Significance: Chronic lung allograft dysfunction (CLAD) is the leading cause of death in transplant patients who survive past the first year post-transplant. Current diagnosis is based on sustained decline in lung function; there is a need for tools that can identify CLAD onset.
Aim: Endoscopic optical coherence tomography (OCT) can visualize structural changes in the small airways, which are of interest in CLAD progression. We aim to identify OCT features in the small airways of lung allografts that correlate with CLAD status.
Approach: Imaging was conducted with an endoscopic rotary pullback OCT catheter during routine bronchoscopy procedures (n = 54), collecting volumetric scans of three segmental airways per patient. Six features of interest were identified, and four blinded raters scored the dataset on the presence and intensity of each feature.
Results: Airway dilation (AD) was the only feature found to significantly (p < 0.003) correlate with CLAD diagnosis (R = 0.40 to 0.61). AD could also be fairly consistently scored between raters (κinter-rater = 0.48, κintra-rater = 0.64). There is a stronger relationship between AD and the combined obstructive and restrictive (BOS + RAS) phenotypes than the obstructive-only (BOS) phenotype for two raters (R = 0.92 , 0.94).
Conclusions: OCT examination of small AD shows potential as a diagnostic indicator for CLAD and CLAD phenotype and merits further exploration.
This study explores endobronchial optical coherence tomography (OCT) imaging of lung transplant patients with chronic lung allograft dysfunction (CLAD). Optical coherence tomography (OCT), the optical analog of ultrasonography with superior resolution (10μm) but shallow (2mm) penetration, allows for the visualization of the early structural changes in the small airways, which is of interest in CLAD progression. Imaging was conducted with a catheter-based rotary OCT probe during routine bronchoscopy procedures, resulting in three-dimension pullbacks of three subsegmental airways per patient (n=9). A scoring rubric for visualized features of interest was used to quantify characteristics of the image set: loss of alveolar visualization, emphysema-like alveolar enlargement, alveolar hyperinflation, airway dilation, excessive mucous, excessive duct-like structures, and an unidentified structure. Four raters, blinded to clinical status, scored the set. Statistical analysis including Pearson correlation coefficients (R), Fleiss’ Kappa (κ) were used on this score set to assess preliminary potential of these features. 3/9 patients met the diagnostic criteria for both obstructive (BOS) and restrictive (RAS) phenotypes of CLAD and 6/9 for solely the obstructive phenotype. The airway dilation feature was found to be significantly associated (p<0.05) with the BOS+RAS diagnosis for three raters (R=0.72-0.94), with fairly consistent rater reliability (κinterrater = 0.25, κintrarater = 0.59). No OCT features were significantly correlated with infection status. Small airway dilation, as measured through catheterized OCT imaging, shows potential for use in detection of CLAD and distinguishing between CLAD phenotypes.
Chronic Lung Allograft Dysfunction (CLAD) remains a significant cause of morbidity and mortality following lung transplantation. Bronchiolitis obliterans Syndrome (BOS) is a predominant phenotype of CLAD primarily affecting the small and subsequently the large airways leading eventually to graft failure. In addition, the allograft airways are also involved in other types of CLAD such as Restrictive Allograft Syndrome (RAS). Freedom from BOS at five years post-transplant is only approximately 50 % among lung transplant recipients.
The diagnosis of CLAD is primarily based on pulmonary function testing and radiographic findings on CT scan. Transbronchial biopsies have a low diagnostic yield due to the multifocal nature of CLAD and the frequent lack of bronchioles in the biopsy specimen. Thus, CLAD is often diagnosed after significant disease progression.
We performed endoscopic OCT as a minimally invasive method to identify early CLAD biomarkers. During 65 routine surveillance and event-initiated bronchoscopies of lung transplant recipients at Vancouver General Hospital, OCT imaging was performed prior to acquiring biopsy samples, with multiple 3D volumetric scans taken at locations as close as possible to those biopsied. OCT has the potential to be advantageous over biopsy because multiple airways in the lung can be quickly surveyed. As a first step towards clinical utility we present our methods for quantifying observable biomarkers including luminal size and alveolar density. Ranges of values are established and correlated with airway generation, time since transplant, and infection status.
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