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Endobronchial Optical Coherence Tomography May Identify Pre-Symptomatic Disease Amongst Patients With Interstitial Lung Abnormalities

Key findings

  • This pilot study investigated endobronchial optical coherence tomography (EB-OCT) in subjects with interstitial lung abnormalities undergoing lung nodule resection, and compared EB-OCT findings against histology and progression outcomes within five years
  • EB-OCT was performed during bronchoscopy immediately prior to lung nodule resection, and all patients were followed for up to five years, including with thin-section CT
  • Fibrosis with microscopic traction bronchiolectasis and/or honeycombing detected by EB-OCT, but not initially visible on CT, was 100% predictive of disease progression, with most patients showing radiologic evidence of progression within two years
  • Patients with early usual interstitial pneumonia detected by EB-OCT developed idiopathic pulmonary fibrosis within 1.5 to three years
  • If these results are validated in larger cohorts, EB-OCT would be a useful adjunct to CT to identify high-risk candidates for inclusion in clinical trials of interventions for pre-symptomatic interstitial lung disease

There's increasing focus on the possibility of treating interstitial lung disease (ILD) at pre-symptomatic stages before lung function declines. Clinical trials of early therapy will require biomarkers that identify pre-symptomatic individuals at high risk of progression to clinical ILD. Incidentally detected interstitial lung abnormalities (ILA) on computed tomography (CT) are linked to increased risk, however, only 30% to 70% of individuals with ILA develop clinically relevant disease.

Endobronchial optical coherence tomography (EB-OCT), a minimally invasive technology, provides rapid, 3D microscopic imaging of the lungs at 200x higher resolution than CT.

Massachusetts General Hospital researchers have published several studies demonstrating EB-OCT can evaluate the subpleural/distal lung rapidly and safely, as well as distinguish early idiopathic pulmonary fibrosis with 100% sensitivity and specificity compared with histology.

Now, in a prospective pilot study, Lida P. Hariri, MD, PhD, a biomedical optical engineer and pulmonary pathologist in the Department of Pathology and Division of Pulmonary and Critical Care Medicine at Mass General, Colleen M. Keyes, MD, MPH, an interventional pulmonologist and intensivist in the Division, and colleagues have determined EB-OCT may complement CT in assessing which individuals with ILA have pre-symptomatic ILD. Their findings appear in a manuscript in the American Journal of Respiratory and Critical Care Medicine.

Methods

The researchers recruited eight patients who had ILA and a lung nodule detected incidentally on CT and were undergoing bronchoscopy and surgical resection. EB-OCT was performed during bronchoscopy immediately prior to resection.

Two pathologists participated in the study:

  • One blinded to histology classified the EB-OCT images as showing or not showing microscopic definite fibrosis, defined as subpleural and/or airway-centered fibrosis with microscopic traction bronchiolectasis or honeycombing
  • One blinded to EB-OCT results interpreted the histology

All patients were followed for up to five years with both clinical exams and thin-section CT.

Results

The team found that:

  • EB-OCT was not associated with any adverse events
  • Histology independently confirmed EB-OCT findings in all patients
  • All patients with microscopic definite fibrosis detected by EB-OCT showed disease progression on CT 1 to 3 years later
  • Two patients had early usual interstitial pneumonia detected on EB-OCT and developed symptomatic idiopathic pulmonary fibrosis 1.5 to 3 years later
  • Patients who didn't have microscopic definite fibrosis detected by EB-OCT had no evidence of progression during 5-year follow-up

Looking Ahead

If these findings are validated in larger cohorts, EB-OCT could be useful as a complement to CT for further assessment of ILA. EB-OCT may be used to identify appropriate candidates for clinical trials of interventions in pre-symptomatic ILD, as well as to provide insight into pathogenesis of early disease.

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Related

Researchers from the Division of Pulmonary and Critical Care Medicine and Department of Pathology found in a prospective study that endobronchial optical coherence tomography, a minimally invasive, real-time imaging modality, is highly accurate for microscopic diagnosis of interstitial lung disease, notably histopathologic diagnosis of usual interstitial pneumonia in patients with a clinical diagnosis of idiopathic pulmonary fibrosis.

Related

Colleen Keyes, MD, MPH, Erik Folch, MD, MSc, and colleagues report initial data from a multicenter trial demonstrating safe use of a shape-sensing robotic-assisted bronchoscopy system to biopsy small peripheral pulmonary nodules in 241 patients.