Impulse oscillometry for the early detection of bronchiolitis obliterans syndrome in bilateral lung transplant recipients
Date
2024
Authors
Crowhurst, Thomas David
Editors
Advisors
Holmes, Mark
Holmes-Liew, Chien-Li
Yeo, Aeneas
Holmes-Liew, Chien-Li
Yeo, Aeneas
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Abstract
Lung transplantation is an established therapy that offers revolutionary morbidity benefits as well as mortality advantage in well-selected patients. However, this complex therapy has the poorest long-term survival of any form of solid organ transplantation. The dominant contributor to poor survival after lung transplantation is chronic lung allograft dysfunction, which is an umbrella term referring to the two distinct phenotypes of bronchiolitis obliterans syndrome and restrictive allograft syndrome. The pathogeneses of these diseases are extraordinarily complex and involve alloimmune and non-alloimmune processes, with each phenotype probably best considered as a separate pathobiological expression of a final common pathway of lung allograft injury involving the generalised superimposition of epithelial to mesenchymal transition and resultant progressive irreversible fibrosis. Nonetheless, despite this complexity, spirometry remains fundamental to the assessment of these disorders and this produces major research and clinical problems. Our currently limited capacity for the early identification and prevention of chronic lung allograft dysfunction represents the most important detractor from the overall value of this remarkable therapy for society. Forced oscillometry technique is an established technology that involves superimposing small impulses on the respiratory system via the mouth and measuring pressure and flow responses to generate various data on airway mechanics. This method has obvious theoretical attractions for lung transplantation including its sensitivity for early obstructive lung disease and its practical characteristics including being non-invasive, inexpensive and very well tolerated. There is expanding interest in oscillometry for the assessment of lung transplant recipients but the field remains troubled by an overall paucity of data, mixed results, methodological limitations and the failure of previous studies to make definitive attempts to answer the most important question: can this technology allow the earlier detection of chronic lung allograft dysfunction? We undertook an ambitious single-centre longitudinal prospective diagnostic study to assess whether oscillometry (1) correlates with spirometry in lung transplant recipients and (2) enables earlier detection of CLAD when compared with spirometry. We focussed on developing a robust methodology with a pure ‘single disease’ consecutive cohort and a sophisticated statistical methodology. We enrolled 91 patients and collected a total of 558 analysable paired oscillometry-spirometry tests, being a greater volume than any earlier published research. We demonstrated statistically significant moderate-to-strong correlations between all relevant oscillometry parameters and spirometry; importantly, we provided detailed within-subject analyses for the first time, greatly enhancing understanding of how oscillometry may behave at the individual patient level. Our multifaceted predictive analysis was negative, with no identified capacity for oscillometry to detect chronic lung allograft dysfunction before spirometry; this is in itself a novel finding from a large and methodologically robust study. Chronic lung allograft dysfunction is the single greatest challenge in the field of lung transplantation despite decades of research. Our data highlight the value and the limitations of oscillometry in this cohort while providing important direction for future research, which we believe should focus on the identification of novel non-spirometric outcome measures and greater collaborative efforts to explore multi-modality prediction models for chronic lung allograft dysfunction.
School/Discipline
Adelaide Medical School
Dissertation Note
Thesis (M.Clin.Sc.) -- University of Adelaide, Adelaide Medical School, 2024
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