Lipid accumulation and interstitial lung disease associated with amikacin liposomal inhalation suspension in patients with Mycobacterium avium complex lung disease: a single-center retrospective cohort study

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 interstitial lung disease (ILD), and underlying pathological mechanisms are unclear. This study aimed to determine the pathophysiological insights of ALIS-associated ILD (A-ILD). 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. Of the 25 patients, 8 developed A-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 A-ILD. In patients with A-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 increased modestly from baseline to the time of A-ILD diagnosis (407 ± 231 vs. 434 ± 250 U/mL), whereas eosinophil count, C-reactive protein, and lactate dehydrogenase levels showed no significant changes. Seven of eight patients with A-ILD exhibited clinical improvement following discontinuation or dose reduction of ALIS; one patient required corticosteroid therapy. Of these eight patients, five continued inhalation therapy on an every-other-day dosing schedule. The sputum culture conversion rate was maintained even among patients with A-ILD (63% vs. 47%; P = 0.673). Lipid deposition in the lungs was observed regardless of the A-ILD status, and no pathognomonic findings specific to A-ILD were identified. A-ILD may occur more often in patients with renal function decline and/or poorer baseline pulmonary function; therefore, closer clinical monitoring for A-ILD may be warranted in this subgroup.