Deteriorating fractional exhaled nitric oxide preceding pneumonitis during immune checkpoint inhibitor therapy: a...

Immune checkpoint inhibitors (ICIs) such as nivolumab have transformed the management of metastatic cutaneous malignant melanoma but are associated with immune-related adverse events, including pulmonary toxicity. Standard monitoring of ICI therapy commonly includes computed tomography (CT) scans, blood tests, and clinical assessment. We report a 78-year-old man with metastatic malignant melanoma treated with nivolumab whose fractional exhaled nitric oxide (Fe_NO) was monitored longitudinally. Baseline Fe_NO had been stable at 40-50 ppb for a decade. After initiation of nivolumab, Fe_NO rose progressively, exceeding 100 ppb after seven cycles and surpassing 250 ppb after 13 cycles, preceding radiological and routine laboratory abnormalities. Fe_NO transiently decreased with inhaled corticosteroid therapy. A CT scan after 19 cycles showed pulmonary opacities and small amount of bilateral pleural effusions consistent with ICI-related pneumonitis. Oral corticosteroids promptly normalised Fe_NO and blood inflammatory markers, and the radiological abnormalities resolved. A milder recurrence occurred seven months later and again responded to systemic corticosteroids. In this patient, Fe_NO elevation preceded conventional indicators of pulmonary toxicity during ICI therapy. These observations support further evaluation of Fe_NO as a potential early biomarker for ICI-related pulmonary toxicity.