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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-021-01615-2

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

COVID-19: Histopathological correlates of imaging patterns on chest computed tomography

Background and objective: Patients with coronavirus disease 2019 (COVID-19) pneumonia present with typical findings on chest computed tomography (CT), but the underlying histopathological patterns are unknown. Through direct regional correlation of imaging findings to histopathological patterns, this study aimed to explain typical COVID-19 CT patterns at tissue level. Methods: Eight autopsy cases were prospectively selected of patients with PCR-proven COVID-19 pneumonia with varying clinical manifestations and causes of death. All had been subjected to chest CT imaging 24–72 h prior to death. Twenty-seven lung areas with typical COVID-19 patterns and two radiologically unaffected pulmonary areas were correlated to histopathological findings in the same lung regions. Results: Two dominant radiological patterns were observed: ground-glass opacity (GGO) (n = 11) and consolidation (n = 16). In seven of 11 sampled areas of GGO, diffuse alveolar damage (DAD) was observed. In four areas of GGO, the histological pattern was vascular damage and thrombosis, with (n = 2) or without DAD (n = 2). DAD was also observed in five of 16 samples derived from areas of radiological consolidation. Seven areas of consolidation were based on a combination of DAD, vascular damage and thrombosis. In four areas of consolidation, bronchopneumonia was found. Unexpectedly, in samples from radiologically unaffected lung parenchyma, evidence was found of vascular damage and thrombosis. Conclusion: In COVID-19, radiological findings of GGO and consolidation are mostly explained by DAD or a combination of DAD and vascular damage plus thrombosis. However, the different typical CT patterns in COVID-19 are not related to specific histopathological patterns. Microvascular damage and thrombosis are even encountered in the radiologically normal lung

Concerns in using multi-detector computed tomography for diagnosing pulmonary embolism in daily practice. A cross-sectional analysis using expert opinion as reference standard

Item does not contain fulltextMulti-detector computed tomography (MDCT) is considered to be the reference standard in diagnosing pulmonary embolism (PE). However, two concerns remain. Firstly, with the introduction of MDCT the prevalence of (sub)segmental emboli increased but the clinical implications of these small clots are uncertain. Secondly, we are not well informed about the number of false-positive CT-scans due to the lack of a gold standard.We used data from a prospective primary care study including patients suspected of pulmonary embolism. CT-scan-reading by the local radiologist in daily care was retrospectively compared with expert reading as reference standard. Final diagnosis was categorized as central/lobar, segmental or subsegmental PE.A total of 79 patients were included. In 3 of 30 patients (10\%) diagnosed with PE by the local radiologist the experts refuted the diagnosis. In 7 of 49 patients (14\%) not diagnosed with PE by the local radiologist the experts confirmed the presence of PE. The experts diagnosed 17 of 32 PE-patients (53\%) with a central or lobar PE. All these 17 patients were also diagnosed with PE by the local radiologist. The experts diagnosed 15 patients with (sub)segmental PE. In 7 of these 15 patients (47\%) the local radiologist refuted PE.Accuracy of MDCT using the expert radiologist as reference standard is not optimal. On the one hand it shows 10\% false-positives exposing patients to anticoagulant treatment unnecessarily. On the other hand small emboli seem to be missed although the clinical implications of this finding are not fully clear

Association of Hyperferritinemia with Distinct Host Response Aberrations in Patients with Community-Acquired Pneumonia

Background: Strongly elevated ferritin levels have been proposed to reflect systemic hyperinflammation in patients admitted to the intensive care unit. Knowledge of the incidence and pathophysiological implications of hyperferritinemia in patients with acute infection admitted to a non-intensive care setting is limited. Methods: We determined the association between hyperferritinemia, defined by 2 cutoff values (500 and 250 ng/mL), and aberrations in key host response mechanisms among patients with community-Acquired pneumonia (CAP) on admission to a general hospital ward (clinicaltrials.gov NCT02928367; trialregister.nl NTR6163). Results: Plasma ferritin levels were higher in patients with CAP (n=174; median [interquartile ranges], 259.5 [123.1-518.3] ng/mL) than in age-and sex-matched controls without infection (n=50; 102.8 [53.5-185.7] ng/mL); P<.001); they were ≥500 ng/mL in 46 patients (26%) and ≥250 ng/mL in 90 (52%). Measurements of 26 biomarkers reflective of distinct pathophysiological domains showed that hyperferritinemia was associated with enhanced systemic inflammation, neutrophil activation, cytokine release, endothelial cell activation and dysfunction, and activation of the coagulation system. Results were robust across different cutoff values. Conclusions: Hyperferritinemia identifies patients with CAP with a broad deregulation of various host response mechanisms implicated in the pathogenesis of sepsis. This could inform future therapeutic strategies targeting subgroups within the CAP population

Ultra-low-dose CT versus chest X-ray for patients suspected of pulmonary disease at the emergency department: a multicentre randomised clinical trial

Background: Chest CT displays chest pathology better than chest X-ray (CXR). We evaluated the effects on health outcomes of replacing CXR by ultra-low-dose chest-CT (ULDCT) in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. Methods: Pragmatic, multicentre, non-inferiority randomised clinical trial in patients suspected of non-traumatic pulmonary disease at the emergency department. Between 31 January 2017 and 31 May 2018, every month, participating centres were randomly allocated to using ULDCT or CXR. Primary outcome was functional health at 28 days, measured by the Short Form (SF)-12 physical component summary scale score (PCS score), non-inferiority margin was set at 1 point. Secondary outcomes included hospital admission, hospital length of stay (LOS) and patients in follow-up because of incidental findings. Results: 2418 consecutive patients (ULDCT: 1208 and CXR: 1210) were included. Mean SF-12 PCS score at 28 days was 37.0 for ULDCT and 35.9 for CXR (difference 1.1; 95% lower CI: 0.003). After ULDCT, 638/1208 (52.7%) patients were admitted (median LOS of 4.8 days; IQR 2.1-8.8) compared with 659/1210 (54.5%) patients after CXR (median LOS 4.6 days; IQR 2.1-8.8). More ULDCT patients were in follow-up because of incidental findings: 26 (2.2%) versus 4 (0.3%). Conclusions: Short-term functional health was comparable between ULDCT and CXR, as were hospital admissions and LOS, but more incidental findings were found in the ULDCT group. Our trial does not support routine use of ULDCT in the work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. Trial registration number: NTR6163