Exercise-Induced Oxygen Desaturation and Outcomes After Nintedanib Therapy for Fibrosing Interstitial Lung Disease in Patients Without Dyspnea

Background: The degree of exercise-induced oxygen desaturation and outcomes following antifibrotic drug therapy in asymptomatic patients with fibrosing interstitial lung disease (FILD) remain unclear. Methods: We compared clinical data, incidence of annual FILD progression, overall survival, and tolerability after initiating nintedanib between 58 patients with dyspnea and 18 patients without. Annual FILD progression was defined as >10% decrease in forced vital capacity (FVC), >15% decrease in diffusing capacity of the lungs for carbon monoxide (D_LCO), developing acute exacerbations, or FILD-related death within 1 year of starting nintedanib. Outcomes between the two groups were adjusted for covariates, including age, gender, FVC, D_LCO, and diagnosis of idiopathic pulmonary fibrosis, all known prognostic factors for FILD. Results: In 6-min walk test, incidence of decrease to <90% of SpO₂ was significantly lower in non-dyspnea group than in dyspnea group (24% vs. 55%, p = 0.028), but incidence of >4% decreases showed no significant difference (71% vs. 89%, p = 0.11) The incidence of annual progression was significantly lower in non-dyspnea than in dyspnea group (17% vs. 53%, adjusted p = 0.026). The relative change in D_LCO was significantly slower in non-dyspnea group (adjusted p = 0.036), but FVC was not (adjusted p = 0.067). Overall survival was longer in non-dyspnea group (adjusted p = 0.0089). The discontinuation rate and therapeutic period of nintedanib were not significantly different between the groups. Conclusions: Asymptomatic patients with FILD have severe exercise-induced oxygen desaturation and better outcomes after nintedanib therapy than symptomatic patients. Antifibrotic drug therapy should not be avoided solely because of a lack of symptoms.