Mid-infrared quantum cascade laser absorption spectroscopy for simultaneous monitoring of fractional exhaled nitric oxide and carbon dioxide: Application in asthma diagnosis and treatment response assessment

Fractional exhaled nitric oxide (FeNO) is a critical biomarker for eosinophilic airway inflammation. This work presents a noninvasive breath analysis system based on quantum cascade laser absorption spectroscopy (QCLAS) for dynamic, concurrent monitoring of FeNO and exhaled carbon dioxide (CO 2 ). To address the spectral overlap between NO absorption and CO 2 interference at 5.26 µm, a custom Herriott-type multi-pass cell operating at sub-atmospheric pressure was employed to spectrally resolve the two targets within a single optical channel. The system achieved a detection limit of 0.2 ppb for NO, with a integration time of 11 s. Clinical validation was conducted on 20 healthy subjects and 34 physician-diagnosed asthma patients. The asthma group exhibited significantly elevated FeNO (53.4 ± 22.1 ppb vs. 18.9 ± 8.3 ppb in healthy controls, p < 0.001) and slightly reduced exhaled CO 2 (4.8%vs. 5.2%). Notably, 12 patients undergoing regular inhaled corticosteroid (ICS) therapy demonstrated a mean FeNO reduction of 47.6% (from 51.0 ± 17.0 ppb to 26.7 ± 8.5 ppb, p < 0.001), confirming the system's sensitivity to therapeutic response.