VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.

VISTA (V domain immunoglobulin suppressor of T cell activation, also called PD-1H [programmed death-1 homolog]), a novel immune regulator expressed on myeloid and T lymphocyte lineages, is upregulated in mouse and human idiopathic pulmonary fibrosis (IPF). However, the significance of VISTA and its therapeutic potential in regulating IPF has yet to be defined. To determine the role of VISTA and its therapeutic potential in IPF, the expression profile of VISTA was evaluated from human single-cell RNA sequencing data (IPF Cell Atlas). Inflammatory response and lung fibrosis were assessed in bleomycin-induced experimental pulmonary fibrosis models in VISTA-deficient mice compared with wild-type littermates. In addition, these outcomes were evaluated after VISTA agonistic antibody treatment in the wild-type pulmonary fibrosis mice. VISTA expression was increased in lung tissue-infiltrating monocytes of patients with IPF. VISTA was induced in the myeloid population, mainly circulating monocyte-derived macrophages, during bleomycin-induced pulmonary fibrosis. Genetic ablation of VISTA drastically promoted pulmonary fibrosis, and bleomycin-induced fibroblast activation was dependent on the interaction between VISTA-expressing myeloid cells and fibroblasts. Treatment with VISTA agonistic antibody reduced fibrotic phenotypes accompanied by the suppression of lung innate immune and fibrotic mediators. In conclusion, these results suggest that VISTA upregulation in pulmonary fibrosis may be a compensatory mechanism to limit inflammation and fibrosis, and stimulation of VISTA signaling using VISTA agonists effectively limits the fibrotic innate immune landscape and consequent tissue fibrosis. Further studies are warranted to test VISTA as a novel therapeutic target for the IPF treatment.

Treatment Outcomes of Cavitary Nodular Bronchiectatic-Type Mycobacterium avium Complex Pulmonary Disease.

We investigated the treatment outcomes of patients with cavitary nodular bronchiectatic (C-NB)-type Mycobacterium avium complex (MAC) pulmonary disease (PD) via outcome comparisons between the fibrocavitary (FC) and C-NB types treated with guideline-based therapy (GBT) composed of daily three-drug oral antibiotics and injectable aminoglycoside. Additionally, we analyzed whether treatment with oral antibiotics alone would result in acceptable outcomes for the C-NB type. From 2002 to 2019, patients with cavitary MAC-PD who received three-drug oral antibiotics with or without an injectable aminoglycoside for ≥1 year were retrospectively enrolled at a tertiary referral center in South Korea. We compared the rates of culture conversion at 12 months according to the radiological type and treatment regimen. The overall culture conversion rate at 12 months of 154 patients with cavitary MAC-PD who received GBT was 75.3%. Among them, the culture conversion rates of 114 patients with the C-NB type were higher than that of 40 patients with the FC-type (80.7% versus 60.0%, respectively; P = 0.009). Of 166 patients with the C-NB-type treated with oral medications with or without an injectable drug, 83.7% achieved culture conversion at 12 months. The conversion rates of those who received oral medications alone and those treated with oral medications and an injectable aminoglycoside were similar (90.4% versus 80.7%, respectively; P = 0.117). In conclusion, the culture conversion rates of the patients with C-NB type treated with GBT were significantly higher than those of patients with the FC type. Additionally, the C-NB type could be treated with oral medications alone.

Stronger correlation of peak oxygen uptake with distance of incremental shuttle walk test than 6-min walk test in patients with COPD: a systematic review and meta-analysis.

BACKGROUND: The 6-min walk test (6MWT) and incremental shuttle walk test (ISWT) are valid and reliable measures to assess exercise capacity of patients with chronic obstructive pulmonary disease (COPD). However, the comparison of correlation between peak oxygen uptake (peak VO2) and 6MWT or ISWT distance has not been investigated. We aimed to investigate the correlation between peak VO2 and 6MWT and ISWT distances in COPD patients through a meta-analysis. METHODS: We systematically searched MEDLINE, Scopus, Embase, and the Cochrane Library up to June, 2020 for studies comparing the correlation of peak VO2 with either 6MWT or ISWT in COPD patients. Meta-analysis was performed with R software using a fixed-effect model. We compared the correlation coefficient and measured the heterogeneity using I2 statistics. RESULTS: We identified 12 studies involving 746 patients. Meta-analysis showed a significant correlation between peak VO2 and 6MWT and ISWT distances (6MWT: r = 0.65, 95% CI 0.61-0.70; ISWT: r = 0.81, 95% CI 0.74-0.85; p < 0.0001). The heterogeneity was lower in ISWT than in 6MWT (6MWT: I2 = 56%, p = 0.02; ISWT: I2 = 0%, p = 0.71). Subgroup analysis showed a higher correlation coefficient in the low exercise capacity group than in the high exercise capacity group in both field tests. CONCLUSIONS: 6MWT and ISWT significantly correlated with peak VO2. Our findings suggest that ISWT has a stronger correlation with peak VO2 than 6MWT. The exercise capacity in COPD patients may affect the strength of the relationship between peak VO2 and walking distance in both field tests, suggesting the importance of using various exercise tests. Trial registration CRD 42020200139 at crd.york.ac.uk/prospero/.

Histiocytic pleural effusion: the strong clue to malignancy.

BACKGROUND: There have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE. METHODS: In this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed. RESULTS: Among the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology. CONCLUSIONS: The leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

ECMO is associated with decreased hospital mortality in COVID-19 ARDS.

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020-December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36-0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11-0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups.

Correlation Comparison and Personalized Utility of Field Walking Tests in Assessing the Exercise Capacity of Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Background: Incremental shuttle walking tests (ISWT) are regarded as valuable alternatives to 6-min walking tests (6MWT) and cardiopulmonary exercise tests (CPET) owing to the maximal and externally paced loading. This study investigated the validity and reliability of ISWT by analyzing the correlation of the distances of two field tests with peak oxygen consumption (VO2) of CPET in patients with COPD. Methods: In this randomized controlled trial, patients with COPD were enrolled from two hospitals. Three assessments were performed for all patients. The ISWT and 6MWT were repeated twice in Hospital 1 to assess reliability. Results: A total of 29 patients were enrolled. The distances of ISWT (0.782, p < 0.001) and 6MWT (0.512, p = 0.005) correlated with peak VO2. The intraclass correlation coefficients of both ISWT (0.988, p < 0.001) and 6MWT (0.959, p < 0.001) was high. Patients with higher peak VO2 walked a longer distance in ISWT than 6MWT (r = 0.590, p < 0.001). Conclusions: The ISWT more highly correlates with peak VO2 than the 6MWT and has excellent reliability in patients with COPD. According to peak VO2, the walking distances of each field test varied, suggesting that the application should be personalized for the exercise capacity.

The Effectiveness of the Use of Regdanvimab (CT-P59) in Addition to Remdesivir in Patients with Severe COVID-19: A Single Center Retrospective Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. METHODS: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. RESULTS: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO2/FiO2 ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. CONCLUSIONS: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir.

The mechanical characteristics and performance evaluation of a newly developed silicone airway stent (GINA stent).

Central airway obstruction (CAO) can be attributed to several benign or malignant conditions. Although surgery is the preferred therapeutic option for the management of CAO, bronchoscopic treatment can be performed in scenarios where the surgical procedure is not possible. Recent years have witnessed several improvements in the field of bronchoscopic treatment, especially with regard to airway stents. Current research involves new attempts to overcome the existing shortcomings pertaining to the stents (migration, mucostasis, and granulation tissue formation). The authors have recently developed a new silicone airway stent (GINA stent) with an anti-migration design, dynamic structure that enables the reduction of stent cross-sectional area, and radio-opacity. The present study aimed to evaluate the mechanical characteristics and performance of the novel GINA stent using a porcine tracheal stenosis model. In the current study, all the tests involved the comparison of the GINA stent [outer diameter (OD, mm): 14; length (L, mm): 55] with the Dumon stent (OD: 14; L: 50). The mechanical tests were performed using a digital force gauge, in order to determine the anti-migration force, expansion force, and flexibility. The present study evaluated the short-term (3 weeks) performance of the two stents after implantation [GINA (n = 4) vs. Dumon (n = 3)] in the porcine tracheal stenosis model. The results pertaining to the comparison of the mechanical properties of the GINA and Dumon stents are stated as follows: anti-migration force (18.4 vs. 12.8 N, P = 0.008); expansion force (11.9 vs. 14.5 N, P = 0.008); and flexibility (3.1 vs. 4.5 N, P = 0.008). The results pertaining to the comparison of the short-term performance of the GINA and Dumon stents are stated as follows: mucus retention (0/4 vs. 0/3); granulation tissue formation (0/4 vs. 0/3); and migration (1/4 vs. 2/3). The GINA stent displayed better mechanical properties and comparable short-term performance, compared to the Dumon stent.