Understanding complex lung function measurements in COPD: forced oscillaton, nitrogen washout, and novel functional imaging techniques

BACKGROUND: The complex physiological abnormalities in chronic obstructive pulmonary disease (COPD) cannot be adequately described by standard laboratory tests of lung function. Advanced lung function measurements provide detailed insight into the pathophysiology of COPD and may complement standard lung function tests. However, despite the availability of commercially-produced devices, these advanced lung function tests have not yet translated into clinical practice. AIM: In people with COPD, to explore the fundamental determinants of advanced lung function measurements by comparing different advanced measurement techniques to clinically-accepted or intuitive physiological measurements. METHODS: Complex lung function measurements including multiple breath nitrogen washout (MBNW), which quantifies ventilation heterogeneity (VH), respiratory system impedance by the forced oscillation technique (FOT), and the functional imaging modalities of 68-gallium “Galligas” positron emission tomography (PET) and pulmonary electrical impedance tomography (EIT) were employed. RESULTS: The novel findings were: PET Galligas distribution was strongly correlated with acinar-zone VH (Sacin) measured by MBNW, with evidence that emphysema extent may be a common determinant; time-based EIT metrics of VH are increased in COPD compared to control volunteers, and relate to FOT measurements, suggesting they reflect complex lung mechanics; the change in FOT measurements following long-acting bronchodilator are proportional to the change in gas trapping/hyperinflation in COPD, suggesting the latter phenomena are important determinants of FOT; and the predicted FOT reactance (Xrs)-lung volume relationship is disrupted in COPD, but is restored when only the “communicating” lung volume is considered, which provides empirical evidence supporting the mathematic theory of FOT. CONCLUSION: This Thesis compares complex lung function measurement techniques with well-known techniques currently in use in clinical practice. In doing so, meaning and relevance is provided to the advanced techniques so that they may be better understood by the clinical community. The Thesis provides insights into fundamental physiological processes in COPD, specifically VH and oscillatory lung mechanics, which furthers our understanding of this complex and heterogeneous disease. The findings presented in this Thesis form the basis for future work on their clinical utility in COPD