Primary mediastinal choriocarcinoma requiring differentiation from non-small cell lung cancer: An autopsy case report.

A 65-year-old man with dyspnea and hemoptysis presented with a right upper lobe mass associated with enlarged mediastinal lymph nodes and bilateral pulmonary nodules on chest computed tomography (CT), suspected lung cancer. Bronchial and CT-guided biopsies revealed poorly differentiated carcinoma. His condition deteriorated rapidly before a definitive diagnosis could be made. Autopsy revealed primary mediastinal choriocarcinoma. Primary mediastinal choriocarcinomas are rare, difficult to diagnose early and have a poor prognosis. In patients with a tumor expanding across the lung and mediastinum and exhibiting pathologic findings of a pooly differentiated carcinoma, we should consider choriocarcinoma, evaluating the serum ß-human chorionic gonadotropin levels.

TNF Superfamily and ILC2 Activation in Asthma.

Eosinophilic asthma is the most prevalent and well-defined phenotype of asthma. Despite a majority of patients responding to corticosteroid therapy and T2 biologics, there remains a subset that have recurrent asthma exacerbations, highlighting a need for additional therapies to fully ameliorate airway eosinophilia. Group 2 innate lymphoid cells (ILC2) are considered key players in the pathogenesis of eosinophilic asthma through the production of copious amounts of type 2 cytokines, namely IL-5 and IL-13. ILC2 numbers are increased in the airways of asthmatics and with the greatest numbers of activated ILC2 detected in sputa from severe prednisone-dependent asthma with uncontrolled eosinophilia. Although epithelial-derived cytokines are important mediators of ILC2 activation, emerging evidence suggests that additional pathways stimulate ILC2 function. The tumor necrosis factor super family (TNFSF) and its receptors (TNFRSF) promote ILC2 activity. In this review, we discuss evidence supporting a relationship between ILC2 and TNFSF/TNFRSF axis in eosinophilic asthma and the role of this relationship in severe asthma with airway autoimmune responses.

[THE EFFICACY OF BRONCHIAL THERMOPLASTY IN LONG-TERM MAINTENANCE OF ADULT PATIENTS WITH MODERATE TO SEVERE ASTHMA].

BACKGROUND AND AIMS: Bronchial thermoplasty (BT) is a bronchoscopic treatment for adult patients with moderate to severe asthma. A systematic review was conducted to examine the efficacy of this treatment. METHODS: Randomized controlled comparing BT to a control in adult patients with moderate to severe asthma were added to the previously conducted systematic review. Literature published prior to July 2022 was selected. RESULTS: Four trials were included in this study. BT resulted in significant improvement in quality of life. However, no significant difference in asthma control was observed. Moreover, the incidence of severe adverse events during the treatment period was increased by BT. Furthermore, BT did not improve lung function, increase withdrawal from oral corticosteroids, reduce frequency of rescue medication usage, or increase the number of symptom-free days. CONCLUSION: From a risk-benefit perspective, there is insufficient evidence to support a recommendation of BT in adult patients with moderate to severe asthma.

Compressed sensing with deep learning reconstruction: Improving capability of gadolinium-EOB-enhanced 3D T1WI.

PURPOSE: The purpose of this study was to determine the utility of compressed sensing (CS) with deep learning reconstruction (DLR) for improving spatial resolution, image quality and focal liver lesion detection on high-resolution contrast-enhanced T1-weighted imaging (HR-CE-T1WI) obtained by CS with DLR as compared with conventional CE-T1WI with parallel imaging (PI). METHODS: Seventy-seven participants with focal liver lesions underwent conventional CE-T1WI with PI and HR-CE-T1WI, surgical resection, transarterial chemoembolization, and radiofrequency ablation, followed by histopathological or >2-year follow-up examinations in our hospital. Signal-to-noise ratios (SNRs) of liver, spleen and kidney were calculated for each patient, after which each SNR was compared by means of paired t-test. To compare focal lesion detection capabilities of the two methods, a 5-point visual scoring system was adopted for a per lesion basis analysis. Jackknife free-response receiver operating characteristic (JAFROC) analysis was then performed, while sensitivity and false positive rates (/data set) for consensus assessment of the two methods were also compared by using McNemar's test or the signed rank test. RESULTS: Each SNR of HR-CE-T1WI was significantly higher than that of conventional CE-T1WI with PI (p < 0.05). Sensitivities for consensus assessment showed that HR-CE-MRI had significantly higher sensitivity than conventional CE-T1WI with PI (p = 0.004). Moreover, there were significantly fewer FP/cases for HR-CE-T1WI than for conventional CE-T1WI with PI (p = 0.04). CONCLUSION: CS with DLR are useful for improving spatial resolution, image quality and focal liver lesion detection capability of Gd-EOB-DTPA enhanced 3D T1WI without any need for longer breath-holding time.

Group III secreted phospholipase A2 -driven lysophospholipid pathway protects against allergic asthma.

Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A2 s (PLA2 s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro-asthmatic lipid mediators, but an understanding of the association between individual PLA2 subtypes and asthma is still incomplete. Here, we show that group III-secreted PLA2 (sPLA2 -III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA2 -III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)-induced asthma model, Pla2g3-/- mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA-specific IgE production, and type 2 cytokine expression as compared to Pla2g3+/+ mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA-challenged Pla2g3-/- mice relative to Pla2g3+/+ mice. LPA receptor 2 (LPA2 ) agonists suppressed thymic stromal lymphopoietin (TSLP) expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in Pla2g3-/- mice, suggesting that sPLA2 -III negatively regulates allergen-induced asthma at least by producing LPA. Thus, the activation of the sPLA2 -III-LPA pathway may be a new therapeutic target for allergic asthma.

Coronary computed tomography angiographic detection of in-stent restenosis via deep learning reconstruction: a feasibility study.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

Area-Detector Computed Tomography for Pulmonary Functional Imaging.

An area-detector CT (ADCT) has a 320-detector row and can obtain isotropic volume data without helical scanning within an area of nearly 160 mm. The actual-perfusion CT data within this area can, thus, be obtained by means of continuous dynamic scanning for the qualitative or quantitative evaluation of regional perfusion within nodules, lymph nodes, or tumors. Moreover, this system can obtain CT data with not only helical but also step-and-shoot or wide-volume scanning for body CT imaging. ADCT also has the potential to use dual-energy CT and subtraction CT to enable contrast-enhanced visualization by means of not only iodine but also xenon or krypton for functional evaluations. Therefore, systems using ADCT may be able to function as a pulmonary functional imaging tool. This review is intended to help the reader understand, with study results published during the last a few decades, the basic or clinical evidence about (1) newly applied reconstruction methods for radiation dose reduction for functional ADCT, (2) morphology-based pulmonary functional imaging, (3) pulmonary perfusion evaluation, (4) ventilation assessment, and (5) biomechanical evaluation.

Capability for dose reduction while maintaining nodule detection: Comparison of silver and copper X-ray spectrum modulation filters for chest CT using a phantom study with different reconstruction methods.

PURPOSE: To compare the capability of CTs obtained with a silver or copper x-ray beam spectral modulation filter (Ag filter and Cu filter) and reconstructed with FBP, hybrid-type IR and deep learning reconstruction (DLR) for radiation dose reduction for lung nodule detection using a chest phantom study. MATERIALS AND METHODS: A chest CT phantom was scanned with a 320-detector row CT with Ag filter at 0.6, 1.6 and 2.5 mGy and Cu filters at 0.6, 1.6, 2.5 and 9.6 mGy, and reconstructed with the aforementioned methods. To compare image quality of all the CT data, SNRs and CNRs for any nodule were calculated for all protocols. To compare nodule detection capability among all protocols, the probability of detection of any nodule was assessed with a 5-point visual scoring system. Then, ROC analyses were performed to compare nodule detection capability of Ag and Cu filters for each radiation dose data with the same method and of the three methods for any radiation dose data and obtained with either filter. RESULTS: At any of the doses, SNR, CNR and area under the curve for the Ag filter were significantly higher or larger than those for the Cu filter (p < 0.05). Moreover, with DLR, those values were significantly higher or larger than all the others for CTs obtained with any of the radiation doses and either filter (p < 0.05). CONCLUSION: The Ag filter and DLR can significantly improve image quality and nodule detection capability compared with the Cu filter and other reconstruction methods at each of radiation doses used.

Effectiveness of deep learning reconstruction on standard to ultra-low-dose high-definition chest CT images.

PURPOSE: Deep learning reconstruction (DLR) has been introduced by major vendors, tested for CT examinations of a variety of organs, and compared with other reconstruction methods. The purpose of this study was to compare the capabilities of DLR for image quality improvement and lung texture evaluation with those of hybrid-type iterative reconstruction (IR) for standard-, reduced- and ultra-low-dose CTs (SDCT, RDCT and ULDCT) obtained with high-definition CT (HDCT) and reconstructed at 0.25-mm, 0.5-mm and 1-mm section thicknesses with 512 × 512 or 1024 × 1024 matrixes for patients with various pulmonary diseases. MATERIALS AND METHODS: Forty age-, gender- and body mass index-matched patients with various pulmonary diseases underwent SDCT (CT dose index volume : mean ± standard deviation, 9.0 ± 1.8 mGy), RDCT (CTDIvol: 1.7 ± 0.2 mGy) and ULDCT (CTDIvol: 0.8 ± 0.1 mGy) at a HDCT. All CT data set were then reconstructed with 512 × 512 or 1024 × 1024 matrixes by means of hybrid-type IR and DLR. SNR of lung parenchyma and probabilities of all lung textures were assessed for each CT data set. SNR and detection performance of each lung texture reconstructed with DLR and hybrid-type IR were then compared by means of paired t tests and ROC analyses for all CT data at each section thickness. RESULTS: Data for each radiation dose showed DLR attained significantly higher SNR than hybrid-type IR for each of the CT data (p < 0.0001). On assessments of all findings except consolidation and nodules or masses, areas under the curve (AUCs) for ULDCT with hybrid-type IR for each section thickness (0.91 ≤ AUC ≤ 0.97) were significantly smaller than those with DLR (0.97 ≤ AUC ≤ 1, p < 0.05) and the standard protocol (0.98 ≤ AUC ≤ 1, p < 0.05). CONCLUSION: DLR is potentially more effective for image quality improvement and lung texture evaluation than hybrid-type IR on all radiation dose CTs obtained at HDCT and reconstructed with each section thickness with both matrixes for patients with a variety of pulmonary diseases.

Advances for Pulmonary Functional Imaging: Dual-Energy Computed Tomography for Pulmonary Functional Imaging.

Dual-energy computed tomography (DECT) can improve the differentiation of material by using two different X-ray energy spectra, and may provide new imaging techniques to diagnostic radiology to overcome the limitations of conventional CT in characterizing tissue. Some techniques have used dual-energy imaging, which mainly includes dual-sourced, rapid kVp switching, dual-layer detectors, and split-filter imaging. In iodine images, images of the lung's perfused blood volume (PBV) based on DECT have been applied in patients with pulmonary embolism to obtain both images of the PE occluding the pulmonary artery and the consequent perfusion defects in the lung's parenchyma. PBV images of the lung also have the potential to indicate the severity of PE, including chronic thromboembolic pulmonary hypertension. Virtual monochromatic imaging can improve the accuracy of diagnosing pulmonary vascular diseases by optimizing kiloelectronvolt settings for various purposes. Iodine images also could provide a new approach in the area of thoracic oncology, for example, for the characterization of pulmonary nodules and mediastinal lymph nodes. DECT-based lung ventilation imaging is also available with noble gases with high atomic numbers, such as xenon, which is similar to iodine. A ventilation map of the lung can be used to image various pulmonary diseases such as chronic obstructive pulmonary disease.

The Functional Role of Group 2 Innate Lymphoid Cells in Asthma.

Asthma is a heterogeneous disease characterized by chronic airway inflammation. Group 2 innate lymphoid cells (ILC2) play an important role in the pathogenesis of asthma. ILC2s lack antigen-specific receptors and respond to epithelial-derived cytokines, leading to the induction of airway eosinophilic inflammation in an antigen-independent manner. Additionally, ILC2s might be involved in the mechanism of steroid resistance. Numerous studies in both mice and humans have shown that ILC2s induce airway inflammation through inflammatory signals, including cytokines and other mediators derived from immune or non-immune cells. ILC2s and T helper type 2 (Th2) cells collaborate through direct and indirect interactions to organize type 2 immune responses. Interestingly, the frequencies or numbers of ILC2 are increased in the blood and bronchoalveolar lavage fluid of asthma patients, and the numbers of ILC2s in the blood and sputum of severe asthmatics are significantly larger than those of mild asthmatics. These findings may contribute to the regulation of the immune response in asthma. This review article highlights our current understanding of the functional role of ILC2s in asthma.

Examination of postmortem changes in the lungs, trachea, and bronchi in a rat model imaged with small-animal computed tomography.

Objectives: As less autopsies are performed, the need for postmortem computed tomography (PMCT) as an alternative is increasing. It is important to know how postmortem changes over time are reflected on CT, in order to improve the diagnostic capability of PMCT and replace forensic pathology evaluations such as time of death estimation. Methods: In this study, we examined temporal changes on postmortem chest CT images of a rat model. After acquiring antemortem images under isoflurane inhalation anesthesia, the rats were euthanized with a rapid intravenous injection of anesthetics. From immediately after death to 48 hours postmortem, chest images were acquired using small-animal CT. The 3D images were then evaluated on a workstation to measure the antemortem and postmortem air content in the lungs, trachea, and bronchi over time. Results: The air content in the lungs decreased, but the air content of the trachea and bronchi temporarily increased 1-12 hours postmortem, then decreased at 48 hours postmortem. Therefore, the measurement of trachea and bronchi volumes on PMCT could be an objective way to estimate the time of death. Conclusions: While the air content of the lungs decreased, the volume of the trachea and bronchi temporarily increased after death, indicating the potential to use such measurements to estimate time of death.

Severe asthma remaining well-controlled after mepolizumab discontinuation: A case report and literature review.

Mepolizumab, a humanized anti-IL-5 monoclonal antibody used for severe asthma, results in a reduced rate of asthma exacerbation, improved lung function, reduced oral corticosteroid use, and improved quality of life. A 62-year-old man using high-dose inhaled corticosteroid visited our hospital because of poorly-controlled asthma. He had eosinophilia in peripheral blood and sputum, and high levels of fraction of exhaled nitric oxide. Therefore, he was treated with mepolizumab for severe asthma. Mepolizumab treatment resulted in significantly improved pulmonary function and reduced frequencies of asthma exacerbations. Because of his good asthma control, mepolizumab treatment was discontinued after 3 years. Since discontinuing mepolizumab, his asthma control has remained without exacerbation. Previous studies suggest that mepolizumab should be continued to sustain clinical benefits. However, cases of long-term controlled asthma have not been reported after mepolizumab withdrawal, and our case may be instructive.

Reverse encoding distortion correction for diffusion-weighted MRI: Efficacy for improving image quality and ADC evaluation for differentiating malignant from benign areas in suspected prostatic cancer patients.

PURPOSE: The purpose of this study was to determine the influenceof reverse encoding distortion correction (RDC) on ADC measurement and its efficacy for improving image quality and diagnostic performance for differentiating malignant from benign prostatic areas on prostatic DWI. METHODS: Forty suspected prostatic cancer patients underwent DWI with or without RDC (i.e. RDC DWI or DWI) using a 3 T MR system as well as pathological examinations. The pathological examination results indicated 86 areas were malignant while 86 out of 394 areas were computationally selected as benign. SNR for benign areas and muscle and ADCs for malignant and benign areas were determined by ROI measurements on each DWI. Moreover, overall image quality was assessed with a 5-point visual scoring system on each DWI. Paired t-test or Wilcoxon's signed rank test was performed to compare SNR and overall image quality for DWIs. ROC analysis was then used to compare the diagnostic performance, and sensitivity (SE), specificity (SP) and accuracy (AC) of ADC were compared between two DWI by means of McNemar's test. RESULTS: SNR and overall image quality of RDC DWI showed significant improvements when compared with those of DWI (p < 0.05). Areas under the curve (AUC), SP and AC of DWI RDC DWI (AUC: 0.85, SP: 72.1%, AC: 79.1%) were significantly better than those of DWI (AUC: 0.79, p = 0.008; SP: 64%, p = 0.02; AC: 74.4%, p = 0.008). CONCLUSION: RDC technique has the potential to improve image quality and ability to differentiate malignant from benign prostatic areas on DWIs of suspected prostatic cancer patients.

Syphilis With Multiple Pulmonary Nodules and Bone Lesions Detected on Computed Tomography and 18F Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography.

Syphilis can cause a wide range of systemic manifestations, such as papular rash, malaise, weight loss, muscle aches, generalized lymphadenopathy, and meningitis. However, pulmonary involvement in patients with secondary syphilis is thought to be relatively rare. Moreover, bone involvement in patients with secondary syphilis is also considered rare, and only a few cases of involvement of lung and bone in such patients have been reported. In this paper, we report a case of secondary syphilis with pulmonary involvement in the form of multiple nodules with low attenuation areas, lymphadenopathy and multiple bone lesions detected on computed tomography and 18F fluorodeoxyglucose-positron emission tomography/computed tomography.

The Therapeutic Potential for Targeting Group 2 Innate Lymphoid Cells in Asthma.

T helper type 2 cells (Th2 cells) and group 2 innate lymphoid cells (ILC2s) play an important role in the pathophysiology of asthma, including airway eosinophilic inflammation. ILC2s are activated by epithelial-derived cytokines [interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP)] from airway epithelial cells, leading to the release of high amounts of type 2 cytokines, such as IL-5 and IL-13. ILC2s induce airway inflammation in an antigen-independent manner, and ILC2s are considered to be involved in the pathogenesis of asthma exacerbation. Furthermore, ILC2 activation might also confer steroid resistance. Many recent studies in humans and mice are increasingly demonstrating that the function of ILC2s is regulated not just by epithelial-derived cytokines but by a variety of cytokines and mediators derived from innate immune cells. Furthermore, the biologics targeting these cytokines and/or their receptors have been shown to reduce asthma exacerbations and improve lung function and quality of life in asthmatics. This article reviews the current treatment landscape for type 2 airway inflammation in asthma and discusses the therapeutic potential for targeting ILC2s.

Comparison of utility of deep learning reconstruction on 3D MRCPs obtained with three different k-space data acquisitions in patients with IPMN.

OBJECTIVE: To compare the utility of deep learning reconstruction (DLR) for improving acquisition time, image quality, and intraductal papillary mucinous neoplasm (IPMN) evaluation for 3D MRCP obtained with parallel imaging (PI), multiple k-space data acquisition for each repetition time (TR) technique (Fast 3D mode multiple: Fast 3Dm) and compressed sensing (CS) with PI. MATERIALS AND METHODS: A total of 32 IPMN patients who had undergone 3D MRCPs obtained with PI, Fast 3Dm, and CS with PI and reconstructed with and without DLR were retrospectively included in this study. Acquisition time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) obtained with all protocols were compared using Tukey's HSD test. Results of endoscopic ultrasound, ERCP, surgery, or pathological examination were determined as standard reference, and distribution classifications were compared among all 3D MRCP protocols by McNemar's test. RESULTS: Acquisition times of Fast 3Dm and CS with PI with and without DLR were significantly shorter than those of PI with and without DLR (p < 0.05). Each MRCP sequence with DLR showed significantly higher SNRs and CNRs than those without DLR (p < 0.05). IPMN distribution accuracy of PI with and without DLR and Fast 3Dm with DLR was significantly higher than that of Fast 3Dm without DLR and CS with PI without DLR (p < 0.05). CONCLUSION: DLR is useful for improving image quality and IPMN evaluation capability on 3D MRCP obtained with PI, Fast 3Dm, or CS with PI. Moreover, Fast 3Dm and CS with PI may play as substitution to PI for MRCP in patients with IPMN. KEY POINTS: • Mean examination times of multiple k-space data acquisitions for each TR and compressed sensing with parallel imaging were significantly shorter than that of parallel imaging (p < 0.0001). • When comparing image quality of 3D MRCPs with and without deep learning reconstruction, deep learning reconstruction significantly improved signal-to-noise ratio and contrast-to-noise ratio (p < 0.05). • IPMN distribution accuracies of parallel imaging with and without deep learning reconstruction (with vs. without: 88.0% vs. 88.0%) and multiple k-space data acquisitions for each TR with deep learning reconstruction (86.0%) were significantly higher than those of others (p < 0.05).

Effects of instructional materials on the proper techniques of inhaler device use.

BACKGROUND: Inhaled medication is the cornerstone of pharmacological treatment for asthma. Poor inhaler techniques are associated with poor asthma control and an increased risk of exacerbations. Leaflets and videos are provided by several pharmaceutical companies to explain the proper techniques to patients. We investigated the effects of instructional materials (leaflet and video) on the patient's inhaler techniques. METHODS: The subjects were 67 medical students at Kagoshima University. They all were provided with two types of inhalation devices: a dry powder inhaler (DPI) and a pressurized metered-dose inhaler (pMDI). The students were assigned to three groups: (1) leaflet, (2) video, and (3) combination (leaflet + video). Pulmonologists observed and assessed the students' use of the devices by using a validated checklist. The percentage of subjects who avoided critical errors was also assessed. Critical errors were errors that affected drug delivery to the lungs substantially. RESULTS: The percentage of overall competence and the number of steps that were mastered out of the 11 steps were higher in the combination group than those in the other two groups. However, only 40% in the combination group were able to successfully execute every critical step. The percentage of subjects who avoided critical errors was also higher in the combination group than in the other groups. CONCLUSIONS: A single form of instructional materials (leaflet or video) was insufficient for acquiring proper inhaler techniques. The combination of two learning materials may help patients with asthma acquire proper inhaler techniques and subsequently, improve their asthma control.

Long-acting muscarinic antagonist regulates group 2 innate lymphoid cell-dependent airway eosinophilic inflammation.

BACKGROUND: Tiotropium bromide, a long-acting muscarinic antagonist, reduces the frequency of exacerbation in patients with moderate to severe asthma, but its underlying mechanism is not clear. Asthma exacerbations are associated with exposure to external stimuli, and group 2 innate lymphoid cells (ILC2s) are considered to be involved in the pathophysiology of asthma exacerbation. We investigated whether tiotropium modulates airway inflammation through ILC2 functions. METHODS: Mice were administered papain intranasally to induce innate-type airway inflammation with or without tiotropium pretreatment, and bronchoalveolar lavage fluids (BALF) and lung tissues were collected. Lung-derived ILC2s and bone marrow-derived basophils were stimulated in vitro with IL-33 in the presence or absence of tiotropium. Muscarinic M3 receptor (M3R) expression on immune cells was assessed by RNA sequence. RESULTS: Papain induced airway eosinophilic inflammation, and tiotropium reduced the numbers of eosinophils in BALF. The concentrations of IL-4, IL-5, and IL-13, and the numbers of ILC2s in BALF were also reduced by tiotropium treatment. However, tiotropium did not affect IL-33-induced IL-5 and IL-13 production from ILC2s, suggesting that tiotropium regulates ILC2s indirectly. Gene-expression analysis showed that basophils predominantly expressed M3R mRNA among murine immune cells. Tiotropium reduced IL-4 production from basophils derived from mouse bone marrow and human basophils after stimulation with IL-33. CONCLUSIONS: These findings suggest that tiotropium attenuates ILC2-dependent airway inflammation by suppressing IL-4 production from basophils and, subsequently, regulating ILC2 activation. The inhibitory effects of long-acting muscarinic antagonists on the innate response may contribute to reducing asthma exacerbation.

Association of computed tomography-derived myocardial mass with fractional flow reserve-verified ischemia or subsequent therapeutic strategy.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)-verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P < 0.001). Addition of MVT to a model including patient characteristics (age, gender), visual assessment (≥ 70% stenosis, high-risk appearance), and quantitative CT vessel parameters [minimal lumen area (MLA), plaque burden at MLA, percent aggregate plaque volume] improved C-index (from 0.745 to 0.778, P = 0.020). Furthermore, of 130 vessels with FFR ≤ 0.80, myocardial volume exposed to ischemia (MVI) was larger in the vessels with early revascularization after FFR examination than those without (37.2 ± 20.0 vs. 26.8 ± 15.0 cm3, P = 0.003), and was independently associated with early revascularization [OR = 1.03, 95% confidence interval (1.02-1.11), P < 0.001]. Using an on-site CT workstation, MVT identified coronary arteries with FFR-verified ischemia easily and non-invasively, and MVI was associated with subsequent therapeutic strategy after FFR examinations.