Lipid Accumulation and Drug-Induced Interstitial Lung Disease Associated with Amikacin Liposomal Inhalation Suspension in Patients with Mycobacterium avium Complex Lung Disease: A Singlecenter Retrospective Cohort Study

Background Amikacin liposomal inhalation suspension (ALIS), an inhaled aminoglycoside, can effectively treat refractory or relapsed Mycobacterium avium complex lung disease (MAC-LD). However, ALIS is associated with drug-induced interstitial lung disease (DI-ILD), and underlying pathological mechanisms for the same are unclear. This study aimed to determine the aetiology and pathological characteristics of ALIS-associated DI-ILD and assess the impact of ALIS on pulmonary pathology. Methods This retrospective cohort study included 25 patients with MAC-LD who received ALIS treatment between September 2021 and October 2024. Clinical data, laboratory findings, high-resolution chest computed tomography results and pathological findings from transbronchial lung biopsy, surgical lung resection and bronchoalveolar lavage were evaluated. Results Of the 25 patients, 8 developed DI-ILD after a mean duration of 98.5 ± 159.8 days following ALIS initiation. Histopathological evaluation showed infiltration of enlarged foamy macrophages containing lipid deposits in patients with and without DI-ILD. In patients with DI-ILD, bronchoalveolar lavage fluid exhibited inflammatory cell infiltration; however, these findings were not diagnostic for a specific entity. Serum Krebs von den Lungen-6 levels significantly increased from baseline to DI-ILD diagnosis (407 ± 231 vs. 434 ± 250 U/mL; P  = 0.0422), whereas eosinophil count, C-reactive protein and lactate dehydrogenase levels did not change significantly. Seven of eight patients with DI-ILD exhibited clinical improvement following ALIS discontinuation or dose reduction; one patient required corticosteroid therapy. Of the 8 patients, 5 continued inhalation therapy by switching to every-other-day dosing. The sputum culture conversion rate was maintained even in patients with DI-ILD (63% vs. 47%; P  = 0.673). Conclusion Lipid deposition within the lungs was observed irrespective of DI-ILD, despite no pathognomonic findings being identified for ALIS-associated DI-ILD. Some patients continued therapy by reducing the dosing frequency while preserving therapeutic efficacy even when DI-ILD occurred.