Electronic Nose-Based Exhaled Volatile Organic Compound Pattern Recognition and Multivariate Signal Analysis for Discriminating Idiopathic Pulmonary Fibrosis from Autoimmune Usual Interstitial Pneumonia

Idiopathic pulmonary fibrosis (IPF) and autoimmune usual interstitial pneumonia (aUIP) share overlapping clinico-radiological features, complicating differential diagnosis. Electronic nose (eNose) technology characterizes exhaled breath profiles (“breathprints”) and may offer a non-invasive diagnostic approach in fibrotic interstitial lung diseases. To evaluate whether eNose breathprint analysis can discriminate between IPF and aUIP. In this cross-sectional study of 60 patients (34 IPF, 26 aUIP), breathprints were analyzed using principal component analysis (PCA, retaining eigenvalues > 1). Group differences were assessed via independent t-tests. Linear discriminant analysis (LDA) with leave-one-out cross-validation evaluated the discriminatory performance of PC combinations. PCA identified four principal components, with PC1 explaining 96% of the total variance. PC1 scores were significantly higher in aUIP compared to IPF (mean difference −0.53; 95% CI −1.04 to −0.02; p = 0.04); PC2-PC4 showed no significant differences (p > 0.3). LDA utilizing PC1 and PC3 achieved a cross-validated classification accuracy of 73.3% (95% CI 60.7–84.4, p < 0.05). eNose-derived breathprints showed preliminary discriminatory potential between IPF and autoimmune UIP, supporting further validation of this non-invasive adjunctive approach. Breathomics represents a promising non-invasive adjunctive tool for phenotyping fibrotic interstitial lung diseases, though larger validation studies integrating clinical and biological data are warranted.