In vivo polarisation sensitive optical coherence tomography for fibrosis assessment in interstitial lung disease: a prospective, exploratory, observational study.

INTRODUCTION: Endobronchial polarisation sensitive optical coherence tomography (EB-PS-OCT) is a bronchoscopic imaging technique exceeding resolution of high-resolution CT (HRCT) by 50-fold. It detects collagen birefringence, enabling identification and quantification of fibrosis. STUDY AIM: To assess pulmonary fibrosis in interstitial lung diseases (ILD) patients with in vivo EB-PS-OCT using histology as reference standard. PRIMARY OBJECTIVE: Visualisation and quantification of pulmonary fibrosis by EB-PS-OCT. SECONDARY OBJECTIVES: Comparison of EB-PS-OCT and HRCT detected fibrosis with histology, identification of ILD histological features in EB-PS-OCT images and comparison of ex vivo PS-OCT results with histology. METHODS: Observational prospective exploratory study. Patients with ILD scheduled for transbronchial cryobiopsy or surgical lung biopsy underwent in vivo EB-PS-OCT imaging prior to tissue acquisition. Asthma patients were included as non-fibrotic controls. Per imaged lung segment, fibrosis was automatically quantified assessing the birefringent area in EB-PS-OCT images. Fibrotic extent in corresponding HRCT areas and biopsies were compared with EB-PS-OCT detected fibrosis. Microscopic ILD features were identified on EB-PS-OCT images and matched with biopsies from the same segment. RESULTS: 19 patients were included (16 ILD; 3 asthma). In 49 in vivo imaged airway segments the parenchymal birefringent area was successfully quantified and ranged from 2.54% (no to minimal fibrosis) to 21.01% (extensive fibrosis). Increased EB-PS-OCT detected birefringent area corresponded to increased histologically confirmed fibrosis, with better predictive value than HRCT. Microscopic ILD features were identified on both in vivo and ex vivo PS-OCT images. CONCLUSIONS: EB-PS-OCT enables pulmonary fibrosis quantification, thereby has potential to serve as an add-on bronchoscopic imaging technique to diagnose and detect (early) fibrosis in ILD.

Bronchoscopic Journey of in vivo Real-Time Microscopic Imaging in ILD: A Case Series.

BACKGROUND: Patients with interstitial lung diseases (ILDs) frequently present with nondiagnostic high-resolution CT (HRCT) scan and bronchoalveolar lavage (BAL) results, resulting in the need for invasive surgical or cryo-lung biopsy that is associated with significant morbidity. Confocal laser endomicroscopy (CLE) and optical coherence tomography (OCT) are high-resolution laser and light-based techniques that provide real-time imaging of the alveolar compartment during bronchoscopy with a different depth and field of view. OBJECTIVES: The aim of the study was to correlate OCT and CLE imaging to HRCT imaging in ILD. METHODS: This is a retrospective case series of 20 ILD patients who underwent alveolar CLE and OCT imaging during a standard bronchoscopy with BAL, followed by a lung biopsy when indicated. CLE and OCT imaging were compared to four main HRCT patterns and histology. The final diagnosis was based on the multidisciplinary discussion diagnosis. RESULTS: Bronchoscopic CLE and OCT imaging were feasible and safe and provided additional high-detailed anatomical information compared to the HRCT. Bronchoscopic real-time CLE was capable of identification of "alveolar cells" (ground glass opacities) and lung fibrosis (increased alveolar elastin fibers). Bronchoscopic real-time OCT allowed for visualization of "patchy fibrotic disease", "honeycombing" (microcysts), and mucosal granulomas in the airways. CONCLUSIONS: Bronchoscopic CLE and OCT of the alveolar compartment is feasible and safe and enables minimally invasive, high-resolution detection of specific ILD features with the potential to improve ILD diagnostics and monitoring and decrease the need for surgical or cryo-lung biopsies.

Cyclophosphamide for interstitial lung disease-associated acute respiratory failure: mortality, clinical response and radiological characteristics.

BACKGROUND: Treatment for interstitial lung disease (ILD) patients with acute respiratory failure (ARF) is challenging, and literature to guide such treatment is scarce. The reported in-hospital mortality rates of ILD patients with ARF are high (62-66%). Cyclophosphamide is considered a second-line treatment in steroid-refractory ILD-associated ARF. The first aim of this study was to evaluate the in-hospital mortality in patients with ILD-associated ARF treated with cyclophosphamide. The second aim was to compare computed tomographic (CT) patterns and physiological and ventilator parameters between survivors and non-survivors. METHODS: Retrospective analysis of patients with ILD-associated ARF treated with cyclophosphamide between February 2016 and October 2017. Patients were categorized into three subgroups: connective tissue disease (CTD)-associated ILD, other ILD or vasculitis. In-hospital mortality was evaluated in the whole cohort and in these subgroups. Clinical response was determined using physiological and ventilator parameters: Sequential Organ Failure Assessment Score (SOFA), PaO2/FiO2 (P/F) ratio and dynamic compliance (Cdyn) before and after cyclophosphamide treatment. The following CT features were quantified: ground-glass opacification (GGO) proportion, reticulation proportion, overall extent of parenchymal disease and fibrosis coarseness score. RESULTS: Fifteen patients were included. The overall in-hospital mortality rate was 40%. In-hospital mortality rates for CTD-associated ILD, other ILD and vasculitis were 20, 57, and 33%, respectively. The GGO proportion (71% vs 45%) was higher in non-survivors. There were no significant differences in the SOFA score, P/F ratio or Cdyn between survivors and non-survivors. However, in survivors the P/F ratio increased from 129 to 220 mmHg and Cdyn from 75 to 92 mL/cmH2O 3 days after cyclophosphamide treatment. In non-survivors the P/F ratio hardly changed (113-114 mmHg) and Cdyn even decreased (27-20 mL/cmH2O). CONCLUSION: In this study, we found a mortality rate of 40% in patients treated with cyclophosphamide for ILD-associated ARF. Connective tissue disease-associated ILD and vasculitis were associated with a lower risk of death. In non-survivors, the CT GGO proportion was significantly higher. The P/F ratio and Cdyn in survivors increased after 3 days of cyclophosphamide treatment.

Bronchial Thermoplasty-Induced Acute Airway Effects Assessed with Optical Coherence Tomography in Severe Asthma.

BACKGROUND: Bronchial thermoplasty (BT) is an endoscopic treatment for severe asthma targeting airway smooth muscle (ASM) with radiofrequent energy. Although implemented worldwide, the effect of BT treatment on the airways is unclear. Optical coherence tomography (OCT) is a novel imaging technique, based on near-infrared light, that generates high-resolution cross-sectional airway wall images. OBJECTIVE: To assess the safety and feasibility of OCT in severe asthma patients and determine acute airway effects of BT by OCT and compare these to the untreated right middle lobe (RML). METHODS: Severe asthma patients were treated with BT (TASMA trial). During the third BT procedure, OCT imaging was performed immediately following BT in the airways of the upper lobes, the right lower lobe treated 6 weeks prior, and the untreated RML. RESULTS: 57 airways were imaged in 15 patients. No adverse events occurred. Three distinct OCT patterns were discriminated: low-intensity scattering pattern of (1) bronchial and (2) peribronchial edema and (3) high-intensity scattering pattern of epithelial sloughing. (Peri)bronchial edema was seen in all BT-treated airways, and less pronounced in only 1/3 of the RML airways. These effects extended beyond the ASM layer and more distal than the directly BT-treated areas and were reduced, but not resolved, after 6 weeks. Epithelial sloughing occurred in 11/14 of the BT-treated airways and was absent in untreated RML airways. CONCLUSIONS: Acute BT effects can be safely assessed with OCT and 3 distinct patterns were identified. The acute effects extended beyond the targeted ASM layer and distal of directly BT-treated airway areas, suggesting that BT might also target smaller distal airways.

Esophageal ultrasound (EUS) assessment of T4 status in NSCLC patients.

BACKGROUND: Mediastinal and central large vessels (T4) invasion by lung cancer is often difficult to assess preoperatively due to the limited accuracy of computed tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the relationship of para-esophageally located lung tumors to surrounding mediastinal structures. AIM: To assess the value of EUS for detecting mediastinal invasion (T4) of centrally located lung tumors. METHODS: Patients who underwent EUS for the diagnosis and staging of lung cancer and in whom the primary tumor was detected by EUS and who subsequently underwent surgical- pathological staging (2000-2016) were retrospectively selected from two university hospitals in The Netherlands. T status of the lung tumor was reviewed based on EUS, CT and thoracotomy findings. Surgical- pathological staging was the reference standard. RESULTS: In 426 patients, a lung malignancy was detected by EUS of which 74 subjects subsequently underwent surgical- pathological staging. 19 patients (26%) were diagnosed with stage T4 based on vascular (n=8, 42%) or mediastinal (n=8, 42%) invasion or both (n=2, 11%), one patient (5%) had vertebral involvement. Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS (n=74); 42%, 95%, 73%, 83%, for chest CT (n=66); 76%, 61%, 41%, 88% and the combination of EUS and chest CT (both positive or negative for T4, (n=34); 83%, 100%, 100% 97%. CONCLUSION: EUS has a high specificity and NPV for the T4 assessment of lung tumors located para-esophageally and offers further value to chest CT scan.

Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses.

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preserved DLCO. Retrospectively, 166 IPAH patients were included and grouped based on a DLCO cut-off value of 45% pred (IPAH(<45%) and IPAH(≥45%)). Clinical characteristics, treatment responses and survival were compared. IPAH(<45%) were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a low DLCO. Age and number of pack years were independently associated with DLCO < 45% pred. IPAH(<45%) showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease. To conclude, a severely reduced DLCO in IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.