Measuring lung inhomogeneity in asthma using a novel non-invasive technique

Introduction: In asthma, there is significant discordance between airflow obstruction on spirometry and disease control e.g. symptoms, exacerbations or treatment response. Gas exchange abnormalities are likely present in asthmatic lungs, even in the absence of spirometric airflow obstruction. We explored whether quantifying lung inhomogeneity (LI) in asthmatic patients using a novel non-invasive technique provides more sensitive physiological markers of disease activity and lung damage. Methods: The technique involves a nitrogen washout protocol (10 min air-breathing, 5 min 100% oxygen-breathing) using a novel device which precisely measures respired gases with laser absorption spectroscopy. The gas-exchange data are fitted to a novel mathematical lung model to obtain LI distribution parameters relative to lung volume for: lung compliance (σCL:VA), vascular conductance (σCd:VA), deadspace (VDtot, σVD:VA) and parameters for ventilation-perfusion relationships (logSDV, logSDQ). Fourteen patients with asthma were studied; four were also studied following salbutamol inhalation. Results: Patients’ age was 52±17 yrs and %FEV1 predicted was 80±21% (mean±SD). Only 8 patients had obstructive spirometry. Compared to 14 healthy volunteers (age 46±24 yrs), asthmatics had significantly reduced total alveolar volume (VAtot) and increased σCL:VA, σCd:VA, logSDV and logSDQ (p Conclusions: We provide evidence for significant lung inhomogeneity in asthma patients, even those with normal spirometry. We show that LI indices may provide more sensitive non-invasive physiological markers of disease change.