Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs

Objective: Chest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA. Methods: The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive. Results: The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%. Conclusion: The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity

Acute Radiological Abnormalities after Bronchial Thermoplasty: A Prospective Cohort Trial

Background: Bronchial thermoplasty (BT) is a novel treatment for severe asthma based on radiofrequency energy delivery to the larger airways. Although impressive radiological abnormalities have been reported, the incidence, pattern, and behavior over time of acute radiological abnormalities following BT are not well established. Objective: To assess the incidence pattern and behavior over time of acute radiological abnormalities following BT. Methods: This is a prospective, observational imaging study of severe asthma patients participating in the TASMA trial. Imaging of the lung (chest X-ray and/or computed tomography [CT]) was performed routinely before and directly after BT, within 6 weeks and at 6 months' follow-up. Results: Thirty-four chest X-rays were performed within <5 h following 34 BT procedures in 12 patients. In 91% of cases, radiological abnormalities were seen, designated as peribronchial consolidations (97%) and/or atelectasis (29%). Ultra-low-dose (ULD) chest CTs were performed following 16 BT procedures showing abnormalities in all. Four different radiological patterns were identi-fied: peribronchial consolidations with surrounding ground glass opacities (94%), atelectasis (38%), partial bronchial occlusions (63%), and bronchial dilatations (19%). No bronchoscopic intervention was needed. At 6 months' follow-up, in a single patient, high-resolution chest CT showed a focal bronchiectasis in a single airway. Conclusions: There is a high incidence of acute radiological abnormalities after BT. Four distinct radiological patterns can be identified on ULD chest CT, which resolve without clinical impact in virtually all cases. (C) 2017 The Author(s) Published by S. Karger AG, Base

Electronic nose technology for detection of invasive pulmonary aspergillosis in prolonged chemotherapy-induced neutropenia: a proof-of-principle study

Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validatio

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

Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs

textabstractObjective: Chest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA. Methods: The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive. Results: The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%. Conclusion: The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity

OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: Chest X-ray or ultra-low-dose chest CT (OPTIMACT) trial - Statistical analysis plan

Background: A chest X-ray is a standard imaging procedure in the diagnostic work-up of patients suspected of having non-traumatic pulmonary disease. Compared to a chest X-ray, an ultra-low-dose (ULD) chest computed tomography (CT) scan provides substantially more detailed information on pulmonary conditions. To what extent this translates into an improvement in patient outcomes and health care efficiency is yet unknown. The OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose chest CT (OPTIMACT) study is a multicenter, pragmatic, non-inferiority randomized controlled trial designed to evaluate replacement of chest X-ray by ULD chest CT in the diagnostic work-up of such patients, in terms of patient-related health outcomes and costs. During randomly assigned periods of 1 calendar month, either conventional chest X-ray or ULD chest CT scan was used as the imaging strategy. This paper presents in detail the statistical analysis plan of the OPTIMACT trial, developed prior to data analysis. Methods/results: Functional health at 28 days is the primary clinical outcome. Functional health at 28 days is measured by the physical component summary scale of the Short Form (SF)-12 questionnaire version 1. Secondary outcomes are mental health (mental component summary scale of the SF-12), length of hospital stay, mortality within 28 days, quality-adjusted life year equivalent during the first 28 days (derived from the EuroQol five-dimension, five-level instrument), correct diagnoses at emergency department discharge as compared to the final post hoc diagnosis at day 28, number of patients in follow-up because of incidental findings on chest X-ray or ULD chest CT, and health care costs. Conclusions: After this pragmatic trial we will have precise estimates of the effectiveness of replacing chest X-ray with ULD chest CT in terms of patient-related health outcomes and costs. Trial registration: Netherlands National Trial Register: NTR6163. Registered on 6 December 2016

Interstitial pneumonitis caused by everolimus: a case-cohort study in renal transplant recipients

The use of inhibitors of the mammalian target of rapamycin (mTORi) in renal transplantation is associated with many side effects, the potentially most severe being interstitial pneumonitis. Several papers have reported on sirolimus-induced pneumonitis, but less is published on everolimus-induced pneumonitis (EIP). Data on risk factors for contracting EIP are even more scarce. In the present case-cohort study in renal transplant recipients (RTR), we aimed to assess the incidence and risk factors of EIP after renal transplantation. This study is a retrospective substudy of a multicenter randomized controlled trial. All patients included in the original trial and treated with prednisolone/everolimus were included in this substudy. RTR who developed EIP were identified as cases. RTR without pulmonary symptoms served as controls. Thirteen of 102 patients (12.7%) developed EIP. We did not find any predisposing factors, especially no correlation with everolimus concentration. On pulmonary CT scan, EIP presented with an organizing pneumonia-like pattern, a nonspecific interstitial pneumonitis-like pattern, or both. Median time (range) to the development of EIP after start of everolimus was 162 (38-407) days. In conclusion, EIP is common in RTR, presenting with an organizing pneumonia, a nonspecific interstitial pneumonitis-like pattern, or both. No predisposing factors could be identified (Trial registration number: NTR567 (www.trialregister.nl), ISRCTN69188731

OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose CT (OPTIMACT)—a randomised controlled trial chest X-ray or ultra-low-dose CT at the ED: design and rationale

Abstract Background Chest X-ray has been the standard imaging method for patients suspected of non-traumatic pulmonary disease at the emergency department (ED) for years. Recently, ultra-low-dose chest computed tomography (ULD chest CT) has been introduced, which provides substantially more detailed information on pulmonary conditions that may cause pulmonary disease, with a dose in the order of chest X-ray (0.1 vs. 0.05 mSv). The OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or CT (OPTIMACT) study is a randomized trial designed to evaluate the effectiveness of replacing chest X-ray for ULD chest CT in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the ED. Methods Two thousand four hundred patients presenting at the ED with pulmonary complaints and suspected of non-traumatic pulmonary disease will be enrolled in this multicenter, pragmatic, randomized trial. During randomly assigned periods of one calendar month, either conventional chest X-ray or ULD chest CT scan will be used as the imaging strategy. Randomization will rely on computer-generated blocks of 2 months to control for seasonal effects. Chest X-ray and ULD chest CT will be performed in a standardized way, after obtaining the clinical history and performing physical examination and initial laboratory tests. The primary outcome measure is functional health at 28 days. Secondary outcome measures are mental health, length of hospital stay, mortality within 28 days, quality-adjusted life years (QALYs) during the first 28 days, correct diagnoses at ED discharge as compared to the final post hoc diagnosis, and number of patients in follow-up because of incidental findings on chest X-ray or ULD chest CT. In an economic evaluation, we will estimate total health care costs during the first 28 days. Discussion This pragmatic trial will clarify the effects of replacing chest X-ray by ULD chest CT in daily practice, in terms of patient-related health outcomes and costs, in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the ED. Trial registration The OPTIMACT trial is registered in the Netherlands National Trial Register under number NTR6163. The date of registration is December 6, 2016