homozygous L483P was associated with HRCT abnormalities suggestive of ILD in univariable analysis (P = 0.013). Among 34 patients undergoing spirometry, 11 (32.4%) had abnormal results, including obstructive (8.8%), restrictive (11.8%), and mixed (11.8%) patterns. Abnormal spirometry was associated with HRCT abnormalities (P < 0.001), while three patients had radiological abnormalities despite preserved spirometry. On multivariable analysis, higher baseline lyso-GL1, type 3 phenotype, and kyphoscoliosis were independently associated with HRCT abnormalities suggestive of ILD. CONCLUSION: Pulmonary abnormalities remained common despite long-term ERT, particularly in type 3 GD. HRCT detected interstitial abnormalities in some patients with preserved spirometry, suggesting that structural pulmonary involvement may precede functional impairment. Individualized respiratory surveillance should be considered, particularly in patients with type 3 GD. WHAT IS KNOWN: • Pulmonary involvement in Gaucher disease ranges from subclinical radiological abnormalities to respiratory impairment and is more frequent in type 3 disease. Its relationship with genotype and lung function remains incompletely defined. WHAT IS NEW: • Pulmonary abnormalities were frequent despite long-term enzyme replacement therapy, particularly in type 3 disease. HRCT detected interstitial abnormalities in patients with normal spirometry, while type 3 phenotype, higher baseline lyso-GL1, and kyphoscoliosis independently predicted pulmonary involvement.