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PurposeTo review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19).Materials and MethodsIn February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid’s secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated.ResultsAll cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC.ConclusionU-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.

Background Pirfenidone, an antifibrotic agent used for the treatment of idiopathic pulmonary fibrosis (IPF), functions by inhibiting myofibroblast differentiation, which is involved in transforming growth factor (TGF)-β1-induced IPF pathogenesis. However, unlike normal lung fibroblasts, the relationship between pirfenidone responses of TGF-β1-induced human fibrotic lung fibroblasts and lung fibrosis has not been elucidated. Methods The effects of pirfenidone were evaluated in lung fibroblasts isolated from fibrotic human lung tissues after TGF-β1 exposure. The ability of two new pharmacological targets of pirfenidone, collagen triple helix repeat containing protein 1(CTHRC1) and four-and-a-half LIM domain protein 2 (FHL2), to mediate contraction of collagen gels and migration toward fibronectin were assessed in vitro. Results Compared to control lung fibroblasts, pirfenidone significantly restored TGF-β1-stimulated fibroblast-mediated collagen gel contraction, migration, and CTHRC1 release in lung fibrotic fibroblasts. Furthermore, pirfenidone attenuated TGF-β1- and CTHRC1-induced fibroblast activity, upregulation of bone morphogenic protein-4(BMP-4)/Gremlin1, and downregulation of α-smooth muscle actin, fibronectin, and FHL2, similar to that observed post-CTHRC1 inhibition. In contrast, FHL2 inhibition suppressed migration and fibronectin expression, but did not downregulate CTHRC1. Conclusions Overall, pirfenidone suppressed fibrotic fibroblast-mediated fibrotic processes via inverse regulation of CTHRC1-induced lung fibroblast activity. Thus, CTHRC1 can be used for predicting pirfenidone response and developing new therapeutic targets for lung fibrosis.

Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1 -/- Rag2 -/- mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1 -/- Rag2 -/- mice as a mouse model for fibrosis research. Idiopathic Pulmonary Fibrosis (IPF) consists of lung inflammation and collagen deposition leading to reduced lung function and non-inducible mouse models are needed. Here the authors show a spontaneous mouse IPF model where Ifngr1 -/- Rag2 -/- mice show enhanced ILC2 activation and function along with pathology similar to IPF.

Background Lung transplantation is a vital therapeutic option for patients with advanced interstitial lung diseases (ILDs) unresponsive to conventional treatments. In Japan, challenges for this treatment include a long waiting period (average, 2.5 year) and the absence of a comprehensive scoring system. Identifying predictors of survival and transplantation outcomes is critical for improving patient management and optimizing donor lung allocation. This study aimed to examine the clinical characteristics and outcomes of Japanese ILD patients referred for lung transplantation, focusing on factors associated with death and transplantation as competing risks. Methods This retrospective, single-center study included patients with ILD referred to a lung transplant clinic between April 2009 and March 2020. Patients were followed until death or study-end censoring. Diagnoses were established through multidisciplinary discussion, incorporating surgical lung biopsy, bronchoscopic examinations, and high-resolution computed tomography. Statistical analyses (R 4.4.2) treated death and transplantation as competing events. Univariate and multivariate Fine–Gray models were used to evaluate factors influencing the subdistribution hazard ratio (sHR) for death. Cumulative incidence functions for death and transplantation were compared using the Gray test. Results Among 65 patients (mean age, 52.0 ± 7.9 years; 66% male), 15% underwent transplantation and 42% died before transplantation. The median time to transplantation was 585 days. Univariate Fine–Gray analysis showed that log-transformed C-reactive protein (CRP_ln) was significantly associated with increased mortality risk, whereas partial pressure of oxygen in arterial blood (PaO₂) and percent predicted diffusing capacity of the lung for carbon monoxide (%DLCO) were significantly associated with low mortality risk. Multivariate analysis confirmed that CRP_ln and PaO 2 independently influenced mortality. Significant differences in the cumulative incidence of death were observed for PaO₂ (cutoff, 80 Torr), %DLCO (cutoff, 40%), and home oxygen therapy. For transplantation probability, Krebs von den Lungen-6 (KL-6; cutoff, 1,400 U/mL) showed a significant difference ( p  = 0.03). Conclusions In Japanese ILD patients referred for lung transplantation, PaO₂, %DLCO, and CRP_ln were independent predictors of mortality. KL-6 was associated with transplantation probability. Continuous monitoring of these biomarkers could aid in the efficient allocation of donor lungs, given the scarcity of donors and prolonged waiting times in Japan.

The pathological classification of nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap (NSIP/OP overlap) remains complex due to overlapping pathological features, and its heterogeneity is not well understood. We retrospectively analysed adult patients with interstitial lung disease (ILD) diagnosed with NSIP/OP overlap via surgical lung biopsy. Patients were pathologically subclustered using an unbiased clustering method, and clinical, radiological, and prognostic differences were examined. Among 38 patients, two pathological clusters were identified: Cluster 1, characterized by fibrotic changes with mild inflammation, and Cluster 2, exhibiting intense inflammation with fibrosis. While both clusters initially responded well to treatment, Cluster 2 demonstrated progressive ILD deterioration and a higher frequency of pulmonary fibrosis. Cluster 2 was also associated with hypoxia, reduced pulmonary function, elevated erythrocyte sedimentation rate, and greater consolidation on chest computed tomography. Based on these findings, we have identified NSIP/OP overlap is a heterogeneous and progressive disease and pathological findings at diagnosis significantly influence both initial ILD severity and long-term prognosis. Our findings highlight the need for tailored long-term management strategies based on early histopathological evaluation.

Background In the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity compared with placebo, with side-effects that were manageable for most patients. We used data from the INBUILD trial to characterize further the safety and tolerability of nintedanib. Methods Patients with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), who had experienced progression of ILD within the 24 months before screening despite management deemed appropriate in clinical practice, were randomized to receive nintedanib 150 mg twice daily or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg twice daily. We assessed adverse events and dose adjustments over the whole trial. Results A total of 332 patients received nintedanib and 331 received placebo. Median exposure to trial drug was 17.4 months in both treatment groups. Adverse events led to treatment discontinuation in 22.0% of patients treated with nintedanib and 14.5% of patients who received placebo. The most frequent adverse event was diarrhea, reported in 72.3% of patients in the nintedanib group and 25.7% of patients in the placebo group. Diarrhea led to treatment discontinuation in 6.3% of patients in the nintedanib group and 0.3% of the placebo group. In the nintedanib and placebo groups, respectively, 48.2% and 15.7% of patients had ≥ 1 dose reduction and/or treatment interruption. Serious adverse events were reported in 44.3% of patients in the nintedanib group and 49.5% of patients in the placebo group. The adverse event profile of nintedanib was generally consistent across subgroups based on age, sex, race and weight, but nausea, vomiting and dose reductions were more common among female than male patients. Conclusions The adverse event profile of nintedanib in patients with progressive fibrosing ILDs other than IPF is consistent with its established safety and tolerability profile in patients with IPF and characterized mainly by gastrointestinal events, particularly diarrhea. Management of adverse events using symptomatic therapies and dose adjustment is important to minimize the impact of adverse events and help patients remain on therapy. Trial registration Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178 Graphical Abstract A video abstract summarizing the key results presented in this manuscript is available at: https://www.globalmedcomms.com/respiratory/cottin/INBUILDsafety .

In this systematic review and meta-analysis, we sought to evaluate the prevalence of cardiac involvement in patients with COVID-19 using cardiac magnetic resonance imaging. A literature review was performed to investigate the left ventricular (LV) and right ventricular (RV) ejection fraction (EF), the prevalence of LV late gadolinium enhancement (LGE), pericardial enhancement, abnormality on T1 mapping, and T2 mapping/T2-weighted imaging (T2WI), and myocarditis (defined by modified Lake Louis criteria). Pooled mean differences (MD) between COVID-19 patients and controls for LVEF and RVEF were estimated using random-effects models. We included data from 10.462 patients with COVID-19, comprising 1.010 non-athletes and 9.452 athletes from 29 eligible studies. The meta-analysis showed a significant difference between COVID-19 patients and controls in terms of LVEF [MD = − 2.84, 95% confidence interval (CI) − 5.11 to − 0.56, p  < 0.001] and RVEF (MD = − 2.69%, 95% CI − 4.41 to − 1.27, p  < 0.001). However, in athletes, no significant difference was identified in LVEF (MD = − 0.74%, 95% CI − 2.41 to − 0.93, p  = 0.39) or RVEF (MD = − 1.88%, 95% CI − 5.21 to 1.46, p  = 0.27). In non-athletes, the prevalence of LV LGE abnormalities, pericardial enhancement, T1 mapping, T2 mapping/T2WI, myocarditis were 27.5% (95%CI 17.4–37.6%), 11.9% (95%CI 4.1–19.6%), 39.5% (95%CI 16.2–62.8%), 38.1% (95%CI 19.0–57.1%) and 17.6% (95%CI 6.3–28.9%), respectively. In athletes, these values were 10.8% (95%CI 2.3–19.4%), 35.4% (95%CI − 3.2 to 73.9%), 5.7% (95%CI − 2.9 to 14.2%), 1.9% (95%CI 1.1–2.7%), 0.9% (0.3–1.6%), respectively. Both LVEF and RVEF were significantly impaired in COVID-19 patients compared to controls, but not in athletes. In addition, the prevalence of myocardial involvement is not negligible in patients with COVID-19.

The aim of this study was to investigate the prevalence and prognostic value of coronary artery disease (CAD) and heart failure (HF) in patients with idiopathic pulmonary fibrosis (IPF). Thirteen hundred and fifty-eight patients with interstitial lung disease [851 (62%) males, mean age: 68 ± 10 years] were retrospectively analyzed. CAD was defined as (1) the presence of a clinical diagnosis of angina pectoris, (2) clinical diagnosis of a myocardial infarction, and (3) coronary angiography showing ≥ 1 vessel with a stenosis of > 75%. The definition of HF was made according to the modified Framingham criteria. Compared to the non-IPF group ( n  = 790), the IPF group ( n  = 568) had a significantly higher prevalence of CAD (9.3% vs. 4.4%, p  < 0.001) and HF (8.2% vs. 3.7%, p  < 0.001). During a median follow-up of 1.6 years, 152 deaths were identified. The patients with HF had a significantly worse prognosis than those without HF both in the non-IPF group and IPF group (both p  < 0.05). However, the prognosis did not significantly differ between the patients with CAD and those without CAD both in the non-IPF group and IPF group. The presence of HF was an independent predictor of death in the IPF [hazard ratio (HR) 3.67, 95% confidence interval (CI) 1.57–8.56, p  = 0.0025] and non-IPF (HR 5.07, 95% CI 1.44–17.86, p  = 0.011) patients. The prevalence of CAD and HF was significantly higher in IPF than non-IPF patients. In addition, the presence of HF was a significant prognostic factor for both IPF and non-IPF patients. These results indicated that the importance of HF as a comorbidity for patients with ILD.

Purity is a component of morality, which relates to perceptions of cleanliness (i.e., physical aspect) and divinity (i.e., symbolic aspect). Purity violations threaten one's traditional values and beliefs and motivate people to recover purity by avoiding something atypical. Like the physical aspect of purity, violating the symbolic aspect of purity can lead people to recover the purity status by excluding out-group members. However, this link is possibly influenced by psychological essentialism, which is the degree of one's perceptions about a clearly built boundary between social categories (e.g., men and women). Therefore, this study investigated the moderating role of essentialist beliefs in the relationship between purity-related morality in a symbolic sense and exclusionary attitudes toward foreigners. Two experimental studies were conducted in Japan, where immigrants play an essential role in securing the working-age population because of its recent \"super-aged\" situation. It was predicted that only lower essentialists would be sensitive to the threat, but not higher essentialists. The results did not support the hypothesis in the expected direction, but some valuable implications and suggestions for future research were made. In particular, this study revealed that symbolic purity may play a role in intergroup relations.