Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study

Abstract

Background: Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function.

Methods: This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM.

Results: Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM.

Conclusion: Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

FIGURE 1

FEV₁ annual rates of variation in the studied LAM population during the follow-up period. Data are presented as mean±se. a) FEV₁ annual rate of variation in 82 patients with LAM: −51.7±4.7 mL ·year⁻¹ (95% CI −61.1– −42.3). b) FEV₁ annual rates of variation in 63 patients with S-LAM versus 19 patients with TSC-LAM: −55.8±5.08 mL·year⁻¹ (95% CI −65.3– −45.7) versus −31.7±10.6 mL·year⁻¹ (CI 95% −52.9– –10.5). FEV₁: forced expiratory volume in 1 s; LAM: lymphangioleiomyomatosis; S-LAM: sporadic lymphangioleiomyomatosis; TSC-LAM: lymphangioleiomyomatosis associated with tuberous sclerosis complex.

FIGURE 2

High-resolution computed tomography (CT) of the chest images of patients with LAM show multiple and regular thin-walled pulmonary cysts. Cysts are depicted in blue and represent areas with voxels with an attenuation of −950 HU or lower. a) Axial and b) coronal CT scans demonstrate few scattered cysts occupying 0.20% of the total lung volume. c) Axial and d) coronal CT scans show diffuse pulmonary cysts occupying 9.41% of the total lung volume.

FIGURE 3

a) Axial thoracic computed tomography (CT) image shows ground-glass opacities associated with diffuse lung cysts (green arrows); b) axial thoracic CT images demonstrates lymphangioleiomyoma (green arrow); c) abdominal CT image shows left renal angiomyolipoma (green arrow) in a patient with previous right nephrectomy; d) axial thoracic CT scan demonstrates noncalcified nodules (green arrows) suggestive of multifocal micronodular pneumocyte hyperplasia associated with diffuse lung cysts.