Predictive markers of exertional desaturation in health screening-detected interstitial lung abnormalities: insights from a multicenter observational study (Kumamoto ILA study in Japan: KILA-J)

Interstitial lung abnormalities (ILAs) are often incidentally detected during health screening programs; however, the impact of exertional desaturation and its predictive factors remain unclear. This study aimed to assess the usefulness of the 6-minute walk test (6MWT) and identify the frequency of desaturation, along with its predictors, in patients with ILA. In this multicenter prospective observational study, we enrolled patients with ILA identified through health screening. Participants underwent 6MWT, spirometry, chest computed tomography (CT), and other assessments. Desaturation during 6MWT was defined using two criteria: i) minimum oxygen saturation (SpO 2 ) < 90% and ii) ΔSpO 2 (the difference between resting and minimum SpO 2 ) ≥ 4%. Comparative and multivariable analyses were conducted to identify predictive factors for desaturation. Among 365 enrolled ILA cases, desaturation occurred in 45 (12.3%) using the minimum SpO 2 < 90% criterion and 145 (39.7%) using ΔSpO 2 ≥ 4%. Both criteria revealed significant intergroup differences in the modified Medical Research Council (mMRC) scores, forced vital capacity, diffusing capacity of the lungs for carbon monoxide (DLco), serum biomarkers, peripheral blood monocyte counts, CT-based ILA extent, and CT findings (prevalence of traction bronchiectasis, honeycombing, and fibrotic ILA pattern). Multivariable analysis identified mMRC score (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.122–4.429; p = 0.022), serum lactate dehydrogenase level (OR, 1.007; 95% CI, 1.001–1.012; p = 0.014), and monocyte count (OR, 1.004; 95% CI, 1.001–1.006; p = 0.005) as factors independently associated with a minimum SpO 2 < 90%, while PaO 2 (OR, 0.977; 95% CI, 0.955–0.999; p = 0.043), serum Krebs von den Lungen-6 (KL-6) level (OR, 1.001; 95% CI, 1.001–1.002; p = 0.006) and CT-based ILA extent (OR, 1.025; 95% CI, 1.001–1.050; p = 0.041) were independently associated with a ΔSpO 2 ≥ 4%. Notably, %DLco was independently associated with both criteria (minimum SpO 2 < 90%: OR, 0.946; 95% CI, 0.925–0.968; p < 0.001; ΔSpO 2 ≥ 4%: OR, 0.973; 95% CI 0.961–0.985; p < 0.001), with cutoff values of 74.7% and 83.3%, respectively. Stratifying ILA into three grades based on the degree of desaturation (Grade 1: minimum SpO 2 ≥ 90% with ΔSpO 2 < 4%; Grade 2: minimum SpO 2 ≥ 90% with ΔSpO 2 ≥ 4%; Grade 3: minimum SpO 2 < 90%) showed significant differences in clinical parameters. Exertional desaturation is prevalent in patients with ILA. Reduced DLco was consistently associated with both definitions of desaturation. Our results underscore the importance of incorporating a 6MWT-based desaturation assessment into the initial ILA evaluation protocol. UMIN000045149/1 December 2021.