International validation of electronic nose technology as diagnostic tool for fibrotic interstitial lung diseases

Publication: Formsma BJ, van der Sar IG, Yazbeck L, Kreuter M, Cottin V, Polke M, Corte TJ, Tran M, Molyneaux PL, Moor CC, Wijsenbeek MS. International validation of electronic nose technology as diagnostic tool for fibrotic interstitial lung diseases. American Journal of Respiratory and Critical Care Medicine, 2026, in press

Aim: To externally validate eNose technology to differentiate various ILDs in an international multicenter cohort.

Highlights
• This study is the first large multicenter cohort study externally validating eNose technology as non-invasive diagnostic tool for fibrotic intersitital
lung diseases. eNose could distinguish individual ILDs with a high accuracy.

Introduction

Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of rare lung diseases. Symptoms of ILD are non-specific, and diagnosis requires multiple investigations including invasive procedures. Therefore, diagnostic delay is common. Previous single-center studies showed that profiling of exhaled volatile organic compounds using non-invasive electronic nose (eNose) sensor technology has potential as diagnostic tool for ILD. We aimed to validate eNose technology to differentiate various ILDs in an international multicenter cohort.

Methods

We included patients with an ILD diagnosis established in a multidisciplinary team (MDT) discussion and pulmonary fibrosis on HRCT scan in five international ILD expert centers. An eNose (SpiroNose®) was used for exhaled breath analysis. We compared eNose breath profiles of different ILD subtypes versus all other ILDs as a group, and across six different ILD subtypes. Breath profiles were analyzed with partial least squares discriminant and receiver operating characteristic analyses. Models were trained on data from a selection of centers and externally validated in other centers.  

Predicted probability of lung cancer

Results

Breath profiles of 587 patients were analyzed. Comparing breath profiles of ILD subtypes versus all other ILDs resulted in area under the curve values (AUCs) ranging from 0.88-0.92 in the training set and 0.75-0.95 in the validation set. ILD subtypes could be discriminated with AUCs ranging from 0.95-0.98 in the training set and 0.83-0.93 in the validation set.

Discussion

This international study demonstrates that eNose technology accurately differentiates breath profiles from patients with various ILDs. eNose technology holds potential as easy point-of-care tool for diagnosis of fILDs.