Potential association of bronchoalveolar lavage lipid-laden macrophages with disease severity and corticosteroid response in interstitial lung disease: a pilot study.

Background: Lipid-laden macrophages (LLMs) have been shown to be associated with lung inflammation and fibrosis. However, the clinical significance of LLM in interstitial lung disease (ILD) remains unclear. We conducted a retrospective study with the aim of evaluating whether the LLM index in bronchoalveolar lavage fluid (BALF) is a reliable biomarker reflecting disease severity and responsiveness to steroid treatment in patients with ILD. Methods: Patients who underwent bronchoscopy with Oil Red O staining for the evaluation of ILD between 2022 and 2023 were consecutively recruited. ILD was diagnosed based on chest computed tomography findings and clinical evaluation, in accordance with the official guidelines. LLM indices were calculated based on the staining intensity of macrophages in BALF. Disease severity was evaluated cross-sectionally based on baseline pulmonary function tests, and its correlation with the LLM index was assessed using Spearman's correlation analysis. Furthermore, in patients with ILD who received steroid treatment, the association between the LLM index and therapeutic response was retrospectively evaluated. Results: Among 19 cases, the median age was 69 years, and 12 patients were male. Eleven cases had a history of smoking. ILD subtypes included hypersensitivity pneumonitis (n=5), collagen vascular disease-related interstitial pneumonia (n=4), interstitial pneumonia with autoimmune features (n=2), idiopathic pulmonary fibrosis (n=2), cryptogenic organizing pneumonia (n=2), nonspecific interstitial pneumonia (n=1), desquamative interstitial pneumonia (n=1), respiratory bronchiolitis-associated ILD (n=1), and drug-induced pneumonia (n=1). The LLM index was negatively correlated with the percentage of predicted forced vital capacity (ρ=-0.5638, P=0.02) and positively correlated with the neutrophil fraction in BALF (ρ=0.4938, P=0.03). Furthermore, among the 10 cases in which corticosteroids were administered after bronchoscopy, the LLM index was negatively correlated with the reduction in serum KL-6 level from baseline to 3 months after treatment (ρ=-0.7983, P<0.01). Conclusions: Although limited by the small sample size, heterogeneous populations, and the pilot nature of this study, our findings suggest that the LLM index in BALF may be associated with disease severity and short-term corticosteroid response in patients with ILD. These findings should be validated in prospective studies with larger sample sizes.