Volatile organic compounds in exhaled breath for the detection of interstitial lung disease (VISION)

1.1 Interstitial lung disease
Interstitial lung disease (ILD) refers to a collective of respiratory diseases
characterized by inflammation and fibrosis (scarring) of the pulmonary
parenchyma. Among the known causes are systemic diseases, such as systemic
sclerosis (SSc). Likewise, post COVID-19 may cause post-infectious damage to
the pulmonary parenchyma leading to fibrosis. Patients with post-COVID-19 are
by definition free of SARS-CoV2, the virus causing COVID-19. Fibrosis is an
irreversible process and early detection of (SSc-)ILD is of pivotal importance.
The golden standard for diagnosis is a chest high-resolution computed
tomography (HRCT). However, this technique is considerably invasive as it
requires a relatively high dose of radiation exposure in a particularly
delicate area. [4, 5] Applying eNose technology during regular spirometry to
obtain breath profiles may be a potent tool for non-invasive ILD detection.

1.2 Breath profiles from exhaled human breath
Exhaled breath contains volatile organic compounds (VOCs) that originate from
both systemic and local metabolic processes, and which can be associated with
normal physiology or pathophysiological inflammation or oxidative activity. In
eNose technology, cross-reactive sensor arrays interact with the VOCs,
resulting in a firing pattern. Probabilistic pattern recognition is applied to
capture the full mixture of VOCs in exhaled air, corrected for ambient air,
without identification of the individual components. [6-9] It has already been
shown that eNose technology can be applied to distinguish lung cancer,
inflammatory diseases and infectious diseases with accuracies comparable or
even superior to traditional diagnostic tests [6, 11-15]. When clinically
validated and accepted in daily practice, molecular profiling of exhaled air
may provide a non-invasive, rapid point-of-care tool for the diagnosis and
stratification of ILD.

The exhaled breath is real-time measured (< 1 minute) [10] by the eNose, and
immediately transmitted to the online server BreathBase, where data is
automatically may be analyzed and may online be shared between clinicians at
multiple sites [16].

We hypothesize that exhaled breath analysis by eNose: is able to discriminate
between patients with ILD, at risk for ILD (including post COVID-19 patients)
and without ILD.

This will be a prospective single-center case-control study in Leiden
University Medical Center (LUMC). Patients who visit the outpatient clinic at
the Department of Pulmonology are eligible for the study. Demographic data,
medical history and routine clinical parameters of the individuals will be
collected at baseline after obtaining informed consents. eNose measurements
will be performed at baseline and at routine standard of care checkups.

Burden: extra measuring time of 1 minute, 10 minutes of data acquisition
Risk: none.